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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 7649257    154 IGNNIQLTCHSAEGSPSPQYSWKSYNAQNQQRPLTQP----VSGEPLLLKNISTETAGYYICTSSN 215
Cdd:pfam00047  10 EGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHdngrTTQSSLLISNVTKEDAGTYTCVVNN 75

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7649257      38 SVTLPCTYNTYVSDREgFIQW-DKLLRSQTERVVTWNFVTKKYiYGNRYENRVRVSNDAELSNASITIDQLTMDDNGTYE 116
Cdd:smart00406   1 SVTLSCKFSGSTFSSY-YVSWvRQPPGKGLEWLGYIGSNGSSY-YQESYKGRFTISKDTSKNDVSLTISNLRVEDTGTYY 78

                   ...
gi 7649257     117 CSV 119
Cdd:smart00406  79 CAV 81

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 7649257    154 IGNNIQLTCHSAEGSPSPQYSWKSYNAQNQQRPLTQP----VSGEPLLLKNISTETAGYYICTSSN 215
Cdd:pfam00047  10 EGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHdngrTTQSSLLISNVTKEDAGTYTCVVNN 75

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7649257  139 VPPSKPDcSIQGEMVIgnniqLTChSAEGSPSPQYSWK-SYNAQNQQRPLTQPVSGE-------PLLLKNISTETAGYYI 210
Cdd:cd05734   6 VQPNDQD-GIYGKAVV-----LNC-SADGYPPPTIVWKhSKGSGVPQFQHIVPLNGRiqllsngSLLIKHVLEEDSGYYL 78

                ....*...
gi 7649257  211 CTSSNDVG 218
Cdd:cd05734  79 CKVSNDVG 86

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7649257      38 SVTLPCTYNTYVSDREgFIQW-DKLLRSQTERVVTWNFVTKKYiYGNRYENRVRVSNDAELSNASITIDQLTMDDNGTYE 116
Cdd:smart00406   1 SVTLSCKFSGSTFSSY-YVSWvRQPPGKGLEWLGYIGSNGSSY-YQESYKGRFTISKDTSKNDVSLTISNLRVEDTGTYY 78

                   ...
gi 7649257     117 CSV 119
Cdd:smart00406  79 CAV 81

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 7649257    154 IGNNIQLTCHSAEGSPSPQYSWKSYNAQNQQRPLTQP----VSGEPLLLKNISTETAGYYICTSSN 215
Cdd:pfam00047  10 EGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHdngrTTQSSLLISNVTKEDAGTYTCVVNN 75

Immunoglobulin Variable (IgV) domain of T cell Immunoglobulin Domain and Mucin Domain 3 (Tim-3), and similar domains; The members here are composed of the immunoglobulin variable (IgV) domain of T cell immunoglobulin domain and mucin domain 3 (Tim-3; also known as Hepatitis A virus cellular receptor 2 (HAVcr-2) and Cluster of Differentiation 366 (CD366)) and similar proteins. TIM-3 is a checkpoint inhibitor in immune responses to tumors, as well as involved in chronic viral infections. Thus, Tim-3 has emerged as one of most promising immune checkpoint targets for cancer immunotherapy. Tim-3 is highly expressed on Th1 lymphocytes and CD11b(+) macrophages and is upregulated on activated T and myeloid cells. TIM-3 regulates macrophage, activation and inhibits Th1 mediated immune responses to promote immunological tolerance. There are three TIM family members in humans (TIM-1, TIM-3, and TIM-4) and eight members in mice (TIM-1 to TIM-8). The IgV domain of human TIM-3 has been shown to bind ligands such as carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), high mobility group protein B1 (HMGB1)and galectin-9 (GAL9). The binding of GAL9 to TIM-3 can negatively regulate Th1 immune response, enhance immune tolerance and inhibit anti#tumor immunity. Dysregulation of the TIM-3/GAL9 pathway is implicated in numerous chronic autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7649257   32 RAARGRSVTLPCTYNTYVSDREGFIQWDK--LLRSQTERVVTWnfvTKKYIYGNRYENRVRVSNDAELSNASITIDQLTM 109
Cdd:cd20982   4 RAEVGHNAYLPCSYTTAAPGNLVPVCWGKgaCPVSYCGNVLLR---TDERDVTYQKSSRYQLKGDFSKGDVSLTIENVTL 80

