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 67906204  30 MEVTAPTTLSVLNGSDTRLPCTFNSCYTVnHKQFSLNWTYQECN-NCTEEMFLQFRMKIINLKLERFGDRVEFSGNPSKY 108
Cdd:cd05715   1 MEVYTPRELNVLNGSDVRLTCTFTSCYTV-GDAFSVTWTYQPEGgNTTESMFHYSKGKPYILKVGRFKDRVSWAGNPSKK 79

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 67906204 109 DVSVTLKNVQLEDEGIYNCYITNPPDRHRGHGKIYLQV 146
Cdd:cd05715  80 DASIVISNLQFSDNGTYTCDVKNPPDIVGGHGEIRLYV 117

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 67906204  30 MEVTAPTTLSVLNGSDTRLPCTFNSCYTVnHKQFSLNWTYQECN-NCTEEMFLQFRMKIINLKLERFGDRVEFSGNPSKY 108
Cdd:cd05715   1 MEVYTPRELNVLNGSDVRLTCTFTSCYTV-GDAFSVTWTYQPEGgNTTESMFHYSKGKPYILKVGRFKDRVSWAGNPSKK 79

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 67906204 109 DVSVTLKNVQLEDEGIYNCYITNPPDRHRGHGKIYLQV 146
Cdd:cd05715  80 DASIVISNLQFSDNGTYTCDVKNPPDIVGGHGEIRLYV 117

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67906204     47 RLPCTF----NSCYTVNhkqfslnWTYQECNNCTEeMFLQFRMKIINLKLERFGDRVEFSGNPSKYDVSVTLKNVQLEDE 122
Cdd:smart00406   3 TLSCKFsgstFSSYYVS-------WVRQPPGKGLE-WLGYIGSNGSSYYQESYKGRFTISKDTSKNDVSLTISNLRVEDT 74

                   ....*
gi 67906204    123 GIYNC 127
Cdd:smart00406  75 GTYYC 79

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 67906204  30 MEVTAPTTLSVLNGSDTRLPCTFNSCYTVnHKQFSLNWTYQECN-NCTEEMFLQFRMKIINLKLERFGDRVEFSGNPSKY 108
Cdd:cd05715   1 MEVYTPRELNVLNGSDVRLTCTFTSCYTV-GDAFSVTWTYQPEGgNTTESMFHYSKGKPYILKVGRFKDRVSWAGNPSKK 79

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 67906204 109 DVSVTLKNVQLEDEGIYNCYITNPPDRHRGHGKIYLQV 146
Cdd:cd05715  80 DASIVISNLQFSDNGTYTCDVKNPPDIVGGHGEIRLYV 117

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67906204  30 MEVTAPTTLSVLNGSDTRLPCTFNSCYTVNhKQFSLNWTYQECNNCTEEMFLQFRMKIINLKLERFGDRVEFSGNPSKYD 109
Cdd:cd05880   1 IEVYTSKEVEAVNGTDVRLKCTFSSSAPIG-DTLVITWNFRPLDGGREESVFYYHKRPYPPPDGRFKGRVVWDGNIMRRD 79

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 67906204 110 VSVTLKNVQLEDEGIYNCYITNPPDRHRGHGKIYLQV 146
Cdd:cd05880  80 ASILIWQLQPTDNGTYTCQVKNPPDVHGPIGEIRLRV 116

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67906204     47 RLPCTF----NSCYTVNhkqfslnWTYQECNNCTEeMFLQFRMKIINLKLERFGDRVEFSGNPSKYDVSVTLKNVQLEDE 122
Cdd:smart00406   3 TLSCKFsgstFSSYYVS-------WVRQPPGKGLE-WLGYIGSNGSSYYQESYKGRFTISKDTSKNDVSLTISNLRVEDT 74

                   ....*
gi 67906204    123 GIYNC 127
Cdd:smart00406  75 GTYYC 79

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 67906204  40 VLNGSDTRLPCTFNSCYTVNHKQFSLNW----TYQECNNCTEEMFLQFRMKiinlklERFGDRVE-FSGNPSKYDVSVTL 114
Cdd:cd20934   9 ALVGTDATLRCSFSPEPGFSLAQLSVFWqltdTKQLVHSFTESQDQGRDQG------SAYANRTAlFPDLLAQGNASLRL 82

