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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326 304 PPRVVSLEEPELRLEHCIEFVVRGNPPPTLHWLHNGQPLRESKIIHVEYYQEG---EISEGCLLFNKPTHYNNGNYTLIA 380
Cdd:cd04971    1 APVIVRLEEPELRHHWCIPFTVRGNPKPTLTWYHNGAVLNESDYIRTEIHYEAatpTEYHGCLKFDNPTHVNNGNYTLVA 80

                         90
                 ....*....|....*.
gi 767984326 381 KNPLGTANQTINGHFL 396
Cdd:cd04971   81 SNEYGQDSKSISAHFM 96

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326  214 VSHVNLTVREGDNAVITCNGS-GSPLPDVDWIVTGLQSINTHQTNLNWTNVHAINLTLVNVTSEDNGfTLTCIAENVVGM 292
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAG-TYTCVVNNPGGS 79

                  ....*..
gi 767984326  293 SNASVAL 299
Cdd:pfam00047  80 ATLSTSL 86

Leucine rich repeat N-terminal domain; Leucine Rich Repeats pfam00560 are short sequence motifs present in a number of proteins with diverse functions and cellular locations. Leucine Rich Repeats are often flanked by cysteine rich domains. This domain is often found at the N-terminus of tandem leucine rich repeats.

                          10        20
                  ....*....|....*....|.
gi 767984326   31 ACPANCVCSKTEINCRRPDDG 51
Cdd:pfam01462   1 ACPVPCHCSATVVNCSDRGLT 21

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326 304 PPRVVSLEEPELRLEHCIEFVVRGNPPPTLHWLHNGQPLRESKIIHVEYYQEG---EISEGCLLFNKPTHYNNGNYTLIA 380
Cdd:cd04971    1 APVIVRLEEPELRHHWCIPFTVRGNPKPTLTWYHNGAVLNESDYIRTEIHYEAatpTEYHGCLKFDNPTHVNNGNYTLVA 80

                         90
                 ....*....|....*.
gi 767984326 381 KNPLGTANQTINGHFL 396
Cdd:cd04971   81 SNEYGQDSKSISAHFM 96

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326  214 VSHVNLTVREGDNAVITCNGS-GSPLPDVDWIVTGLQSINTHQTNLNWTNVHAINLTLVNVTSEDNGfTLTCIAENVVGM 292
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAG-TYTCVVNNPGGS 79

                  ....*..
gi 767984326  293 SNASVAL 299
Cdd:pfam00047  80 ATLSTSL 86

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326 210 PEISVSHVNLTVREGDNAVITCNGSGSPLPDVDWIVTG--LQSINTHQTnlnwTNVHAINLTLVNVTSEDNGfTLTCIAE 287
Cdd:cd20976    2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAqpLQYAADRST----CEAGVGELHIQDVLPEDHG-TYTCLAK 76

                         90
                 ....*....|....
gi 767984326 288 NVVGMSNASVALTV 301
Cdd:cd20976   77 NAAGQVSCSAWVTV 90

Leucine rich repeat C-terminal domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 767984326   160 NFFNCSCDIRWMQLWQEQGEAKLNSQNLYCINADGSQLPLFRMNIS 205
Cdd:smart00082   1 NPFICDCELRWLLRWLQANEHLQDPVDLRCASPSSLRGPLLELLHS 46

Leucine-rich repeat (LRR) protein [Transcription];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326  75 DISRN-ITSI--HIENWRSLHTLNAVDMEL---------YTGLQKLTIKNSGLRSIqPRAFAKNPHLRYINLSSNRLTTL 142
Cdd:COG4886  119 DLSGNqLTDLpeELANLTNLKELDLSNNQLtdlpeplgnLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLSNNQITDL 197

