Immunoglobulin (Ig)-like domain of protein zero (P0); 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 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.

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gi 1046899324  20 VEWFYRPEGGKDFL-IYEYRNGHQEVES--PFQGRLQWNGSKDLQDVSITVLNVTLNDSGLYTCNV 82
Cdd:cd05879    35 FTWHYQPDGSRDAIsIFHYGKGQPYIDNvgPFKERIEWVGNPSRKDGSIVIHNLDYTDNGTFTCDV 100

Immunoglobulin (Ig)-like domain of protein zero (P0); 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 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1046899324  20 VEWFYRPEGGKDFL-IYEYRNGHQEVES--PFQGRLQWNGSKDLQDVSITVLNVTLNDSGLYTCNV 82
Cdd:cd05879    35 FTWHYQPDGSRDAIsIFHYGKGQPYIDNvgPFKERIEWVGNPSRKDGSIVIHNLDYTDNGTFTCDV 100

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1046899324  14 VEATTVVEWFYRPE--GGKDFLIYEYRNGHQEVESPFQGRLQWNGSKDLQDVSITVLNVTLNDSGLYTCNV 82
Cdd:cd05880    29 IGDTLVITWNFRPLdgGREESVFYYHKRPYPPPDGRFKGRVVWDGNIMRRDASILIWQLQPTDNGTYTCQV 99

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1046899324  20 VEWFYRPEGGKDFLIYEYRNGH--QEVESPFQGRLQWNGSKDLQDVSITVLNVTLNDSGLYTCNV 82
Cdd:cd20960    36 IEWLLLPSDKVEKVVITYSGDRvyNHYYPALKGRVAFTSNDLSGDASLNISNLKLSDTGTYQCKV 100

First immunoglobulin variable (IgV) domain of DNAX accessory molecule 1, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of DNAX accessory molecule 1 (DNAM-1, also known as CD226). DNAM-1 is a transmembrane protein having two Ig-like domains. It is an adhesion molecule which plays a part in tumor-directed cytotoxicity and adhesion in natural killer (NK) cells and T lymphocytes. It has been shown to regulate the NK cell killing of several tumor types, including myeloma cells and ovarian carcinoma cells. DNAM-1 interacts specifically with poliovirus receptor (PVR; CD155) and nectin -2 (CD211), other members of the Ig superfamily. DNAM-1 is expressed in most peripheral T cells, NK cells, monocytes and a subset of B lymphocytes.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046899324   1 MKLRCIsCMKREEVeatTVVEWFYRPEGGKDFLIYEYRNGhQEVESPFQGRLQW-NGSKDLQDVSITVLNVTLNDSGLYT 79
Cdd:cd05889    17 MSLECV-YPSTGIL---TQVEWTKIGGQKDNIAVYHPTHG-MHIRKPYAGRVYFlNSTMASNNMSLSFRNASEDDVGYYS 91

                  .
gi 1046899324  80 C 80
Cdd:cd05889    92 C 92

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.

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gi 1046899324  50 GRLQWNGSKDLQDVSITVLNVTLNDSGLYTCNV 82
Cdd:cd20982    58 SRYQLKGDFSKGDVSLTIENVTLADSGIYCCRI 90

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046899324  17 TTVVEWfYR--PEGGKDFLIYEYrNGHQEVESPFQGRLQWNGSKDlQDVSITVLNVTLNDSGLYTCNVSR 84
Cdd:cd00099    28 STYIYW-YRqkPGQGPEFLIYLS-SSKGKTKGGVPGRFSGSRDGT-SSFSLTISNLQPEDSGTYYCAVSE 94