Immunoglobulin variable (IgV)-like domain in complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the immunoglobulin variable (IgV) region of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also known as Z39Ig and V-set and Ig domain-containing 4 (VSIG4) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. Like all members of this family, the CRIg domain contains two beta-sheets: one composed of strands A', G, F, C, C' and C", and the other of strands B, E and D. The complement system is an important part of the innate immune system and is required for removal of pathogens from the bloodstream. After exposure to pathogens, the third component of the complement system, C3, is cleaved to C3b which, after recruitment of factor B, initiates formation of the alternative pathway convertases. CRIg, a complement receptor expressed on macrophages, binds to C3b and iC3b mediating phagocytosis of the particles. It is also a potent inhibitor of the alternative pathway convertases and a negative regulator of T cell activation. 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, 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383872567  21 PILEVPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQRGSDPVTIFLRDSSGDHIQQAKYQGRLHVSHKVPGDVSLQL 100
Cdd:cd16089    1 PILEGPESITGPWKGSVNLPCTYVPEEGYTQVLVKWLVQRDSDPVTIFLRDSSGDHIQQAKYRGRLEVSKDTPGDVSLQL 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 383872567 101 STLEMDDRSHYTCEVTWQTPDGNQVVRDKITELRVQK 137
Cdd:cd16089   81 DTLEMDDRGHYTCQVTWQTPDGNLIVREKTTELRVQK 117

Immunoglobulin variable (IgV)-like domain in complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the immunoglobulin variable (IgV) region of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also known as Z39Ig and V-set and Ig domain-containing 4 (VSIG4) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. Like all members of this family, the CRIg domain contains two beta-sheets: one composed of strands A', G, F, C, C' and C", and the other of strands B, E and D. The complement system is an important part of the innate immune system and is required for removal of pathogens from the bloodstream. After exposure to pathogens, the third component of the complement system, C3, is cleaved to C3b which, after recruitment of factor B, initiates formation of the alternative pathway convertases. CRIg, a complement receptor expressed on macrophages, binds to C3b and iC3b mediating phagocytosis of the particles. It is also a potent inhibitor of the alternative pathway convertases and a negative regulator of T cell activation. 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, 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383872567  21 PILEVPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQRGSDPVTIFLRDSSGDHIQQAKYQGRLHVSHKVPGDVSLQL 100
Cdd:cd16089    1 PILEGPESITGPWKGSVNLPCTYVPEEGYTQVLVKWLVQRDSDPVTIFLRDSSGDHIQQAKYRGRLEVSKDTPGDVSLQL 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 383872567 101 STLEMDDRSHYTCEVTWQTPDGNQVVRDKITELRVQK 137
Cdd:cd16089   81 DTLEMDDRGHYTCQVTWQTPDGNLIVREKTTELRVQK 117

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 383872567  142 KPTVTTGSGyGFTVPQGMRISLQCQARGSPPISYIWYKQQTNNQE-----PIKVATLSTLLFKPAVIADSGSYFCTAK 214
Cdd:pfam13927   1 KPVITVSPS-SVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgstrsRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383872567   24 EVPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQR-GSDPVTIFLR--DSSGDHIQQAKYQGRLHVShkvPGDVSLQL 100
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEASTSVYWYRQPpGKGPTFLIAYysNGSEEGVKKGRFSGRGDPS---NGDGSLTI 77

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 383872567  101 STLEMDDRSHYTCEVTwqtpDGNQVVRDKITELRV 135
Cdd:pfam07686  78 QNLTLSDSGTYTCAVI----PSGEGVFGKGTRLTV 108