                         90
                 ....*....|....*...
gi 767984326 143 SWQLFQTLSLRELQLEQN 160
Cdd:COG4886  198 PEPLGNLTNLEELDLSGN 215

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767984326   325 VRGNPPPTLHWLHNG-QPLRESKIIHVEYYQegeiSEGCLLFNKPTHYNNGNYTLIAKNPLGTANQTIN 392
Cdd:smart00410  18 ASGSPPPEVTWYKQGgKLLAESGRFSVSRSG----STSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326 304 PPRVVSLEEPELRLEHCIEFVVRGNPPPTLHWLHNGQPLRESKIIHVEYYQEG---EISEGCLLFNKPTHYNNGNYTLIA 380
Cdd:cd04971    1 APVIVRLEEPELRHHWCIPFTVRGNPKPTLTWYHNGAVLNESDYIRTEIHYEAatpTEYHGCLKFDNPTHVNNGNYTLVA 80

                         90
                 ....*....|....*.
gi 767984326 381 KNPLGTANQTINGHFL 396
Cdd:cd04971   81 SNEYGQDSKSISAHFM 96

Leucine rich repeat C-terminal motif; This entry represents the Leucine Rich Repeat C-terminal (LRRCT) capping motif from TRK receptors.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 767984326  163 NCSCDIRWMQLWQEQGEAKLNSQNLYCINaDGSQLPLFRMNISQCD 208
Cdd:pfam16920   1 RCSCDIRWLQLWQEEGLAGLGTQQLYCLN-DGSKIPLQSMNIPNCG 45

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326   218 NLTVREGDNAVITCNGSGSPLPDVDWIVTGLQSInTHQTNLNWTNVHAI-NLTLVNVTSEDNGfTLTCIAENVVGMSNAS 296
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLL-AESGRFSVSRSGSTsTLTISNVTPEDSG-TYTCAATNSSGSASSG 80

                   ....*
gi 767984326   297 VALTV 301
Cdd:smart00410  81 TTLTV 85

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326 210 PEISVSHVNLTVREGDNAVITCNGSGSPLPDVDWIVTG--LQSINTHQTnlnwTNVHAINLTLVNVTSEDNGfTLTCIAE 287
Cdd:cd20976    2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAqpLQYAADRST----CEAGVGELHIQDVLPEDHG-TYTCLAK 76

                         90
                 ....*....|....
gi 767984326 288 NVVGMSNASVALTV 301
Cdd:cd20976   77 NAAGQVSCSAWVTV 90

Leucine rich repeat C-terminal domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 767984326   160 NFFNCSCDIRWMQLWQEQGEAKLNSQNLYCINADGSQLPLFRMNIS 205
Cdd:smart00082   1 NPFICDCELRWLLRWLQANEHLQDPVDLRCASPSSLRGPLLELLHS 46

Fourth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; The members here are composed of the fourth 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326 211 EISVSHVNLTVREGDNAVITCNGSGSPLPDVDWIVTGLQSintHQTNLNWTNVHAINLTLVNVTSEDNGFTLTCIAENVV 290
Cdd:cd04972    1 TLKIQMPNASVDVGDDVLLQCQVEGQGLEQAGWILTELEQ---SATVMKSGSLPSLGLTLANVTSDLNRKNVTCWAENDV 77

                         90
                 ....*....|.
gi 767984326 291 GMSNASVALTV 301
Cdd:cd04972   78 GRAEVSVQVNV 88

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326 217 VNLTVREGDNAVITCNGSGSPLPDVDWIVTG--LQSINTHQTNLNwtnvhaiNLTLVNVTSEDNGfTLTCIAENVVGMSN 294
Cdd:cd05725    5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDgeLPKGRYEILDDH-------SLKIRKVTAGDMG-SYTCVAENMVGKIE 76

                 ....*..
gi 767984326 295 ASVALTV 301
Cdd:cd05725   77 ASATLTV 83

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767984326 227 AVITCNGSGSPLPDVDWIVTGLQSINTHQTNLNWTNVHAiNLTLVNVTSEDNGfTLTCIAENVVGMSNASVA 298
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNG-TLTISNVTLEDSG-TYTCVASNSAGGSASASV 70

