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 555290119  25 DAHVRGYVGEKIKLKCTFKSTSDVTDKLTIDWTYRPPSSSHTVSIFHYQSFQ-YPTTAGTFRDRISWVGNVYKGDASISI 103
Cdd:cd05715    6 PRELNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKGKpYILKVGRFKDRVSWAGNPSKKDASIVI 85

                         90       100
                 ....*....|....*....|..
gi 555290119 104 SNPTIKDNGTFSCAVKNPPDVH 125
Cdd:cd05715   86 SNLQFSDNGTYTCDVKNPPDIV 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 555290119  25 DAHVRGYVGEKIKLKCTFKSTSDVTDKLTIDWTYRPPSSSHTVSIFHYQSFQ-YPTTAGTFRDRISWVGNVYKGDASISI 103
Cdd:cd05715    6 PRELNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKGKpYILKVGRFKDRVSWAGNPSKKDASIVI 85

                         90       100
                 ....*....|....*....|..
gi 555290119 104 SNPTIKDNGTFSCAVKNPPDVH 125
Cdd:cd05715   86 SNLQFSDNGTYTCDVKNPPDIV 107

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290119    36 IKLKCTFkSTSDVTDkLTIDWTYRPPSSShtVSIFHYQSFQYPTT-AGTFRDRISWVGNVYKGDASISISNPTIKDNGTF 114
Cdd:smart00406   2 VTLSCKF-SGSTFSS-YYVSWVRQPPGKG--LEWLGYIGSNGSSYyQESYKGRFTISKDTSKNDVSLTISNLRVEDTGTY 77

                   ....
gi 555290119   115 SCAV 118
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 555290119  25 DAHVRGYVGEKIKLKCTFKSTSDVTDKLTIDWTYRPPSSSHTVSIFHYQSFQ-YPTTAGTFRDRISWVGNVYKGDASISI 103
Cdd:cd05715    6 PRELNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKGKpYILKVGRFKDRVSWAGNPSKKDASIVI 85

                         90       100
                 ....*....|....*....|..
gi 555290119 104 SNPTIKDNGTFSCAVKNPPDVH 125
Cdd:cd05715   86 SNLQFSDNGTYTCDVKNPPDIV 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 555290119  23 FQDAHVRGYVGEKIKLKCTFKSTSDVTDKLTIDWTYRPPSSSHTVSIFHYQSFQ-YPTTAGTFRDRISWVGNVYKGDASI 101
Cdd:cd05879    4 YTDREVYGTVGSDVTLSCSFWSSEWISDDISFTWHYQPDGSRDAISIFHYGKGQpYIDNVGPFKERIEWVGNPSRKDGSI 83

                         90       100
                 ....*....|....*....|...
gi 555290119 102 SISNPTIKDNGTFSCAVKNPPDV 124
Cdd:cd05879   84 VIHNLDYTDNGTFTCDVKNPPDI 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 555290119  32 VGEKIKLKCTFKSTSDVTDKLTIDWTYRPPSSSHTVSIFHYQSFQYPTTAGTFRDRISWVGNVYKGDASISISNPTIKDN 111
Cdd:cd20960   14 AGENVTLPCHHQLGLEDQGTLDIEWLLLPSDKVEKVVITYSGDRVYNHYYPALKGRVAFTSNDLSGDASLNISNLKLSDT 93

                         90
                 ....*....|....
gi 555290119 112 GTFSCAVKNPPDVH 125
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 555290119  22 FFQDAHVRGYVGEKIKLKCTFKSTSDVtdklTIDWTYrpPSSSHTVSIFHYQSFQYPTTAGTFRDRISWVGN-VYKGDAS 100
Cdd:cd16091    1 AVSEVIVVCLLSEDCILPCSFTPGSEV----VIHWYK--QDSDIKVHSYYYGKDQLESQDQRYRNRTSLFKDqISNGNAS 74

                         90       100
                 ....*....|....*....|
gi 555290119 101 ISISNPTIKDNGTFSCAVKN 120
Cdd:cd16091   75 LLLRRVQLQDEGRYKCYTST 94

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 555290119  27 HVRGYVGEKIKLKCTFksTSDVTDKLT-IDWTYRPPSSSHTVSIFHYQ---SFQYPttagtFRDRISWV-GNVYKGDASI 101
Cdd:cd05718    8 EVTGFLGGSVTLPCSL--TSPGTTKITqVTWMKIGAGSSQNVAVFHPQygpSVPNP-----YAERVEFLaARLGLRNATL 80

                         90
                 ....*....|....*
gi 555290119 102 SISNPTIKDNGTFSC 116
Cdd:cd05718   81 RIRNLRVEDEGNYIC 95

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290119    27 HVRGYVGEKIKLKCTFKSTSDVTdkltIDWtYRPPSSSHTvsifhyqsfqypttagtFRDRISWVGNvyKGDASISISNP 106
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPE----VTW-YKQGGKLLA-----------------ESGRFSVSRS--GSTSTLTISNV 58

                           90       100
                   ....*....|....*....|....*....
gi 555290119   107 TIKDNGTFSCAVKNPPDVHHNIpmTELTV 135
Cdd:smart00410  59 TPEDSGTYTCAATNSSGSASSG--TTLTV 85

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 555290119  28 VRGYVGEKIKLKCTFKSTSDVTDKLTIDWtyRPPSSSHTVSIFHyqsfqyPTTAGTFR--DRISWVG---NVYKGDASIS 102
Cdd:cd20989    9 VRGFLGGSVTLPCHLLPPNMVTHVSQVTW--QRHDEHGSVAVFH------PKQGPSFPesERLSFVAarlGAELRNASLA 80

                         90
                 ....*....|....
gi 555290119 103 ISNPTIKDNGTFSC 116
Cdd:cd20989   81 MFGLRVEDEGNYTC 94

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 555290119  25 DAHVRGYVGEKIKLKCTFKSTSDVTDKLTIDWTYRPPSSSHTVSIfhYQSFQYPTTAGTFRDRISWVGNVYKgDASISIS 104
Cdd:cd05886    6 NDSMSGFIGTDVVLHCSFANPLPSVKITQVTWQKSTNGSKQNVAI--YNPSMGVSVLPPYRERVTFLNPSFT-DGTIRLS 82

                         90
                 ....*....|..
gi 555290119 105 NPTIKDNGTFSC 116
Cdd:cd05886   83 RLELEDEGVYIC 94