NCBI Conserved Domain Search

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 203.64 E-value: 2.12e-61

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   97 GPVFVQEPDDVIFPTDSDEKKVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLIDGTFIISNPSELRDSGLYQCLATN 176
Cdd:cd05848      1 GPVFVQEPDDAIFPTDSDEKKVILNCEARGNPVPTYRWLRNGTEIDTESDYRYSLIDGNLIISNPSEVKDSGRYQCLATN 80

                           90
                   ....*....|....*.
gi 1907197658  177 SFGSILSREATLQFAY 192
Cdd:cd05848     81 SIGSILSREALLQFAY 96

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 177.44 E-value: 3.54e-52

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   97 GPVFVQEPDDVIFPTDSDEKKVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLIDGTFIISNPSELRDSGLYQCLATN 176
Cdd:cd04967      1 GPVFEEQPDDTIFPEDSDEKKVALNCRARANPVPSYRWLMNGTEIDLESDYRYSLVDGTLVISNPSKAKDAGHYQCLATN 80

                           90
                   ....*....|....*.
gi 1907197658  177 SFGSILSREATLQFAY 192
Cdd:cd04967     81 TVGSVLSREATLQFGY 96

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 154.16 E-value: 4.29e-44

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  411 PSFELNQVKKSIIVTKDRGVLIECEPQGSPKPAISWRKGDKAVRANKRIAILPDGSLRILNASKADEGKYICQGVNIFGS 490
Cdd:cd04969      1 PDFELNPVKKKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGK 80


                   ....*....
gi 1907197658  491 AEIIASLSV 499
Cdd:cd04969     81 ANSTGSLSV 89

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 141.15 E-value: 1.79e-39

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  231 PKIEVHFPFTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLRKSQAVLEIPNLQLDDAGIYECTAENSRGKNS 310
Cdd:cd04968      1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDT 80


                   ....*...
gi 1907197658  311 FRGQLQIF 318
Cdd:cd04968     81 VQGRIIVQ 88

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 134.21 E-value: 6.40e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  501 EPTRIELTPKRTELTVGESIVLNCKAIHDASLDVTFYWTLKGQPIDFEKEGGHFENIRAQASSADLMIRNILLMHAGRYG 580
Cdd:cd04970      1 DATRITLAPSNADITVGENATLQCHASHDPTLDLTFTWSFNGVPIDLEKIEGHYRRRYGKDSNGDLEIVNAQLKHAGRYT 80

                           90       100
                   ....*....|....*....|..
gi 1907197658  581 CRVQTTADSVSDEAELLVRGPP 602
Cdd:cd04970     81 CTAQTVVDSDSASATLVVRGPP 102

Sixth immunoglobulin (Ig) domain of contactin-4; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-4. Contactins are neural cell adhesion molecules, and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. Highest expression of contactin-4 is in testes, thyroid, small intestine, uterus, and brain. Contactin-4 plays a role in the response of neuroblastoma cells to differentiating agents, such as retinoids. The contactin 4 gene is associated with cerebellar degeneration in spinocerebellar ataxia type 16.

Pssm-ID: 409439 Cd Length: 102 Bit Score: 133.21 E-value: 1.34e-36

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  501 EPTRIELTPKRTELTVGESIVLNCKAIHDASLDVTFYWTLKGQPIDFEKEGGHFENIRAQASSADLMIRNILLMHAGRYG 580
Cdd:cd05853      1 DPTRVMVPPSSMDVTVGESIVLPCQVSHDHSLDIVFTWSFNGHLIDFQKDGDHFERVGGQDSAGDLMIRSIQLKHAGKYV 80

                           90       100
                   ....*....|....*....|..
gi 1907197658  581 CRVQTTADSVSDEAELLVRGPP 602
Cdd:cd05853     81 CMVQTSVDKLSAAADLIVRGPP 102

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 131.18 E-value: 4.83e-36

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  323 WVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSRVDTVNGILAIQSVNQSDAGMYQCLAENKYGAIYASA 402
Cdd:cd05728      2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYASA 81


                   ....
gi 1907197658  403 ELKI 406
Cdd:cd05728     82 ELAV 85

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 121.57 E-value: 1.46e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   96 YGPVFVQEPDDVIFPTDSDEKKVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLIDGTFIISNPSELRDSGLYQCLAT 175
Cdd:cd05850      1 YGPVFEEQPSSTLFPEGSAEEKVTLACRARASPPATYRWKMNGTELKMEPDSRYRLVAGNLVISNPVKAKDAGSYQCLAS 80

                           90
                   ....*....|....*..
gi 1907197658  176 NSFGSILSREATLQFAY 192
Cdd:cd05850     81 NRRGTVVSREASLRFGF 97

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 120.06 E-value: 4.23e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   97 GPVFVQEPDDVIFPTDSDEKKVALNCEVRGNPSPSYRWLRNGTEIALESDyRYSLIDGTFIISNPSELRDSGLYQCLATN 176
Cdd:cd05849      1 GPVFEEQPIDTIYPEESTEGKVSVNCRARANPFPIYKWRKNNLDIDLTND-RYSMVGGNLVINNPDKYKDAGRYVCIVSN 79

                           90
                   ....*....|....*.
gi 1907197658  177 SFGSILSREATLQFAY 192
Cdd:cd05849     80 IYGKVRSREATLSFGY 95

Sixth immunoglobulin (Ig) domain of contactin-2; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells (AC) in the developing chick retina, corresponding to the period of formation and maturation of AC processes.

Pssm-ID: 409440 Cd Length: 102 Bit Score: 118.99 E-value: 1.36e-31

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  501 EPTRIELTPKRTELTVGESIVLNCKAIHDASLDVTFYWTLKGQPIDFEKEGGHFENIRAQASSADLMIRNILLMHAGRYG 580
Cdd:cd05854      1 DATKITLAPSSADINQGENLTLQCHASHDPTMDLTFTWSLDDFPIDLDKPNGHYRRMEVKETIGDLVIVNAQLSHAGTYT 80

                           90       100
                   ....*....|....*....|..
gi 1907197658  581 CRVQTTADSVSDEAELLVRGPP 602
Cdd:cd05854     81 CTAQTVVDSASASATLVVRGPP 102

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 95.47 E-value: 1.43e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  231 PKIEVHFPfTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLRKSQAVLEIPNLQLDDAGIYECTAENSRGKNS 310
Cdd:cd05851      2 ADINVKFK-DTYALKGQNVTLECFALGNPVPVIRWRKILEPMPATAEISMSGAVLKIFNIQPEDEGTYECEAENIKGKDK 80


                   ....*..
gi 1907197658  311 FRGQLQI 317
Cdd:cd05851     81 HQARVYV 87

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 87.36 E-value: 1.08e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  411 PSFELNQVKKSIIVTKDRGVLIECEPQGSPKPAISWRKGDKAVRANKRIAILPDGSLRILNASKADEGKYICQGVNIFGS 490
Cdd:cd05852      1 PTFEFNPMKKKILAAKGGRVIIECKPKAAPKPKFSWSKGTELLVNNSRISIWDDGSLEILNITKLDEGSYTCFAENNRGK 80


                   ....*....
gi 1907197658  491 AEIIASLSV 499
Cdd:cd05852     81 ANSTGVLSV 89

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 80.99 E-value: 2.44e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  100 FVQEPDDVIfptDSDEKKVALNCEVRGNPSPSYRWLRNGTEIALESDYRY-SLIDGTFIISNPSELR----DSGLYQCLA 174
Cdd:cd05722      4 FLSEPSDIV---AMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDERRqQLPNGSLLITSVVHSKhnkpDEGFYQCVA 80

                           90
                   ....*....|....*.
gi 1907197658  175 TN-SFGSILSREATLQ 189
Cdd:cd05722     81 QNeSLGSIVSRTARVT 96

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 80.23 E-value: 4.59e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  602 PGPPGVVIVEEITESTATLSWSPATDNHSPISSYNLQARSPFSLGWQTVKTVPevitGDMESAMAVDLNPWVEYEFRVVA 681
Cdd:cd00063      1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTP----GSETSYTLTGLKPGTEYEFRVRA 76

                           90
                   ....*....|....*...
gi 1907197658  682 TNPIGTGDPSiPSRMIRT 699
Cdd:cd00063     77 VNGGGESPPS-ESVTVTT 93

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 78.84 E-value: 1.04e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  411 PSFElnQVKKSIIVTKDRGVLIECEPQGSPKPAISWRKGDKAVRANKRIAILPDG---SLRILNASKADEGKYICQGVNI 487
Cdd:pfam07679    1 PKFT--QKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|..
gi 1907197658  488 FGSAEIIASLSV 499
Cdd:pfam07679   79 AGEAEASAELTV 90

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 75.12 E-value: 2.29e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQK-LNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLL-PQSRVDTVNGILAIQSVNQSDAGMYQCLAENKYGAI 398
Cdd:cd20978      1 PKFIQKpEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQgPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDI 80


                   ....*...
gi 1907197658  399 YASAELKI 406
Cdd:cd20978     81 YTETLLHV 88

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 73.82 E-value: 7.26e-16

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907197658  431 LIECEPQGSPKPAISWRKGDKAVRANKRIAILPDGSLRILNASKADEGKYICQGVNIFGSA 491
Cdd:cd20968     18 VLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIA 78

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 73.30 E-value: 1.23e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  809 APTDVTATSVSVSEIFVVWKHVKESLGRPQGFEIsYWKDTEPEDSVETVRTRGNESFVMLTGLEGNTLYHLTVRAYNGAG 888
Cdd:cd00063      3 PPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVV-EYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGGG 81

                           90
                   ....*....|..
gi 1907197658  889 YGPPSREASTTT 900
Cdd:cd00063     82 ESPPSESVTVTT 93

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 81.20 E-value: 1.68e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  649 TVKTVPEVITGDMESAMAVDLNPWVEYEFRVVATNPIGTGDPSipSRMIRTNEAVPKTAPSNVSGRSGRRHELVIAWEPV 728
Cdd:COG3401    179 AVATTSLTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPS--NEVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPV 256

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  729 SEEfqngEGFGYIVaFRPNGTRGWKEKMVTSSEASkfiYRDESVPPLTPFEVKVGVYNNKGD-GPFSQIVVIcSAEGEPT 807
Cdd:COG3401    257 TES----DATGYRV-YRSNSGDGPFTKVATVTTTS---YTDTGLTNGTTYYYRVTAVDAAGNeSAPSNVVSV-TTDLTPP 327

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  808 AAPTDVTATSVSVSEIFVVWKHVKESLgrPQGFEIsyWKDTEPEDSVETVRTRGNESFVMLTGLEGNTLYHLTVRAYNGA 887
Cdd:COG3401    328 AAPSGLTATAVGSSSITLSWTASSDAD--VTGYNV--YRSTSGGGTYTKIAETVTTTSYTDTGLTPGTTYYYKVTAVDAA 403

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  888 G-YGPPSREASTTT-----KRHPPREPPGNLRWEQQGSQVSLGWEPVRPLANESEVMGYKVFYRQEGhsegqvieTQKPQ 961
Cdd:COG3401    404 GnESAPSEEVSATTasaasGESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDTGNAVPF--------TTTSS 475

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*....
gi 1907197658  962 AVVPLPEAGVYIIEVRAYSEGGDGTASSQIRVPSYSGGKITSAQSTLHS 1010
Cdd:COG3401    476 TVTATTTDTTTANLSVTTGSLVGGSGASSVTNSVSVIGASAAAAVGGAP 524

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 72.44 E-value: 2.18e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  102 QEPDDVI-FPTDSdekkVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSL--IDGTFIISNPSELRDS--GLYQCLATN 176
Cdd:cd05733      6 QSPKDYIvDPRDN----ITIKCEAKGNPQPTFRWTKDGKFFDPAKDPRVSMrrRSGTLVIDNHNGGPEDyqGEYQCYASN 81

                           90
                   ....*....|...
gi 1907197658  177 SFGSILSREATLQ 189
Cdd:cd05733     82 ELGTAISNEIRLV 94

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 71.68 E-value: 2.91e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  809 APTDVTATSVSVSEIFVVWKHVKESLGRPQGFEISYWKDTEPEDSVEtVRTRGNESFVMLTGLEGNTLYHLTVRAYNGAG 888
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNE-ITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGG 80


                   ....*
gi 1907197658  889 YGPPS 893
Cdd:pfam00041   81 EGPPS 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 71.90 E-value: 3.16e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSR--VDTVNGI--LAIQSVNQSDAGMYQCLAENKYG 396
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRfkVTYEGGTytLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 1907197658  397 AIYASAELKI 406
Cdd:pfam07679   81 EAEASAELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 70.67 E-value: 6.05e-15

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907197658  231 PKIEVHfPFTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPS----KSRLRKSQAVLEIPNLQLDDAGIYECTAEN 304
Cdd:pfam13927    2 PVITVS-PSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgstrSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 69.97 E-value: 9.29e-15

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  434 CEPQGSPKPAISWRKGDKAVRANKRIAILPDGSLRILNASKADEGKYICQGVNIFGSAEIIASLSV 499
Cdd:cd05745      9 CEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 69.98 E-value: 1.49e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  231 PKIEVhFPFTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLRKSQ----AVLEIPNLQLDDAGIYECTAENSR 306
Cdd:pfam07679    1 PKFTQ-KPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYeggtYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 1907197658  307 GKNSFRGQLQI 317
Cdd:pfam07679   80 GEAEASAELTV 90

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 68.71 E-value: 4.13e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  328 NDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSRVD-TVNGILAIQSVNQSDAGMYQCLAENKYGAIYASAELKI 406
Cdd:cd20957      9 PVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQiLSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAELKL 88

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 68.82 E-value: 4.26e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   98 PVFVQEPDDVIFPTDSDekkVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLIDG--TFIISNpSELRDSGLYQCLAT 175
Cdd:pfam07679    1 PKFTQKPKDVEVQEGES---ARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGtyTLTISN-VQPDDSGKYTCVAT 76

                           90
                   ....*....|....
gi 1907197658  176 NSFGSIlSREATLQ 189
Cdd:pfam07679   77 NSAGEA-EASAELT 89

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 68.19 E-value: 6.04e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   98 PVFVQEPDDVIfpTDSDEKKVALNCEVRGNPSPSYRWLRNGTEIALESDyRYSLIDGTFIISNPSElRDSGLYQCLATNS 177
Cdd:cd20978      1 PKFIQKPEKNV--VVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPME-RATVEDGTLTIINVQP-EDTGYYGCVATNE 76

                           90
                   ....*....|..
gi 1907197658  178 FGSIlSREATLQ 189
Cdd:cd20978     77 IGDI-YTETLLH 87

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 67.04 E-value: 1.27e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  420 KSIIVTKDRGVLIECEPQGSPKPAISWRK--GDKAVRankRIAILPDGSLRILNASKADEGKYICQGVNIFGSAEIIASL 497
Cdd:cd05725      5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKedGELPKG---RYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATL 81


                   ..
gi 1907197658  498 SV 499
Cdd:cd05725     82 TV 83

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 66.75 E-value: 2.28e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSRVDTV---NGI--LAIQSVNQSDAGMYQCLAENKY 395
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLvreNGRhsLIIEPVTKRDAGIYTCIARNRA 80

                           90
                   ....*....|.
gi 1907197658  396 GAIYASAELKI 406
Cdd:cd05744     81 GENSFNAELVV 91

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 66.70 E-value: 2.29e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  323 WVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPL--LPQSRVDTVNG-ILAIQSVNQSDAGMYQCLAENKYGAIY 399
Cdd:cd04978      2 WIIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIepAPEDMRRTVDGrTLIFSNLQPNDTAVYQCNASNVHGYLL 81