Immunoglobulin variable (IgV)-like domain in complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the immunoglobulin variable (IgV) region of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also known as Z39Ig and V-set and Ig domain-containing 4 (VSIG4) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. Like all members of this family, the CRIg domain contains two beta-sheets: one composed of strands A', G, F, C, C' and C", and the other of strands B, E and D. The complement system is an important part of the innate immune system and is required for removal of pathogens from the bloodstream. After exposure to pathogens, the third component of the complement system, C3, is cleaved to C3b which, after recruitment of factor B, initiates formation of the alternative pathway convertases. CRIg, a complement receptor expressed on macrophages, binds to C3b and iC3b mediating phagocytosis of the particles. It is also a potent inhibitor of the alternative pathway convertases and a negative regulator of T cell activation. 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, 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383872567  21 PILEVPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQRGSDPVTIFLRDSSGDHIQQAKYQGRLHVSHKVPGDVSLQL 100
Cdd:cd16089    1 PILEGPESITGPWKGSVNLPCTYVPEEGYTQVLVKWLVQRDSDPVTIFLRDSSGDHIQQAKYRGRLEVSKDTPGDVSLQL 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 383872567 101 STLEMDDRSHYTCEVTWQTPDGNQVVRDKITELRVQK 137
Cdd:cd16089   81 DTLEMDDRGHYTCQVTWQTPDGNLIVREKTTELRVQK 117

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).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383872567  25 VPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQRG--SDPVTIFlRDSSGDHIqQAKYQGRLHVSHKVPG--DVSLQL 100
Cdd:cd05718    5 VPTEVTGFLGGSVTLPCSLTSPGTTKITQVTWMKIGAgsSQNVAVF-HPQYGPSV-PNPYAERVEFLAARLGlrNATLRI 82

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 383872567 101 STLEMDDRSHYTCEVTwQTPDGNqvvRDKITELRV 135
Cdd:cd05718   83 RNLRVEDEGNYICEFA-TFPQGN---RQGTTWLRV 113

Immunoglobulin (Ig)-like domain of human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in human cartilage link protein (LP; also called hyaluronan and proteoglycan link protein). In cartilage, chondroitin-keratan sulfate proteoglycan (CSPG), aggrecan, forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383872567  35 GDVNLPCTYD---PLQGYTQVLVKWLVQRGSD--PVTIFLrdSSGDHIQQ-AKYQGRLHVSHKVPGDVSLQLSTLEMDDR 108
Cdd:cd05877   13 GNVTLPCRYHyepELSAPRKIRVKWTKLEVDYakEEDVLV--AIGTRHKSyGSYQGRVFLRRADDLDASLVITDLRLEDY 90

                         90       100
                 ....*....|....*....|....*...
gi 383872567 109 SHYTCEVTWQTPDGNQVVrdkitELRVQ 136
Cdd:cd05877   91 GRYRCEVIDGLEDESVVV-----ALRLR 113

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 383872567   154 TVPQGMRISLQCQARGSPPISYIWYKQqtnNQEPI---------KVATLSTLLFKPAVIADSGSYFCTAKGQVGSEQHS 223
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYKQ---GGKLLaesgrfsvsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383872567 143 PTVTTGSGYGF-TVPQGMRISLQCQARGSPPISYIWYK--QQTNNQEPI----KVATLS-TLLFKPAVIADSGSYFCTAK 214
Cdd:cd20953    2 PKIPGLSKSQPlTVSSASSIALLCPAQGYPAPSFRWYKfiEGTTRKQAVvlndRVKQVSgTLIIKDAVVEDSGKYLCVVN 81

                 ....*.
gi 383872567 215 GQVGSE 220
Cdd:cd20953   82 NSVGGE 87

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383872567 143 PTVTTGSgygfTVPQGMRISLQCQAR-GSPPISYIWYKQQT-NNQEPIKVA-----------TLSTLLFKPAVIADSGSY 209
Cdd:cd20950    1 PTVNIPS----SATIGNRAVLTCSEPdGSPPSEYTWFKDGVvMPTNPKSTRafsnssysldpTTGELVFDPLSASDTGEY 76

