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 222418660  31 FSVLGPSGPILAMVGEDADLPCHLFPTMSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAA 110
Cdd:cd05713    1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 222418660 111 LRIHNVTASDSGKYLCYFQDGDFYEKALVELKVA 144
Cdd:cd05713   81 LRIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

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 222418660  31 FSVLGPSGPILAMVGEDADLPCHLFPTMSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAA 110
Cdd:cd05713    1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 222418660 111 LRIHNVTASDSGKYLCYFQDGDFYEKALVELKVA 144
Cdd:cd05713   81 LRIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 222418660    37 SGPILAMVGEDADLPCHLFptmSAETMELKWvsssLRQvvnvyaDGKEVedrqsaPYRGRTSILRDGitaGKAALRIHNV 116
Cdd:smart00410   1 PPSVTVKEGESVTLSCEAS---GSPPPEVTW----YKQ------GGKLL------AESGRFSVSRSG---STSTLTISNV 58

                           90       100
                   ....*....|....*....|....*..
gi 222418660   117 TASDSGKYLCYFQDGDFYEKALVELKV 143
Cdd:smart00410  59 TPEDSGTYTCAATNSSGSASSGTTLTV 85

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 222418660  31 FSVLGPSGPILAMVGEDADLPCHLFPTMSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAA 110
Cdd:cd05713    1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 222418660 111 LRIHNVTASDSGKYLCYFQDGDFYEKALVELKVA 144
Cdd:cd05713   81 LRIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

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 222418660  36 PSGPILAMVGEDADLPCHLFPT--MSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAALRI 113
Cdd:cd20934    3 PEDPVVALVGTDATLRCSFSPEpgFSLAQLSVFWQLTDTKQLVHSFTESQDQGRDQGSAYANRTALFPDLLAQGNASLRL 82

                         90       100       110
                 ....*....|....*....|....*....|..
gi 222418660 114 HNVTASDSGKYLCYFQDGDFyEKALVELKVAA 145
Cdd:cd20934   83 QRVRVADEGSYTCFVSVQDF-GSAAVSLQVAA 113

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 222418660   36 PSGPILAMVGEDADLPCHLFPTMSAETMELKWV----SSSLRQVVNVYADGKEVEdrqsaPYRGRTSILRDgITAGKAAL 111
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSSSMSEASTSVYWYrqppGKGPTFLIAYYSNGSEEG-----VKKGRFSGRGD-PSNGDGSL 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 222418660  112 RIHNVTASDSGKYLCY-FQDGDFYEKALVELKV 143
Cdd:pfam07686  76 TIQNLTLSDSGTYTCAvIPSGEGVFGKGTRLTV 108

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 222418660    47 DADLPCHLFPTmSAETMELKWV-SSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITaGKAALRIHNVTASDSGKYL 125
Cdd:smart00406   1 SVTLSCKFSGS-TFSSYYVSWVrQPPGKGLEWLGYIGSNGSSYYQESYKGRFTISKDTSK-NDVSLTISNLRVEDTGTYY 78

                   .
gi 222418660   126 C 126
Cdd:smart00406  79 C 79

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 222418660  35 GPSGPILAMVGEDADLPCHLF--PTMSAETME---LKW----VSSSLRQVVNVY-ADGKEVEDRQSapYRGRTSILRDGI 104
Cdd:cd05714    2 AESAKVFSHLGGNVTLPCKFYrdPTAFGSGIHkirIKWtkltSDSGYLKEVDVLvAMGNVVYHKKT--YGGRVSVPLKPG 79

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 222418660 105 TAGKAALRIHNVTASDSGKYLCYFQDGDFYEKALVELKV 143
Cdd:cd05714   80 SDSDASLVITDLTASDYGLYRCEVIEGIEDDQDVVALDV 118