                   ....*...
gi 1907197658  400 ASAELKIL 407
Cdd:cd04978     82 ANAFLHVL 89

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 66.81 E-value: 2.34e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   98 PVFVQEPDDVIFPTDSdekKVALNCEVRGNPSPSYRWLRNGTEIALESD----YRYSLIDGTF----IISNPSELRDSGL 169
Cdd:cd07693      1 PRIVEHPSDLIVSKGD---PATLNCKAEGRPTPTIQWLKNGQPLETDKDdprsHRIVLPSGSLfflrVVHGRKGRSDEGV 77

                           90       100
                   ....*....|....*....|..
gi 1907197658  170 YQCLATNSFGSILSREATLQFA 191
Cdd:cd07693     78 YVCVAHNSLGEAVSRNASLEVA 99

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 66.37 E-value: 2.37e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   240 TVTAAKGTTVKMECFALGNPVPTITWMKVNG-YIPSKSRLR----KSQAVLEIPNLQLDDAGIYECTAENSRGKNSFRGQ 314
Cdd:smart00410    3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGkLLAESGRFSvsrsGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82


                    ...
gi 1907197658   315 LQI 317
Cdd:smart00410   83 LTV 85

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 65.81 E-value: 2.56e-13

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  249 VKMECFALGNPVPTITWMKVNGYIPSKSRLRKSQ----AVLEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSelgnGTLTISNVTLEDSGTYTCVASNSAG 63

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 65.81 E-value: 2.85e-13

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  341 ECKATGKPRPTYRWLKNGAPLLPQS----RVDTVNGILAIQSVNQSDAGMYQCLAENKYG 396
Cdd:cd00096      4 TCSASGNPPPTITWYKNGKPLPPSSrdsrRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 65.66 E-value: 3.64e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  324 VQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQS----RVDTVNGILAIQSVNQSDAGMYQCLAEN 393
Cdd:pfam13927    5 TVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGStrsrSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 65.51 E-value: 4.40e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  603 GPPGVVIVEEITESTATLSWSPATDNHSPISSYNLQARSPFSLGWQTVKTVPEVITgdmeSAMAVDLNPWVEYEFRVVAT 682
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITVPGTTT----SVTLTGLKPGTEYEVRVQAV 76


                   ....*....
gi 1907197658  683 NPIGTGDPS 691
Cdd:pfam00041   77 NGGGEGPPS 85

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 65.51 E-value: 5.08e-13

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  240 TVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPS-KSRLRKSQAVLEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd05731      4 STMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKgRTKFENFNKTLKIENVSEADSGEYQCTASNTMG 72

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 65.35 E-value: 5.70e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPL---LPQSRVDTVNGILAIQSVNQSDAGMYQCLAENKYGA 397
Cdd:cd20976      2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLqyaADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQ 81


                   ....*....
gi 1907197658  398 IYASAELKI 406
Cdd:cd20976     82 VSCSAWVTV 90

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 65.41 E-value: 6.79e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  410 PPSFELNQVKKSiiVTKDRGVLIECEPQGSPKPAISWRK------GD-KAVRANKRIAILPDGSLRILNASKADEGKYIC 482
Cdd:cd20954      1 PPRWIVEPVDAN--VAAGQDVMLHCQADGFPTPTVTWKKatgstpGEyKDLLYDPNVRILPNGTLVFGHVQKENEGHYLC 78


                   ....*...
gi 1907197658  483 QGVNIFGS 490
Cdd:cd20954     79 EAKNGIGS 86

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 65.11 E-value: 7.73e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  430 VLIECE-PQGSPKPAISWRKGDKAVR-ANKRIAILPDGSLRILNASKADEGKYICQGVNIFGSAEI-IASLSV 499
Cdd:cd05724     15 AVLECSpPRGHPEPTVSWRKDGQPLNlDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERESrAARLSV 87

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 64.83 E-value: 7.89e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  417 QVKKSIIVTKDRGVLIECEPQGSPKPAISWRKGDKAVRA-NKRIAILPDGSLRILNASKADEGKYICQGVNIFGSAEIIA 495
Cdd:cd20952      4 QGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGkDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSA 83


                   ....
gi 1907197658  496 SLSV 499
Cdd:cd20952     84 VLDV 87

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 64.93 E-value: 9.04e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  332 LDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQS-----RVDTVNGILAIQSVNQSDAGMYQCLAENKYGAIYASAELKI 406
Cdd:cd05729     16 LPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHriggtKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 64.51 E-value: 9.84e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   98 PVFVQEPDDVIFPTDSDekkVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLID--GTFIISNPSElRDSGLYQCLAT 175
Cdd:pfam13927    2 PVITVSPSSVTVREGET---VTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGsnSTLTISNVTR-SDAGTYTCVAS 77


                   .
gi 1907197658  176 N 176
Cdd:pfam13927   78 N 78

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 64.52 E-value: 1.17e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  338 LQWECKATGKPRPTYRWLKNGAPLLPQSRVDTVNGI-LAIQSVNQSDAGMYQCLAENKYGAIYASAELKI 406
Cdd:cd05723     15 IVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHnLQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 71.96 E-value: 1.28e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  598 VRGPPGPPGVVIVEEITESTATLSWSPATDNHSPISSYNLQARSPFSLGWQTVKTVPEVITGDMESAMAVDLNPWVEYEF 677
Cdd:COG3401     32 SGKTILVYLAVVLSVTTKESPGTLLVAAGLSSGGGLGTGGRAGTTSGVAAVAVAAAPPTATGLTTLTGSGSVGGATNTGL 111

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  678 RVVATNPIGTGDPSIPSRMIRTNEAVPKTAPSNVSGRSGRRhelviawEPVSEEFQNGEGFGYIVAFRPNGTRGWKEKMV 757
Cdd:COG3401    112 TSSDEVPSPAVGTATTATAVAGGAATAGTYALGAGLYGVDG-------ANASGTTASSVAGAGVVVSPDTSATAAVATTS 184

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  758 TSSEASKFIYRDESVPPLTPFEVKVGVYNNKGDGPFSQIVVIcSAEGEPTAAPTDVTATSVSVSEIFVVWKHVKESlgRP 837
Cdd:COG3401    185 LTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSV-TTPTTPPSAPTGLTATADTPGSVTLSWDPVTES--DA 261

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  838 QGFEIsyWKDTEPEDSVETVrTRGNESFVMLTGLEGNTLYHLTVRAYNGAG-YGPPSREASTTTKRHPPrEPPGNLRWEQ 916
Cdd:COG3401    262 TGYRV--YRSNSGDGPFTKV-ATVTTTSYTDTGLTNGTTYYYRVTAVDAAGnESAPSNVVSVTTDLTPP-AAPSGLTATA 337

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  917 QGS-QVSLGWEPVrplaNESEVMGYKVFYRQEGHSEGQVI--ETQKPQAVVPLPEAGV-YIIEVRAYSEGGDGTASSQI 991
Cdd:COG3401    338 VGSsSITLSWTAS----SDADVTGYNVYRSTSGGGTYTKIaeTVTTTSYTDTGLTPGTtYYYKVTAVDAAGNESAPSEE 412

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 63.12 E-value: 2.15e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907197658  118 VALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLI--DGTFIISNPSElRDSGLYQCLATNSFGSILSREA 186
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSElgNGTLTISNVTL-EDSGTYTCVASNSAGGSASASV 70

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 63.67 E-value: 2.52e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  238 PFTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSK-SRLRK-SQAVLEIPNLQLDDAGIYECTAENSRGKNSFRGQL 315
Cdd:cd20952      6 PQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKdERITTlENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVL 85


                   ..
gi 1907197658  316 QI 317
Cdd:cd20952     86 DV 87

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 63.72 E-value: 3.09e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWV--QKLNDT--QLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSR-----VDTVNGILAIQSVNQSDAGMYQCLA 391
Cdd:cd05857      1 PYWTnpEKMEKKlhAVPAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRiggykVRNQHWSLIMESVVPSDKGNYTCVV 80

                           90
                   ....*....|....*
gi 1907197658  392 ENKYGAIYASAELKI 406
Cdd:cd05857     81 ENEYGSINHTYHLDV 95

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 63.00 E-value: 3.98e-12

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  122 CEVRGNPSPSYRWLRNGTEIALESdyRYSLIDGTFIISNPSeLRDSGLYQCLATNSFGSI 181
Cdd:cd05728     21 CKASGNPRPAYRWLKNGQPLASEN--RIEVEAGDLRITKLS-LSDSGMYQCVAENKHGTI 77

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 62.03 E-value: 6.81e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  238 PFTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPsKSRLR----KSqavLEIPNLQLDDAGIYECTAENSRGKNSFRG 313
Cdd:cd05725      4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELP-KGRYEilddHS---LKIRKVTAGDMGSYTCVAENMVGKIEASA 79


                   ....
gi 1907197658  314 QLQI 317
Cdd:cd05725     80 TLTV 83

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 62.25 E-value: 7.61e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  238 PFTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLRK-----SQAVLEIPNLQLDDAGIYECTAENSRGKNSFR 312
Cdd:cd05763      6 PHDITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARERRmhvmpEDDVFFIVDVKIEDTGVYSCTAQNSAGSISAN 85


                   ....*
gi 1907197658  313 GQLQI 317
Cdd:cd05763     86 ATLTV 90

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 61.09 E-value: 1.78e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   602 PGPPGVVIVEEITESTATLSWSPATDNH--SPISSYNLQARSPFSlGWQTVKTVPEVitgdmESAMAVDLNPWVEYEFRV 679
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGitGYIVGYRVEYREEGS-EWKEVNVTPSS-----TSYTLTGLKPGTEYEFRV 74


                    ....*....
gi 1907197658   680 VATNPIGTG 688
Cdd:smart00060   75 RAVNGAGEG 83

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 61.13 E-value: 2.23e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  423 IVTKDRGVLIECEPQGSPKPAISWRK--------GDKAVRANKRIAILPDGSLRILNASKADEGKYICQGVNIFGSAEII 494
Cdd:cd05726     10 VVALGRTVTFQCETKGNPQPAIFWQKegsqnllfPYQPPQPSSRFSVSPTGDLTITNVQRSDVGYYICQALNVAGSILAK 89


                   ....*..
gi 1907197658  495 ASLSVKE 501
Cdd:cd05726     90 AQLEVTD 96

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 60.60 E-value: 2.32e-11

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658   335 GSPLQWECKATGKPRPTYRWLKNGA-PLLPQSRV----DTVNGILAIQSVNQSDAGMYQCLAENKYGAIYASAELKI 406
Cdd:smart00410    9 GESVTLSCEASGSPPPEVTWYKQGGkLLAESGRFsvsrSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 60.49 E-value: 3.40e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  329 DTQLDSGSPLQWECKA-TGKPRPTYRWLKNGAPL-LPQSRVDTV-NGILAIQSVNQSDAGMYQCLAENKYGA-IYASAEL 404
Cdd:cd05724      6 DTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLnLDNERVRIVdDGNLLIAEARKSDEGTYKCVATNMVGErESRAARL 85


                   ..
gi 1907197658  405 KI 406
Cdd:cd05724     86 SV 87

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 60.31 E-value: 3.44e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  235 VHFPFTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLRKSQAVLEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd05728      3 LKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGDLRITKLSLSDSGMYQCVAENKHG 75

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 59.13 E-value: 8.13e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  325 QKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSRVDTV-----NGILAIQSVNQSDAGMYQCLAENKYGAIY 399
Cdd:cd20973      2 QTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDqdedgLCSLIISDVCGDDSGKYTCKAVNSLGEAT 81


                   ....*..
gi 1907197658  400 ASAELKI 406
Cdd:cd20973     82 CSAELTV 88

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 59.17 E-value: 1.04e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  329 DTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSR-----VDTVNGILAIQSVNQSDAGMYQCLAENKYGAIYASAE 403
Cdd:cd05763      8 DITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARerrmhVMPEDDVFFIVDVKIEDTGVYSCTAQNSAGSISANAT 87


                   ....
gi 1907197658  404 LKIL 407
Cdd:cd05763     88 LTVL 91

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 58.49 E-value: 1.07e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  430 VLIECEPQGSPKPAISWRKGDKAVRAN---KRIAILPDGSLRILNASKADEGKYICQGVNIFGSAE 492
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSsrdSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 58.57 E-value: 1.13e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907197658  335 GSPLQWECKATGKPRPTYRWLKNGAPLLP-QSRVDTVNGILAIQSVNQSDAGMYQCLAENKYGAI 398
Cdd:cd05731     10 GGVLLLECIAEGLPTPDIRWIKLGGELPKgRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSA 74

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 58.83 E-value: 1.29e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  105 DDVIFPTDSdekkVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSL--IDGTFIISNPSELRD---SGLYQCLATNSFG 179
Cdd:cd05875     10 DYIVDPRDN----ILIECEAKGNPVPTFHWTRNGKFFNVAKDPRVSMrrRSGTLVIDFRGGGRPedyEGEYQCFARNKFG 85

                           90
                   ....*....|
gi 1907197658  180 SILSREATLQ 189
Cdd:cd05875     86 TALSNKIRLQ 95

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 59.18 E-value: 1.31e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  342 CKATGKPRPTYRWLKNGAP--LLPQSRVDTVNGILAIQS-VNQSDAGMYQCLAENKYGAI 398
Cdd:cd04967     26 CRARANPVPSYRWLMNGTEidLESDYRYSLVDGTLVISNpSKAKDAGHYQCLATNTVGSV 85

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 58.42 E-value: 1.80e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQKLNDT--QLDSGSP-LQWECKATGKPRPTYRWLKNGAPLLPQS--RVDTVNGILAIQSVNQS-DAGMYQCLAENK 394
Cdd:cd05848      2 PVFVQEPDDAifPTDSDEKkVILNCEARGNPVPTYRWLRNGTEIDTESdyRYSLIDGNLIISNPSEVkDSGRYQCLATNS 81


                   ....
gi 1907197658  395 YGAI 398
Cdd:cd05848     82 IGSI 85

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 58.01 E-value: 1.83e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   809 APTDVTATSVSVSEIFVVWKHVKESLGRpqGFEISYW-KDTEPEDSVETVRTRGNESFVMLTGLEGNTLYHLTVRAYNGA 887
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGIT--GYIVGYRvEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80


                    ...
gi 1907197658   888 GYG 890
Cdd:smart00060   81 GEG 83

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 58.02 E-value: 2.69e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  410 PPSFELNQVKKSIIVTKDRGVLIECEPQGSPKPAISWRK-GDKAVRANKRIAILPDGS-LRILNASKADEGKYICQGVNI 487
Cdd:cd05730      1 PPTIRARQSEVNATANLGQSVTLACDADGFPEPTMTWTKdGEPIESGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAENK 80

                           90
                   ....*....|..
gi 1907197658  488 FGSAEIIASLSV 499
Cdd:cd05730     81 AGEQEAEIHLKV 92

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 57.95 E-value: 3.30e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPL-----LPQS-RVDTVNGILAIQSV-----NQSDAGMYQC 389
Cdd:cd07693      1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLetdkdDPRShRIVLPSGSLFFLRVvhgrkGRSDEGVYVC 80

                           90
                   ....*....|....*...
gi 1907197658  390 LAENKYG-AIYASAELKI 406
Cdd:cd07693     81 VAHNSLGeAVSRNASLEV 98

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 57.52 E-value: 3.43e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   424 VTKDRG--VLIECEPQGSPKPAISWRK-GDKAVRANKRIAILPDG---SLRILNASKADEGKYICQGVNIFGSAEIIASL 497
Cdd:smart00410    4 VTVKEGesVTLSCEASGSPPPEVTWYKqGGKLLAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASSGTTL 83


                    ..
gi 1907197658   498 SV 499
Cdd:smart00410   84 TV 85

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 57.68 E-value: 3.47e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  100 FVQEPDDVIFPTDSDEkkvALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLIDGTFIISNPSELRDSGLYQCLATNSFG 179
Cdd:cd05868      2 WITAPTNLVLSPGEDG---TLICRANGNPKPSISWLTNGVPIEIAPTDPSRKVDGDTIIFSKVQERSSAVYQCNASNEYG 78