                        90       100
                ....*....|....*....|....
gi 7649257  110 DDNGTYECSVS---LMSDQDVNAK 130
Cdd:cd20982  81 ADSGIYCCRIQipgIMNDEKFNLK 104

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 7649257   32 RAARGRSVTLPCTY----NTYVSDregfIQWDKLLRSQTERVVTWNfVTKKYIYGNRYENRVR-VSNDAELSNASITIDQ 106
Cdd:cd05718  10 TGFLGGSVTLPCSLtspgTTKITQ----VTWMKIGAGSSQNVAVFH-PQYGPSVPNPYAERVEfLAARLGLRNATLRIRN 84

                        90
                ....*....|...
gi 7649257  107 LTMDDNGTYECSV 119
Cdd:cd05718  85 LRVEDEGNYICEF 97

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7649257  139 VPPSKPDcSIQGEMVIgnniqLTChSAEGSPSPQYSWK-SYNAQNQQRPLTQPVSGE-------PLLLKNISTETAGYYI 210
Cdd:cd05734   6 VQPNDQD-GIYGKAVV-----LNC-SADGYPPPTIVWKhSKGSGVPQFQHIVPLNGRiqllsngSLLIKHVLEEDSGYYL 78

                ....*...
gi 7649257  211 CTSSNDVG 218
Cdd:cd05734  79 CKVSNDVG 86

First immunoglobulin (Ig) domain of nectin-4, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-4 (also known as poliovirus receptor related protein 4 or LNIR receptor). Nectin-4 belongs to the nectin family, which is comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which participate in adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. For example nectin-4 trans-interacts with nectin-1. Nectin-4 has also been shown to interact with the actin filament-binding protein, afadin. Unlike the other nectins, which are widely expressed in adult tissues, nectin-4 is mainly expressed during embryogenesis, and is not detected in normal adult tissue or in serum. Nectin-4 is re-expressed in breast carcinoma, and patients having metastatic breast cancer have a circulating form of nectin-4 formed from the ectodomain

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7649257   29 DILRAARGRSVTLPCTYNTYVSDREGFIQWDKL-LRSQTERVVTWNFVTKKYIYGNrYENRVRVSNDAELSNASITIDQL 107
Cdd:cd05888   1 DVVTVVLGQDAKLPCFYRGDSGEQVGQVAWARVdAGEGAQEIALLHSKYGLHVFPA-YEGRVEQPPPPRPADGSVLLRNA 79

                        90       100
                ....*....|....*....|....*....
gi 7649257  108 TMDDNGTYECSVSLMSDQDVNAKSRVRLL 136
Cdd:cd05888  80 VQADEGEYECRVSTFPAGNFQAELRLRVL 108

First Ig-like domain of Junctional adhesion molecule-1 (JAM1)and similar domains; a member of the V-set of IgSF domains; The members here are composed of the first Ig-like domain of Junctional Adhesion Molecule-1 (JAM1)and similar domains. 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 first Ig-like domain of JAM1 is a member of the V-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C'-C" in the other.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7649257   23 TVETTQDILRAARGRSVTLPCTYNTYVSDREgfIQWDKLLRSQTERVVTWNFVTKKYiygnryENRvrvsndAELSNASI 102
Cdd:cd20946   1 TVPSSQQVVTVVENQEVILSCKTPKKTSSPR--VEWKKLQRDVTFVVFQNNKIQGDY------KGR------AEILGTNI 66

