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 578822014  14 LEIRADAHVRGYVGEKIKLKCTFKSTSDVTDKLTIDWTYRPPSSSHTVSIFHYQSFQ-YPTTAGTFRDRISWVGNVYKGD 92
Cdd:cd05715    1 MEVYTPRELNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKGKpYILKVGRFKDRVSWAGNPSKKD 80

                         90       100
                 ....*....|....*....|....*..
gi 578822014  93 ASISISNPTIKDNGTFSCAVKNPPDVH 119
Cdd:cd05715   81 ASIVISNLQFSDNGTYTCDVKNPPDIV 107

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 578822014  14 LEIRADAHVRGYVGEKIKLKCTFKSTSDVTDKLTIDWTYRPPSSSHTVSIFHYQSFQ-YPTTAGTFRDRISWVGNVYKGD 92
Cdd:cd05715    1 MEVYTPRELNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKGKpYILKVGRFKDRVSWAGNPSKKD 80

                         90       100
                 ....*....|....*....|....*..
gi 578822014  93 ASISISNPTIKDNGTFSCAVKNPPDVH 119
Cdd:cd05715   81 ASIVISNLQFSDNGTYTCDVKNPPDIV 107

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822014    30 IKLKCTFkSTSDVTDkLTIDWTYRPPSSShtVSIFHYQSFQYPTT-AGTFRDRISWVGNVYKGDASISISNPTIKDNGTF 108
Cdd:smart00406   2 VTLSCKF-SGSTFSS-YYVSWVRQPPGKG--LEWLGYIGSNGSSYyQESYKGRFTISKDTSKNDVSLTISNLRVEDTGTY 77

                   ....
gi 578822014   109 SCAV 112
Cdd:smart00406  78 YCAV 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 578822014  14 LEIRADAHVRGYVGEKIKLKCTFKSTSDVTDKLTIDWTYRPPSSSHTVSIFHYQSFQ-YPTTAGTFRDRISWVGNVYKGD 92
Cdd:cd05715    1 MEVYTPRELNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKGKpYILKVGRFKDRVSWAGNPSKKD 80

                         90       100
                 ....*....|....*....|....*..
gi 578822014  93 ASISISNPTIKDNGTFSCAVKNPPDVH 119
Cdd:cd05715   81 ASIVISNLQFSDNGTYTCDVKNPPDIV 107

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 578822014  14 LEIRADAHVRGYVGEKIKLKCTFKSTSDVTDKLTIDWTYRPPSSSHTVSIFHYQSFQ-YPTTAGTFRDRISWVGNVYKGD 92
Cdd:cd05879    1 IVVYTDREVYGTVGSDVTLSCSFWSSEWISDDISFTWHYQPDGSRDAISIFHYGKGQpYIDNVGPFKERIEWVGNPSRKD 80

                         90       100
                 ....*....|....*....|....*.
gi 578822014  93 ASISISNPTIKDNGTFSCAVKNPPDV 118
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 578822014  26 VGEKIKLKCTFKSTSDVTDKLTIDWTYRPPSSSHTVSIFHYQSFQYPTTAGTFRDRISWVGNVYKGDASISISNPTIKDN 105
Cdd:cd20960   14 AGENVTLPCHHQLGLEDQGTLDIEWLLLPSDKVEKVVITYSGDRVYNHYYPALKGRVAFTSNDLSGDASLNISNLKLSDT 93

                         90
                 ....*....|....
gi 578822014 106 GTFSCAVKNPPDVH 119
Cdd:cd20960   94 GTYQCKVKKAPGYA 107

Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822014  18 ADAHVRGYVGEKIKLKCTFKSTSDVtdklTIDWTYrpPSSSHTVSIFHYQSFQYPTTAGTFRDRISWVGN-VYKGDASIS 96
Cdd:cd16091    3 SEVIVVCLLSEDCILPCSFTPGSEV----VIHWYK--QDSDIKVHSYYYGKDQLESQDQRYRNRTSLFKDqISNGNASLL 76