                   ....
gi 1907197658  180 SILS 183
Cdd:cd05868     79 YLLA 82

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 57.57 E-value: 3.96e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  231 PKIEVHFPfTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLRKSQAV---------LEIPNLQLDDAGIYECT 301
Cdd:cd20956      2 PVLLETFS-EQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVGDYVtsdgdvvsyVNISSVRVEDGGEYTCT 80

                           90
                   ....*....|....*.
gi 1907197658  302 AENSRGKNSFRGQLQI 317
Cdd:cd20956     81 ATNDVGSVSHSARINV 96

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 57.12 E-value: 4.06e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  324 VQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQ-SRVDTV-NGILAIQSVNQSDAGMYQCLAENKYGAIYAS 401
Cdd:cd20952      3 LQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKdERITTLeNGSLQIKGAEKSDTGEYTCVALNLSGEATWS 82


                   ....*
gi 1907197658  402 AELKI 406
Cdd:cd20952     83 AVLDV 87

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 57.02 E-value: 4.85e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  411 PSFElNQVKKSIIVTKDRGVLIECEPQGSPKPAISWRKGDKAVRANKRIAILPDGSLRILNASKADEGKYICQGVNIFGS 490
Cdd:cd20978      1 PKFI-QKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGD 79


                   ....*....
gi 1907197658  491 AEIIASLSV 499
Cdd:cd20978     80 IYTETLLHV 88

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 57.03 E-value: 5.22e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  120 LNCEV-RGNPSPSYRWLRNGTEIALESDYRYSLIDGTFIISNPsELRDSGLYQCLATNSFGSILSREATL 188
Cdd:cd05724     17 LECSPpRGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLLIAEA-RKSDEGTYKCVATNMVGERESRAARL 85

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 57.08 E-value: 5.55e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907197658  341 ECKATGKPRPTYRWLKNGAPLLPQSRVDTV-NGILAIQSVNQSDAGMYQCLAENKYGAIYASAEL 404
Cdd:cd04969     23 ECKPKASPKPTISWSKGTELLTNSSRICILpDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSL 87

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 56.98 E-value: 6.01e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907197658  238 PFTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLR----KSQAVLEIPNLQLDDAGIYECTAENSRGK 308
Cdd:cd05747     10 PRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQitstEYKSTFEISKVQMSDEGNYTVVVENSEGK 84

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 57.03 E-value: 6.48e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSRVDTV---NGI--LAIQSVNQSDAGMYQCLAENKY 395
Cdd:cd20990      1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLvreNGVhsLIIEPVTSRDAGIYTCIATNRA 80

                           90
                   ....*....|.
gi 1907197658  396 GAIYASAELKI 406
Cdd:cd20990     81 GQNSFNLELVV 91

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 55.27 E-value: 1.20e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  430 VLIECEPQGSPKPAISWRKGDKAVRANKRIAILPDGSLRILNASKADEGKYICQGVNIFGSAEIIASLS 498
Cdd:cd05746      1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 56.05 E-value: 1.22e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   98 PVFVQEPDDVifpTDSDEKKVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLIDG--TFIISNPSElRDSGLYQCLAT 175
Cdd:cd20972      2 PQFIQKLRSQ---EVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDlhSLIIAEAFE-EDTGRYSCLAT 77


                   ....*
gi 1907197658  176 NSFGS 180
Cdd:cd20972     78 NSVGS 82

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409412 Cd Length: 85 Bit Score: 55.64 E-value: 1.58e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  232 KIEVHFPFTVTAAKGTTVKMECFALG-NPVPTITWMKVNGYIPSksRLRKSQAVLEIPNLQLDDAGIYECTAENSR 306
Cdd:cd05754      2 QVTVEEPRSQEVRPGADVSFICRAKSkSPAYTLVWTRVNGTLPS--RAMDFNGILTIRNVQLSDAGTYVCTGSNML 75

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 55.59 E-value: 1.64e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  238 PFTVTAAKGTTVKMECFALGNPVPTITWMKvNGYIP----SKSRLRKSQAVLEIPNLQLDDAGIYECTAEN-SRGKNSFR 312
Cdd:cd20970      9 SFTVTAREGENATFMCRAEGSPEPEISWTR-NGNLIiefnTRYIVRENGTTLTIRNIRRSDMGIYLCIASNgVPGSVEKR 87


                   ....*
gi 1907197658  313 GQLQI 317
Cdd:cd20970     88 ITLQV 92

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 55.20 E-value: 1.93e-09

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658   118 VALNCEVRGNPSPSYRWLRNGTEIALESDyRYSLI----DGTFIISNpSELRDSGLYQCLATNSFGSIlSREATLQ 189
Cdd:smart00410   12 VTLSCEASGSPPPEVTWYKQGGKLLAESG-RFSVSrsgsTSTLTISN-VTPEDSGTYTCAATNSSGSA-SSGTTLT 84

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 55.37 E-value: 2.26e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  322 HWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNG-----APLLPQSRVDTVNGILAiqSVNQSDAGMYQCLAENKYG 396
Cdd:cd05868      1 YWITAPTNLVLSPGEDGTLICRANGNPKPSISWLTNGvpieiAPTDPSRKVDGDTIIFS--KVQERSSAVYQCNASNEYG 78

                           90
                   ....*....|.
gi 1907197658  397 AIYASAELKIL 407
Cdd:cd05868     79 YLLANAFVNVL 89

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 55.38 E-value: 2.40e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  102 QEPDDVIfpTDSDEKkVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLI--DGTFIISNPSELRD---SGLYQCLATN 176
Cdd:cd05874      6 QSPKDYI--VDPREN-IVIQCEAKGKPPPSFSWTRNGTHFDIDKDPKVTMKpnTGTLVINIMNGEKAeayEGVYQCTARN 82


                   ....*..
gi 1907197658  177 SFGSILS 183
Cdd:cd05874     83 ERGAAVS 89

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 54.76 E-value: 2.85e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  101 VQEPDDVIFptdSDEKKVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLIDGTFII-SNPSElRDSGLYQCLATNSFG 179
Cdd:cd04978      3 IIEPPSLVL---SPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIfSNLQP-NDTAVYQCNASNVHG 78


                   ...
gi 1907197658  180 SIL 182
Cdd:cd04978     79 YLL 81

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 54.40 E-value: 5.62e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  411 PSFELNQVKKSIIVTKDrgVLIECEPQGSPKPAISWRKGDKAVRANKR--IAILPDG--SLRILNASKADEGKYICQGVN 486
Cdd:cd20975      1 PTFKVSLMDQSVREGQD--VIMSIRVQGEPKPVVSWLRNRQPVRPDQRrfAEEAEGGlcRLRILAAERGDAGFYTCKAVN 78

                           90
                   ....*....|...
gi 1907197658  487 IFGSAEIIASLSV 499
Cdd:cd20975     79 EYGARQCEARLEV 91

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 54.04 E-value: 6.35e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  424 VTKDRGVLIECEPQGSPKPAISWRKGDKAVRANKRIAILPDG----SLRILNASKADEGKYICQGVNIFGSAEIIASLSV 499
Cdd:cd05744     12 VQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVREngrhSLIIEPVTKRDAGIYTCIARNRAGENSFNAELVV 91

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 53.76 E-value: 6.52e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  240 TVTAAKGTTVKMECFALGNPVPTITWMKVNGYI-PSKSRLRKSQAVLEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd05876      4 SLVALRGQSLVLECIAEGLPTPTVKWLRPSGPLpPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLG 72

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 54.13 E-value: 6.66e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSRVDTVNG----ILAIQSVNQSDAGMYQCLAENKYG 396
Cdd:cd20972      2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEgdlhSLIIAEAFEEDTGRYSCLATNSVG 81

                           90
                   ....*....|
gi 1907197658  397 AIYASAELKI 406
Cdd:cd20972     82 SDTTSAEIFV 91

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 53.79 E-value: 7.11e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  232 KIEVHfPFTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLrksqAVLE-----IPNLQLDDAGIYECTAENSR 306
Cdd:cd20968      1 KITRP-PTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRI----AVLEsgslrIHNVQKEDAGQYRCVAKNSL 75


                   .
gi 1907197658  307 G 307
Cdd:cd20968     76 G 76

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 53.75 E-value: 8.77e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  322 HWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAP---LLPQSRVDTVNGILAIQSVNQSDAGMYQCLAENKYGAI 398
Cdd:cd05867      1 YWTRRPQSHLYGPGETARLDCQVEGIPTPNITWSINGAPiegTDPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHGNL 80


                   ....*....
gi 1907197658  399 YASAELKIL 407
Cdd:cd05867     81 LANAHVHVV 89

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 53.30 E-value: 9.70e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  238 PFTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLR-KSQAVLEIPNLQLDDAGIYECTAENSRGKNSFRGQLQ 316
Cdd:cd20957      8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQiLSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAELK 87


                   .
gi 1907197658  317 I 317
Cdd:cd20957     88 L 88

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 52.99 E-value: 1.05e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  335 GSPLQWECKATGKPRPTYRWLKNGAPLLP-QSRVDTVNGILAIQSVNQSDAGMYQCLAENKYGA 397
Cdd:cd05876     10 GQSLVLECIAEGLPTPTVKWLRPSGPLPPdRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGS 73

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409412 Cd Length: 85 Bit Score: 52.94 E-value: 1.28e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907197658  335 GSPLQWECKATGK-PRPTYRWLKNGAPLlPQSRVDTvNGILAIQSVNQSDAGMYQCLAENKYGAIYASAEL 404
Cdd:cd05754     16 GADVSFICRAKSKsPAYTLVWTRVNGTL-PSRAMDF-NGILTIRNVQLSDAGTYVCTGSNMLDTDEATATL 84

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 52.57 E-value: 1.43e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  410 PPSFELNqvKKSIIVTKDRGVLIECEPQGSPKPAISWRKGDKA---VRANKRIAILPDGSLRILNASKADEGKYICQGVN 486
Cdd:pfam13927    1 KPVITVS--PSSVTVREGETVTLTCEATGSPPPTITWYKNGEPissGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 52.50 E-value: 1.86e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   99 VFVQEPDDVIFPTDSDekkVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLIDGTFIISNpSELRDSGLYQCLATNSF 178
Cdd:cd20952      1 IILQGPQNQTVAVGGT---VVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKG-AEKSDTGEYTCVALNLS 76


                   ....*.
gi 1907197658  179 GSILSR 184
Cdd:cd20952     77 GEATWS 82

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 52.50 E-value: 2.17e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   98 PVFVQEPDDVifpTDSDEKKVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLIDG---TFIISNPSElRDSGLYQCLA 174
Cdd:cd05744      1 PHFLQAPGDL---EVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENgrhSLIIEPVTK-RDAGIYTCIA 76


                   ....*
gi 1907197658  175 TNSFG 179
Cdd:cd05744     77 RNRAG 81

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 52.50 E-value: 2.22e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  907 EPPGNLRWEQQGS-QVSLGWEPvrPLANESEVMGYKVFYRQEGHSEGQVIETQKP---QAVVP-LPEAGVYIIEVRAYSE 981
Cdd:cd00063      2 SPPTNLRVTDVTStSVTLSWTP--PEDDGGPITGYVVEYREKGSGDWKEVEVTPGsetSYTLTgLKPGTEYEFRVRAVNG 79

                           90
                   ....*....|..
gi 1907197658  982 GGDGTASSQIRV 993
Cdd:cd00063     80 GGESPPSESVTV 91

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 52.39 E-value: 2.77e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  419 KKSIIVTKDRG--VLIECEPQGSPKPAISW---RKGDKAVRANKRIAILPDGSLRILNASKADEGKYICQGVNIFGSAEI 493
Cdd:cd20969      7 RKAQQVFVDEGhtVQFVCRADGDPPPAILWlspRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSM 86


                   ....*.
gi 1907197658  494 IASLSV 499
Cdd:cd20969     87 PAHLHV 92

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 51.81 E-value: 2.96e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658  240 TVTAAKGTTVKMECFA-LGNPVPTITWMKVNGYIPS-----KSRLRKSQAVLEIPNLQLDDAGIYECTAENSRGKNS 310
Cdd:pfam00047    5 TVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIEslkvkHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSAT 81

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 51.63 E-value: 3.43e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  335 GSPLQWECKATGKPRPTYRWLKNGAPLlPQSRVDTV-NGILAIQSVNQSDAGMYQCLAENKYGAIYASAELKI 406
Cdd:cd05725     12 DDSAEFQCEVGGDPVPTVRWRKEDGEL-PKGRYEILdDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 52.01 E-value: 3.45e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  231 PKIEVHFPFTVTAAKGTTVKMECFALGNPVPTITWMKvNGYIPSKSRLRK--SQAVLEIPNLQLDDAGIYECTAENSRGK 308
Cdd:cd20978      1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLH-NGKPLQGPMERAtvEDGTLTIINVQPEDTGYYGCVATNEIGD 79

First immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409547 Cd Length: 99 Bit Score: 52.03 E-value: 3.71e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   97 GPVFVQEPDDVIFPTDSDEKKValNCEVRGNPSPSYRWLR-NGTEIALESDYRYSLIDGTFIISnPSELRD------SGL 169
Cdd:cd20955      1 GPVFLKEPTNRIDFSNSTGAEI--ECKASGNPMPEIIWIRsDGTAVGDVPGLRQISSDGKLVFP-PFRAEDyrqevhAQV 77

                           90
                   ....*....|....*.
gi 1907197658  170 YQCLATNSFGSILSRE 185
Cdd:cd20955     78 YACLARNQFGSIISRD 93

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 52.27 E-value: 3.74e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  322 HWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGA--------PLLPQSRVD-TVNGILAIQSVNQSDAGMYQCLAE 392
Cdd:cd05726      1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSqnllfpyqPPQPSSRFSvSPTGDLTITNVQRSDVGYYICQAL 80

                           90
                   ....*....|....
gi 1907197658  393 NKYGAIYASAELKI 406
Cdd:cd05726     81 NVAGSILAKAQLEV 94

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 51.54 E-value: 4.42e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907197658  241 VTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLRK-SQAVLEIPNLQLDDAGIYECTAENSRGKNSFRGQLQI 317
Cdd:cd05852     12 ILAAKGGRVIIECKPKAAPKPKFSWSKGTELLVNNSRISIwDDGSLEILNITKLDEGSYTCFAENNRGKANSTGVLSV 89

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 50.95 E-value: 4.67e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  246 GTTVKMECFALGNPVPTITWMKVNGYIPSKSRLRKS----QAVLEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd05743      1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITseggYGTLTIRDVKESDQGAYTCEAINTRG 66

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 51.78 E-value: 4.68e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907197658  246 GTTVKMECFALGNPVPTITWMKVNG--YIPSKSRLRKSQAVLEIPNLQLDDAGIYECTAENSRGK 308
Cdd:cd05856     19 GSSVRLKCVASGNPRPDITWLKDNKplTPPEIGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGE 83

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 51.70 E-value: 5.05e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSR---VDTVNGI--LAIQSVNQSDAGMYQCLAENKY 395
Cdd:cd20975      1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRrfaEEAEGGLcrLRILAAERGDAGFYTCKAVNEY 80

                           90
                   ....*....|.
gi 1907197658  396 GAIYASAELKI 406
Cdd:cd20975     81 GARQCEARLEV 91

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 51.04 E-value: 5.24e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   99 VFVQEPDDVIFptdsdekkvalNCEVRGNPSPSYRWLRNGtEIALESDYryslidgtFIISNPSELR-------DSGLYQ 171
Cdd:cd05723      7 IYAHESMDIVF-----------ECEVTGKPTPTVKWVKNG-DVVIPSDY--------FKIVKEHNLQvlglvksDEGFYQ 66