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 7649257  103 TIDQLTMDDNGTYECSVSLMSDQDVNAKSRVRLLVL 138
Cdd:cd20946  67 TIKNVTRSDSGKYRCEVSARSDGQNLGEVTVTLEVL 102

Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7649257   22 LTVETTQDILRAARGRSVTLPCTYNTYVSDREGF-IQWDKLLRSQTERVVTWNFVTKkyIYGNRYEN---RVR-VSNDAE 96
Cdd:cd20960   1 LLITSAQTEIKKVAGENVTLPCHHQLGLEDQGTLdIEWLLLPSDKVEKVVITYSGDR--VYNHYYPAlkgRVAfTSNDLS 78

                        90       100
                ....*....|....*....|...
gi 7649257   97 lSNASITIDQLTMDDNGTYECSV 119
Cdd:cd20960  79 -GDASLNISNLKLSDTGTYQCKV 100

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 7649257  155 GNNIQLTChSAEGSPSPQYSWK-----SYNAQNQQRPLTQPVSGEpLLLKNISTETAGYYICTSSNDVGIESCNITV 226
Cdd:cd05763  14 GSTARLEC-AATGHPTPQIAWQkdggtDFPAARERRMHVMPEDDV-FFIVDVKIEDTGVYSCTAQNSAGSISANATL 88

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 7649257  155 GNNIQLTCHsAEGSPSPQYSWK-------------SYNaqnqqrPLTQPVSGEPLLLKNISTETAGYYICTSSNDVG 218
Cdd:cd20954  16 GQDVMLHCQ-ADGFPTPTVTWKkatgstpgeykdlLYD------PNVRILPNGTLVFGHVQKENEGHYLCEAKNGIG 85

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 7649257  155 GNNIQLTCHsAEGSPSPQYSWKSYNAQNQQRP----LTQPVSGE-PLLLKNISTETAGYYICTSSNDVGIESCN 223
Cdd:cd05892  15 GDPVRLECQ-ISAIPPPQIFWKKNNEMLQYNTdrisLYQDNCGRiCLLIQNANKKDAGWYTVSAVNEAGVVSCN 87

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 7649257  144 PDCsiqgEMVIGNNIQLTChSAEGSPSPQYSWkSYNAQNQQ----RPLTQPVSGEpLLLKNISTETAGYYICTSSNDVGI 219
Cdd:cd20976   9 KDL----EAVEGQDFVAQC-SARGKPVPRITW-IRNAQPLQyaadRSTCEAGVGE-LHIQDVLPEDHGTYTCLAKNAAGQ 81

                ....*..
gi 7649257  220 ESCNITV 226
Cdd:cd20976  82 VSCSAWV 88

First immunoglobulin (Ig) variable (V) domain of rat MRC OX-2 antigen, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of rat MRC OX-2 antigen (also known as CD200) and similar proteins. MRC OX-2 is a membrane glycoprotein expressed in a variety of lymphoid and non-lymphoid cells in rats. It has a similar broad distribution pattern in humans. MRC OX-2 may regulate myeloid cell activity. The protein has an extracellular portion containing two Ig-like domains, a transmembrane portion, and a cytoplasmic portion.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7649257   32 RAARGRSVTLPCTYntyvSDREGFIQ--WDKLLRSQTERVVTWNFVTKKYIYGnRYENRVRVSNdAELSNASITIDQLTM 109
Cdd:cd05846   9 RAVLGGNATLSCNL----TLPEEVLQvtWQKIKASSPENIVTYSKKYGVKIQP-SYVRRISFTS-SGLNSTSITIWNVTL 82

                ....*....
gi 7649257  110 DDNGTYECS 118
Cdd:cd05846  83 EDEGCYKCL 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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 7649257  158 IQLTChSAEGSPSPQYSWKSYNAQNQQRPLTQPVSGEP---LLLKNISTETAGYYICTSSNDVG 218
Cdd:cd00096   1 VTLTC-SASGNPPPTITWYKNGKPLPPSSRDSRRSELGngtLTISNVTLEDSGTYTCVASNSAG 63

