Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31542623    30 YTSGALEAVNGTDVRLKCTFSSFaPVGDALTVTWNFRPRDGGREQFVFYYHmdPFRPMsGRFKDRVVWDGNPERYDVSIL 109
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSS-MSEASTSVYWYRQPPGKGPTFLIAYYS--NGSEE-GVKKGRFSGRGDPSNGDGSLT 76

                          90       100       110
                  ....*....|....*....|....*....|....
gi 31542623   110 LWKLQFDDNGTYTCQVkNPPDVDGLVGTIRLSVV 143
Cdd:pfam07686  77 IQNLTLSDSGTYTCAV-IPSGEGVFGKGTRLTVL 109

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 31542623  27 VEIYTSGALEAVNGTDVRLKCTFSSFAPVGDALTVTWNFRPRDGGREQFVFYYH-MDPFRPMSGRFKDRVVWDGNPERYD 105
Cdd:cd05715   1 MEVYTPRELNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGNTTESMFHYSkGKPYILKVGRFKDRVSWAGNPSKKD 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 31542623 106 VSILLWKLQFDDNGTYTCQVKNPPDVDGLVGTIRLSV 142
Cdd:cd05715  81 ASIVISNLQFSDNGTYTCDVKNPPDIVGGHGEIRLYV 117

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31542623    30 YTSGALEAVNGTDVRLKCTFSSFaPVGDALTVTWNFRPRDGGREQFVFYYHmdPFRPMsGRFKDRVVWDGNPERYDVSIL 109
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSS-MSEASTSVYWYRQPPGKGPTFLIAYYS--NGSEE-GVKKGRFSGRGDPSNGDGSLT 76

                          90       100       110
                  ....*....|....*....|....*....|....
gi 31542623   110 LWKLQFDDNGTYTCQVkNPPDVDGLVGTIRLSVV 143
Cdd:pfam07686  77 IQNLTLSDSGTYTCAV-IPSGEGVFGKGTRLTVL 109

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 31542623  34 ALEAVNGTDVRLKCTFSSFAPVGDALTVTWNFRPRDGGREQFVFYYHMDPFRPMSGRFKDRVVWDGNPERYDVSILLWKL 113
Cdd:cd20960   9 EIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDKVEKVVITYSGDRVYNHYYPALKGRVAFTSNDLSGDASLNISNL 88

                        90
                ....*....|....*...
gi 31542623 114 QFDDNGTYTCQVKNPPDV 131
Cdd:cd20960  89 KLSDTGTYQCKVKKAPGY 106

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 31542623  40 GTDVRLKCTFSSFAPVGdalTVTWnFRPRDGGREQFVFYYHMDpFRPMSGRFKDRVVWDGNPERYdvSILLWK-LQFDDN 118
Cdd:cd00099  13 GESVTLSCEVSSSFSST---YIYW-YRQKPGQGPEFLIYLSSS-KGKTKGGVPGRFSGSRDGTSS--FSLTISnLQPEDS 85

                        90       100
                ....*....|....*....|....*..
gi 31542623 119 GTYTCQVKNPPDVDGLV---GTiRLSV 142
Cdd:cd00099  86 GTYYCAVSESGGTDKLTfgsGT-RLTV 111

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 31542623  40 GTDVRLKCTFSSFAPVGDALTVTWnfRPRDGGREQFVFYYHMDPFRPMSGRFKDRVVWDgNPERYDVSILLWKLQFDDNG 119
Cdd:cd05886  14 GTDVVLHCSFANPLPSVKITQVTW--QKSTNGSKQNVAIYNPSMGVSVLPPYRERVTFL-NPSFTDGTIRLSRLELEDEG 90

                        90
                ....*....|
gi 31542623 120 TYTCQVKNPP 129
Cdd:cd05886  91 VYICEFATFP 100

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31542623    40 GTDVRLKCTFSSFAPvgdALTVTWNfrpRDGGREQFVFYYHmdpfrpmsgrfkdrvvwDGNPERYDVSILLWKLQFDDNG 119
Cdd:pfam00047  11 GDSATLTCSASTGSP---GPDVTWS---KEGGTLIESLKVK-----------------HDNGRTTQSSLLISNVTKEDAG 67

                          90
                  ....*....|...
gi 31542623   120 TYTCQVKNPPDVD 132
Cdd:pfam00047  68 TYTCVVNNPGGSA 80

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 31542623  37 AVNGTDVRLKCTF--SSFAPVGDaltVTWnFRPRDGGREQFVFYYHMDPFRPMSGRFKDRVVWDGNPERYDVSILLWKLQ 114
Cdd:cd05888   5 VVLGQDAKLPCFYrgDSGEQVGQ---VAW-ARVDAGEGAQEIALLHSKYGLHVFPAYEGRVEQPPPPRPADGSVLLRNAV 80

                        90
                ....*....|....*
gi 31542623 115 FDDNGTYTCQVKNPP 129
Cdd:cd05888  81 QADEGEYECRVSTFP 95

First Ig-like domain of Junctional adhesion molecule-1 (JAM1)and similar domains; a member of the V-set of IgSF domains; The members here are composed of the first Ig-like domain of Junctional Adhesion Molecule-1 (JAM1)and similar domains. JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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. The first Ig-like domain of JAM1 is a member of the V-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C'-C" in the other.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31542623  37 AVNGTDVRLKCTFSSFApvgDALTVTWNFRPRDggrEQFVFYYHMDpfrpMSGRFKDRVVWDGnperydVSILLWKLQFD 116
Cdd:cd20946  11 VVENQEVILSCKTPKKT---SSPRVEWKKLQRD---VTFVVFQNNK----IQGDYKGRAEILG------TNITIKNVTRS 74

                        90
                ....*....|....
gi 31542623 117 DNGTYTCQVKNPPD 130
Cdd:cd20946  75 DSGKYRCEVSARSD 88

Immunoglobulin Variable (IgV) domain of B7-H3, a member of the B7 family of immune checkpoint molecules; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H3 also known as CD276), a member of the B7 family of immune checkpoint molecules. B7-H3 is an important immune checkpoint member of the B7 family and shares homology with other B7 ligands such as programmed death ligand 1 (PD-L1). The B7 family molecules interact with CD28 on T-cells to provide co-stimulatory signals that regulate T-cell activation and T-helper cell differentiation. Although B7-H3 has been shown to have both co-stimulatory and co-inhibitory effects on T-cell responses, the most current studies describe B7-H3 as a T cell inhibitor that promotes tumor aggressiveness and proliferation. Moreover, B7-H3 is highly overexpressed on a wide range of human solid cancers and promotes tumor growth, metastasis, and drug resistance. Thus, B7-H3 expression in tumors often correlates with both negative prognosis and poor clinical outcome in cancer patients. B7-H3 protein contains a predicted signal peptide, V- and C-like Ig domains (IgV and IgC), a transmembrane region, and an intracellular tail.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31542623  40 GTDVRLKCTFS---SFAPvgDALTVTWNFRprDGGREQFVFYYHMDPFRPMSGRFKDRV------VWDGNperydVSILL 110
Cdd:cd20934  12 GTDATLRCSFSpepGFSL--AQLSVFWQLT--DTKQLVHSFTESQDQGRDQGSAYANRTalfpdlLAQGN-----ASLRL 82

                        90
                ....*....|....*.
gi 31542623 111 WKLQFDDNGTYTCQVK 126
Cdd:cd20934  83 QRVRVADEGSYTCFVS 98