                           90
                   ....*....|..
gi 1907197658  172 CLATNSFGSILS 183
Cdd:cd05723     67 CIAENDVGNAQA 78

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 51.49 E-value: 5.24e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  504 RIELTPKRTELTVGESIVLNCKAIHDASLDVTfyWTLKGQPIdfeKEGGHFeNIRAQASSADLMIRNILLMHAGRYGCRV 583
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEVS--WFKDGQPL---RSSDRF-KVTYEGGTYTLTISNVQPDDSGKYTCVA 75

                           90
                   ....*....|....*
gi 1907197658  584 QTTADSVSDEAELLV 598
Cdd:pfam07679   76 TNSAGEAEASAELTV 90

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 51.47 E-value: 5.62e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  342 CKATGKPRPTYRWLKNGAPLLPQSRVDTVN---GILAIQSVNQSDAGMYQCLAENKYGAIYASAELKILA 408
Cdd:cd05730     25 CDADGFPEPTMTWTKDGEPIESGEEKYSFNedgSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKVFA 94

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 51.32 E-value: 6.06e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  335 GSPLQWECKATGKPRPTYRWLKNGAPL---LPQSRVDTVNGILAIQSV-----NQSDAGMYQCLAENK-YGAI 398
Cdd:cd05722     16 GGPVVLNCSAESDPPPKIEWKKDGVLLnlvSDERRQQLPNGSLLITSVvhskhNKPDEGFYQCVAQNEsLGSI 88

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 51.40 E-value: 6.18e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  420 KSIIVTKDRGVLIECEPQGSPKPAISWRKGDKAVRANKRIA-----ILPDGSLRILNA-----SKADEGKYICQGVNIFG 489
Cdd:cd07693      8 SDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPrshriVLPSGSLFFLRVvhgrkGRSDEGVYVCVAHNSLG 87


                   ..
gi 1907197658  490 SA 491
Cdd:cd07693     88 EA 89

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 50.87 E-value: 7.67e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  341 ECKATGKPRPTYRWLKNGAPLLPQSRVDTV----NGILAIQSVN---QSDAGMYQCLAENKYGA 397
Cdd:cd05733     22 KCEAKGNPQPTFRWTKDGKFFDPAKDPRVSmrrrSGTLVIDNHNggpEDYQGEYQCYASNELGT 85

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 51.07 E-value: 7.94e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658  246 GTTVKMECFALGNPVPTITWMKVNG-----YIPSKSRLRKSQAVLEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd05729     19 ANKVRLECGAGGNPMPNITWLKDGKefkkeHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYG 85

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 51.08 E-value: 8.96e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  342 CKATGKPRPTYRWLKNGAPLL--PQSRVDTVNGILAIQS-VNQSDAGMYQCLAENKYGAI 398
Cdd:cd05850     27 CRARASPPATYRWKMNGTELKmePDSRYRLVAGNLVISNpVKAKDAGSYQCLASNRRGTV 86

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 50.66 E-value: 9.05e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  118 VALNCEVRGNPSPSYRWLRNGTEI-ALESDYRYSLIDGTFIISNpSELRDSGLYQCLATNSFGSIL 182
Cdd:cd05867     17 ARLDCQVEGIPTPNITWSINGAPIeGTDPDPRRHVSSGALILTD-VQPSDTAVYQCEARNRHGNLL 81

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 50.72 E-value: 1.07e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  432 IECEPQGSPKPAISWRKGDKAV--RANKRIAILPDGS-LRILNASKADEGKYICQGVNIFGSAEIIASLSVKE 501
Cdd:cd05736     20 LRCHAEGIPLPRVQWLKNGMDInpKLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNEGGVDEDISSLFVED 92

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 50.63 E-value: 1.10e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  335 GSPLQWECKATGKPRPTYRWLKNGAPLLPQS--RVDTVNGILAIQSVNQSDAGMYQCLAENKYGAIYASAELKI 406
Cdd:cd05856     19 GSSVRLKCVASGNPRPDITWLKDNKPLTPPEigENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGEINATYKVDV 92

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 50.47 E-value: 1.14e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907197658  333 DSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSRVDTV----NGILAIQSVNQSDAGMYQCLAENKYGAIYASAELKI 406
Cdd:cd20969     15 DEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLtvfpDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 50.58 E-value: 1.15e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  420 KSIIVTKDRG--VLIECEPQGSPKPAISWRKGDKAVRA-NKRIAILPDGS-LRILNASKADEGKYICQGVN-IFGSAEII 494
Cdd:cd20970      8 PSFTVTAREGenATFMCRAEGSPEPEISWTRNGNLIIEfNTRYIVRENGTtLTIRNIRRSDMGIYLCIASNgVPGSVEKR 87


                   ....*
gi 1907197658  495 ASLSV 499
Cdd:cd20970     88 ITLQV 92

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 49.93 E-value: 1.41e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658  114 DEKKVALNCEVRGNPSPSYRWLRNgtEIALESDYRYSLID-GTFIISNPSElRDSGLYQCLATNSFGSILSREATLQ 189
Cdd:cd20968     13 EGLKAVLPCTTMGNPKPSVSWIKG--DDLIKENNRIAVLEsGSLRIHNVQK-EDAGQYRCVAKNSLGIAYSKPVTIE 86

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 49.91 E-value: 1.46e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  421 SIIVTKDRGVLIECEPQGSPKPAISWRKGDKAVRANKRIAILPDGSLRILNASKADEGKYICQGVNIFGSAEIIASLSVK 500
Cdd:cd05876      4 SLVALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARHAYYVTVE 83

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 50.11 E-value: 1.61e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658  335 GSPLQWECKATGKPRPTYRWLKNGAPLLPQS-----RVDTVNGI--LAIQSVNQSDAGMYQCLAENKYGAIYASAEL 404
Cdd:cd20951     15 KSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSipgkyKIESEYGVhvLHIRRVTVEDSAVYSAVAKNIHGEASSSASV 91

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 49.87 E-value: 2.01e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  332 LDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSRV---------DTVNGILAIQSVNQSDAGMYQCLAENKYGAIYASA 402
Cdd:cd20956     13 LQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFrvgdyvtsdGDVVSYVNISSVRVEDGGEYTCTATNDVGSVSHSA 92


                   ....
gi 1907197658  403 ELKI 406
Cdd:cd20956     93 RINV 96

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 49.43 E-value: 2.10e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   509 PKRTELTVGESIVLNCKAIHDASLDVTFYWTlKGQPIdfeKEGGHFEnIRAQASSADLMIRNILLMHAGRYGCRVQTTAD 588
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQ-GGKLL---AESGRFS-VSRSGSTSTLTISNVTPEDSGTYTCAATNSSG 75

                            90
                    ....*....|
gi 1907197658   589 SVSDEAELLV 598
Cdd:smart00410   76 SASSGTTLTV 85

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 49.50 E-value: 2.27e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  430 VLIECEPQGSPKPAISWRKGDKAVRANKRIAILPDGSLRILNASKADEGKYICQGVNIFGSAEIIASLSV 499
Cdd:cd05723     15 IVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 49.43 E-value: 2.32e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  325 QKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQS---RVDTVNGILAIQSVNQSDAGMYQCLAENK 394
Cdd:cd20970      7 QPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNtryIVRENGTTLTIRNIRRSDMGIYLCIASNG 79

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 49.37 E-value: 2.70e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  246 GTTVKMECFALGNPVPTITWMkVNGY----IPSKSRLRKSQAVLEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd04978     14 GETGELICEAEGNPQPTITWR-LNGVpiepAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHG 78

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 49.56 E-value: 2.71e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  237 FPFTVTAAKGTTVKMECFALGNPVPTITWMKVN---GYIPSKSRLRKSQAVLEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd20976      7 VPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAqplQYAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAG 80

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 49.45 E-value: 2.89e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  241 VTAAKGTTVKMECFALGNPVPTITWMK-----------VNGYIPSKSRLRKSQavLEIPNLQLDDAGIYECTAENSRGKN 309
Cdd:cd05732     11 QTAVELEQITLTCEAEGDPIPEITWRRatrgisfeegdLDGRIVVRGHARVSS--LTLKDVQLTDAGRYDCEASNRIGGD 88


                   .
gi 1907197658  310 S 310
Cdd:cd05732     89 Q 89

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 49.25 E-value: 2.99e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  420 KSIIVTKDRGVLIECEPQGSPKPAISWRKGDKAVRANKRIAiLPDGSLRILNASKADEGKYICQGVNIFG 489
Cdd:cd05851      9 KDTYALKGQNVTLECFALGNPVPVIRWRKILEPMPATAEIS-MSGAVLKIFNIQPEDEGTYECEAENIKG 77

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 49.57 E-value: 3.02e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907197658  342 CKATGKPRPTYRWLKNGAPL-LPQSRVDTVNGILAIQSVNQS-DAGMYQCLAENKYGAIYAS 401
Cdd:cd05849     26 CRARANPFPIYKWRKNNLDIdLTNDRYSMVGGNLVINNPDKYkDAGRYVCIVSNIYGKVRSR 87

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 48.33 E-value: 3.22e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  338 LQWECKATGKPRPTYRWLKNGAPLLPQSRVD-TVNGILAIQSVNQSDAGMYQCLAENKYGaiYASAELKI 406
Cdd:cd05746      1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHiSPEGYLAIRDVGVADQGRYECVARNTIG--YASVSMVL 68

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 49.08 E-value: 3.44e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907197658  116 KKVALNCEVRGNPSPSYRWLRNGTEIALE---SDYRYSLIDGTFIISN--PSelrDSGLYQCLATNSFGSI 181
Cdd:cd05857     20 NTVKFRCPAAGNPTPTMRWLKNGKEFKQEhriGGYKVRNQHWSLIMESvvPS---DKGNYTCVVENEYGSI 87

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 48.40 E-value: 3.48e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  245 KGTTVKMECFALGNPVPTITWMKVNGYIPSKSR-LRKSQAVLEIPNLQLDDAGIYECTAENSRGKNSFRGQLQI 317
Cdd:cd05745      1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRhLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 49.00 E-value: 3.59e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  243 AAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLR-KSQAVLEIPNLQLDDAGIYECTAENSRGKNSFRGQLQI 317
Cdd:cd04969     14 AAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICiLPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 49.03 E-value: 3.91e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  334 SGSPLQWECKATGKPRP-TYRWLKNGAPL-----LPQSRVDTVNGILAIQSVNQSDAGMYQCLAENKYGAIYASAELKI 406
Cdd:cd20959     16 VGMRAQLHCGVPGGDLPlNIRWTLDGQPIsddlgITVSRLGRRSSILSIDSLEASHAGNYTCHARNSAGSASYTAPLTV 94

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 48.33 E-value: 4.11e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907197658  249 VKMECFALGNPVPTITWMKVNGYIPSKSRLRKSQA-VLEIPNLQLDDAGIYECTAENSRGKNSFRGQL 315
Cdd:cd05746      1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEgYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 48.66 E-value: 4.37e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  333 DSGSPLQWECKATGK-PRPTYRWLKNGAPL---LPQS---RVDTVNGILAIQSVNQSDAGMYQCLAENKYGAIYASAELK 405
Cdd:cd05750     12 QEGSKLVLKCEATSEnPSPRYRWFKDGKELnrkRPKNikiRNKKKNSELQINKAKLEDSGEYTCVVENILGKDTVTGNVT 91


                   .
gi 1907197658  406 I 406
Cdd:cd05750     92 V 92

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

Pssm-ID: 409417 Cd Length: 95 Bit Score: 48.77 E-value: 4.59e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658  117 KVALNCEVRGNPSPSYRWLRNGTEIA-LESDYRYSLIDGTFIIsNPSELRDSGLYQCLATNSFGSILS-REATLQFA 191
Cdd:cd05760     18 RVTLRCHIDGHPRPTYQWFRDGTPLSdGQGNYSVSSKERTLTL-RSAGPDDSGLYYCCAHNAFGSVCSsQNFTLSII 93

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 48.35 E-value: 4.63e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  238 PFTVTAAKGTTVKMECFALGNPVPTITWMKvNG--YIPSKSRLRKSQAVLEIPNLQLDDAGIYECTAENSRGKNSFRGQL 315
Cdd:cd05723      4 PSNIYAHESMDIVFECEVTGKPTPTVKWVK-NGdvVIPSDYFKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQL 82


                   ..
gi 1907197658  316 QI 317
Cdd:cd05723     83 II 84

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 48.85 E-value: 4.66e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907197658  423 IVTKDRGVLIECEPQGSPKPAISWRKGDKAV---RANKRIAILPDGSLRILNASKADEGKYICQGVNIFGS 490
Cdd:cd05738     10 VVEKARTATMLCAASGNPDPEISWFKDFLPVdtaTSNGRIKQLRSGALQIENSEESDQGKYECVATNSAGT 80

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 48.16 E-value: 5.20e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  116 KKVALNCEVRGNPSPSYRWLRNGTEIaleSDYryslidGTFIISNPSElRDSGLYQCLATNSFGSILSREATLQ 189
Cdd:pfam13895   15 EPVTLTCSAPGNPPPSYTWYKDGSAI---SSS------PNFFTLSVSA-EDSGTYTCVARNGRGGKVSNPVELT 78

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 47.77 E-value: 6.58e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  231 PKIEVHFPftvTAAKGTTVKMECFALGNPVPTITWMKVNgyipskSRLRKSQAVLeIPNLQLDDAGIYECTAENSRGKNS 310
Cdd:pfam13895    2 PVLTPSPT---VVTEGEPVTLTCSAPGNPPPSYTWYKDG------SAISSSPNFF-TLSVSAEDSGTYTCVARNGRGGKV 71


                   ..
gi 1907197658  311 FR 312
Cdd:pfam13895   72 SN 73

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 48.31 E-value: 6.79e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  238 PFTVTAAKGTTVKMECFALGNPVPTITWMKvngYIPSKSRL--RKSQAV----------LEIPNLQLDDAGIYECTAENS 305
Cdd:cd05765      7 PTHQTVKVGETASFHCDVTGRPQPEITWEK---QVPGKENLimRPNHVRgnvvvtnigqLVIYNAQPQDAGLYTCTARNS 83


                   ..
gi 1907197658  306 RG 307
Cdd:cd05765     84 GG 85

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 48.26 E-value: 7.23e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  707 APSNVSGRSGRRHELVIAWEPVSEEfqNGEGFGYIVAFRPNGTRGWKEkmVTSSEASKFIYRDESVPPLTPFEVKVGVYN 786
Cdd:cd00063      3 PPTNLRVTDVTSTSVTLSWTPPEDD--GGPITGYVVEYREKGSGDWKE--VEVTPGSETSYTLTGLKPGTEYEFRVRAVN 78

                           90
                   ....*....|...
gi 1907197658  787 NKGDGPFSQIVVI 799
Cdd:cd00063     79 GGGESPPSESVTV 91

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 47.84 E-value: 9.52e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  117 KVALNCEVRGNPSPSYRWlRNGTEIALESDYRYSLIDGTFIISNPSELrDSGLYQCLATNSFGS 180
Cdd:cd04969     19 DVIIECKPKASPKPTISW-SKGTELLTNSSRICILPDGSLKIKNVTKS-DEGKYTCFAVNFFGK 80

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 47.40 E-value: 1.13e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  421 SIIVTKDRGVLIECEPQGSPKPAISWRK--GDkavrankriaiLPDG---------SLRILNASKADEGKYICQGVNIFG 489
Cdd:cd05731      4 STMVLRGGVLLLECIAEGLPTPDIRWIKlgGE-----------LPKGrtkfenfnkTLKIENVSEADSGEYQCTASNTMG 72

                           90
                   ....*....|.
gi 1907197658  490 SAEIIASLSVK 500
Cdd:cd05731     73 SARHTISVTVE 83

