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 971374752  24 EEETITGLFSKDVILPCPFSPGNDEVIHWNKENKN--VHSYYKQKDQLKDQHPDYRNRTHLFLQNIALGNASLKLSNVTL 101
Cdd:cd16091    3 SEVIVVCLLSEDCILPCSFTPGSEVVIHWYKQDSDikVHSYYYGKDQLESQDQRYRNRTSLFKDQISNGNASLLLRRVQL 82

                         90       100
                 ....*....|....*....|....*
gi 971374752 102 SDEGLYQCYVGTEKAKTEVDVMLQV 126
Cdd:cd16091   83 QDEGRYKCYTSTIIGNQESFVNLKV 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 971374752  24 EEETITGLFSKDVILPCPFSPGNDEVIHWNKENKN--VHSYYKQKDQLKDQHPDYRNRTHLFLQNIALGNASLKLSNVTL 101
Cdd:cd16091    3 SEVIVVCLLSEDCILPCSFTPGSEVVIHWYKQDSDikVHSYYYGKDQLESQDQRYRNRTSLFKDQISNGNASLLLRRVQL 82

                         90       100
                 ....*....|....*....|....*
gi 971374752 102 SDEGLYQCYVGTEKAKTEVDVMLQV 126
Cdd:cd16091   83 QDEGRYKCYTSTIIGNQESFVNLKV 107

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971374752    35 DVILPCPFSPGNDEVIHWnkenknvhsyYKQKDQLkdqhPDYRNRTHLFLQNialGNASLKLSNVTLSDEGLYQCYVGTE 114
Cdd:smart00410  11 SVTLSCEASGSPPPEVTW----------YKQGGKL----LAESGRFSVSRSG---STSTLTISNVTPEDSGTYTCAATNS 73

                           90
                   ....*....|..
gi 971374752   115 KAKTEVDVMLQV 126
Cdd:smart00410  74 SGSASSGTTLTV 85

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 971374752  217 LSKAEGSSTAISCEHSNiaLHAEDLTVV-W-RLNKNAAISVL---ASFNGTFQIYQPRVQI----NQQNFSLSISDLNVD 287
Cdd:pfam07686   6 VTVALGGSVTLPCTYSS--SMSEASTSVyWyRQPPGKGPTFLiayYSNGSEEGVKKGRFSGrgdpSNGDGSLTIQNLTLS 83

                          90       100
                  ....*....|....*....|....*.
gi 971374752  288 DSGDYVCNISTP------HYTRLTVT 307
Cdd:pfam07686  84 DSGTYTCAVIPSgegvfgKGTRLTVL 109

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 971374752  24 EEETITGLFSKDVILPCPFSPGNDEVIHWNKENKN--VHSYYKQKDQLKDQHPDYRNRTHLFLQNIALGNASLKLSNVTL 101
Cdd:cd16091    3 SEVIVVCLLSEDCILPCSFTPGSEVVIHWYKQDSDikVHSYYYGKDQLESQDQRYRNRTSLFKDQISNGNASLLLRRVQL 82

                         90       100
                 ....*....|....*....|....*
gi 971374752 102 SDEGLYQCYVGTEKAKTEVDVMLQV 126
Cdd:cd16091   83 QDEGRYKCYTSTIIGNQESFVNLKV 107

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971374752  28 ITGLFSKDVILPCPFSP----GNDEVIhW--NKENKNVHSYYKQKDQLKDQHPDYRNRTHLFLQNIALGNASLKLSNVTL 101
Cdd:cd05713   10 ILALVGEDAELPCHLSPkmsaEHMEVR-WfrSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVALRIHNVRP 88

                         90       100
                 ....*....|....*....|....*
gi 971374752 102 SDEGLYQCYVGTEKAKTEVDVMLQV 126
Cdd:cd05713   89 SDEGQYTCFFRSGSFYEEATLELKV 113

Immunoglobulin Variable (IgV) domain of Programmed death ligand 1 (PD-L1); The members here are composed of the immunoglobulin variable (IgV) domain of Programmed death ligand 1 (PD-L1; also known as Cluster of Differentiation 274 (CD274)). PD-L1 is a cell-surface ligand that competes with PD-L2 for binding to the immunosuppressive receptor programmed death-1 (PD-1). PD-1 is a member of the B7 family that plays an important role in negatively regulating immune responses upon interaction with its two ligands, PD-L1 or PD-L2. Like PD-L2, PD-L1 interacts with PD-1 and suppresses T cell proliferation and cytokine production. The PD-1 receptor is expressed on the surface of activated T cells, while PD-L1 is expressed on cancer cells. When PD-1 and PD-L1 bind together, they form a molecular shield protecting tumor cells from being destroyed by the immune system. Thus, inhibiting the binding of PD-L1 to PD-1 with an antibody leads to killing of tumor cells by T cells. PD-1 inhibitors (such as Pembrolizumab, Nivolumab, and Cemiplimab) and PD-L1 inhibitors (such as Atezolizumab, Avelumab, and Durvalumab ) are an emerging class of immunotherapy that stimulate lymphocytes against tumor cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971374752  32 FSKDVILPCPFsPGNDE------VIHWNKENKNVHSYYKQKDQLKDQHPDYRNRTHLFLQNIALGNASLKLSNVTLSDEG 105
Cdd:cd20947   12 YGSNMTIECKF-PVEKQldlaalIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAG 90