                         90
                 ....*....|....*...
gi 383872567 210 FCTAKGQVGSEQHSDIVK 227
Cdd:cd20950   77 SCEARNGYGTPMRSNAVR 94

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 383872567 153 FTVPQGMRISLQCQARGSPPISYIWYKQ-----QTNNQEPIKVATLSTLLFKPAVIADSGSYFCTAKGQVGSEQ 221
Cdd:cd20969   12 VFVDEGHTVQFVCRADGDPPPAILWLSPrkhlvSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDS 85

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 383872567 154 TVPQGMRISLQCQARG-SPPISYIWYK--QQTNNQEPIKVATL-----STLLFKPAVIADSGSYFCTAKGQVG 218
Cdd:cd05750   10 TVQEGSKLVLKCEATSeNPSPRYRWFKdgKELNRKRPKNIKIRnkkknSELQINKAKLEDSGEYTCVVENILG 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 383872567 160 RISLQCQARGSPPISYIWYKQQTN-NQEPIKVATL---STLLFKPAVIADSGSYFCTAKGQVGS 219
Cdd:cd05848   21 KVILNCEARGNPVPTYRWLRNGTEiDTESDYRYSLidgNLIISNPSEVKDSGRYQCLATNSIGS 84

Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383872567  29 VTGPWKGDVNLPCTYDPLQgytQVLVKWLVQRGSDPVTIFLRDSsgDHI--QQAKYQGR--LHVSHKVPGDVSLQLSTLE 104
Cdd:cd16091    7 VVCLLSEDCILPCSFTPGS---EVVIHWYKQDSDIKVHSYYYGK--DQLesQDQRYRNRtsLFKDQISNGNASLLLRRVQ 81

                         90       100
                 ....*....|....*....|
gi 383872567 105 MDDRSHYTCEVTwqTPDGNQ 124
Cdd:cd16091   82 LQDEGRYKCYTS--TIIGNQ 99

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 383872567 164 QCQARGSPPISYIWYK--QQTNNQEPIKVATlSTLLFKPAVIADSGSYFCTAKGQVGS 219
Cdd:cd05728   20 ECKASGNPRPAYRWLKngQPLASENRIEVEA-GDLRITKLSLSDSGMYQCVAENKHGT 76

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 383872567 155 VPQGMRISLQCQARGSPPISYIWYKqqtnNQEPIKVA----------TLSTLLFKPAVIADSGSYFCTAKGQVGSEQHS 223
Cdd:cd05857   16 VPAANTVKFRCPAAGNPTPTMRWLK----NGKEFKQEhriggykvrnQHWSLIMESVVPSDKGNYTCVVENEYGSINHT 90

Immunoglobulin Variable (IgV) domain of B7-H3, a member of the B7 family of immune checkpoint molecules; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H3 also known as CD276), a member of the B7 family of immune checkpoint molecules. B7-H3 is an important immune checkpoint member of the B7 family and shares homology with other B7 ligands such as programmed death ligand 1 (PD-L1). The B7 family molecules interact with CD28 on T-cells to provide co-stimulatory signals that regulate T-cell activation and T-helper cell differentiation. Although B7-H3 has been shown to have both co-stimulatory and co-inhibitory effects on T-cell responses, the most current studies describe B7-H3 as a T cell inhibitor that promotes tumor aggressiveness and proliferation. Moreover, B7-H3 is highly overexpressed on a wide range of human solid cancers and promotes tumor growth, metastasis, and drug resistance. Thus, B7-H3 expression in tumors often correlates with both negative prognosis and poor clinical outcome in cancer patients. B7-H3 protein contains a predicted signal peptide, V- and C-like Ig domains (IgV and IgC), a transmembrane region, and an intracellular tail.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383872567  24 EVPES-VTGPWKGDVNLPCTYDPLQGYT--QVLVKWLVQRGSDPVTIFLRDSSGDHIQQAKYQGRLHVSHK--VPGDVSL 98
Cdd:cd20934    1 RVPEDpVVALVGTDATLRCSFSPEPGFSlaQLSVFWQLTDTKQLVHSFTESQDQGRDQGSAYANRTALFPDllAQGNASL 80