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 47.20 E-value: 1.20e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658  437 QGSPKPAISWRKGDKAVRANKRIAI---LPDGSLRILNASKADEGKYICQGVNIFGSAEiiASLSVK 500
Cdd:cd05748     17 KGRPTPTVTWSKDGQPLKETGRVQIettASSTSLVIKNAKRSDSGKYTLTLKNSAGEKS--ATINVK 81

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 47.55 E-value: 1.22e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  118 VALNCEVRGNPSPSYRWLRNGTEIALESDYRYslidGTFIIS--------NPSELR--DSGLYQCLATNSFGSI 181
Cdd:cd20956     19 VSLKCVASGNPLPQITWTLDGFPIPESPRFRV----GDYVTSdgdvvsyvNISSVRveDGGEYTCTATNDVGSV 88

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 47.70 E-value: 1.25e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  245 KGTTVKMECFALGNPVPTITWMKvnGYIP-----SKSRLRKSQA-VLEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd05738     13 KARTATMLCAASGNPDPEISWFK--DFLPvdtatSNGRIKQLRSgALQIENSEESDQGKYECVATNSAG 79

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 47.33 E-value: 1.26e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907197658  432 IECEPQGSPKPAISWRKGDKAVRAN----KRIAILPDGsLRILNASKADEGKYICQGVNIFGSAEIIASLSV 499
Cdd:cd20949     19 ILCEVKGEPQPNVTWHFNGQPISASvadmSKYRILADG-LLINKVTQDDTGEYTCRAYQVNSIASDMQERTV 89

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 47.18 E-value: 1.38e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907197658  432 IECEPQGSPKPAISWRKGDKAVRANKRIAILPDG----SLRILNASKADEGKYICQGVNIFGSAEIIASLSV 499
Cdd:cd20973     17 FDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEdglcSLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 88

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 47.12 E-value: 1.54e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  118 VALNCEVRGNPSPSYRWLRNGTEI-ALESDYRYSLIDGTFIISNPSELrDSGLYQCLATNSFGSILSREATLQ 189
Cdd:cd20970     20 ATFMCRAEGSPEPEISWTRNGNLIiEFNTRYIVRENGTTLTIRNIRRS-DMGIYLCIASNGVPGSVEKRITLQ 91

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 47.00 E-value: 1.55e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  101 VQEPDDVIFPTDsdeKKVALNCEVRGNPSPSYRWLRNGTEIALEsdyRYS-LIDGTFIISNPSELrDSGLYQCLATNSFG 179
Cdd:cd05725      1 VKRPQNQVVLVD---DSAEFQCEVGGDPVPTVRWRKEDGELPKG---RYEiLDDHSLKIRKVTAG-DMGSYTCVAENMVG 73

                           90
                   ....*....|
gi 1907197658  180 SIlSREATLQ 189
Cdd:cd05725     74 KI-EASATLT 82

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 47.40 E-value: 1.59e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   98 PVFVQEPDDVifpTDSDEKKVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLIDGTF--IISNPSELRDSGLYQCLAT 175
Cdd:cd20990      1 PHFLQAPGDL---TVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVhsLIIEPVTSRDAGIYTCIAT 77


                   ....
gi 1907197658  176 NSFG 179
Cdd:cd20990     78 NRAG 81

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 47.11 E-value: 1.61e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907197658  245 KGTTVKMECFALGNPVPTITWMKVNGYIPSKSR----LRKSQAV-LEIPNLQLDDAGIYECTAENSRGKNSFRGQLQI 317
Cdd:cd05744     14 EGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAhkmlVRENGRHsLIIEPVTKRDAGIYTCIARNRAGENSFNAELVV 91

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 47.24 E-value: 1.73e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658  116 KKVALNCEVRGNPSPSYRWLRNGTEIALESDyRYSLIDGTFIISNPSEL-RDSGLYQCLATNSFGSI 181
Cdd:cd20976     17 QDFVAQCSARGKPVPRITWIRNAQPLQYAAD-RSTCEAGVGELHIQDVLpEDHGTYTCLAKNAAGQV 82

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 47.24 E-value: 1.82e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  425 TKDRGVLIECEPQGSPKPAISW-RKGDKA-VRANKRIAILpDGSLRILNASKA-DEGKYICQGVNIFGS 490
Cdd:cd05848     17 SDEKKVILNCEARGNPVPTYRWlRNGTEIdTESDYRYSLI-DGNLIISNPSEVkDSGRYQCLATNSIGS 84

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 46.43 E-value: 2.02e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907197658  240 TVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLR----KSQAVLEIPNLQLDDAGIYECTAENSRGKNS 310
Cdd:cd05748      1 TIVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQiettASSTSLVIKNAKRSDSGKYTLTLKNSAGEKS 75

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 46.85 E-value: 2.18e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  342 CKATGKPRPTYRWLKNGAPLLPQSRVDTV-NGILAIQSVNQSDAGMYQCLAENKYGAIYA 400
Cdd:cd20968     21 CTTMGNPKPSVSWIKGDDLIKENNRIAVLeSGSLRIHNVQKEDAGQYRCVAKNSLGIAYS 80

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 46.93 E-value: 2.36e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907197658  122 CEVRGNPSPSYRWLRNGTEI-ALESDYRYSLIDGTFIISNPSELRDSGLYQCLATNSFGSILSREATL 188
Cdd:cd05738     21 CAASGNPDPEISWFKDFLPVdTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAGTRYSAPANL 88

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 46.43 E-value: 2.73e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907197658  235 VHFPFTVTAAKGTTVKMECFALGNPVPTITWmKVNGyIP-----SKSRLRKSQAVLEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd05867      3 TRRPQSHLYGPGETARLDCQVEGIPTPNITW-SING-APiegtdPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHG 78

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 46.54 E-value: 2.84e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  342 CKATGKPRPTYRWLKNGAPLLPQSRVDTV----NGILAIQSVNQSDAGMYQCLAENKYGAIYAS 401
Cdd:cd05738     21 CAASGNPDPEISWFKDFLPVDTATSNGRIkqlrSGALQIENSEESDQGKYECVATNSAGTRYSA 84

Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptors TrkA, TrkB, and TrkC, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors. They are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkA, TrkB, and TrkC share significant sequence homology and domain organization. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrkA, TrkB, and TrkC mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. TrkA is recognized by NGF. TrkB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. TrkC is recognized by NT-3. NT-3 is promiscuous as in some cell systems it activates TrkA and TrkB receptors. TrkA is a receptor found in all major NGF targets, including the sympathetic, trigeminal, and dorsal root ganglia, cholinergic neurons of the basal forebrain, and the striatum. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. The TrkC gene is expressed throughout the mammalian nervous system. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409360 Cd Length: 96 Bit Score: 46.63 E-value: 3.04e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658  124 VRGNPSPSYRWLRNGTEIaLESDYRYSLID----------GTFIISNPSELrDSGLYQCLATNSFGS 180
Cdd:cd04971     22 VRGNPKPTLTWYHNGAVL-NESDYIRTEIHyeaatpteyhGCLKFDNPTHV-NNGNYTLVASNEYGQ 86

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R); member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (also known as Flt-1), VEGFR-2 (also known as KDR or Flk-1) and VEGFR-3 (also known as Flt-4). VEGF_A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF, VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-2 and -1 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth.

Pssm-ID: 409448 Cd Length: 102 Bit Score: 46.67 E-value: 3.43e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  505 IELTPKR-TELTVGESIVLNCKAIHDASLDVTFYWTLKGQPidfEKEGGHFENIRAQAS------SADLMIRNILLMHAG 577
Cdd:cd05862      3 VQLSPPKpVELLVGEKLVLNCTARTELNVGVDFQWDYPGKK---EQRRASVRRRRKQQSseatefSSTLTIDNVTLSDKG 79

                           90       100
                   ....*....|....*....|.
gi 1907197658  578 RYGCRVQTTADSVSDEAELLV 598
Cdd:cd05862     80 LYTCAASSGPMFKKNSTSVIV 100

First immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The first Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409571 Cd Length: 91 Bit Score: 46.41 E-value: 3.44e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   98 PVFVQEPDDVIFptdSDEKKVALNCEVRGNPSP-SYRWLRNGTEIAL-ESDYRYSLIDGTFIISNPSElRDSGLYQCLAT 175
Cdd:cd20979      1 PVLKEQPAEVLF---REGQPTVLECVTEGGDQGvKYSWLKDGKSFNWqEHNVAQRKDEGSLVFLKPQA-SDEGQYQCFAE 76


                   ....*....
gi 1907197658  176 NSFGSILSR 184
Cdd:cd20979     77 TPAGVASSR 85

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 45.70 E-value: 3.58e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  335 GSPLQWECKATGKPRPTYRWLKNGAPL-LPQSRVDTVNGILAIQSVNQSDAGMYQCLAENKYGAIYASAELKI 406
Cdd:cd05745      2 GQTVDFLCEAQGYPQPVIAWTKGGSQLsVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 45.76 E-value: 4.75e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658  341 ECKATGKPRPTYRWLKNGAPLLPQSRVDTV-NGILAIQSVNQSDAGMYQCLAENKYGAIYASAELKI 406
Cdd:cd05852     23 ECKPKAAPKPKFSWSKGTELLVNNSRISIWdDGSLEILNITKLDEGSYTCFAENNRGKANSTGVLSV 89

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 46.06 E-value: 4.87e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907197658  117 KVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLIDG---TFIISNpSELRDSGLYQCLATNSFGSI 181
Cdd:cd05729     21 KVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEkgwSLIIER-AIPRDKGKYTCIVENEYGSI 87

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 45.16 E-value: 7.58e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  335 GSPLQWECKATGKPRPTYRWLKNGAPLLPQSRVDTV--NGILAIQSVNQSDAGMYQCLAENKYGAIYASAELKI 406
Cdd:cd05764     15 GQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVydNGTLDILITTVKDTGAFTCIASNPAGEATARVELHI 88

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 45.33 E-value: 7.63e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907197658  119 ALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLI-DGTFIISNPSELRDSGLYQCLATNSFG 179
Cdd:cd05736     19 SLRCHAEGIPLPRVQWLKNGMDINPKLSKQLTLIaNGSELHISNVRYEDTGAYTCIAKNEGG 80

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 45.33 E-value: 8.74e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  231 PKIEVhFPFTVTAAKGTTVKMECFALGNPVPTITWMK----VNGYIPSKSRLRKSQAVLEIPNLQLDDAGIYECTAENSR 306
Cdd:cd05736      1 PVIRV-YPEFQAKEPGVEASLRCHAEGIPLPRVQWLKngmdINPKLSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEG 79


                   .
gi 1907197658  307 G 307
Cdd:cd05736     80 G 80

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 45.36 E-value: 9.11e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  249 VKMECFALGNPVPTITW-----------MKVNGYIPSKSRLRKSQavLEIPNLQLDDAGIYECTAENSRGKNS 310
Cdd:cd05869     20 ITLTCEASGDPIPSITWrtstrnisseeKTLDGHIVVRSHARVSS--LTLKYIQYTDAGEYLCTASNTIGQDS 90

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 45.23 E-value: 9.11e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  246 GTTVKMECFALGNPVPTITWMK----------VNGYipsKSRLRKSQAVLE--IPNlqldDAGIYECTAENSRG 307
Cdd:cd05857     19 ANTVKFRCPAAGNPTPTMRWLKngkefkqehrIGGY---KVRNQHWSLIMEsvVPS----DKGNYTCVVENEYG 85

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

Pssm-ID: 409417 Cd Length: 95 Bit Score: 45.30 E-value: 9.26e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  342 CKATGKPRPTYRWLKNGAPLLPQSRVDTVNG---ILAIQSVNQSDAGMYQCLAENKYGAIYAS 401
Cdd:cd05760     23 CHIDGHPRPTYQWFRDGTPLSDGQGNYSVSSkerTLTLRSAGPDDSGLYYCCAHNAFGSVCSS 85

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 44.50 E-value: 1.05e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  345 TGKPRPTYRWLKNGAPLLPQSRVDT----VNGILAIQSVNQSDAGMYQCLAENKYGAiyASAELKI 406
Cdd:cd05748     17 KGRPTPTVTWSKDGQPLKETGRVQIettaSSTSLVIKNAKRSDSGKYTLTLKNSAGE--KSATINV 80

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 44.53 E-value: 1.07e-05

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   908 PPGNLRWEQQGS-QVSLGWEPVRPLANESEVMGYKVFYRQEGHSEGQVIETQKPQAVV--PLPEAGVYIIEVRAYSEGGD 984
Cdd:smart00060    3 PPSNLRVTDVTStSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWKEVNVTPSSTSYTltGLKPGTEYEFRVRAVNGAGE 82


                    .
gi 1907197658   985 G 985
Cdd:smart00060   83 G 83

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 44.40 E-value: 1.08e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  335 GSPLQWECKATGKPRPTYRWLKNGAPLLPQSRVDTVN----GILAIQSVNQSDAGMYQCLAENKYGAIYA 400
Cdd:cd05743      1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITSeggyGTLTIRDVKESDQGAYTCEAINTRGMVFG 70

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 44.70 E-value: 1.11e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSRVDTV----NGILAIQSVNQS--DAGMYQCLAENK 394
Cdd:cd05893      1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIqrdlDGTCSLHTTASTldDDGNYTIMAANP 80

                           90
                   ....*....|..
gi 1907197658  395 YGAIYASAELKI 406
Cdd:cd05893     81 QGRISCTGRLMV 92

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 44.81 E-value: 1.24e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  110 PTDSDEKKVALNCE-VRGNPSPSYRWLRNGTEIALESDYRYSLIDG---TFIISNPSELRDSGLYQCLATNSFG 179
Cdd:cd05750      9 QTVQEGSKLVLKCEaTSENPSPRYRWFKDGKELNRKRPKNIKIRNKkknSELQINKAKLEDSGEYTCVVENILG 82

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 44.39 E-value: 1.25e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658  424 VTKDRGVLIECEPQGSPKPAISWRKGD-KAVRANKRIAILPDGSLRILNASKADEGKYICQGVNIFGSAEIIASLSV 499
Cdd:cd05764     12 VLEGQRATLRCKARGDPEPAIHWISPEgKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVELHI 88

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 44.70 E-value: 1.30e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  417 QVKKSIIVTKDRGVLIECEPQGSPKPAISWRKGDK--AVRANKRIAILPD-GSLRILNAS---KADEGKYICQGVNIFGS 490
Cdd:cd05733      6 QSPKDYIVDPRDNITIKCEAKGNPQPTFRWTKDGKffDPAKDPRVSMRRRsGTLVIDNHNggpEDYQGEYQCYASNELGT 85


                   .
gi 1907197658  491 A 491
Cdd:cd05733     86 A 86

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 44.70 E-value: 1.35e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907197658  118 VALNCEVRGNPSPSYRWLRNGTEIALESDYrYSL---IDGTFII-SNPSELRDSGLYQCLATNSFGSI 181
Cdd:cd05893     18 VTFTCRVAGNPKPKIYWFKDGKQISPKSDH-YTIqrdLDGTCSLhTTASTLDDDGNYTIMAANPQGRI 84

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 44.44 E-value: 1.43e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  434 CEPQGSPKPAISWRKGDKAVRANKRIAILPDGSLRILNASKADEGKYICQGVNIFGSAEIIASL 497
Cdd:cd20957     23 CSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAEL 86

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 44.37 E-value: 1.49e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907197658  430 VLIECEPQGSPKPAISWRKGDKAVRAN-KRIAILPDGS----LRILNASKADEGKYICQGVNIFGSAEIIASLSV 499
Cdd:cd05892     18 VRLECQISAIPPPQIFWKKNNEMLQYNtDRISLYQDNCgricLLIQNANKKDAGWYTVSAVNEAGVVSCNARLDV 92