                         90
                 ....*....|....*...
gi 578822014  97 ISNPTIKDNGTFSCAVKN 114
Cdd:cd16091   77 LRRVQLQDEGRYKCYTST 94

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 578822014  20 AHVRGYVGEKIKLKCTFKSTSDVTDkltIDWTYRPPSSSHTVSIFHYQSFQYPTTAGTFRDRIS-WVGNVYKGDASISIS 98
Cdd:cd20984    5 KHLAGNIGEDGILSCTFTPDIKLSD---IVIQWLKEGDSGLVHEFKEGKDELSRQSPMFRGRTSlFADQVHVGNASLRLK 81

                         90
                 ....*....|....*.
gi 578822014  99 NPTIKDNGTFSCAVKN 114
Cdd:cd20984   82 NVQLTDAGTYLCIISN 97

First immunoglobulin variable (IgV) domain of nectin-2, nectin-like protein 5, and similar domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-2 (also known as poliovirus receptor related protein 2 or Cluster of Differentiation 112 (CD112)), nectin-like protein 5 (CD155), and similar proteins. Nectins and Nectin-like molecules are a family of Ca(2+)-independent immunoglobulin-like transmembrane glycoproteins belonging to the class of adhesion receptors, consisting of nine members (nectins 1 through 4 and nectin-like proteins 1 through 5). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as Necl-5, or PVR. In contrast to all other family members, CD155 lacks self-adhesion capacity, yet it shares with nectins the feature to interact with other nectins. For instance, CD155 heterophilically trans-interacts with nectin-3, thereby contributing significantly to the establishment of adherens junctions between epithelial cells. This group belongs to the Constant 1 (C1)-set of IgSF domains, which has one beta-sheet that is formed by strands A-B-E-D and the other strands by G-F-C-C'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822014  16 IRADAHVRGYVGEKIKLKCTFKSTSDVTDKLTIDWtyRPPSSSHTVSIFHyqsfqyPTTAGTFR--DRISWVG---NVYK 90
Cdd:cd20989    3 VQVPPEVRGFLGGSVTLPCHLLPPNMVTHVSQVTW--QRHDEHGSVAVFH------PKQGPSFPesERLSFVAarlGAEL 74

                         90       100
                 ....*....|....*....|
gi 578822014  91 GDASISISNPTIKDNGTFSC 110
Cdd:cd20989   75 RNASLAMFGLRVEDEGNYTC 94

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822014    21 HVRGYVGEKIKLKCTFKSTSDVTdkltIDWTYRPPSSShtvsifhyqsfqypttagTFRDRISWVGNvyKGDASISISNP 100
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPE----VTWYKQGGKLL------------------AESGRFSVSRS--GSTSTLTISNV 58

                           90       100
                   ....*....|....*....|....*....
gi 578822014   101 TIKDNGTFSCAVKNPPDVHHNIpmTELTV 129
Cdd:smart00410  59 TPEDSGTYTCAATNSSGSASSG--TTLTV 85

First immunoglobulin variable (IgV) domain of nectin-1, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-1 (also known as poliovirus receptor related protein 1 (PVRL1) or cluster of differentiation (CD) 111). Nectin-1 belongs to the nectin family comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. In addition nectins heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls), nectin-1 for example, has been shown to trans-interact with Necl-1. Nectins also interact with various other proteins, including the actin filament (F-actin)-binding protein, afadin. Mutation in the human nectin-1 gene is associated with cleft lip/palate ectodermal dysplasia syndrome (CLPED1). Nectin-1 is a major receptor for herpes simplex virus through interaction with the viral envelope glycoprotein D.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822014  16 IRADAHVRGYVGEKIKLKCTFKSTSDVTDKLTIDWTYRPPSSSHTVSIfhYQSFQYPTTAGTFRDRISWVGNVYKgDASI 95
Cdd:cd05886    3 VQVNDSMSGFIGTDVVLHCSFANPLPSVKITQVTWQKSTNGSKQNVAI--YNPSMGVSVLPPYRERVTFLNPSFT-DGTI 79

                         90
                 ....*....|....*
gi 578822014  96 SISNPTIKDNGTFSC 110
Cdd:cd05886   80 RLSRLELEDEGVYIC 94