                         90       100
                 ....*....|....*....|....*..
gi 383872567  99 QLSTLEMDDRSHYTCEVTWQTPDGNQV 125
Cdd:cd20934   81 RLQRVRVADEGSYTCFVSVQDFGSAAV 107

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 383872567 155 VPQGMRISLQCQARGSPPISYIWYKQQTN--NQEPIKVATLSTLLFKPAVIADSGSYFCTAKGQVGS 219
Cdd:cd04969   14 AAKGGDVIIECKPKASPKPTISWSKGTELltNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGK 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 383872567 160 RISLQCQARGSPPISYIWYKQQTNNQEPIKV----------ATLSTLLFKPAVIADSGSYFCTAKGQVGSEQHS 223
Cdd:cd05869   19 QITLTCEASGDPIPSITWRTSTRNISSEEKTldghivvrshARVSSLTLKYIQYTDAGEYLCTASNTIGQDSQS 92

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 383872567 154 TVPQGMRISLQCQARGSPPISYIWYKQ--QTNNQEPIKVATLSTLLFKPAVIADSGSYFCTAKGQVGSEQH 222
Cdd:cd05731    6 MVLRGGVLLLECIAEGLPTPDIRWIKLggELPKGRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSARH 76

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 383872567 143 PTVTTGSGYGFTVPQGMRISLQCQARGSPPISYIWykqqTNNQEPIKVATLSTLLFKPaviaDSGSYFCTAKG 215
Cdd:cd05733    1 PTITEQSPKDYIVDPRDNITIKCEAKGNPQPTFRW----TKDGKFFDPAKDPRVSMRR----RSGTLVIDNHN 65

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 383872567  154 TVPQGMRISLQCQAR-GSPPISYIWYKQQTNNQEPIKVA------TLSTLLFKPAVIADSGSYFCTA 213
Cdd:pfam00047   7 TVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVKhdngrtTQSSLLISNVTKEDAGTYTCVV 73

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 383872567 157 QGMRISLQCQARGSPPISYIWYKQQT--NNQEPIK--VAT-------LSTLLFKPAVIADSGSYFCTA 213
Cdd:cd05735   17 KGQKKEMSCTAHGEKPIIVRWEKEDTiiNPSEMSRylVTTkevgdevISTLQILPTVREDSGFFSCHA 84

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

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 383872567 154 TVPQGMRISLQCQARGSPPISYIWYKQqtNNQEPIKVATLST-----LLFKPAVIADSGSYFCTAKGQVGS 219
Cdd:cd20952   10 TVAVGGTVVLNCQATGEPVPTISWLKD--GVPLLGKDERITTlengsLQIKGAEKSDTGEYTCVALNLSGE 78

Immunoglobulin (Ig)-like domain of class III semaphorin Sema3; The members here are composed of the immunoglobulin (Ig)-like domain of Sema3 and similar proteins. Semaphorins are classified based on structural features additional to the Sema domain. Sema3 is a Class III semaphorin that is secreted. It is a vertebrate class having a Sema domain, an Ig domain, a short basic domain. They have been shown to be axonal guidance cues and have a part in the regulation of the cardiovascular, immune, and respiratory systems. Sema3A, the prototype member of this class III subfamily, induces growth cone collapse and is an inhibitor of axonal sprouting. In perinatal rat cortex, it acts as a chemoattractant and functions to direct the orientated extension of apical dendrites. It may play a role, prior to the development of apical dendrites, in signaling the radial migration of newborn cortical neurons towards the upper layers. Sema3A selectively inhibits vascular endothelial growth factor receptor (VEGF)-induced angiogenesis and induces microvascular permeability. This group also includes Sema3B, -C, -D, -E, -G.

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                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 383872567 163 LQCQARgSPPISYIWYKQQTNNQ--EPIK-----VATLSTLLFKPAVIADSGSYFCTA 213
Cdd:cd05871   17 LECLPK-SPQATVKWLFQRGGDQrkEEVKseerlIVTDRGLLLRSLQRSDAGVYTCQA 73