                 ....*.
gi 971374752 106 LYQCYV 111
Cdd:cd20947   91 VYRCMI 96

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 971374752   24 EEETITGLFSKDVILPCPFSPGNDE---VIHWNKEN-----KNVHSYYKQKDQlkdqHPDYRNRTHLfLQNIALGNASLK 95
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSSSMSEastSVYWYRQPpgkgpTFLIAYYSNGSE----EGVKKGRFSG-RGDPSNGDGSLT 76

                          90
                  ....*....|....*...
gi 971374752   96 LSNVTLSDEGLYQCYVGT 113
Cdd:pfam07686  77 IQNLTLSDSGTYTCAVIP 94

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 971374752  20 WGSREEETITGLFSKDVILPCPFSPGNDEV----IHW-----NKENKNVHSYYKQKdQLKDQHPDYRNRTHlFLQNIALG 90
Cdd:cd20960    2 LITSAQTEIKKVAGENVTLPCHHQLGLEDQgtldIEWlllpsDKVEKVVITYSGDR-VYNHYYPALKGRVA-FTSNDLSG 79

                         90       100
                 ....*....|....*....|.
gi 971374752  91 NASLKLSNVTLSDEGLYQCYV 111
Cdd:cd20960   80 DASLNISNLKLSDTGTYQCKV 100

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 971374752  25 EETITGLFSKDVILPCPF-SPGNDEV--IHWNKENKNVH---SYYKQKDQLKDQHPdYRNRTHLFLQNIALGNASLKLSN 98
Cdd:cd05718    6 PTEVTGFLGGSVTLPCSLtSPGTTKItqVTWMKIGAGSSqnvAVFHPQYGPSVPNP-YAERVEFLAARLGLRNATLRIRN 84

                         90
                 ....*....|....*
gi 971374752  99 VTLSDEGLYQCYVGT 113
Cdd:cd05718   85 LRVEDEGNYICEFAT 99

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 971374752  36 VILPCPFSPGNDEVIHWNKENKNVHSYYKQKDQLKDqhpdyrnrthlflqnialGNASLKLSNVTLSDEGLYQCYV 111
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSEL------------------GNGTLTISNVTLEDSGTYTCVA 58

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 971374752  26 ETITGLFSKDVILPCPFSPG-----NDEVIHWNKEN-KNVHSYY-KQKDQLKDQHPDYRNRTHLFLQNIALGNASLKLSN 98
Cdd:cd20935    1 KEVRAMVGSDVELSCICPEGsrfdlNDLYVYWQISEsETVVTYHlPQNSSLENVDSHYRNRALLSLDSMKQGDFSLRLFN 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 971374752  99 VTLSDEGLYQCYVGTEkaKTEVDVMLQVQV 128
Cdd:cd20935   81 VTPQDEQKFHCLVFSQ--SLELQKVLEVVV 108

Immunoglobulin variable domain (IgV) in Cluster of Differentiation (CD) 80; The members here are composed of the immunoglobulin variable region (IgV) in the Cluster of Differentiation (CD) 80). Glycoproteins B7-1 (also known as cluster of differentiation (CD) 80) and B7-2 (also known as CD86) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (also known as cluster of differentiation 152/CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. CD80 contains two Ig-like domains, an amino-terminal immunoglobulin variable (IgV)-like domain characteristic of adhesion molecules and a membrane proximal immunoglobulin constant (IgC)-like domain similar to the constant domains of antigen receptors. Members of the Ig family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and Major Histocompatibility Complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, and the IgC domain is involved in oligomerization and molecular interactions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971374752  36 VILPCPFSPGNDEV----IHWNKENKNVHSYYKQKdqlKDQHPDYRNRTHLFLQNialgNASLKLSNVTLSDEGLYQCYV 111
Cdd:cd16086   12 ALLSCDYNVSVDELaqvrIYWQKDDKMVLTIISGD---VKVWPEYKNRTLFDITN----NLSIVILALRLSDRGTYTCVV 84

                         90       100
                 ....*....|....*....|
gi 971374752 112 -----GTEKAKTEVDVMLQV 126
Cdd:cd16086   85 qkkerGAYKREHLASVTLSV 104