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 44.42 E-value: 1.53e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  242 TAAKGTTVKMECFALG-NPVPTITWMK----VNGYIPSKSRLRKSQ--AVLEIPNLQLDDAGIYECTAENSRGKNSFRGQ 314
Cdd:cd05750     10 TVQEGSKLVLKCEATSeNPSPRYRWFKdgkeLNRKRPKNIKIRNKKknSELQINKAKLEDSGEYTCVVENILGKDTVTGN 89


                   ...
gi 1907197658  315 LQI 317
Cdd:cd05750     90 VTV 92

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 44.58 E-value: 1.66e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  325 QKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLL----PQSRVDTVNGILAIQSVNQSDA----GMYQCLAENKYG 396
Cdd:cd05875      6 QSAKDYIVDPRDNILIECEAKGNPVPTFHWTRNGKFFNvakdPRVSMRRRSGTLVIDFRGGGRPedyeGEYQCFARNKFG 85

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 44.10 E-value: 1.76e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  241 VTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRlrksQAV-----LEIPNLQLD-DAGIYECTAENSRGkNSFRGQ 314
Cdd:cd20958     10 LTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHR----QRVfpngtLVIENVQRSsDEGEYTCTARNQQG-QSASRS 84


                   ...
gi 1907197658  315 LQI 317
Cdd:cd20958     85 VFV 87

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409444 Cd Length: 105 Bit Score: 44.57 E-value: 1.77e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  231 PKIEVHFPFTVTAAKGTTVKMECFALGNPVPTITWMK---VNGY------IPSKSRLR--------KSQAVLEIPNLQLD 293
Cdd:cd05858      1 PILQAGLPANTSVVVGTDAEFVCKVYSDAQPHIQWLKhveKNGSkygpdgLPYVEVLKtagvnttdKEIEVLYLRNVTFE 80

                           90
                   ....*....|....
gi 1907197658  294 DAGIYECTAENSRG 307
Cdd:cd05858     81 DAGEYTCLAGNSIG 94

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 44.56 E-value: 1.90e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  238 PFTVTAAKGTTVKMECFALGNPVPTITWMK---VNGYIPSK-----SRLRKSQ-AVLEIPNLQLDDAGIYECTAENSRGK 308
Cdd:cd05726      6 PRDQVVALGRTVTFQCETKGNPQPAIFWQKegsQNLLFPYQppqpsSRFSVSPtGDLTITNVQRSDVGYYICQALNVAGS 85


                   ....*....
gi 1907197658  309 NSFRGQLQI 317
Cdd:cd05726     86 ILAKAQLEV 94

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 44.10 E-value: 1.94e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907197658  116 KKVALNCEVRGNPSPSYRWLRNGteIALESDYRYSLI-DGTFIISNPSELRDSGLYQCLATNSFGSILSREATLQ 189
Cdd:cd20958     16 QTLRLHCPVAGYPISSITWEKDG--RRLPLNHRQRVFpNGTLVIENVQRSSDEGEYTCTARNQQGQSASRSVFVK 88

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 43.93 E-value: 1.95e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  238 PFTVTAAKGTTVKMECFA-LGNPVPTITWMKVNGYIPSKSRLRK--SQAVLEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd05724      4 PSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRivDDGNLLIAEARKSDEGTYKCVATNMVG 76

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 44.20 E-value: 2.03e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  411 PSFELNQVKKSIIVTKDRgVLIECEPQGSPKPAISWRKGDK--AVRANKRIAILP-DGSLRILNASKAD----EGKYICQ 483
Cdd:cd05875      1 PTITKQSAKDYIVDPRDN-ILIECEAKGNPVPTFHWTRNGKffNVAKDPRVSMRRrSGTLVIDFRGGGRpedyEGEYQCF 79


                   ....*...
gi 1907197658  484 GVNIFGSA 491
Cdd:cd05875     80 ARNKFGTA 87

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 43.71 E-value: 2.14e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  334 SGSPLQWECKATGKPRPTYRWLKNGAPLlPQSRVDTV--NGILAIQSVNQ-SDAGMYQCLAENKYG 396
Cdd:cd20958     14 AGQTLRLHCPVAGYPISSITWEKDGRRL-PLNHRQRVfpNGTLVIENVQRsSDEGEYTCTARNQQG 78

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The second Ig-like domain of JAM1 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, the A strand of the I-set is discontinuous but lacks a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.

Pssm-ID: 409542 Cd Length: 97 Bit Score: 44.23 E-value: 2.19e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907197658  346 GKPRPTYRWLKNGAPLL--PQS---------RVDTVNGILAIQSVNQSDAGMYQCLAENKYG 396
Cdd:cd20950     24 GSPPSEYTWFKDGVVMPtnPKStrafsnssySLDPTTGELVFDPLSASDTGEYSCEARNGYG 85

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 44.17 E-value: 2.25e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  342 CKATGKPRPTYRWLKNGAPLLP-QSRVDTV--NGI-LAIQSVNQSDAGMYQCLAENKYG 396
Cdd:cd05736     22 CHAEGIPLPRVQWLKNGMDINPkLSKQLTLiaNGSeLHISNVRYEDTGAYTCIAKNEGG 80

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 43.56 E-value: 2.35e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  908 PPGNLRW-EQQGSQVSLGWEPvrPLANESEVMGYKVFYRQEGHSEG---QVIETQKPQAVVPLPEAGV-YIIEVRAYSEG 982
Cdd:pfam00041    2 APSNLTVtDVTSTSLTVSWTP--PPDGNGPITGYEVEYRPKNSGEPwneITVPGTTTSVTLTGLKPGTeYEVRVQAVNGG 79


                   ....*.
gi 1907197658  983 GDGTAS 988
Cdd:pfam00041   80 GEGPPS 85

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 43.76 E-value: 2.36e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  100 FVQEPDDVIFPTDSDEKkvaLNCEVRGNPSPSYRWLRNG-TEIALESDYRYSLI--DGTFIISNpSELRDSGLYQCLATN 176
Cdd:cd05763      2 FTKTPHDITIRAGSTAR---LECAATGHPTPQIAWQKDGgTDFPAARERRMHVMpeDDVFFIVD-VKIEDTGVYSCTAQN 77

                           90
                   ....*....|..
gi 1907197658  177 SFGSIlSREATL 188
Cdd:cd05763     78 SAGSI-SANATL 88

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 43.92 E-value: 2.67e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  241 VTAAKGTTVKMECFALGNPVPTITWMKVNGYI---PSKSRLRK-SQAVLEIPNLQLDDAGIYECTAENSRGKNSFRGQLQ 316
Cdd:cd20969     12 VFVDEGHTVQFVCRADGDPPPAILWLSPRKHLvsaKSNGRLTVfPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLH 91


                   .
gi 1907197658  317 I 317
Cdd:cd20969     92 V 92

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 43.88 E-value: 2.73e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPL----LPQSRVDTVNGI--LAIQSVNQSDAGMYQCLAENK 394
Cdd:cd20974      1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVIststLPGVQISFSDGRakLSIPAVTKANSGRYSLTATNG 80

                           90
                   ....*....|...
gi 1907197658  395 YGAIYASAELKIL 407
Cdd:cd20974     81 SGQATSTAELLVL 93

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 43.84 E-value: 2.74e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907197658  238 PFTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSR-LRKSQAV-------LEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd20954      8 PVDANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGEYKdLLYDPNVrilpngtLVFGHVQKENEGHYLCEAKNGIG 85

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 43.69 E-value: 3.04e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  231 PKIeVHFPFTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLRKSQAVLeIPNLQL------------DDAGIY 298
Cdd:cd07693      1 PRI-VEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHRIV-LPSGSLfflrvvhgrkgrSDEGVY 78


                   ....*....
gi 1907197658  299 ECTAENSRG 307
Cdd:cd07693     79 VCVAHNSLG 87

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 43.00 E-value: 3.55e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  118 VALNCEVRGNPSPSYRWLRNGTEIALesDYRYS-LIDGTFIISNpSELRDSGLYQCLATNSFGS 180
Cdd:cd05745      5 VDFLCEAQGYPQPVIAWTKGGSQLSV--DRRHLvLSSGTLRISR-VALHDQGQYECQAVNIVGS 65

IL-beta-binding protein; Provisional

Pssm-ID: 165149 [Multi-domain] Cd Length: 326 Bit Score: 46.93 E-value: 3.62e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  315 LQIFTYPHWVQKLNDTQ-LDSG-----------SPLQWECKATGKPRPTYR-----WLKNGAP---LLPqsrVDTVNGIL 374
Cdd:PHA02785     9 LPIFFYSSFVQTFNAPEcIDKGqyfasfmelenEPVILPCPQINTLSSGYNildilWEKRGADndrIIP---IDNGSNML 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  375 aIQSVNQSDAGMYQCLAENKYGAIYASAELKILASPPSfELNQVKKSIIVTKDRGVLIECePQGSPKPA------ISWRk 448
Cdd:PHA02785    86 -ILNPTQSDSGIYICITKNETYCDMMSLNLTIVSVSES-NIDLISYPQIVNERSTGEMVC-PNINAFIAsnvnadIIWS- 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  449 GDKAVRaNKRIAILPDGSLRILNASKADEGKYICQGVNIFGSAEIIASLSVKEPTRIELTPKRTEL------TVGESIVL 522
Cdd:PHA02785   162 GHRRLR-NKRLKQRTPGIITIEDVRKNDAGYYTCVLKYIYGDKTYNVTRIVKLEVRDRIIPPTMQLpegvvtSIGSNLTI 240

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1907197658  523 NCK-AIHDASLDVTFYWTLKGQPIDFEKEGG 552
Cdd:PHA02785   241 ACRvSLRPPTTDADVFWISNGMYYEEDDEDG 271

Immunoglobulin-like domain of human nephrin and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain in human nephrin and similar proteins. Nephrin is an integral component of the slit diaphragm and is a central component of the glomerular ultrafilter. Nephrin plays a structural role and has a role in signaling. Nephrin is a transmembrane protein having a short intracellular portion, an extracellular portion comprised of eight Ig-like domains, and one fibronectin type III-like domain. The extracellular portions of nephrin from neighboring foot processes of separate podocyte cells may interact with each other, and in association with other components of the slit diaphragm form a porous molecular sieve within the slit pore. The intracellular portion of nephrin is associated with linker proteins, which connect nephrin to the actin cytoskeleton. The intracellular portion is tyrosine phosphorylated, and mediates signaling from the slit diaphragm into the podocytes.

Pssm-ID: 143250 Cd Length: 109 Bit Score: 43.77 E-value: 3.75e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  114 DEKKVA-LNCEVRGNPSPSYRWLRNGTEIALEsDYRYS--------LIDGTFIISNPSELRDSGLYQCLATNSFGS 180
Cdd:cd05773     21 DGSSDAnLVCQAQGVPRVQFRWAKNGVPLDLG-NPRYEettehtgtVHTSILTIINVSAALDYALFTCTAHNSLGE 95

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 43.15 E-value: 4.31e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907197658  116 KKVALNCEVRGNPSPSYRWLRNGTE-IALESDYRYSLIDGTFIISNPSELRDSGLYQCLATNSFG 179
Cdd:cd20969     18 HTVQFVCRADGDPPPAILWLSPRKHlVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGG 82

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 43.22 E-value: 4.81e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPL-LPQSRV-----DTVNGILAIQSVNQSDAGMYQCLAENK 394
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLqYNTDRIslyqdNCGRICLLIQNANKKDAGWYTVSAVNE 80

                           90
                   ....*....|..
gi 1907197658  395 YGAIYASAELKI 406
Cdd:cd05892     81 AGVVSCNARLDV 92

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 43.07 E-value: 5.02e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLK--NGAP-----LLPQSRVDTV-NGILAIQSVNQSDAGMYQCLAE 392
Cdd:cd20954      2 PRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKatGSTPgeykdLLYDPNVRILpNGTLVFGHVQKENEGHYLCEAK 81


                   ....*
gi 1907197658  393 NKYGA 397
Cdd:cd20954     82 NGIGS 86

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 42.56 E-value: 6.08e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  106 DVIFPTDSDEKkvaLNCEVRGNPSPSYRWLRNGTEIAlESDYRYSLIDG----TFIISNPSElRDSGLYQCLATNSFGsi 181
Cdd:cd20973      6 DKEVVEGSAAR---FDCKVEGYPDPEVKWMKDDNPIV-ESRRFQIDQDEdglcSLIISDVCG-DDSGKYTCKAVNSLG-- 78


                   ....*.
gi 1907197658  182 lsrEAT 187
Cdd:cd20973     79 ---EAT 81

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 42.79 E-value: 6.37e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907197658  115 EKK-VALNCEVRGNPSPSYRWLRNGTEI---ALESDYRYSLIDG--TFIISNpSELRDSGLYQCLATNSFGSILS 183
Cdd:cd20951     14 EKSdAKLRVEVQGKPDPEVKWYKNGVPIdpsSIPGKYKIESEYGvhVLHIRR-VTVEDSAVYSAVAKNIHGEASS 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 42.17 E-value: 6.39e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  504 RIELTPKRTELTVGESIVLNCKAihDASLDVTFYWTLKGQPIDfekeGGHFENIRAQASSADLMIRNILLMHAGRYGCRV 583
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEA--TGSPPPTITWYKNGEPIS----SGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

Pssm-ID: 409404 Cd Length: 102 Bit Score: 42.91 E-value: 6.62e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  505 IELTPK--RTELTVGESIVLNCKAIHDASLDVTFYWTLKGqpidfEKEGGHF---ENIRAQASSAD-----LMIRNILLM 574
Cdd:cd05742      3 LELSPNaePTVLPQGETLVLNCTANVNLNEVVDFQWTYPS-----EKEGKLAllkPDIKVDWSEPGefvstLTIPEATLK 77

                           90
                   ....*....|.
gi 1907197658  575 HAGRYGCRVQT 585
Cdd:cd05742     78 DSGTYTCAARS 88

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 42.53 E-value: 6.76e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  411 PSFELNQvKKSIIVTKDRGVLIECEPQGSPKPAISWRKGDKAVRANKRIAIlPDGSLRILNASKADEGKYICQGVNIFG 489
Cdd:cd04968      1 PSIKVRF-PADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITT-SEPVLEIPNVQFEDEGTYECEAENSRG 77

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409444 Cd Length: 105 Bit Score: 43.02 E-value: 7.23e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  335 GSPLQWECKATGKPRPTYRWLK-----------NGAP---LLPQSRVDTVNG---ILAIQSVNQSDAGMYQCLAENKYGA 397
Cdd:cd05858     16 GTDAEFVCKVYSDAQPHIQWLKhvekngskygpDGLPyveVLKTAGVNTTDKeieVLYLRNVTFEDAGEYTCLAGNSIGI 95

                           90
                   ....*....|
gi 1907197658  398 IYASAELKIL 407
Cdd:cd05858     96 SHHSAWLTVL 105

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 42.48 E-value: 7.32e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  410 PPSFELNQVKKSIIVTKdrGVLIECEPQGSPKPAISWRKGDKA--------VRANKRIAILPDGSLRILNASKADEGKYI 481
Cdd:cd05734      1 PPRFVVQPNDQDGIYGK--AVVLNCSADGYPPPTIVWKHSKGSgvpqfqhiVPLNGRIQLLSNGSLLIKHVLEEDSGYYL 78


                   ....*....
gi 1907197658  482 CQGVNIFGS 490
Cdd:cd05734     79 CKVSNDVGA 87

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 42.61 E-value: 7.49e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907197658  432 IECEPQGSPKPAISWRKG---DKAVRANKRIAILP-DGSLRILNASKADEGKYICQGVNIFGSAEIIASLSV 499
Cdd:cd05763     19 LECAATGHPTPQIAWQKDggtDFPAARERRMHVMPeDDVFFIVDVKIEDTGVYSCTAQNSAGSISANATLTV 90

