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 147904557  33 LEISADAHVRGYVGEKIKLKCTFKSSSDVTDKLTIDWTYRPPSSSRTESIFHYQSFQ-YPTTAGTFRDRISWAGNVYKGD 111
Cdd:cd05715    1 MEVYTPRELNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKGKpYILKVGRFKDRVSWAGNPSKKD 80

                         90       100
                 ....*....|....*....|....*.
gi 147904557 112 ASISISNPTLKDNGTFSCAVKNPPDV 137
Cdd:cd05715   81 ASIVISNLQFSDNGTYTCDVKNPPDI 106

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 147904557  33 LEISADAHVRGYVGEKIKLKCTFKSSSDVTDKLTIDWTYRPPSSSRTESIFHYQSFQ-YPTTAGTFRDRISWAGNVYKGD 111
Cdd:cd05715    1 MEVYTPRELNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKGKpYILKVGRFKDRVSWAGNPSKKD 80

                         90       100
                 ....*....|....*....|....*.
gi 147904557 112 ASISISNPTLKDNGTFSCAVKNPPDV 137
Cdd:cd05715   81 ASIVISNLQFSDNGTYTCDVKNPPDI 106

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 147904557    49 IKLKCTFKSSSdvTDKLTIDWtYRPPSSSRTESIFHYQSFQYPTTAGTFRDRISWAGNVYKGDASISISNPTLKDNGTFS 128
Cdd:smart00406   2 VTLSCKFSGST--FSSYYVSW-VRQPPGKGLEWLGYIGSNGSSYYQESYKGRFTISKDTSKNDVSLTISNLRVEDTGTYY 78

                   ...
gi 147904557   129 CAV 131
Cdd:smart00406  79 CAV 81

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 147904557  33 LEISADAHVRGYVGEKIKLKCTFKSSSDVTDKLTIDWTYRPPSSSRTESIFHYQSFQ-YPTTAGTFRDRISWAGNVYKGD 111
Cdd:cd05715    1 MEVYTPRELNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKGKpYILKVGRFKDRVSWAGNPSKKD 80

                         90       100
                 ....*....|....*....|....*.
gi 147904557 112 ASISISNPTLKDNGTFSCAVKNPPDV 137
Cdd:cd05715   81 ASIVISNLQFSDNGTYTCDVKNPPDI 106

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 147904557  33 LEISADAHVRGYVGEKIKLKCTFKSSSDVTDKLTIDWTYRPPSSSRTESIFHYQSFQ-YPTTAGTFRDRISWAGNVYKGD 111
Cdd:cd05879    1 IVVYTDREVYGTVGSDVTLSCSFWSSEWISDDISFTWHYQPDGSRDAISIFHYGKGQpYIDNVGPFKERIEWVGNPSRKD 80

                         90       100
                 ....*....|....*....|....*.
gi 147904557 112 ASISISNPTLKDNGTFSCAVKNPPDV 137
Cdd:cd05879   81 GSIVIHNLDYTDNGTFTCDVKNPPDI 106

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 147904557  45 VGEKIKLKCTFKSSSDVTDKLTIDWTYRPPSSSRTESIFHYQSFQYPTTAGTFRDRISWAGNVYKGDASISISNPTLKDN 124
Cdd:cd20960   14 AGENVTLPCHHQLGLEDQGTLDIEWLLLPSDKVEKVVITYSGDRVYNHYYPALKGRVAFTSNDLSGDASLNISNLKLSDT 93

