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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910411  20 LTLVAPSSVF-EGDSIVLKCQGEQNWKIQKMAYHKDNKELSVFKKFSDFLIQSAVLSDSGNYFCStkGQLFLWDKTSNIV 98
Cdd:cd05753    2 LLLQAPSAVVfEGEPLTLRCHGWKDKKVHKVTYYKDGKALKFSYENSNFSIPQATLSDSGSYHCS--GTVRIKRRSSESV 79

                 ....
gi 767910411  99 KIKV 102
Cdd:cd05753   80 NITV 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767910411  299 RPVLTLRSPGAQAAVGDLLELHCEAlRGSPPILYQFYHEDVTLGNSSAPSGGGASFNLSL-----TAEHSGNYSCEANN 372
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEA-TGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLtisnvTRSDAGTYTCVASN 78

Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910411  20 LTLVAPSSVF-EGDSIVLKCQGEQNWKIQKMAYHKDNKELSVFKKFSDFLIQSAVLSDSGNYFCStkGQLFLWDKTSNIV 98
Cdd:cd05753    2 LLLQAPSAVVfEGEPLTLRCHGWKDKKVHKVTYYKDGKALKFSYENSNFSIPQATLSDSGSYHCS--GTVRIKRRSSESV 79

                 ....
gi 767910411  99 KIKV 102
Cdd:cd05753   80 NITV 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767910411  299 RPVLTLRSPGAQAAVGDLLELHCEAlRGSPPILYQFYHEDVTLGNSSAPSGGGASFNLSL-----TAEHSGNYSCEANN 372
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEA-TGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLtisnvTRSDAGTYTCVASN 78

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910411   23 VAPSSVFEGDSIVLKCQGEQNWKIqKMAYHKDNKELSvfkKFSDFLIQSAVLSDSGNYFCSTkgQLFLWDKTSNIVKIKV 102
Cdd:pfam13895   6 PSPTVVTEGEPVTLTCSAPGNPPP-SYTWYKDGSAIS---SSPNFFTLSVSAEDSGTYTCVA--RNGRGGKVSNPVELTV 79

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 767910411 317 LELHCEAlRGSPPILYQFYHEDVTLGNSSAPSGGGASFNLSLT-----AEHSGNYSCEANNGLGAQCSEAV 382
Cdd:cd00096    1 VTLTCSA-SGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTisnvtLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910411  108 RPVLTAS--SFQPIEGGPVSLKCETRLSPQrLDVQlqfcFFRENQVLGSGWSSSPE-------LQISAVWSEDTGSYWCK 178
Cdd:pfam13927   1 KPVITVSpsSVTVREGETVTLTCEATGSPP-PTIT----WYKNGEPISSGSTRSRSlsgsnstLTISNVTRSDAGTYTCV 75

                  ..
gi 767910411  179 AE 180
Cdd:pfam13927  76 AS 77

Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910411  20 LTLVAPSSVF-EGDSIVLKCQGEQNWKIQKMAYHKDNKELSVFKKFSDFLIQSAVLSDSGNYFCStkGQLFLWDKTSNIV 98
Cdd:cd05753    2 LLLQAPSAVVfEGEPLTLRCHGWKDKKVHKVTYYKDGKALKFSYENSNFSIPQATLSDSGSYHCS--GTVRIKRRSSESV 79

                 ....
gi 767910411  99 KIKV 102
Cdd:cd05753   80 NITV 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767910411  299 RPVLTLRSPGAQAAVGDLLELHCEAlRGSPPILYQFYHEDVTLGNSSAPSGGGASFNLSL-----TAEHSGNYSCEANN 372
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEA-TGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLtisnvTRSDAGTYTCVASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767910411  216 VTEGQKLILLCSVAGGTGNvTFSWYR---EATGTSMGKKTQRSLSAELEIPAVKESDAGKYYCRADN 279
Cdd:pfam13927  13 VREGETVTLTCEATGSPPP-TITWYKngePISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910411  302 LTLRSPGAQAAVGDLLELHCEALrGSPPILYQFYHEDVTLgnssapSGGGASFNLSLTAEHSGNYSCEANNGLGAQCSEA 381
Cdd:pfam13895   2 PVLTPSPTVVTEGEPVTLTCSAP-GNPPPSYTWYKDGSAI------SSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNP 74