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 42.57 E-value: 7.53e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  410 PPSFelNQVKKSIIVTKDRGVLIECEPQGSPKPAISWRKGDKAVRANKRIAILPDG---SLRILNASKADEGKYICQGVN 486
Cdd:cd20972      1 PPQF--IQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGdlhSLIIAEAFEEDTGRYSCLATN 78

                           90
                   ....*....|...
gi 1907197658  487 IFGSAEIIASLSV 499
Cdd:cd20972     79 SVGSDTTSAEIFV 91

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 42.48 E-value: 7.97e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  231 PKIEvhfPFTV---TAAKGTTVKMECFALGNPVP-TITWMKVNGYIP-----SKSRLRKSQAVLEIPNLQLDDAGIYECT 301
Cdd:cd20959      2 PRII---PFAFgegAAQVGMRAQLHCGVPGGDLPlNIRWTLDGQPISddlgiTVSRLGRRSSILSIDSLEASHAGNYTCH 78

                           90
                   ....*....|....*.
gi 1907197658  302 AENSRGKNSFRGQLQI 317
Cdd:cd20959     79 ARNSAGSASYTAPLTV 94

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 42.20 E-value: 8.20e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658  433 ECEPQGSPKPAISWRKGDKAVRANKRIAILpDGSLRILNASKADEGKYICQGVNIFGSAEIIASLSV 499
Cdd:cd05728     20 ECKASGNPRPAYRWLKNGQPLASENRIEVE-AGDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 42.09 E-value: 8.36e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  430 VLIECEPQGSPKPAISWRKGDKAVRANKRIAILPD---GSLRILNASKADEGKYICQGVNIFG 489
Cdd:cd05743      4 VEFTCVATGVPTPIINWRLNWGHVPDSARVSITSEggyGTLTIRDVKESDQGAYTCEAINTRG 66

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 42.28 E-value: 9.17e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907197658  341 ECKATGKPRPTYRWLKNGAPL----LPQSRVDTVNGILAIQSVNQSDA----GMYQCLAENKYGA 397
Cdd:cd05874     22 QCEAKGKPPPSFSWTRNGTHFdidkDPKVTMKPNTGTLVINIMNGEKAeayeGVYQCTARNERGA 86

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 41.69 E-value: 1.44e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  231 PKIEVHFPFTVtAAKGTTVKMECFALGNPVPTITWMKVNG-YIPSKSR-LRKSQAVLEIPNLQLDDAGIYECTAENSRGK 308
Cdd:cd05764      1 PLITRHTHELR-VLEGQRATLRCKARGDPEPAIHWISPEGkLISNSSRtLVYDNGTLDILITTVKDTGAFTCIASNPAGE 79


                   ....*....
gi 1907197658  309 NSFRGQLQI 317
Cdd:cd05764     80 ATARVELHI 88

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 41.82 E-value: 1.45e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  104 PDDVifpTDSDEKKVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLIDGTF----IISNPSElrDSGLYQCLATNSFG 179
Cdd:cd05891      8 PDVV---TIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEQGKYasltIKGVTSE--DSGKYSINVKNKYG 82

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 41.61 E-value: 1.57e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907197658  324 VQKLNDTQLDSGSPLQWECKATGkPRPTYRWLKNGAPLLPQSRVDTVNG--ILAIQSVNQSDAGMYQCLAEN 393
Cdd:cd05740      4 ISSNNSNPVEDKDAVTLTCEPET-QNTSYLWWFNGQSLPVTPRLTLSNGnrTLTLLNVTREDAGAYQCEISN 74

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 41.69 E-value: 1.80e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  421 SIIVTKDRG-VLIECEPQGSPKPAISWRKGDKAVR--ANKRIAILPDGSLRILN-----ASKADEGKYICQGVN-IFGS 490
Cdd:cd05722      9 SDIVAMRGGpVVLNCSAESDPPPKIEWKKDGVLLNlvSDERRQQLPNGSLLITSvvhskHNKPDEGFYQCVAQNeSLGS 87

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 41.48 E-value: 2.04e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  100 FVQEPDDVIFptdSDEKKVALNCEVRGNPSPSYRWLRNGTEIAL------ESDYRYSLID-GTFIISNpSELRDSGLYQC 172
Cdd:cd05726      2 FVVKPRDQVV---ALGRTVTFQCETKGNPQPAIFWQKEGSQNLLfpyqppQPSSRFSVSPtGDLTITN-VQRSDVGYYIC 77

                           90
                   ....*....|..
gi 1907197658  173 LATNSFGSILSR 184
Cdd:cd05726     78 QALNVAGSILAK 89

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 40.86 E-value: 2.08e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  707 APSNVSGRSGRRHELVIAWEPVseEFQNGEGFGYIVAFRP-NGTRGWKEKMVTSSEASkfiYRDESVPPLTPFEVKVGVY 785
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPP--PDGNGPITGYEVEYRPkNSGEPWNEITVPGTTTS---VTLTGLKPGTEYEVRVQAV 76


                   ....*....
gi 1907197658  786 NNKGDGPFS 794
Cdd:pfam00041   77 NGGGEGPPS 85

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 41.16 E-value: 2.13e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  342 CKATGKPRPTYRWLKNGAPLLPQSRVDTVNGILA----IQSVNQSDAGMYQCLAENKYG 396
Cdd:cd20949     21 CEVKGEPQPNVTWHFNGQPISASVADMSKYRILAdgllINKVTQDDTGEYTCRAYQVNS 79

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 41.14 E-value: 2.30e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   98 PVFVQEPDDVIFPTDSDekkVALNCEVRGNPSPSYRWLRN-GTEIALESDYRYS-----LIDGTFIISNPSELRDsGLYQ 171
Cdd:cd20954      2 PRWIVEPVDANVAAGQD---VMLHCQADGFPTPTVTWKKAtGSTPGEYKDLLYDpnvriLPNGTLVFGHVQKENE-GHYL 77

                           90
                   ....*....|...
gi 1907197658  172 CLATNSFGSILSR 184
Cdd:cd20954     78 CEAKNGIGSGLSK 90

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 40.46 E-value: 2.44e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  327 LNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSRvdtvngiLAIQSVNQSDAGMYQCLAENKYG 396
Cdd:pfam13895    6 PSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPN-------FFTLSVSAEDSGTYTCVARNGRG 68

First immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK). Tyro3 together with Axl and Mer form the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3 and Mer are widely expressed in adult tissues, though they show higher expression in the brain, in the lymphatic and vascular systems, and in the testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

Pssm-ID: 409553 Cd Length: 87 Bit Score: 40.89 E-value: 2.77e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  332 LDSGSPLQWECKATGKPRPTYRWLKNGAPL-------LPQSRVDTVnGILAIQSVNQSDAGMYQCLAEN 393
Cdd:cd20961      5 VSQGQPVKLNCSVEGMEEPDIQWVKDGAVVqnldqlyIPVSEQHWI-GFLSLKSVERSDAGRYWCQVED 72

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 41.04 E-value: 2.81e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  104 PDDVifpTDSDEKKVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLIDG---TFIISNPSElRDSGLYQCLATNSFGS 180
Cdd:cd05737      8 PDVV---TIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGrtvYFTINGVSS-EDSGKYGLVVKNKYGS 83

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 40.24 E-value: 2.91e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  118 VALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLiDGTFIISNPSeLRDSGLYQCLATNSFGS 180
Cdd:cd05746      1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISP-EGYLAIRDVG-VADQGRYECVARNTIGY 61

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 40.94 E-value: 3.04e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQ--------SRVDTV-NGILAIQSVNQSDAGMYQCLA 391
Cdd:cd05734      2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPQfqhivplnGRIQLLsNGSLLIKHVLEEDSGYYLCKV 81


                   ....*.
gi 1907197658  392 ENKYGA 397
Cdd:cd05734     82 SNDVGA 87

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 40.74 E-value: 3.52e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  416 NQVKKSIIVTKDRGVLIECEPQGSPKPAISW-RKGDK-AVRANKRIAILPD-GSL--RILNASKAD--EGKYICQGVNIF 488
Cdd:cd05874      5 HQSPKDYIVDPRENIVIQCEAKGKPPPSFSWtRNGTHfDIDKDPKVTMKPNtGTLviNIMNGEKAEayEGVYQCTARNER 84


                   ...
gi 1907197658  489 GSA 491
Cdd:cd05874     85 GAA 87

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 40.47 E-value: 3.81e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  236 HF---PFTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKS---RLRKSQAV--LEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd20990      2 HFlqaPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSahkMLVRENGVhsLIIEPVTSRDAGIYTCIATNRAG 81

                           90
                   ....*....|
gi 1907197658  308 KNSFRGQLQI 317
Cdd:cd20990     82 QNSFNLELVV 91

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409540 Cd Length: 76 Bit Score: 40.17 E-value: 3.87e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  246 GTTVKMECFALGNPVPTITWmKVNGyipsksRLRKSQAVLEIPNLQLDDAGIYECTAENS 305
Cdd:cd20948     10 GENLNLSCHAASNPPAQYSW-TING------TFQTSSQELFLPAITENNEGTYTCSAHNS 62

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 40.26 E-value: 4.00e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  113 SDEKKVALNCEVR-GNPSPSYRWLRNGTEIALESDY---RYSLIDGTFIISNPSElRDSGLYQCLATNSFGSILSR 184
Cdd:pfam00047    9 LEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVkhdNGRTTQSSLLISNVTK-EDAGTYTCVVNNPGGSATLS 83

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 40.28 E-value: 4.64e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907197658  432 IECEPQGSPKPAISWRKGDKAVRANKRIAILPD----GSLRILNASKADEGKYICQGVNIFGSAEIIASLSV 499
Cdd:cd05891     21 LTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEqgkyASLTIKGVTSEDSGKYSINVKNKYGGETVDVTVSV 92

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 39.87 E-value: 5.07e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907197658  242 TAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLRKSQ-----AVLEIPNLQLDDAGIYECTAENSRGK 308
Cdd:cd20973      8 EVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQdedglCSLIISDVCGDDSGKYTCKAVNSLGE 79

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 40.30 E-value: 5.29e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  242 TAAKGTTVKMECFALGNPVPTITWMKVNGYIPS---KSRLRKSQAVLEIPNLQLDDAGIYECTAENSRGKNSFRGQLQIF 318
Cdd:cd05730     14 TANLGQSVTLACDADGFPEPTMTWTKDGEPIESgeeKYSFNEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKVF 93

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 39.82 E-value: 5.54e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  421 SIIVTKDRGVLIECEPQGSPKPAISWRKGDKAVRANK---RIAILPDGS-LRILNASKADEGKYICQGVNIFGsaEIIAS 496
Cdd:cd05894      4 TIVVVAGNKLRLDVPISGEPAPTVTWSRGDKAFTATEgrvRVESYKDLSsFVIEGAEREDEGVYTITVTNPVG--EDHAS 81


                   ....
gi 1907197658  497 LSVK 500
Cdd:cd05894     82 LFVK 85

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 40.01 E-value: 6.19e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  116 KKVALNCEVRGNPSPSYRWLRNGTEIALESDY--RYSLIDGTFIIsNPSELRDSGLYQCLATNSFG 179
Cdd:cd20949     15 QSATILCEVKGEPQPNVTWHFNGQPISASVADmsKYRILADGLLI-NKVTQDDTGEYTCRAYQVNS 79

Immunoglobulin-like Ig0 domain of basigin-1 (BSG1) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of the collagenase stimulatory factor, basigin-1 (BSG1; also known as Cluster of Differentiation 147 (CD147) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN)) and similar proteins. CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. It is expressed in nearly all cells including platelets and fibroblasts and is involved in inflammatory diseases, and cancer progression. CD147 is highly expressed in several cancers and used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified: CD147 Ig1-Ig2 (also called Basigin-2) that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 (also called Basigin-1) that is retinal specific and implicated in retinoblastoma. Studies showed that CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 dimer is the functional unit required for activity.

Pssm-ID: 409534 Cd Length: 116 Bit Score: 40.72 E-value: 6.37e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  246 GTTVKMECFALGNPVPTITWMKVNGYiPSK--------SRLRK----------SQAVLEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd20940     15 GDSVELHCEAVGSPIPEIQWWFEGQE-PNEicsqlwdgARLDRvhinatyhqhATSTISIDNLTEEDTGTYECRASNDPD 93


                   ....*
gi 1907197658  308 KNSFR 312
Cdd:cd20940     94 RNHLT 98

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 39.55 E-value: 8.08e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907197658  430 VLIECEPQGSPKPAISWRKGDKAVRANKRIAILPDGSLRILNASKA-DEGKYICQGVNIFG 489
Cdd:cd05849     22 VSVNCRARANPFPIYKWRKNNLDIDLTNDRYSMVGGNLVINNPDKYkDAGRYVCIVSNIYG 82

Second immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. DSCAM is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409545 Cd Length: 95 Bit Score: 39.83 E-value: 8.12e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  118 VALNCEVRGNPSPSYRWLR--NGT--EIALESDYRYSLIDGTFIISNpSELRDSGLYQCLATNSFG 179
Cdd:cd20953     21 IALLCPAQGYPAPSFRWYKfiEGTtrKQAVVLNDRVKQVSGTLIIKD-AVVEDSGKYLCVVNNSVG 85

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 39.65 E-value: 8.67e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  335 GSPLQWECKATGKPRPTYRWLKNGAPLLPQSRVDTVN----GILAIQSVNQSDAGMYQCLAENKYG 396
Cdd:cd05747     18 GESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSteykSTFEISKVQMSDEGNYTVVVENSEG 83

Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptors TrkA, TrkB, and TrkC, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors. They are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkA, TrkB, and TrkC share significant sequence homology and domain organization. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrkA, TrkB, and TrkC mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. TrkA is recognized by NGF. TrkB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. TrkC is recognized by NT-3. NT-3 is promiscuous as in some cell systems it activates TrkA and TrkB receptors. TrkA is a receptor found in all major NGF targets, including the sympathetic, trigeminal, and dorsal root ganglia, cholinergic neurons of the basal forebrain, and the striatum. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. The TrkC gene is expressed throughout the mammalian nervous system. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409360 Cd Length: 96 Bit Score: 39.31 E-value: 9.89e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907197658  345 TGKPRPTYRWLKNGAPLLPQS------RVDTVN-----GILAIQSVNQSDAGMYQCLAENKYG 396
Cdd:cd04971     23 RGNPKPTLTWYHNGAVLNESDyirteiHYEAATpteyhGCLKFDNPTHVNNGNYTLVASNEYG 85

Fifth domain (immunoglobulin-like) of Trk receptor TrkB; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptor, TrkB, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors, which mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. Trks are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkB shares significant sequence homology and domain organization with TrkA and TrkC. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrKB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. In some cell systems NT-3 can activate TrkA and TrkB receptors. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. This group belongs to the I-set of IgSF domains

Pssm-ID: 409441 Cd Length: 94 Bit Score: 39.45 E-value: 1.05e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  330 TQLDSGSPLQWEC---KATGKPRPTYRWLKNGAPLLPQ----SRVDTVN-----GILAIQSVNQSDAGMYQCLAENKYG 396
Cdd:cd05855      5 TFLELPTRDHHWCipfTVKGNPKPTLQWFHEGAILNESeyicTKIHVINnteyhGCLQLDNPTHLNNGIYTLVAKNEYG 83

Second Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the second Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 409392 Cd Length: 88 Bit Score: 39.09 E-value: 1.09e-03

                           10        20
                   ....*....|....*....|....*
gi 1907197658  201 RSAVSVREGQGVVLMCSPPPHSPGV 225
Cdd:cd05727      2 RDEVKVKEGWGVVLFCDPPPHYPDL 26

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 39.40 E-value: 1.11e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  515 TVGESIVLNCkAIHDASLDVTFYWTLKGQPIDfEKEGGHFENIRAQASSadLMIRNILLMHAGRYGCRVQTTADSVSDEA 594
Cdd:cd20959     15 QVGMRAQLHC-GVPGGDLPLNIRWTLDGQPIS-DDLGITVSRLGRRSSI--LSIDSLEASHAGNYTCHARNSAGSASYTA 90