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7649257   33 AARGRSVTLPCTYNTYVSDreGFIQWDKLLRSQT-ERVVTWNfvTKKYIYGNRYENRVRVSNDAElSNASITIDQLTMDD 111
Cdd:cd00099  10 VQEGESVTLSCEVSSSFSS--TYIYWYRQKPGQGpEFLIYLS--SSKGKTKGGVPGRFSGSRDGT-SSFSLTISNLQPED 84

                ....*....
gi 7649257  112 NGTYECSVS 120
Cdd:cd00099  85 SGTYYCAVS 93

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 7649257  155 GNNIQLTChSAEGSPSPQYSWKsyNAQNQQRPLTQPVS----GEPLLLKNISTETAGYYICTSSNDVG 218
Cdd:cd20970  17 GENATFMC-RAEGSPEPEISWT--RNGNLIIEFNTRYIvrenGTTLTIRNIRRSDMGIYLCIASNGVP 81

N-terminal immunoglobulin (Ig)-like domain of the signaling lymphocyte activation molecule (SLAM) family; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the signaling lymphocyte activation molecule (SLAM) family and similar proteins. The SLAM family is a group of immune-cell specific receptors that can regulate both adaptive and innate immune responses. Members of this group include proteins such as CD84, SLAM (CD150), Ly-9 (CD229), NTB-A (ly-108, SLAM6), 19A (CRACC), and SLAMF9. The genes coding for the SLAM family are nested on chromosome 1, in humans at 1q23, and in mice at 1H2. The SLAM family is a subset of the CD2 family, which also includes CD2 and CD58 located on chromosome 1 at 1p13 in humans. In mice, CD2 is located on chromosome 3, and there is no CD58 homolog. The SLAM family proteins are organized as an extracellular domain with either two or four Ig-like domains, a single transmembrane segment, and a cytoplasmic region having Tyr-based motifs. The extracellular domain is organized as a membrane-distal Ig variable (IgV) domain that is responsible for ligand recognition and a membrane-proximal truncated Ig constant-2 (IgC2) domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7649257   36 GRSVTLPctYNTYVSDREGFIQWdklLRSQTERVVTWNFVTKKYI--YGNRYENRVRVSNDaelsNASITIDQLTMDDNG 113
Cdd:cd16842   8 GGSVTFP--LNISDGQEIENITW---SFKTSLAVIAPGEGGAPEIiiTDKSYKERLNISQN----DYSLQISNLTMEDAG 78

                        90
                ....*....|..
gi 7649257  114 TYECSVSLMSDQ 125
Cdd:cd16842  79 SYRARINTKNSR 90

First immunoglobulin variable (IgV) domain of nectin-2, nectin-like protein 5, and similar domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-2 (also known as poliovirus receptor related protein 2 or Cluster of Differentiation 112 (CD112)), nectin-like protein 5 (CD155), and similar proteins. Nectins and Nectin-like molecules are a family of Ca(2+)-independent immunoglobulin-like transmembrane glycoproteins belonging to the class of adhesion receptors, consisting of nine members (nectins 1 through 4 and nectin-like proteins 1 through 5). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as Necl-5, or PVR. In contrast to all other family members, CD155 lacks self-adhesion capacity, yet it shares with nectins the feature to interact with other nectins. For instance, CD155 heterophilically trans-interacts with nectin-3, thereby contributing significantly to the establishment of adherens junctions between epithelial cells. This group belongs to the Constant 1 (C1)-set of IgSF domains, which has one beta-sheet that is formed by strands A-B-E-D and the other strands by G-F-C-C'.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7649257   36 GRSVTLPC-----TYNTYVSDregfIQWDKLLRSQTERVvtwnFVTKKyiyGNRYENRVRVS-----NDAELSNASITID 105
Cdd:cd20989  14 GGSVTLPChllppNMVTHVSQ----VTWQRHDEHGSVAV----FHPKQ---GPSFPESERLSfvaarLGAELRNASLAMF 82

