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 308736968 109 HVEVKGYEDGGIHLECRSTGWYPQP-QIQWSNAKGENIPAVEAP-VVADGVGLYEVAASVIMRGGSGEGVSCIIRNSLLG 186
Cdd:cd21029    7 LSSRPSPGDGHLQLSCHVTGFYPRPiEVTWLRDGQEQMDGTQSGgILPNHDGTYQLRKTLDIAPGEGAGYSCRVDHSSLK 86

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 308736968    2 VGEDADLPCHLFPTMSAETMELKWV----SSSLRQVVNVYADGKEVEdrqsaPYRGRTSILRDgITAGKAALRIHNVTAS 77
Cdd:pfam07686  10 LGGSVTLPCTYSSSMSEASTSVYWYrqppGKGPTFLIAYYSNGSEEG-----VKKGRFSGRGD-PSNGDGSLTIQNLTLS 83

                          90       100
                  ....*....|....*....|....*
gi 308736968   78 DSGKYLCY-FQDGDFYEKALVELKV 101
Cdd:pfam07686  84 DSGTYTCAvIPSGEGVFGKGTRLTV 108

Immunoglobulin domain of Cluster of Differentiation (CD) 1; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin domain of Cluster of Differentiation (CD) 1. CD1 family of transmembrane glycoproteins, are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. They mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. The human genome contains five CD1 family genes (CD1a, CD1b, CD1c, CD1d, and CD1e) organized in a cluster on chromosome 1. The CD1 family members are thought to differ in their cellular localization and specificity for particular lipid ligands. CD1a localizes to the plasma membrane and to recycling vesicles of the early endocytic system. Alternative splicing results in multiple transcript variants. Immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I alpha chain. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells. C1-set Ig domains have one beta sheet that is formed by strands A, B, E, and D and the other strands by G, F, C, and C'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308736968 109 HVEVKGYEDGGIHLECRSTGWYPQP-QIQWSNAKGENIPAVEAP-VVADGVGLYEVAASVIMRGGSGEGVSCIIRNSLLG 186
Cdd:cd21029    7 LSSRPSPGDGHLQLSCHVTGFYPRPiEVTWLRDGQEQMDGTQSGgILPNHDGTYQLRKTLDIAPGEGAGYSCRVDHSSLK 86

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 308736968   2 VGEDADLPCHLFPTMSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAALRIHNVTASDSGK 81
Cdd:cd20984   11 IGEDGILSCTFTPDIKLSDIVIQWLKEGDSGLVHEFKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRLKNVQLTDAGT 90

                 ....
gi 308736968  82 YLCY 85
Cdd:cd20984   91 YLCI 94

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 308736968   1 MVGEDADLPCHLFPT--MSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAALRIHNVTASD 78
Cdd:cd20934   10 LVGTDATLRCSFSPEpgFSLAQLSVFWQLTDTKQLVHSFTESQDQGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVAD 89

                         90       100
                 ....*....|....*....|....*
gi 308736968  79 SGKYLCYFQDGDFyEKALVELKVAA 103
Cdd:cd20934   90 EGSYTCFVSVQDF-GSAAVSLQVAA 113

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308736968     5 DADLPCHLFPTmSAETMELKWV-SSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITaGKAALRIHNVTASDSGKYL 83
Cdd:smart00406   1 SVTLSCKFSGS-TFSSYYVSWVrQPPGKGLEWLGYIGSNGSSYYQESYKGRFTISKDTSK-NDVSLTISNLRVEDTGTYY 78

                   .
gi 308736968    84 C 84
Cdd:smart00406  79 C 79

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 308736968   2 VGEDADLPCHLfpTMSAE---TMELKWV---SSSLRQVVNVYADGKeVEDRQSAPYRGRTSILRDGItAGKAALRIHNVT 75
Cdd:cd20960   14 AGENVTLPCHH--QLGLEdqgTLDIEWLllpSDKVEKVVITYSGDR-VYNHYYPALKGRVAFTSNDL-SGDASLNISNLK 89

                         90       100
                 ....*....|....*....|....*
gi 308736968  76 ASDSGKYLCYFQDGDFYEKALVELK 100
Cdd:cd20960   90 LSDTGTYQCKVKKAPGYAWSKITLI 114

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        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308736968   2 VGEDADLPCHLFPTMSAETMELKWVSSSLR--QVVNV--YADGKEVEDRQSAPYRgrtsiLRDGITAGKAALRIHNVTAS 77
Cdd:cd20982    7 VGHNAYLPCSYTTAAPGNLVPVCWGKGACPvsYCGNVllRTDERDVTYQKSSRYQ-----LKGDFSKGDVSLTIENVTLA 81

                         90       100
                 ....*....|....*....|....*.
gi 308736968  78 DSGKYLCYFQ-DGDFY-EKALVELKV 101
Cdd:cd20982   82 DSGIYCCRIQiPGIMNdEKFNLKLVI 107