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767984326 325 VRGNPPPTLHWLHNGQPL-RESKIIHVEyyqegeisEGCLLFNKPTHYNNGNYTLIAKNPLGT 386
Cdd:cd20978   25 VTGVPQPKITWLHNGKPLqGPMERATVE--------DGTLTIINVQPEDTGYYGCVATNEIGD 79

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767984326 325 VRGNPPPTLHWLHNGQPLRESKIIHVEYYQEGEISegcLLFNKPTHYNNGNYTLIAKNPLGTANQT 390
Cdd:cd20973   21 VEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCS---LIISDVCGDDSGKYTCKAVNSLGEATCS 83

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767984326 325 VRGNPPPTLHWLHNGQPLR-ESKI--IHVEYYQEGEISEGCLLFNKpthynnGNYTLIAKNPLGTANQT 390
Cdd:cd05857   28 AAGNPTPTMRWLKNGKEFKqEHRIggYKVRNQHWSLIMESVVPSDK------GNYTCVVENEYGSINHT 90

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767984326 324 VVRGNPPPTLHWLHNGQPLRESKIIHVEYYQegeiSEGCLLFNKPTHYNNGNYTLIAKNPLGTANQTI 391
Cdd:cd00096    6 SASGNPPPTITWYKNGKPLPPSSRDSRRSEL----GNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767984326 327 GNPPPTLHWLHNGQPLRESKIIHVEYYQEGEISEgcLLFNKPTHYNNGNYTLIAKNPLGTANQTINGH 394
Cdd:cd05750   26 ENPSPRYRWFKDGKELNRKRPKNIKIRNKKKNSE--LQINKAKLEDSGEYTCVVENILGKDTVTGNVT 91

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767984326 319 HCIEFVVRGNPPPTLHWLHNGQPLRESKIIHVEyyqEGEISEgCLLFNKPTHYNNGNYTLIAKNPLGTANQTIN 392
Cdd:cd05748   10 LRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIE---TTASST-SLVIKNAKRSDSGKYTLTLKNSAGEKSATIN 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326 219 LTVREGDNAVITCNGSGSPLPDVDWIVTGlQSINTHQTNLNWTNVHAINLTLVNVTSEDNGfTLTCIAENVVGMSNASVA 298
Cdd:cd20949    9 TTVKEGQSATILCEVKGEPQPNVTWHFNG-QPISASVADMSKYRILADGLLINKVTQDDTG-EYTCRAYQVNSIASDMQE 86

                 ...
gi 767984326 299 LTV 301
Cdd:cd20949   87 RTV 89

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326  304 PPRVVSLEEPELRLE------HCIefvVRGNPPPTLHWLHNGQPLRESKIihveYYQEGEISEGCLLFNKPTHYNNGNYT 377
Cdd:pfam13927   1 KPVITVSPSSVTVREgetvtlTCE---ATGSPPPTITWYKNGEPISSGST----RSRSLSGSNSTLTISNVTRSDAGTYT 73

                  ....*
gi 767984326  378 LIAKN 382
Cdd:pfam13927  74 CVASN 78

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326 321 IEFVVRGNPPPTLHWLHNGQPLRESKIIHVeyYQEGEISEgcLLFNKPTHYNNGNYTLIAKNPLGTANQT 390
Cdd:cd20972   21 LECRVTGNPTPVVRWFCEGKELQNSPDIQI--HQEGDLHS--LIIAEAFEEDTGRYSCLATNSVGSDTTS 86

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326 208 DLPEISVSHVNLTVREGDNAVITCNGSGSPLPDVdwivTGLQSINTHQTNLNWTNVH---------AINLTLVNVTSEDN 278
Cdd:cd04970    1 DATRITLAPSNADITVGENATLQCHASHDPTLDL----TFTWSFNGVPIDLEKIEGHyrrrygkdsNGDLEIVNAQLKHA 76

                         90       100
                 ....*....|....*....|....*..
gi 767984326 279 GfTLTCIAENVVGMSNASVALTVYYPP 305
Cdd:cd04970   77 G-RYTCTAQTVVDSDSASATLVVRGPP 102