                        90
                ....*....|..
gi 7649257  106 QLTMDDNGTYEC 117
Cdd:cd20989  83 GLRVEDEGNYTC 94

Immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core protein (CSPG); The members here are composed of the immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core proteins (CSPGs). Included in this group are the Ig domains of other CSPGs: versican, and neurocan. In CSPGs, this Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggrecan and versican have a wide distribution in connective tissue and extracellular matrices. Neurocan is localized almost exclusively in nervous tissue. 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 7649257   31 LRAARGRSVTLPC----------TYNTYVSDRegfIQWDKLLRSQTERVVTWNFVTKKYIY--GNRYENRVRVSNDAEL- 97
Cdd:cd05878   7 VRVLLGTSVTLPCyfidpphpvtPSTAPLAPR---IKWSKVSVDGKKEKEVVLLVATEGRVrvNSAYQGRVSLPNYPAIp 83

                        90       100
                ....*....|....*....|..
gi 7649257   98 SNASITIDQLTMDDNGTYECSV 119
Cdd:cd05878  84 SDATLEVQSLRASDSGLYRCEV 105

Immunoglobulin (Ig)-like domain of epithelial V-like antigen (EVA) 1; The members here are composed of the immunoglobulin (Ig) domain of epithelial V-like antigen 1 (EVA 1). EVA is also known as myelin protein zero-like 2. EVA is an adhesion molecule and may play a role in the structural organization of the thymus and early lymphocyte development.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7649257   27 TQDILRAARGRSVTLPCTYNTY--VSDregfiqwdkllrsqtERVVTWNFVTKK--------YIYGN-------RYENRV 89
Cdd:cd05880   5 TSKEVEAVNGTDVRLKCTFSSSapIGD---------------TLVITWNFRPLDggreesvfYYHKRpypppdgRFKGRV 69

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 7649257   90 RVSNDAELSNASITIDQLTMDDNGTYECSVSLMSDQDV 127
Cdd:cd05880  70 VWDGNIMRRDASILIWQLQPTDNGTYTCQVKNPPDVHG 107

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 7649257     35 RGRSVTLPCTyntyVSDREGFIQwdkllrsqtervVTWnFVTKKYIYGNRYENRvrvsNDAELSNASITIDQLTMDDNGT 114
Cdd:pfam00047  10 EGDSATLTCS----ASTGSPGPD------------VTW-SKEGGTLIESLKVKH----DNGRTTQSSLLISNVTKEDAGT 68

                  ....*.
gi 7649257    115 YECSVS 120
Cdd:pfam00047  69 YTCVVN 74

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 7649257  155 GNNIQLTCHSAEGSPSPQYSW-KSYNAQNQQRPLTQPVSGEP----LLLKNISTETAGYYICTSSNDVGIESCNITV 226
Cdd:cd05750  14 GSKLVLKCEATSENPSPRYRWfKDGKELNRKRPKNIKIRNKKknseLQINKAKLEDSGEYTCVVENILGKDTVTGNV 90

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), neurocan; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), neurocan. In CSPGs, the Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, the CSPG aggrecan (not included in this group) forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Unlike aggrecan which is widely distributed in connective tissue and extracellular matrices, neurocan is localized almost exclusively in nervous tissue. 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 7649257   27 TQDILRAARGRSVTLPCTYN---TYVSDREG-FIQWDKL----LRSQTERVVTWNFVTKkyiYGNRYENRVRV-SNDAEL 97
Cdd:cd05902   3 TAPPVRRPLSSSVLLPCVFTlppSASSPPEGpRIKWTKLstsgGQQQRPVLVARDNVVR---VAKAFQGRVSLpGYPKNR 79

                        90       100
                ....*....|....*....|....
gi 7649257   98 SNASITIDQLTMDDNGTYECSVSL 121
Cdd:cd05902  80 YNASLVLSRLRYSDSGTYRCEVVL 103