                  ....*
gi 767910411  382 VPVSI 386
Cdd:pfam13895  75 VELTV 79

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 767910411 208 EIRAPGGQvtEGQKLILLCSVAGGTGNVTFSWYREatGTSMGKKTQRSL-------SAELEIPAVKESDAGKYYCRADN 279
Cdd:cd05750    5 EMKSQTVQ--EGSKLVLKCEATSENPSPRYRWFKD--GKELNRKRPKNIkirnkkkNSELQINKAKLEDSGEYTCVVEN 79

Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also referred to 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. CRIg plays a role in the complement system, an 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767910411  27 SVFEGDSIVLKCQGEQNWKIQKMAYHK--DNKELSVFKKFSDFLIQSAVLSDSGNYFCSTKGQLFLwDKTSNIVKIKVQ 103
Cdd:cd16082    9 TVPQGMRISLQCQAWGSPPISYVWYKEqtNNQEPIKVAALSTLLFKPAVVADSGSYFCTAKGRVGS-EQRSDIVKFVVK 86

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 767910411 317 LELHCEAlRGSPPILYQFYHEDVTLGNSSAPSGGGASFNLSLT-----AEHSGNYSCEANNGLGAQCSEAV 382
Cdd:cd00096    1 VTLTCSA-SGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTisnvtLEDSGTYTCVASNSAGGSASASV 70

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 767910411 216 VTEGQKLILLCSVAGGTGNVTFSWYREATGTSM--------------GKKTQR-------SLSAELEIPAVKESDAGKYY 274
Cdd:cd00099   10 VQEGESVTLSCEVSSSFSSTYIYWYRQKPGQGPefliylssskgktkGGVPGRfsgsrdgTSSFSLTISNLQPEDSGTYY 89

                 .
gi 767910411 275 C 275
Cdd:cd00099   90 C 90

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767910411 218 EGQKLILLCSVAGGTGNVTFSWYREATGTSMGKK--TQRSLSAELEIPAVKESDAGKYYCRADNGHVPIQSKVV 289
Cdd:cd20979   14 EGQPTVLECVTEGGDQGVKYSWLKDGKSFNWQEHnvAQRKDEGSLVFLKPQASDEGQYQCFAETPAGVASSRVI 87

C17orf99 Ig domain; This Ig domain is found in tandem in the uncharacterized human protein C17orf99, which is found across mammalian species.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767910411  314 GDLLELHCEALRGSPPILYQFYHED-VTLGNSSAPSGGGASFNLSLTAEHSG---NYSCEANNGLGAQCSEAV 382
Cdd:pfam17736  16 GRRVLISCHASQGSPPITYSLVGSDgIVVAKKIPLHGEPANFSLNITLKSSPdllTYQCQAANTSGTQVSSLR 88

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910411 203 SNVSLEIRAPGGQVTEGQKLILLCSVAGgTGNVTFSWYRE-------ATGTSMgkktqRSLSAELEIPAVKESDAGKYYC 275
Cdd:cd20970    1 PVISTPQPSFTVTAREGENATFMCRAEG-SPEPEISWTRNgnliiefNTRYIV-----RENGTTLTIRNIRRSDMGIYLC 74

                         90
                 ....*....|..
gi 767910411 276 RADNGHVPIQSK 287
Cdd:cd20970   75 IASNGVPGSVEK 86

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 767910411  27 SVFEGDSIVLKCQGEQNWKIQKMAYHKDNKELSVF----------KKFSDFLIQSAVLSDSGNYFCSTKGQL 88
Cdd:cd05750   10 TVQEGSKLVLKCEATSENPSPRYRWFKDGKELNRKrpknikirnkKKNSELQINKAKLEDSGEYTCVVENIL 81

