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 37221189  31 FSVLGPSGPILAMVGEDADLPCHLFPTMSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAA 110
Cdd:cd05713   1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 37221189 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 37221189  31 FSVLGPSGPILAMVGEDADLPCHLFPTMSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAA 110
Cdd:cd05713   1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 37221189 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 37221189     37 SGPILAMVGEDADLPCHLFptmSAETMELKWvsssLRQvvnvyaDGKEVedrqsaPYRGRTSILRDGitaGKAALRIHNV 116
Cdd:smart00410   1 PPSVTVKEGESVTLSCEAS---GSPPPEVTW----YKQ------GGKLL------AESGRFSVSRSG---STSTLTISNV 58

                           90       100
                   ....*....|....*....|....*..
gi 37221189    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 37221189  31 FSVLGPSGPILAMVGEDADLPCHLFPTMSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAA 110
Cdd:cd05713   1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 37221189 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 37221189  36 PSGPILAMVGEDADLPCHLFPT--MSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAALRI 113
Cdd:cd20934   3 PEDPVVALVGTDATLRCSFSPEpgFSLAQLSVFWQLTDTKQLVHSFTESQDQGRDQGSAYANRTALFPDLLAQGNASLRL 82

                        90       100       110
                ....*....|....*....|....*....|..
gi 37221189 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 37221189    36 PSGPILAMVGEDADLPCHLFPTMSAETMELKWV----SSSLRQVVNVYADGKEVEdrqsaPYRGRTSILRDgITAGKAAL 111
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSSSMSEASTSVYWYrqppGKGPTFLIAYYSNGSEEG-----VKKGRFSGRGD-PSNGDGSL 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 37221189   112 RIHNVTASDSGKYLCY-FQDGDFYEKALVELKV 143
Cdd:pfam07686  76 TIQNLTLSDSGTYTCAvIPSGEGVFGKGTRLTV 108

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37221189     47 DADLPCHLFPTmSAETMELKWV-SSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITaGKAALRIHNVTASDSGKYL 125
Cdd:smart00406   1 SVTLSCKFSGS-TFSSYYVSWVrQPPGKGLEWLGYIGSNGSSYYQESYKGRFTISKDTSK-NDVSLTISNLRVEDTGTYY 78

                   .
gi 37221189    126 C 126
Cdd:smart00406  79 C 79

Immunoglobulin (Ig)-like domain of human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in human cartilage link protein (LP; also called hyaluronan and proteoglycan link protein). In cartilage, chondroitin-keratan sulfate proteoglycan (CSPG), aggrecan, forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. 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 37221189  36 PSGPILAMVGEDADLPCHLF--PTMSAET-MELKW--VSSSLRQVVNVY-ADGKEveDRQSAPYRGRTSILRDGitAGKA 109
Cdd:cd05877   3 VQAKVFSHRGGNVTLPCRYHyePELSAPRkIRVKWtkLEVDYAKEEDVLvAIGTR--HKSYGSYQGRVFLRRAD--DLDA 78

                        90       100       110
                ....*....|....*....|....*....|....
gi 37221189 110 ALRIHNVTASDSGKYLCYFQDGDFYEKALVELKV 143
Cdd:cd05877  79 SLVITDLRLEDYGRYRCEVIDGLEDESVVVALRL 112

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 37221189  42 AMVGEDADLPCHLFPTMSAETMELKWVSSSLR--QVVNV--YADGKEVEDRQSAPYRgrtsiLRDGITAGKAALRIHNVT 117
Cdd:cd20982   5 AEVGHNAYLPCSYTTAAPGNLVPVCWGKGACPvsYCGNVllRTDERDVTYQKSSRYQ-----LKGDFSKGDVSLTIENVT 79

                        90       100
                ....*....|....*....|....*...
gi 37221189 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 37221189  79 YADGKEVEDRQSAPYRGRTSILRDGITAGKAALRIHNVTASDSGKYLCYFQDG 131
Cdd:cd20947  47 FVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYG 99

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 37221189  42 AMVGEDADLPCHLFPTMSAETMELKW--VSSSLRQVVNVYADGKEVEDRqsAPYRGRTSILRDGITAGKAALRIHNVTAS 119
Cdd:cd05718  11 GFLGGSVTLPCSLTSPGTTKITQVTWmkIGAGSSQNVAVFHPQYGPSVP--NPYAERVEFLAARLGLRNATLRIRNLRVE 88

                ....*....
gi 37221189 120 DSGKYLCYF 128
Cdd:cd05718  89 DEGNYICEF 97

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 37221189  34 LGPSGPILAMVGEDADLPCHL--FPTM------SAETMELKWV-------SSSLRQVVNVYADGKEVEDRQSapYRGRTS 98
Cdd:cd05901   1 VRKSSRVHGSLSGSVVLPCRFstLPTLppsyniTSEFLRIKWTkiqvdknGKDHKETTVLVAQNGIIKIGQE--YMGRVS 78

                        90       100
                ....*....|....*....|....*...
gi 37221189  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 37221189  42 AMVGEDADLPChLFPTMSA---ETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAALRIHNVTA 118
Cdd:cd20935   5 AMVGSDVELSC-ICPEGSRfdlNDLYVYWQISESETVVTYHLPQNSSLENVDSHYRNRALLSLDSMKQGDFSLRLFNVTP 83

                ....*...
gi 37221189 119 SDSGKYLC 126
Cdd:cd20935  84 QDEQKFHC 91

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 37221189  44 VGEDADLPCHLF-PTMSAETMELKWVSSSLRQVVNVYADGKEVedrqSAPYRGRTSILRDGITAG--KAALRIHNVTASD 120
Cdd:cd20989  13 LGGSVTLPCHLLpPNMVTHVSQVTWQRHDEHGSVAVFHPKQGP----SFPESERLSFVAARLGAElrNASLAMFGLRVED 88

                ....*...
gi 37221189 121 SGKYLCYF 128
Cdd:cd20989  89 EGNYTCEF 96

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 37221189  46 EDADLPCHLFPTMSAETMELKWVSSSLRQVVnvYADGKevedrQSAPYRGRTSILrdgitagKAALRIHNVTASDSGKYL 125
Cdd:cd20946  15 QEVILSCKTPKKTSSPRVEWKKLQRDVTFVV--FQNNK-----IQGDYKGRAEIL-------GTNITIKNVTRSDSGKYR 80

                        90       100
                ....*....|....*....|.
gi 37221189 126 CYF---QDGDFYEKALVELKV 143
Cdd:cd20946  81 CEVsarSDGQNLGEVTVTLEV 101