                   ....
gi 1907197658  595 ELLV 598
Cdd:cd20959     91 PLTV 94

Second immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of this group show that the second Ig domain lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409557 Cd Length: 101 Bit Score: 39.54 E-value: 1.15e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907197658  432 IECE-PQGSPKPAISWRK---GDKA---VRANKRIAILPDGSLRILNASKADEG---KYICQGVN 486
Cdd:cd20965     22 LDCNvPPGYPKPTIEWKKqlvSDSSkadTILDRRITISPNGDLYFTNVTKEDVStdyKYVCVAKT 86

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 39.10 E-value: 1.15e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  430 VLIECEP-QGSPKPAISWRKGDKA-------VRANKRIAILpdgSLRILNASKADEGKYICQGVNIFGSAEIIASL 497
Cdd:pfam00047   14 ATLTCSAsTGSPGPDVTWSKEGGTlieslkvKHDNGRTTQS---SLLISNVTKEDAGTYTCVVNNPGGSATLSTSL 86

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 38.93 E-value: 1.24e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907197658  251 MECFALGNPVPTITWMKvNG--YIPSK-----SRLRKSQAVLEIPNLQLDD-AGIYECTAENSRG 307
Cdd:cd05733     21 IKCEAKGNPQPTFRWTK-DGkfFDPAKdprvsMRRRSGTLVIDNHNGGPEDyQGEYQCYASNELG 84

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 38.72 E-value: 1.45e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  242 TAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLRKSQA----VLEIPNLQLDDAGIYECTAENSRGKNSFRGQLQI 317
Cdd:cd20972     12 EVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEgdlhSLIIAEAFEEDTGRYSCLATNSVGSDTTSAEIFV 91

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 38.34 E-value: 1.49e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907197658  335 GSPLQWECKATGKPRPTYRWLKNGAPLLPQSRVDTVNGILAIQSVNQSdaGMYQCLAENKYGAIYASAELKI 406
Cdd:cd05739     12 GGSVNLTCVAVGAPMPYVKWMKGGEELTKEDEMPVGRNVLELTNIYES--ANYTCVAISSLGMIEATAQVTV 81

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 38.73 E-value: 1.76e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907197658  335 GSPLQWECKATGKPRPTYRWLKNGAPL--LPQSRVDTVNG---ILAIQSVNQSDAGMYQCLAENKYGA 397
Cdd:cd05737     16 GKTLNLTCNVWGDPPPEVSWLKNDQALafLDHCNLKVEAGrtvYFTINGVSSEDSGKYGLVVKNKYGS 83

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 38.36 E-value: 1.79e-03

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658   707 APSNVSGRSGRRHELVIAWEPVSEEFQNGEGFGYIVAFRPNGTRgWKEKMVTSSEASkfiYRDESVPPLTPFEVKVGVYN 786
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSE-WKEVNVTPSSTS---YTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 1907197658   787 NKGDG 791
Cdd:smart00060   79 GAGEG 83

First immunoglobulin variable (IgV) domain of poliovirus receptor (PVR, also known as CD155 and necl-5), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (necl-5)). Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), that result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted; CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" with a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the first Ig-like domain of nectin-1 (also known as poliovirus receptor related protein(PVRL)1; CD111), nectin-3 (also known as PVRL 3), nectin-4 (also known as PVRL4; LNIR receptor)and DNAX accessory molecule 1 (DNAM-1; CD226).

Pssm-ID: 409383 Cd Length: 113 Bit Score: 38.97 E-value: 2.03e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  233 IEVHFPFTVTAAKGTTVKMECfALGNPVPT----ITWMKVNG--------YIPSK----------------SRLRKSQAV 284
Cdd:cd05718      1 QRVQVPTEVTGFLGGSVTLPC-SLTSPGTTkitqVTWMKIGAgssqnvavFHPQYgpsvpnpyaerveflaARLGLRNAT 79

                           90
                   ....*....|....*.
gi 1907197658  285 LEIPNLQLDDAGIYEC 300
Cdd:cd05718     80 LRIRNLRVEDEGNYIC 95

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 38.56 E-value: 2.18e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  231 PKIEVHF-PFTVTAakGTTVKMECFALGNPVPTITWMKVNGYIPSKSRLRKSQ-------AVLEIPNLQLDDAGIYECTA 302
Cdd:cd20951      1 PEFIIRLqSHTVWE--KSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKieseygvHVLHIRRVTVEDSAVYSAVA 78


                   ....*
gi 1907197658  303 ENSRG 307
Cdd:cd20951     79 KNIHG 83

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409398 Cd Length: 101 Bit Score: 38.62 E-value: 2.39e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907197658  116 KKVALNCEVRGNPSPSYRWLRNGTEIALESDYRYSLI---DGTFIISN----PSELRDSGLYQCLATNSFG 179
Cdd:cd05735     19 QKKEMSCTAHGEKPIIVRWEKEDTIINPSEMSRYLVTtkeVGDEVISTlqilPTVREDSGFFSCHAINSYG 89

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 38.15 E-value: 2.50e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  245 KGTTVKMECFALGNPVPTITWMKVNGYIPSKS------RLRKSQAVLEIPNLQLDDAGIYECTAENSRGKNSFRGQLQI 317
Cdd:cd05893     14 EGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSdhytiqRDLDGTCSLHTTASTLDDDGNYTIMAANPQGRISCTGRLMV 92

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 38.24 E-value: 2.70e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  104 PDDVIFPTDSDE---KKVALNCEVRGNPSPSYRW-------LRNGTEIALESDYRYSLIDGTFIISNPSElRDSGLYQCL 173
Cdd:cd05734      2 PRFVVQPNDQDGiygKAVVLNCSADGYPPPTIVWkhskgsgVPQFQHIVPLNGRIQLLSNGSLLIKHVLE-EDSGYYLCK 80

                           90
                   ....*....|.
gi 1907197658  174 ATNSFGSILSR 184
Cdd:cd05734     81 VSNDVGADISK 91

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409563 Cd Length: 93 Bit Score: 38.22 E-value: 2.73e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  321 PHWVQKLNDTQLDSGSPLQWECKATGKPRPTYRWLKNGAPLLPQSRVDTVNG-----ILAIQSVN-QSDAGMYQCLAENK 394
Cdd:cd20971      2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIQEfkggyHQLIIASVtDDDATVYQVRATNQ 81


                   ..
gi 1907197658  395 YG 396
Cdd:cd20971     82 GG 83

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 38.00 E-value: 2.79e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  410 PPSFelNQVKKSIIVTKDRGVLIECEPQGSPKPAISW-RKGDKAVRANKRIAILPD-GSLRILNASKADEGKYICQGVNI 487
Cdd:cd20976      1 APSF--SSVPKDLEAVEGQDFVAQCSARGKPVPRITWiRNAQPLQYAADRSTCEAGvGELHIQDVLPEDHGTYTCLAKNA 78

                           90
                   ....*....|..
gi 1907197658  488 FGSAEIIASLSV 499
Cdd:cd20976     79 AGQVSCSAWVTV 90

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 38.10 E-value: 3.13e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  415 LNQVKKSIIVTKDRGVLIECEPQGSPKPAISWRKGDKAVRANK--RIAI-LPDGS--LRILNASKADEGKYICQGVNIFG 489
Cdd:cd20974      3 FTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTlpGVQIsFSDGRakLSIPAVTKANSGRYSLTATNGSG 82

                           90
                   ....*....|.
gi 1907197658  490 SAEIIASLSVK 500
Cdd:cd20974     83 QATSTAELLVL 93

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The second Ig-like domain of JAM1 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, the A strand of the I-set is discontinuous but lacks a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.

Pssm-ID: 409542 Cd Length: 97 Bit Score: 38.07 E-value: 3.19e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907197658  117 KVALNC-EVRGNPSPSYRWLRNGTEIALE-------SDYRYSLIDGTF-IISNPSELRDSGLYQCLATNSFGSILSREA 186
Cdd:cd20950     14 RAVLTCsEPDGSPPSEYTWFKDGVVMPTNpkstrafSNSSYSLDPTTGeLVFDPLSASDTGEYSCEARNGYGTPMRSNA 92

Fifth domain (immunoglobulin-like) of Trk receptor TrkB; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptor, TrkB, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors, which mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. Trks are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkB shares significant sequence homology and domain organization with TrkA and TrkC. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrKB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. In some cell systems NT-3 can activate TrkA and TrkB receptors. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. This group belongs to the I-set of IgSF domains

Pssm-ID: 409441 Cd Length: 94 Bit Score: 37.53 E-value: 3.88e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  124 VRGNPSPSYRWLRNGtEIALESDYRYSLI--------DGTFIISNPSELrDSGLYQCLATNSFG 179
Cdd:cd05855     22 VKGNPKPTLQWFHEG-AILNESEYICTKIhvinnteyHGCLQLDNPTHL-NNGIYTLVAKNEYG 83

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 37.39 E-value: 3.90e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907197658  120 LNCEVRGNPSPSYRWLRNGTEIALESDYRYSLiDGTFIISNPSElRDSGLYQCLATNSFGSI 181
Cdd:cd05731     15 LECIAEGLPTPDIRWIKLGGELPKGRTKFENF-NKTLKIENVSE-ADSGEYQCTASNTMGSA 74

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

Pssm-ID: 409368 Cd Length: 88 Bit Score: 37.44 E-value: 4.04e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  246 GTTVKMECFALGNPVPtITWM----KVNGYIPSKSRLRKSQAVLeIPNLQLDDAGIYECTAENS 305
Cdd:cd04979     11 GDTVILSCSVKSNNAP-VTWIhngkKVPRYRSPRLVLKTERGLL-IRSAQEADAGVYECHSGER 72

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 37.49 E-value: 4.07e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907197658  432 IECEPQG-SPKPAISWRKGDKAVRANKRIAILPDGS-----LRILNASKADEGKYICQGVNIFGSAEIIASLSV 499
Cdd:cd05750     19 LKCEATSeNPSPRYRWFKDGKELNRKRPKNIKIRNKkknseLQINKAKLEDSGEYTCVVENILGKDTVTGNVTV 92

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1. NCAM-1 plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-nonNCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves the Ig1, Ig2, and Ig3 domains. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409366 Cd Length: 95 Bit Score: 37.62 E-value: 4.15e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  238 PFTVTAAKGTTVKMECFALGNPvPTITWMKVNG--YIPSKSRLRKSQ-----AVLEIPNLQLDDAGIYECTAENSRGKNS 310
Cdd:cd04977      7 PSYAEISVGESKFFLCKVSGDA-KNINWVSPNGekVLTKHGNLKVVNhgsvlSSLTIYNANINDAGIYKCVATNGKGTES 85

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 37.65 E-value: 4.28e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  115 EKKVALNCEVRGNPSPSYRW---LRNGTE--------IALESDYRYSLIDGTFIisnpsELRDSGLYQCLATNSFG 179
Cdd:cd05869     17 EEQITLTCEASGDPIPSITWrtsTRNISSeektldghIVVRSHARVSSLTLKYI-----QYTDAGEYLCTASNTIG 87

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 37.51 E-value: 4.28e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658  120 LNCEVRGNPSPSYRWLRNGTEIAleSDYRYSLIDGTFIISNPSELRDSGLYQCLATN 176
Cdd:cd20957     21 FNCSVTGNPIHTVLWMKDGKPLG--HSSRVQILSEDVLVIPSVKREDKGMYQCFVRN 75

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 37.65 E-value: 4.38e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907197658  241 VTAAKGTTVKMECFALGNPVPTITWMK-VNGYIPSKS----------RLRKSQAVLEIPNLQLDDAGIYECTAENSRG 307
Cdd:cd05870     11 ETTVENGAATLSCKAEGEPIPEITWKRaSDGHTFSEGdkspdgrievKGQHGESSLHIKDVKLSDSGRYDCEAASRIG 88

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 36.92 E-value: 4.85e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907197658  520 IVLNCKAihDASLDVTFYWTLKGQPIDFEKEgghfENIRAQASSADLMIRNILLMHAGRYGCRVQ 584
Cdd:cd00096      1 VTLTCSA--SGNPPPTITWYKNGKPLPPSSR----DSRRSELGNGTLTISNVTLEDSGTYTCVAS 59

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 37.47 E-value: 4.95e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658  118 VALNCEV-RGNPSPSYRWLRNGTEIALESDYRYSLIDG-TFIISNPS-ELRDSGLYQCLATNSFGSI 181
Cdd:cd20959     20 AQLHCGVpGGDLPLNIRWTLDGQPISDDLGITVSRLGRrSSILSIDSlEASHAGNYTCHARNSAGSA 86

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 37.19 E-value: 5.15e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  508 TPKRTELTVGESIVLNCKAIHDASLDVTfyWTLKGQPIDFEKegghfeniRAQASSADLMIRNILLMHAGRYGCRVQTTA 587
Cdd:cd05728      5 VISDTEADIGSSLRWECKASGNPRPAYR--WLKNGQPLASEN--------RIEVEAGDLRITKLSLSDSGMYQCVAENKH 74

                           90
                   ....*....|.
gi 1907197658  588 DSVSDEAELLV 598
Cdd:cd05728     75 GTIYASAELAV 85

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409363 Cd Length: 102 Bit Score: 37.40 E-value: 5.62e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907197658  335 GSPLQWECKATGKPRPTYRWLK----NGAPL----LPQSRVDTVNGI--------LAIQSVNQSDAGMYQCLAENKYGAI 398
Cdd:cd04974     16 GSDVEFHCKVYSDAQPHIQWLKhvevNGSKYgpdgLPYVTVLKVAGVnttgeentLTISNVTFDDAGEYICLAGNSIGLS 95


                   ....*..
gi 1907197658  399 YASAELK 405
Cdd:cd04974     96 FHSAWLT 102

First immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The first Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409571 Cd Length: 91 Bit Score: 37.16 E-value: 6.05e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  335 GSPLQWECKATGKPRPT-YRWLKNGAPL-LPQSRVDTVN--GILAIQSVNQSDAGMYQCLAENKYG 396
Cdd:cd20979     15 GQPTVLECVTEGGDQGVkYSWLKDGKSFnWQEHNVAQRKdeGSLVFLKPQASDEGQYQCFAETPAG 80

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 36.42 E-value: 7.58e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907197658  246 GTTVKMECFALGNPVPTITWMKVNGYIPSKSRLRKSQAVLEIPNLQldDAGIYECTAENSRG 307
Cdd:cd05739     12 GGSVNLTCVAVGAPMPYVKWMKGGEELTKEDEMPVGRNVLELTNIY--ESANYTCVAISSLG 71

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 36.81 E-value: 8.08e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907197658  430 VLIECEPQGSPKPAISWRKGDKAVRANKRIAILPDG----SLRILNASKADEGKYICQGVNIFGSAE 492
Cdd:cd05729     22 VRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEekgwSLIIERAIPRDKGKYTCIVENEYGSIN 88

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 36.56 E-value: 8.32e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907197658  240 TVTAAKGTTVKMECFALGNPVPTITWMKvNGYIPSKSRL-------RKSQAVLEIPNLQLDDAGIYECTAENSRGK 308
Cdd:cd20974      9 SVVVLEGSTATFEAHVSGKPVPEVSWFR-DGQVISTSTLpgvqisfSDGRAKLSIPAVTKANSGRYSLTATNGSGQ 83

Second immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. DSCAM is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409545 Cd Length: 95 Bit Score: 36.75 E-value: 9.22e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907197658  342 CKATGKPRPTYRWLK------NGAPLLPQSRVDTVNGILAIQSVNQSDAGMYQCLAENKYG 396
Cdd:cd20953     25 CPAQGYPAPSFRWYKfiegttRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVG 85