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326 210 PEISVSHVNLTVREGDNAVITCNGSGSPLPDVDWIVTGLqSINTHQTN-----LNWTNVHainltLVNVTSEDNGfTLTC 284
Cdd:cd05736    1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGM-DINPKLSKqltliANGSELH-----ISNVRYEDTG-AYTC 73

                 ....*...
gi 767984326 285 IAENVVGM 292
Cdd:cd05736   74 IAKNEGGV 81

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767984326 326 RGNPPPTLHWLHNGQPLRESKiIHVEyyqegEISEGCLLFNKPTHYNNGNYTLIAKNPLGT 386
Cdd:cd05724   23 RGHPEPTVSWRKDGQPLNLDN-ERVR-----IVDDGNLLIAEARKSDEGTYKCVATNMVGE 77

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326 208 DLPEISVSHVNLTVREGDNAVITCNGSGSPLPDVD--WIVTG----LQSINTHQTNLNWTNVHAiNLTLVNVTSEDNGfT 281
Cdd:cd05854    1 DATKITLAPSSADINQGENLTLQCHASHDPTMDLTftWSLDDfpidLDKPNGHYRRMEVKETIG-DLVIVNAQLSHAG-T 78

                         90       100
                 ....*....|....*....|....
gi 767984326 282 LTCIAENVVGMSNASVALTVYYPP 305
Cdd:cd05854   79 YTCTAQTVVDSASASATLVVRGPP 102

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767984326 325 VRGNPPPTLHWLHNGQPLRESKiIHVEYYQE-GEISegcLLFNKPTHYNNGNYTLIAKNPLGTA 387
Cdd:cd05744   24 VSGLPTPDLFWQLNGKPVRPDS-AHKMLVREnGRHS---LIIEPVTKRDAGIYTCIARNRAGEN 83

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326  210 PEISVShvNLTVREGDNAVITCNGSGSPLPDVDWiVTGLQSINTHQtnlnwtnvhaiNLTLVNVTSEDNGfTLTCIAEN- 288
Cdd:pfam13895   2 PVLTPS--PTVVTEGEPVTLTCSAPGNPPPSYTW-YKDGSAISSSP-----------NFFTLSVSAEDSG-TYTCVARNg 66

                          90
                  ....*....|...
gi 767984326  289 VVGMSNASVALTV 301
Cdd:pfam13895  67 RGGKVSNPVELTV 79

Leucine-rich repeat (LRR) protein [Transcription];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326  75 DISRN-ITSIH--IENWRSLHTLNA-------VDMELY--TGLQKLTIKNSGLRSIqPRAFAKNPHLRYINLSSNRLTTL 142
Cdd:COG4886  142 DLSNNqLTDLPepLGNLTNLKSLDLsnnqltdLPEELGnlTNLKELDLSNNQITDL-PEPLGNLTNLEELDLSGNQLTDL 220

                         90
                 ....*....|....*...
gi 767984326 143 SWQLFQTLSLRELQLEQN 160
Cdd:COG4886  221 PEPLANLTNLETLDLSNN 238

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326 219 LTVREGDNAVITCNGSGSPLPDVDWIVTGLQSI-NTHQTNLNWTNVHAINLTlvnvTSEDNGfTLTCIAENVVGMSNASV 297
Cdd:cd05764   10 LRVLEGQRATLRCKARGDPEPAIHWISPEGKLIsNSSRTLVYDNGTLDILIT----TVKDTG-AFTCIASNPAGEATARV 84

                 ....
gi 767984326 298 ALTV 301
Cdd:cd05764   85 ELHI 88

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984326 210 PEISVSHVNLTVREGDNAVITCNGSGSPLPDVDWiVTGLQSINTHQTNLNWTNV---HA--INLTLVNVTSEDNGFTLtC 284
Cdd:cd05869    3 PKITYVENQTAMELEEQITLTCEASGDPIPSITW-RTSTRNISSEEKTLDGHIVvrsHArvSSLTLKYIQYTDAGEYL-C 80