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767910411 209 IRAPGGQVTEGQKLILLCSVAGGTG-NVTfsWY---REATGTSMGKKTQRSLSAELEIPAVKESDAGKYYCRADN 279
Cdd:cd20949    4 ENAYVTTVKEGQSATILCEVKGEPQpNVT--WHfngQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQ 76

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 767910411 216 VTEGQKLILLCSVAGGTGNVTFSWYREATGTSMGKKTQRSLS----------AELEIPAVKESDAGKYYCRADNGH-VPI 284
Cdd:cd20950    9 ATIGNRAVLTCSEPDGSPPSEYTWFKDGVVMPTNPKSTRAFSnssysldpttGELVFDPLSASDTGEYSCEARNGYgTPM 88

                 ....*....
gi 767910411 285 QSKVVNIPV 293
Cdd:cd20950   89 RSNAVRMEA 97

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767910411  27 SVFEGDSIVLKCQGEQNWKIQKMAYHKDNKELSVF-----------KKFSDFLIQSAVLSDSGNYFCSTKGQL 88
Cdd:cd05895   10 EVAAGSKLVLRCETSSEYPSLRFKWFKNGKEINRKnkpenikiqkkKKKSELRINKASLADSGEYMCKVSSKL 82

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767910411 214 GQVTEGQKLILLCSVAGGTGNVTFSWYREAT------GTSMGKKTQRSLSaeLEIPAVKESDAGKYYCRADN 279
Cdd:cd20959   12 GAAQVGMRAQLHCGVPGGDLPLNIRWTLDGQpisddlGITVSRLGRRSSI--LSIDSLEASHAGNYTCHARN 81

Gammadelta T-cell antigen receptor, variable (V) domain; The members here are composed of the immunoglobulin (Ig) variable (V) domain of the gamma/delta T-cell receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are heterodimers consisting of alpha and beta chains or gamma and delta chains. Each chain contains a variable (V) and a constant (C) region. The majority of T cells contain alpha/beta TCRs, but a small subset contain gamma/delta TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. Gamma/delta TCRs recognize intact protein antigens; they recognize protein antigens directly and without antigen processing, and MHC independently of the bound peptide. Gamma/delta T cells can also be stimulated by non-peptide antigens such as small phosphate- or amine-containing compounds. The variable domain of gamma/delta TCRs is responsible for antigen recognition and is located at the N-terminus of the receptor. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910411 216 VTEGQKLILLCSVAGGT-GNVTFSWYREATGTSM-------------------GKKTQRSLSAELEIPAVKESDAGKYYC 275
Cdd:cd20988   10 VSVGKPVTLKCSMKGEAiSNYYINWYRKTQGNTMtfiyreggiygpgfkdnfrGDIDSSNNLAVLKILEASERDEGSYYC 89

                 ....
gi 767910411 276 RADN 279
Cdd:cd20988   90 ASDT 93

Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910411 302 LTLRSPGAQAAVGDLLELHCEALRGSPPILYQFYHEDVTLGNSSApsgggaSFNLSL---TAEHSGNYSCEANNGLGAQC 378
Cdd:cd05753    2 LLLQAPSAVVFEGEPLTLRCHGWKDKKVHKVTYYKDGKALKFSYE------NSNFSIpqaTLSDSGSYHCSGTVRIKRRS 75

                 ....*...
gi 767910411 379 SEAVPVSI 386
Cdd:cd05753   76 SESVNITV 83

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767910411  304 LRSPGAQAAVGDLLELHCEALRGSPPILYQFYHEDVTLGNS-----SAPSGGGASFNLS-LTAEHSGNYSCEANNGLG 375
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESlkvkhDNGRTTQSSLLISnVTKEDAGTYTCVVNNPGG 78