                         90
                 ....*....|...
gi 147904557 125 GTFSCAVKNPPDV 137
Cdd:cd20960   94 GTYQCKVKKAPGY 106

Immunoglobulin Variable (IgV) domain of B7-H4; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H4 (also known as B7-S1, B7x, or Vtcn1). B7-H4 is one of the B7 family of immune-regulatory ligands that act as negative regulators of T cell function; it contains one IgV domain and one IgC domain. The B7-family consists of structurally related cell-surface protein ligands, which bind to receptors on lymphocytes that regulate immune responses. The binding of B7-H4 to unidentified receptors results in the inhibition of TCR-mediated T cell proliferation, cell-cycle progression and IL-2 production. As a co-inhibitory molecule, B7-H4 is widely expressed in tumor tissues and its expression is significantly associated with poor prognosis in human cancers such as glioma, pancreatic cancer, oral squamous cell carcinoma, renal cell carcinoma, and lung cancer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 147904557  34 EISAdAHVRGYVGEKIKLKCTFKSSSDVTDkLTIDWTYRPPSSSRTEsiFHYQSFQYPTTAGTFRDRIS-WAGNVYKGDA 112
Cdd:cd20984    1 TVTA-KHLAGNIGEDGILSCTFTPDIKLSD-IVIQWLKEGDSGLVHE--FKEGKDELSRQSPMFRGRTSlFADQVHVGNA 76

                         90       100
                 ....*....|....*....|.
gi 147904557 113 SISISNPTLKDNGTFSCAVKN 133
Cdd:cd20984   77 SLRLKNVQLTDAGTYLCIISN 97

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 147904557  45 VGEKIKLKCTFKSSSDVTdklTIDWtYRPPSSSRTESIFhYQSFQYPTTAGTFRDRISWAGNVYKgDASISISNPTLKDN 124
Cdd:cd00099   12 EGESVTLSCEVSSSFSST---YIYW-YRQKPGQGPEFLI-YLSSSKGKTKGGVPGRFSGSRDGTS-SFSLTISNLQPEDS 85

                         90       100
                 ....*....|....*....|....*.
gi 147904557 125 GTFSCAVKNPPDVYHNI--PLTELTV 148
Cdd:cd00099   86 GTYYCAVSESGGTDKLTfgSGTRLTV 111

Immunoglobulin (Ig)-like domain of human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in human cartilage link protein (LP; also called hyaluronan and proteoglycan link protein). In cartilage, chondroitin-keratan sulfate proteoglycan (CSPG), aggrecan, forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. 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 147904557  36 SADAHVRGYVGEKIKLKCTF--KSSSDVTDKLTIDWTYRPPSSSRTESIF-----HYQSFqypttaGTFRDRISWAGnVY 108
Cdd:cd05877    2 TVQAKVFSHRGGNVTLPCRYhyEPELSAPRKIRVKWTKLEVDYAKEEDVLvaigtRHKSY------GSYQGRVFLRR-AD 74

                         90       100
                 ....*....|....*....|...
gi 147904557 109 KGDASISISNPTLKDNGTFSCAV 131
Cdd:cd05877   75 DLDASLVITDLRLEDYGRYRCEV 97

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
                 ....*....|....*....|....*....|
gi 147904557 105 GNVYKGDASISISNPTLKDNGTFSCAVKNP 134
Cdd:cd20982   64 GDFSKGDVSLTIENVTLADSGIYCCRIQIP 93

First immunoglobulin variable (IgV) domain of nectin-3 (also known as poliovirus receptor related protein 3), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3 (PVRL3) or cluster of differentiation (CD) 113). Nectin-3 belongs to the nectin family 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, during spermatid development, the nectin-3,-2 trans-interaction is required for the formation of Sertoli cell-spermatid junctions in testis, and during morphogenesis of the ciliary body, the nectin-3,-1 trans-interaction is important for apex-apex adhesion between the pigment and non-pigment layers of the ciliary epithelia. Nectins also heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls); nectin-3 for example, trans-interacts with Necl-5, regulating cell movement and proliferation. Other proteins with which nectin-3 interacts include the actin filament-binding protein, afadin, integrin alpha-beta3, Par-3, and PDGF receptor; its interaction with PDGF receptor regulates the latter's signaling for anti-apoptosis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 147904557  38 DAHVRGYVGEKIKLKCTFksssDVTDKLT-IDWTYRPPSSSRTESIFHYQ-SFQYPttaGTFRDRISWAgNVYKGDASIS 115
Cdd:cd05887    6 EPHVTAVWGKNVSLKCLI----EVNETITqISWEKIHGKSSQTVAVHHPQyGISIQ---GEYQGRVSFK-NYSLNDATIT 77

                         90       100
                 ....*....|....*....|
gi 147904557 116 ISNPTLKDNGTFSCAVKNPP 135
Cdd:cd05887   78 LHNVGFSDSGKYICKAVTFP 97