Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357795  29 PGSIQVARGQPAVLPCTFTTSAALIN-LNVIWMVTPLsNANQPEQVILYQGGQMFDGAP-RFHGRVGFTGTMPATNVSIF 106
Cdd:cd05715     6 PRELNVLNGSDVRLTCTFTSCYTVGDaFSVTWTYQPE-GGNTTESMFHYSKGKPYILKVgRFKDRVSWAGNPSKKDASIV 84

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1214357795 107 INNTQLSDTGTYQCLVNNLPDIggrnIGVTG 137
Cdd:cd05715    85 ISNLQFSDNGTYTCDVKNPPDI----VGGHG 111

Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357795  29 PGSIQVARGQPAVLPCTFTTSAALIN-LNVIWMVTPLsNANQPEQVILYQGGQMFDGAP-RFHGRVGFTGTMPATNVSIF 106
Cdd:cd05715     6 PRELNVLNGSDVRLTCTFTSCYTVGDaFSVTWTYQPE-GGNTTESMFHYSKGKPYILKVgRFKDRVSWAGNPSKKDASIV 84

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1214357795 107 INNTQLSDTGTYQCLVNNLPDIggrnIGVTG 137
Cdd:cd05715    85 ISNLQFSDNGTYTCDVKNPPDI----VGGHG 111

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 1214357795  28 SPGSIQVARGQPAVLPCTFTTSAALIN-LNVIWMVTPLSNAnqPEQVILYQGGQMF---DGapRFHGRVGFTGTMPATNV 103
Cdd:cd05880     5 TSKEVEAVNGTDVRLKCTFSSSAPIGDtLVITWNFRPLDGG--REESVFYYHKRPYpppDG--RFKGRVVWDGNIMRRDA 80

                          90       100
                  ....*....|....*....|....*..
gi 1214357795 104 SIFINNTQLSDTGTYQCLVNNLPDIGG 130
Cdd:cd05880    81 SILIWQLQPTDNGTYTCQVKNPPDVHG 107

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357795   29 PGSIQVARGQPAVLPCTFTTSAaliNLNVIWMvtplsnaNQPEQVILYQGGqmfdgaprfhgrvgFTGTMPATNVSIFIN 108
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSP---PPEVTWY-------KQGGKLLAESGR--------------FSVSRSGSTSTLTIS 56

                           90
                   ....*....|....*.
gi 1214357795  109 NTQLSDTGTYQCLVNN 124
Cdd:smart00410  57 NVTPEDSGTYTCAATN 72

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 1214357795  31 SIQVARGQPAVLPCTFTTSAALINLNVIWMvtpLSNANQPEQVIL---YQGGQMFDGAprFHGRVGFTGTMPATNVSIFI 107
Cdd:cd05888     2 VVTVVLGQDAKLPCFYRGDSGEQVGQVAWA---RVDAGEGAQEIAllhSKYGLHVFPA--YEGRVEQPPPPRPADGSVLL 76

                          90
                  ....*....|....*....
gi 1214357795 108 NNTQLSDTGTYQCLVNNLP 126
Cdd:cd05888    77 RNAVQADEGEYECRVSTFP 95

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 1214357795  25 VSESPGSIQVARGQPAVLPCTFTTSaaLINLNVIWMVTPLsnaNQPEQVILYQGGQMFDGAPRFHGRvgFTGTMPATNVS 104
Cdd:cd00099     1 VTQSPRSLSVQEGESVTLSCEVSSS--FSSTYIYWYRQKP---GQGPEFLIYLSSSKGKTKGGVPGR--FSGSRDGTSSF 73

                          90
                  ....*....|....*..
gi 1214357795 105 IF-INNTQLSDTGTYQC 120
Cdd:cd00099    74 SLtISNLQPEDSGTYYC 90

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357795  31 SIQVARGQPAVLPCTFTTSAALINLNVIWMVTPLSNAnqpeqVILYQGGQMFDG--APRFHGRVGFT-GTMPATNVSIFI 107
Cdd:cd05713     9 PILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPV-----VHLYRDGQDQEEeqMPEYRGRTELLkDAIAEGSVALRI 83

                          90
                  ....*....|....*.
gi 1214357795 108 NNTQLSDTGTYQCLVN 123
Cdd:cd05713    84 HNVRPSDEGQYTCFFR 99

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) alpha chain and similar proteins; The members here are composed of the immunoglobulin (Ig) variable domain of the alpha chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta polypeptide chains with variable (V) and constant (C) regions. This group represents the variable domain of the alpha chain of TCRs and also includes the variable domain of delta chains of TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357795  25 VSESPGSIQVARGQPAVLPCTFTTSAaliNLNVIWMVtplSNANQPEQVILYQGgqmFDGAPRFHGRVGFTGTMPATNVS 104
Cdd:cd04983     1 VTQSPQSLSVQEGENVTLNCNYSTST---FYYLFWYR---QYPGQGPQFLIYIS---SDSGNKKKGRFSATLDKSRKSSS 71