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 222418660  42 AMVGEDADLPCHLFPTMSAETMELKWVSSSLR--QVVNV--YADGKEVEDRQSAPYRgrtsiLRDGITAGKAALRIHNVT 117
Cdd:cd20982    5 AEVGHNAYLPCSYTTAAPGNLVPVCWGKGACPvsYCGNVllRTDERDVTYQKSSRYQ-----LKGDFSKGDVSLTIENVT 79

                         90       100
                 ....*....|....*....|....*...
gi 222418660 118 ASDSGKYLCYFQ-DGDFY-EKALVELKV 143
Cdd:cd20982   80 LADSGIYCCRIQiPGIMNdEKFNLKLVI 107

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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 222418660  79 YADGKEVEDRQSAPYRGRTSILRDGITAGKAALRIHNVTASDSGKYLCYFQDG 131
Cdd:cd20947   47 FVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYG 99

Immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core protein (CSPG); The members here are composed of the immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core proteins (CSPGs). Included in this group are the Ig domains of other CSPGs: 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. 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 222418660  35 GPSGPILAMVGEDADLPCHLF-------PTMSAETMELKW-----VSSSLRQVVNVYADGKEVEDRQSapYRGRTSILRD 102
Cdd:cd05878    2 PQSSPVRVLLGTSVTLPCYFIdpphpvtPSTAPLAPRIKWskvsvDGKKEKEVVLLVATEGRVRVNSA--YQGRVSLPNY 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 222418660 103 GITAGKAALRIHNVTASDSGKYLCYFQDGDFYEKALVELKV 143
Cdd:cd05878   80 PAIPSDATLEVQSLRASDSGLYRCEVMHGIEDSQDTVELVV 120

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), versican; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), versican. In CSPGs, the 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, the CSPG aggrecan (not included in this group) forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Like aggrecan, versican has a wide distribution in connective tissue and extracellular matrices. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. 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 222418660  34 LGPSGPILAMVGEDADLPCHL--FPTM------SAETMELKWV-------SSSLRQVVNVYADGKEVEDRQSapYRGRTS 98
Cdd:cd05901    1 VRKSSRVHGSLSGSVVLPCRFstLPTLppsyniTSEFLRIKWTkiqvdknGKDHKETTVLVAQNGIIKIGQE--YMGRVS 78

                         90       100
                 ....*....|....*....|....*...
gi 222418660  99 ILRDGITAGKAALRIHNVTASDSGKYLC 126
Cdd:cd05901   79 VPSHPEDQGDASLTIVKLRASDAGVYRC 106

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 222418660  42 AMVGEDADLPChLFPTMSA---ETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAALRIHNVTA 118
Cdd:cd20935    5 AMVGSDVELSC-ICPEGSRfdlNDLYVYWQISESETVVTYHLPQNSSLENVDSHYRNRALLSLDSMKQGDFSLRLFNVTP 83

                 ....*...
gi 222418660 119 SDSGKYLC 126
Cdd:cd20935   84 QDEQKFHC 91

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 222418660  47 DADLPCHLFPTMSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDgiTAGKAALRIHNVTASDSGKYLC 126
Cdd:cd16089   16 SVNLPCTYVPEEGYTQVLVKWLVQRDSDPVTIFLRDSSGDHIQQAKYRGRLEVSKD--TPGDVSLQLDTLEMDDRGHYTC 93

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 222418660  46 EDADLPCHLFPTMSAETMELKWVSSSLRQVVnvYADGKevedrQSAPYRGRTSILrdgitagKAALRIHNVTASDSGKYL 125
Cdd:cd20946   15 QEVILSCKTPKKTSSPRVEWKKLQRDVTFVV--FQNNK-----IQGDYKGRAEIL-------GTNITIKNVTRSDSGKYR 80

                         90       100
                 ....*....|....*....|.
gi 222418660 126 CYF---QDGDFYEKALVELKV 143
Cdd:cd20946   81 CEVsarSDGQNLGEVTVTLEV 101