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 971374752  28 ITGLFSKDVILPCPFSPGNDEV----IHWNK--ENKNVHSYYKQKDqlkdqhPDYRNRTHL-FL---QNIALGNASLKLS 97
Cdd:cd20989    9 VRGFLGGSVTLPCHLLPPNMVThvsqVTWQRhdEHGSVAVFHPKQG------PSFPESERLsFVaarLGAELRNASLAMF 82

                         90       100       110
                 ....*....|....*....|....*....|
gi 971374752  98 NVTLSDEGLYQCYVGT-EKAKTEVDVMLQV 126
Cdd:cd20989   83 GLRVEDEGNYTCEFATfPQGSRSGDTWLRV 112

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 971374752  36 VILPCPFSP-GNDEVIHWNKENKNVHSYYKQKDQLKDqhpDYRNRTHLFlqnialgNASLKLSNVTLSDEGLYQCYVGTE 114
Cdd:cd20946   17 VILSCKTPKkTSSPRVEWKKLQRDVTFVVFQNNKIQG---DYKGRAEIL-------GTNITIKNVTRSDSGKYRCEVSAR 86

                         90
                 ....*....|....*.
gi 971374752 115 KAKT---EVDVMLQVQ 127
Cdd:cd20946   87 SDGQnlgEVTVTLEVL 102

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 971374752  26 ETITGLFSKDVILPCPFSPGNDEVIH---WNKENKNVHSYYKQKDQLKD--QHPDYRNRTHLFLQniALGNASLKLSNVT 100
Cdd:cd16089    7 ESITGPWKGSVNLPCTYVPEEGYTQVlvkWLVQRDSDPVTIFLRDSSGDhiQQAKYRGRLEVSKD--TPGDVSLQLDTLE 84

                         90       100       110
                 ....*....|....*....|....*....|..
gi 971374752 101 LSDEGLYQCYV-----GTEKAKTEVDVMLQVQ 127
Cdd:cd16089   85 MDDRGHYTCQVtwqtpDGNLIVREKTTELRVQ 116

First (N-terminal) immunoglobulin (Ig)-like domain of the nectin-like molecules; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 (CADM3)), Necl-2 (CADM1), Necl-3 (CADM2), and similar proteins. At least five nectin-like molecules have been identified (Necl-1 to Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1, Necl-2, and Necl-3 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue, and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Necl-3 accumulates in central and peripheral nervous system tissue and has been shown to selectively interact with oligodendrocytes. This group also contains Class-I MHC-restricted T-cell-associated molecule (CRTAM), whose expression pattern is consistent with its expression in Class-I MHC-restricted T-cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971374752  26 ETITGLFSKDVILPCPFSPGNDEVIHWNKENKNVhSYYKQKDQLKDqhpdyrNRTHLFlqNIALGNASLKLSNVTLSDEG 105
Cdd:cd05717    4 QDVTVVEGETLTLKCQVSLRDDSSLQWLNPNGQT-IYFNDKRALRD------SRYQLL--NHSASELSISVSNVTLSDEG 74

                         90
                 ....*....|...
gi 971374752 106 LYQCYVGTEKAKT 118
Cdd:cd05717   75 VYTCLHYTDPVST 87

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 971374752   27 TITGLFSKDVILPCPFSPGNDEV-IHWNKENKNVHsyykqkdqLKDQHPDYRNRThlflqnialGNASLKLSNVTLSDEG 105
Cdd:pfam00047   5 TVTVLEGDSATLTCSASTGSPGPdVTWSKEGGTLI--------ESLKVKHDNGRT---------TQSSLLISNVTKEDAG 67

                  ....*.
gi 971374752  106 LYQCYV 111
Cdd:pfam00047  68 TYTCVV 73

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 971374752  212 SMQDQLSKAEGSSTAISCEHSNIAlhaEDLTVVWRLNKNAAISVLASFNGTFQIYQprvqinqqnFSLSISDLNVDDSGD 291
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGS---PGPDVTWSKEGGTLIESLKVKHDNGRTTQ---------SSLLISNVTKEDAGT 68

                  ....*....
gi 971374752  292 YVCNISTPH 300
Cdd:pfam00047  69 YTCVVNNPG 77

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 971374752 220 AEGSSTAISCEHSNIALHAEDLTVVWR---LNKNAAISVLASFNGtfQIYQP-------RVQ----INQQNFSLSISDLN 285
Cdd:cd05715   12 LNGSDVRLTCTFTSCYTVGDAFSVTWTyqpEGGNTTESMFHYSKG--KPYILkvgrfkdRVSwagnPSKKDASIVISNLQ 89

                         90
                 ....*....|....
gi 971374752 286 VDDSGDYVCNISTP 299
Cdd:cd05715   90 FSDNGTYTCDVKNP 103

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
                 ....*....|....*....|....*....|....*...
gi 971374752 275 QNFSLSISDLNVDDSGDYVCNIST-PHYTRLTVTTLQV 311
Cdd:cd20989   75 RNASLAMFGLRVEDEGNYTCEFATfPQGSRSGDTWLRV 112