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 308736968   3 GEDADLPCHLFPTMSAETMELKW--VSSSLRQVVNVYADGKEVEDRqsAPYRGRTSILRDGITAGKAALRIHNVTASDSG 80
Cdd:cd05718   14 GGSVTLPCSLTSPGTTKITQVTWmkIGAGSSQNVAVFHPQYGPSVP--NPYAERVEFLAARLGLRNATLRIRNLRVEDEG 91

                 ....*.
gi 308736968  81 KYLCYF 86
Cdd:cd05718   92 NYICEF 97

Immunoglobulin (Ig)-like domain of chondroitin sulfate proteoglycans (CSPGs), human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in chondroitin sulfate proteoglycans (CSPGs) and human cartilage link protein (LP). Included in this group are the CSPGs aggrecan, versican, and neurocan. In CSPGs, this Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggrecan and versican have a wide distribution in connective tissue and extracellular matrices. Neurocan is localized almost exclusively in nervous tissue. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. There is considerable evidence that HA-binding CSPGs are involved in developmental processes in the central nervous system. 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 308736968   3 GEDADLPCHLF--PTMSAETME---LKW----VSSSLRQVVNVY-ADGKEVEDRQSapYRGRTSILRDGITAGKAALRIH 72
Cdd:cd05714   12 GGNVTLPCKFYrdPTAFGSGIHkirIKWtkltSDSGYLKEVDVLvAMGNVVYHKKT--YGGRVSVPLKPGSDSDASLVIT 89

                         90       100
                 ....*....|....*....|....*....
gi 308736968  73 NVTASDSGKYLCYFQDGDFYEKALVELKV 101
Cdd:cd05714   90 DLTASDYGLYRCEVIEGIEDDQDVVALDV 118

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 308736968   5 DADLPCHLFPTMSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDgiTAGKAALRIHNVTASDSGKYLC 84
Cdd:cd16089   16 SVNLPCTYVPEEGYTQVLVKWLVQRDSDPVTIFLRDSSGDHIQQAKYRGRLEVSKD--TPGDVSLQLDTLEMDDRGHYTC 93

Immunoglobulin Variable (IgV) domain of B7-H2 (B7 homolog 2); The members here are composed of the immunoglobulin variable (IgV) domain of B7-H2 (B7 homolog 2 also known as ICOSL (inducible T cell costimulator ligand) or CD275). B7-H2 is a ligand for the T-cell-specific cell surface receptor ICOS and acts as a costimulatory signal for T-cell proliferation and cytokine secretion. The interaction of ICOS with ICOSL (B7-H2) regulates T cell activation and expansion, is involved in T cell dependent B cell activation, and T-helper cell differentiation. It is a member of the B7 family of immune regulatory proteins and shares homology with other B7 ligands, such as B7-1, B7-2, B7-H1 (PD-L1), PD-L2, and B7-H3. The extracellular domains of B7 proteins contain two Ig-like domains and all members have short cytoplasmic domains. These ligands are typically expressed on antigen presenting cells (such as macrophages, B cells and dendritic cells) and have the ability to regulate T-cell proliferation and function. Tumor cells are also capable of expressing the B7 family members in order to evade immune surveillance.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308736968   1 MVGEDADLPChLFPTMSA---ETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAALRIHNVTAS 77
Cdd:cd20935    6 MVGSDVELSC-ICPEGSRfdlNDLYVYWQISESETVVTYHLPQNSSLENVDSHYRNRALLSLDSMKQGDFSLRLFNVTPQ 84

                 ....*..
gi 308736968  78 DSGKYLC 84
Cdd:cd20935   85 DEQKFHC 91

Immunoglobulin domain of Cluster of Differentiation (CD) 1; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin domain of Cluster of Differentiation (CD) 1. CD1 family of transmembrane glycoproteins, are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. They mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. The human genome contains five CD1 family genes (CD1a, CD1b, CD1c, CD1d, and CD1e) organized in a cluster on chromosome 1. The CD1 family members are thought to differ in their cellular localization and specificity for particular lipid ligands. CD1a localizes to the plasma membrane and to recycling vesicles of the early endocytic system. Alternative splicing results in multiple transcript variants. Immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I alpha chain. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells. C1-set Ig domains have one beta sheet that is formed by strands A, B, E, and D and the other strands by G, F, C, and C'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308736968 109 HVEVKGYEDGGIHLECRSTGWYPQP-QIQWSNAKGENIPAVEAP-VVADGVGLYEVAASVIMRGGSGEGVSCIIRNSLLG 186
Cdd:cd21029    7 LSSRPSPGDGHLQLSCHVTGFYPRPiEVTWLRDGQEQMDGTQSGgILPNHDGTYQLRKTLDIAPGEGAGYSCRVDHSSLK 86

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
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 308736968  49 APYRGRTSILrdgitagKAALRIHNVTASDSGKYLCYF---QDGDFYEKALVELKV 101
Cdd:cd20946   53 GDYKGRAEIL-------GTNITIKNVTRSDSGKYRCEVsarSDGQNLGEVTVTLEV 101