                        90
                ....*....|....*
gi 67906204 115 KNVQLEDEGIYNCYI 129
Cdd:cd20934  83 QRVRVADEGSYTCFV 97

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 67906204  43 GSDTRLPCTF-NSCYTVNHKQFslnwTYQECNNCTEEMFLQFRMKIINLKLERFGDRVEFSgNPSKYDVSVTLKNVQLED 121
Cdd:cd05886  14 GTDVVLHCSFaNPLPSVKITQV----TWQKSTNGSKQNVAIYNPSMGVSVLPPYRERVTFL-NPSFTDGTIRLSRLELED 88

                        90
                ....*....|....*.
gi 67906204 122 EGIYNCYITNPPDRHR 137
Cdd:cd05886  89 EGVYICEFATFPTGNR 104

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 67906204  38 LSVLNGSDTRLPCTFNSCYTVnhkqfSLNWTYQECNNCTEEMFLQfrMKIINLKLERFGDRVE-FSGNPSKYDVSVTLKN 116
Cdd:cd16091   7 VVCLLSEDCILPCSFTPGSEV-----VIHWYKQDSDIKVHSYYYG--KDQLESQDQRYRNRTSlFKDQISNGNASLLLRR 79

                        90
                ....*....|....*
gi 67906204 117 VQLEDEGIYNCYITN 131
Cdd:cd16091  80 VQLQDEGRYKCYTST 94

Immunoglobulin variable (IgV)-like domain in complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the immunoglobulin variable (IgV) region of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also known as Z39Ig and V-set and Ig domain-containing 4 (VSIG4) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. Like all members of this family, the CRIg domain contains two beta-sheets: one composed of strands A', G, F, C, C' and C", and the other of strands B, E and D. The complement system is an important part of the innate immune system and is required for removal of pathogens from the bloodstream. After exposure to pathogens, the third component of the complement system, C3, is cleaved to C3b which, after recruitment of factor B, initiates formation of the alternative pathway convertases. CRIg, a complement receptor expressed on macrophages, binds to C3b and iC3b mediating phagocytosis of the particles. It is also a potent inhibitor of the alternative pathway convertases and a negative regulator of T cell activation. 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, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67906204  32 VTAPTTLSVLNGSDTRLPCTFN--SCYTvnhkQFSLNWTYQECNNCTEeMFLQfRMKIINLKLERFGDRVEFSGNPSKyD 109
Cdd:cd16089   3 LEGPESITGPWKGSVNLPCTYVpeEGYT----QVLVKWLVQRDSDPVT-IFLR-DSSGDHIQQAKYRGRLEVSKDTPG-D 75

                        90       100
                ....*....|....*....|.
gi 67906204 110 VSVTLKNVQLEDEGIYNCYIT 130
Cdd:cd16089  76 VSLQLDTLEMDDRGHYTCQVT 96

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 67906204  35 PTTLSVLNGSDTRLPCTFNSCYTVNhkqfSLNWtYQECNNCTEEmFLqFRMKIINLKL-ERFGDRVEFSGNPSKyDVSVT 113
Cdd:cd00099   5 PRSLSVQEGESVTLSCEVSSSFSST----YIYW-YRQKPGQGPE-FL-IYLSSSKGKTkGGVPGRFSGSRDGTS-SFSLT 76

                        90
                ....*....|....
gi 67906204 114 LKNVQLEDEGIYNC 127
Cdd:cd00099  77 ISNLQPEDSGTYYC 90

Immunoglobulin Variable (IgV) domain at the N-terminus of CD33 and related Siglecs (sialic acid-binding Ig-like lectins); The members here are composed of the immunoglobulin (Ig) domain at the N-terminus of Cluster of Differentiation (CD) 33 and related Siglecs (sialic acid-binding Ig-like lectins). Siglec refers to a structurally related protein family that specifically recognizes sialic acid in oligosaccharide chains of glycoproteins and glycolipids. Siglecs are type I transmembrane proteins, organized as an extracellular module composed of Ig-like domains, an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains, followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG, the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11.

                        10        20        30
                ....*....|....*....|....*....|....
gi 67906204  93 ERFGDRVEFSGNPSKYDVSVTLKNVQLEDEGIYN 126
Cdd:cd05712  63 ESTQGRFRLLGDPGKKNCSLSISDARPEDSGKYF 96