                          90
                  ....*....|....*.
gi 1214357795 105 IFINNTQLSDTGTYQC 120
Cdd:cd04983    72 LHISAAQLSDSAVYFC 87

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 1214357795  37 GQPAVLPCTFTTSAALINLNVIWMvtpLSNANQPEQVILYQGGQMFDGAPRFHGRVGFT-GTMPATNVSIFINNTQLSDT 115
Cdd:cd05718    14 GGSVTLPCSLTSPGTTKITQVTWM---KIGAGSSQNVAVFHPQYGPSVPNPYAERVEFLaARLGLRNATLRIRNLRVEDE 90

                          90       100
                  ....*....|....*....|....*
gi 1214357795 116 GTYQCLVNNLPdiGGRNIGVTGLTV 140
Cdd:cd05718    91 GNYICEFATFP--QGNRQGTTWLRV 113

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 1214357795  37 GQPAVLPCTFTTSAALinLNVIWMVTplsNANQPEQVILYQGGQMFDGAPRFHGRVGFTGTMPaTNVSIFINNTQLSDTG 116
Cdd:cd05846    13 GGNATLSCNLTLPEEV--LQVTWQKI---KASSPENIVTYSKKYGVKIQPSYVRRISFTSSGL-NSTSITIWNVTLEDEG 86

                          90       100
                  ....*....|....*....|....
gi 1214357795 117 TYQCLVNNLPDigGRNIGVTGLTV 140
Cdd:cd05846    87 CYKCLFNTFPD--GIKSGTACLTV 108

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 1214357795  31 SIQVARGQPAVLPCTFTTSAALINLNVIWM--VTPLSnanQPEQVILYQGGqmFDGAPRFHGRVGFTGTMPATNVSIFIN 108
Cdd:cd20982     2 EYRAEVGHNAYLPCSYTTAAPGNLVPVCWGkgACPVS---YCGNVLLRTDE--RDVTYQKSSRYQLKGDFSKGDVSLTIE 76

                          90
                  ....*....|....
gi 1214357795 109 NTQLSDTGTYQCLV 122
Cdd:cd20982    77 NVTLADSGIYCCRI 90

Immunoglobulin variable domain (IgV) in Cluster of Differentiation (CD) 86; The members here are composed of the immunoglobulin variable region (IgV) in the Cluster of Differentiation (CD) 86). Glycoproteins B7-1 (also known as cluster of differentiation (CD) 80) and B7-2 (also known as CD86) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (also known as CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. The CTLA-4 and B7-2 monomers are both two-layer beta-sandwiches that display the chain topology characteristic of the immunoglobulin variable (V-type) domains present in antigen receptors. The front and back sheets of B7-2 are composed of AGFCC'C" and BED strands, respectively. Members of the IgV family 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357795  40 AVLPCTFTTSA--ALINLNVIWMvtplsnaNQPEQVI--LYQGGQMFDG-APRFHGRVGFTgtmpATNVSIFINNTQLSD 114
Cdd:cd16087    11 AYLPCQFKNPQniSLSELVVFWQ-------DQKKLVLyeLYLGKEKLDNvNSKYIGRTSFD----QENWTLQLHNVQIKD 79

                  ....*...
gi 1214357795 115 TGTYQCLV 122
Cdd:cd16087    80 QGTYQCFI 87

Immunoglobulin (Ig) light chain, kappa type, variable (V) domain; The members here are composed of the immunoglobulin (Ig) light chain, kappa type, variable (V) domain. This group contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology. 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 composed of a constant domain (CL) and a variable domain (VL). There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determines the type of immunoglobulin formed: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which seem to be functionally identical, and can associate with any of the heavy chains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1214357795  23 LEVSESPGSIQVARGQPAVLPCTFTTSAALINLNviWMvtpLSNANQPEQVILYQGGQMFDGAPrfhGRvgFTGTMPATN 102
Cdd:cd04980     1 IVMTQSPASLSVSPGERVTISCKASQSISSNYLA--WY---QQKPGQAPKLLIYYASTLHSGVP---SR--FSGSGSGTD 70

                          90
                  ....*....|....*....
gi 1214357795 103 VSIFINNTQLSDTGTYQCL 121
Cdd:cd04980    71 FTLTISSVEPEDAAVYYCQ 89

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 1214357795  68 NQPEQVILYQGGQMFDGAPRFHGRVGFTgtmpatNVSIFINNTQLSDTGTYQCLVNN 124
Cdd:cd00096    10 NPPPTITWYKNGKPLPPSSRDSRRSELG------NGTLTISNVTLEDSGTYTCVASN 60