First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the first 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1133968592  25 AVVNLDPKWVRVLEEDSVTLRCQGTFSPEDNSIKWFHNESLIPHQDANYVIQSARVKDSGMYRCQTALSTISDPVQLEV 103
Cdd:cd05752     1 AVVSLDPPWTTVFQGEKVTLTCQGFYSPEQNSTQWYHNGTLISSTSSSYRIVAATVNDSGEYRCQTQGSSLSDPVHLEV 79

First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the first 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1133968592  25 AVVNLDPKWVRVLEEDSVTLRCQGTFSPEDNSIKWFHNESLIPHQDANYVIQSARVKDSGMYRCQTALSTISDPVQLEV 103
Cdd:cd05752     1 AVVSLDPPWTTVFQGEKVTLTCQGFYSPEQNSTQWYHNGTLISSTSSSYRIVAATVNDSGEYRCQTQGSSLSDPVHLEV 79

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1133968592  26 VVNLDPKWVRVLEEDSVTLRCQGTFSPEdNSIKWFHNESLIPHQD----------ANYVIQSARVKDSGMYRCQ 89
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEATGSPP-PTITWYKNGEPISSGStrsrslsgsnSTLTISNVTRSDAGTYTCV 75

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1133968592   31 PKWVRVLEEDSVTLRCQGTFSPeDNSIKWFHNESLIPHQDANY-----------VIQSARVKDSGMYRCQTALSTISD-- 97
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSP-PPEVTWYKQGGKLLAESGRFsvsrsgststlTISNVTPEDSGTYTCAATNSSGSAss 79

                   ....*.
gi 1133968592   98 PVQLEV 103
Cdd:smart00410  80 GTTLTV 85

IL-1 receptor-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1133968592  61 HNEslIPHQDANYVIQSARVKDSGMYRCQTALSTISD--PVQLEVHMGWLLLQttkwlFQEGDPIHLRCHSwqNRPVRK- 137
Cdd:PHA02826   90 HNE--IGDRSENLWIGNVINIDEGIYICTISSGNICEesTIRLTFDSGTINYQ-----FNSGKDSKLHCYG--TDGISSt 160

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1133968592 138 -----VTYLQNGK---GKKYFH---ENSELLIPKATHNDSGSYFCRGLIGHNN 179
Cdd:PHA02826  161 fkdytLTWYKNGNivlYTDRIQlrnNNSTLVIKSATHDDSGIYTCNLRFNKNS 213

First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the first 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1133968592  25 AVVNLDPKWVRVLEEDSVTLRCQGTFSPEDNSIKWFHNESLIPHQDANYVIQSARVKDSGMYRCQTALSTISDPVQLEV 103
Cdd:cd05752     1 AVVSLDPPWTTVFQGEKVTLTCQGFYSPEQNSTQWYHNGTLISSTSSSYRIVAATVNDSGEYRCQTQGSSLSDPVHLEV 79

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1133968592  26 VVNLDPKWVRVLEEDSVTLRCQGTFSPEdNSIKWFHNESLIPHQD----------ANYVIQSARVKDSGMYRCQ 89
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEATGSPP-PTITWYKNGEPISSGStrsrslsgsnSTLTISNVTRSDAGTYTCV 75

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1133968592 119 EGDPIHLRCHSWQNrPVRKVTYLQNGKgkkYFHENSELLIPKATHNDSGSYFCRGLIGHNNKSSASFRIS 188
Cdd:pfam13895  13 EGEPVTLTCSAPGN-PPPSYTWYKDGS---AISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPVELT 78

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1133968592  35 RVLEEDSVTLRCQGTFSPEDNsIKWFHNESLIPhQDANYVIQSARVKDSGMYRCQ---TALSTISDPVQLEV 103
Cdd:pfam13895  10 VVTEGEPVTLTCSAPGNPPPS-YTWYKDGSAIS-SSPNFFTLSVSAEDSGTYTCVarnGRGGKVSNPVELTV 79

Immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors, Natural killer inhibitory receptors (KIRs) and similar domains; member of Immunoglobulin Constant-2 set of IgSF domains; The members here are composed of the first and second immunoglobulin (Ig)-like domains found in Leukocyte Ig-like receptors (LILRs), Natural killer inhibitory receptors (KIRs, also known as also known as cluster of differentiation (CD) 158), and similar proteins. This group includes LILRB1 (also known as LIR-1), LILRA5 (also known as LIR9), an activating natural cytotoxicity receptor NKp46, the immune-type receptor glycoprotein VI (GPVI), and the IgA-specific receptor Fc-alphaRI (also known as cluster of differentiation (CD) 89). LILRs are a family of immunoreceptors expressed on expressed on T and B cells, on monocytes, dendritic cells, and subgroups of natural killer (NK) cells. The human LILR family contains nine proteins (LILRA1-3, and 5, and LILRB1-5). From functional assays, and as the cytoplasmic domains of various LILRs, for example LILRB1, LILRB2 (also known as LIR-2), and LILRB3 (also known as LIR-3) contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs), it is thought that LIR proteins are inhibitory receptors. Of the eight LIR family proteins, only LILRB1, and LILRB2, show detectable binding to class I MHC molecules; ligands for the other members have yet to be determined. The extracellular portions of the different LIR proteins contain different numbers of Ig-like domains for example, four in the case of LILRB1, and LILRB2, and two in the case of LILRB4 (also known as LIR-5). The activating natural cytotoxicity receptor NKp46 is expressed in natural killer cells, and is organized as an extracellular portion having two Ig-like extracellular domains, a transmembrane domain, and a small cytoplasmic portion. GPVI, which also contains two Ig-like domains, participates in the processes of collagen-mediated platelet activation and arterial thrombus formation. Fc-alphaRI is expressed on monocytes, eosinophils, neutrophils, and macrophages; it mediates IgA-induced immune effector responses such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and respiratory burst. Killer cell immunoglobulin-like receptors (KIRs; also known as CD158 for human KIR) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. KIRs are a family of highly polymorphic activating and inhibitory receptors that serve as key regulators of human NK cell function. The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The major ligands for KIR are MHC class I (HLA-A, -B or -C) molecules.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1133968592  36 VLEEDSVTLRCQGT-------FSPEDNSIKWFHNESLIPHQDANYVIQSARVKDSGMYRCQTALSTI----SDPVQLEV 103
Cdd:cd16843    12 VPLGENVTIRCQGPpeavlfqLYKEGNSLSQGTVREKEPQNKAEFYIPHMDRNHAGRYRCRYRSGTLwsepSDPLELVV 90

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1133968592  42 VTLRCQGTFSPEDnSIKWFHNESLIPHQ----------DANYVIQSARVKDSGMYRCQ 89
Cdd:cd00096     1 VTLTCSASGNPPP-TITWYKNGKPLPPSsrdsrrselgNGTLTISNVTLEDSGTYTCV 57

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 1133968592 116 LFQEGDPIHLRCHSWQNRPVRKVTYLQNGKGK----KYFHEN-----SELLIPKATHNDSGSYFCRgliGHNNKSSASFR 186
Cdd:pfam00047   7 TVLEGDSATLTCSASTGSPGPDVTWSKEGGTLieslKVKHDNgrttqSSLLISNVTKEDAGTYTCV---VNNPGGSATLS 83

                  ...
gi 1133968592 187 ISL 189
Cdd:pfam00047  84 TSL 86

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 1133968592  34 VRVLEEDSVTLRCQGTFSPEDnSIKWFHNESLIPHQDANYV---------IQSARVKDSGMYRC 88
Cdd:cd20970    12 VTAREGENATFMCRAEGSPEP-EISWTRNGNLIIEFNTRYIvrengttltIRNIRRSDMGIYLC 74

Immunoglobulin I-set domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1133968592  31 PKWVRVLEEDSVTLRCQGTFSPeDNSIKWFHNESLIP----------HQDANYVIQSARVKDSGMYRCQ 89
Cdd:pfam07679   7 PKDVEVQEGESARFTCTVTGTP-DPEVSWFKDGQPLRssdrfkvtyeGGTYTLTISNVQPDDSGKYTCV 74

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1133968592 116 LFQEGDPIHLRCHSWQNRpVRKVTYLQNGKGKKYFHENSE------LLIPKATHNDSGSYFC 171
Cdd:cd04979     7 SVKEGDTVILSCSVKSNN-APVTWIHNGKKVPRYRSPRLVlktergLLIRSAQEADAGVYEC 67

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 1133968592 123 IHLRCHSwQNRPVRKVTYLQNGK--------GKKYFHENSELLIPKATHNDSGSYFCRGLIGHNNKSSASF 185
Cdd:cd00096     1 VTLTCSA-SGNPPPTITWYKNGKplppssrdSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

CH3 domain (third constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, gamma, and delta chains, and CH4 domain (fourth constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, epsilon, and mu chains; member of the C1-set of I; The members here are composed of the third and fourth immunoglobulin constant domain (IgC) of alpha, delta, gamma and alpha, epsilon, and mu heavy chains, respectively. This domain is found on the Fc fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1133968592  35 RVLEEDSVTLRC--QGtFSPEDNSIKWFHNESliPHQDANYViQSARVKDSG 84
Cdd:cd05768    12 ELSLNETVTLTClvKG-FYPEDIFVSWLQNGE--PLPSADYK-TTAPVPESD 59