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 1720417551 302 PKIQLHLAN---KDPLPSLVCSIAGYYPLDVGVTWIREELGGIPAQVS--GASFSSLRQSTMGTYSISSTVMADPG--PT 374
Cdd:cd05771     1 PRVRLSPKNlvkPDLPQTLSCHIAGYYPLDVDVEWLREEPGGSESQVSrdGVSLSSHRQSVDGTYSISSYLTLEPGteNR 80

                          90       100
                  ....*....|....*....|
gi 1720417551 375 GATYTCQVAHVSLEEPLTTS 394
Cdd:cd05771    81 GATYTCRVTHVSLEEPLSVS 100

Tapasin-R immunoglobulin-like domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain on Tapasin-R. Tapasin is a V-C1 (variable-constant) immunoglobulin superfamily molecule present in the endoplasmic reticulum (ER), where it links MHC class I molecules to the transporter associated with antigen processing (TAP). Tapasin-R is a tapasin-related protein that contains similar structural motifs to Tapasin, with some marked differences, especially in the V domain, transmembrane and cytoplasmic regions. The majority of Tapasin-R is located within the ER; however, there may be some expression of Tapasin-R at the cell surface. Tapasin-R lacks an obvious ER retention signal.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 302 PKIQLHLAN---KDPLPSLVCSIAGYYPLDVGVTWIREELGGIPAQVS--GASFSSLRQSTMGTYSISSTVMADPG--PT 374
Cdd:cd05771     1 PRVRLSPKNlvkPDLPQTLSCHIAGYYPLDVDVEWLREEPGGSESQVSrdGVSLSSHRQSVDGTYSISSYLTLEPGteNR 80

                          90       100
                  ....*....|....*....|
gi 1720417551 375 GATYTCQVAHVSLEEPLTTS 394
Cdd:cd05771    81 GATYTCRVTHVSLEEPLSVS 100

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 298 ILAPPKIQLHLANkdplpSLVCSIAGYYPLDVGVTWIReelGGIPAQvSGASFSSLRQSTMGTYSISS--TVMADPGPTG 375
Cdd:pfam07654   3 VFPPSPEELGKPN-----TLTCLVTGFYPPDITVTWLK---NGQEVT-EGVKTTPPSPNSDWTYQLSSylTVTPSDWESG 73

                          90
                  ....*....|..
gi 1720417551 376 ATYTCQVAHVSL 387
Cdd:pfam07654  74 DEYTCRVEHEGL 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 1720417551 202 LGSSVSLHCSFSMAPGLDLTGVEWRLQHKGSGQ--LVYSWKTGQGQAKRKGATlEPEELLRAGNASLTLPNLTLKDEGNY 279
Cdd:pfam07686  10 LGGSVTLPCTYSSSMSEASTSVYWYRQPPGKGPtfLIAYYSNGSEEGVKKGRF-SGRGDPSNGDGSLTIQNLTLSDSGTY 88

                          90
                  ....*....|
gi 1720417551 280 ICQISTSLYQ 289
Cdd:pfam07686  89 TCAVIPSGEG 98

Tapasin-R immunoglobulin-like domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain on Tapasin-R. Tapasin is a V-C1 (variable-constant) immunoglobulin superfamily molecule present in the endoplasmic reticulum (ER), where it links MHC class I molecules to the transporter associated with antigen processing (TAP). Tapasin-R is a tapasin-related protein that contains similar structural motifs to Tapasin, with some marked differences, especially in the V domain, transmembrane and cytoplasmic regions. The majority of Tapasin-R is located within the ER; however, there may be some expression of Tapasin-R at the cell surface. Tapasin-R lacks an obvious ER retention signal.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 302 PKIQLHLAN---KDPLPSLVCSIAGYYPLDVGVTWIREELGGIPAQVS--GASFSSLRQSTMGTYSISSTVMADPG--PT 374
Cdd:cd05771     1 PRVRLSPKNlvkPDLPQTLSCHIAGYYPLDVDVEWLREEPGGSESQVSrdGVSLSSHRQSVDGTYSISSYLTLEPGteNR 80

                          90       100
                  ....*....|....*....|
gi 1720417551 375 GATYTCQVAHVSLEEPLTTS 394
Cdd:cd05771    81 GATYTCRVTHVSLEEPLSVS 100

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DM; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DM. Human HLA-DM plays a critical role in antigen presentation to CD4 T cells by catalyzing the exchange of peptides bound to MHC class II molecules. Type 1 diabetes is correlated with DM activation and it is also implicated in viral infections such as herpes simplex virus, celiac disease, multiple sclerosis, other autoimmune diseases, and leukemia. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 300 APPKIQLHLA---NKDPLPSLVCSIAGYYPLDVGVTWIREelGGIPAQVSGASFSSLRqstMG--TYSISSTVMADPGPt 374
Cdd:cd21002     2 RPPSVRVAPTtpfNTREPVMLACHVWGFYPADVTITWLKN--GDPVAPHSSAPKTAQP---NGdwTYQTQVTLAVTPSP- 75

                          90
                  ....*....|....*...
gi 1720417551 375 GATYTCQVAHVSLEEPLT 392
Cdd:cd21002    76 GDTYTCSVQHASLPEPLL 93

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720417551  316 SLVCSIAGYYPLDVGVTWIReelGGIPAQvSGASFSSLRQSTMGTYSISSTV---MADPGPtGATYTCQVAHVSLEEP 390
Cdd:smart00407   3 TLVCLVSGFYPPDITVTWLR---NGQEVT-EGVSTTDPLKNSDGTYFLSSYLtvpASTWES-GDVYTCQVTHEGLKEP 75

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 298 ILAPPKIQLHLANkdplpSLVCSIAGYYPLDVGVTWIReelGGIPAQvSGASFSSLRQSTMGTYSISS--TVMADPGPTG 375
Cdd:pfam07654   3 VFPPSPEELGKPN-----TLTCLVTGFYPPDITVTWLK---NGQEVT-EGVKTTPPSPNSDWTYQLSSylTVTPSDWESG 73

                          90
                  ....*....|..
gi 1720417551 376 ATYTCQVAHVSL 387
Cdd:pfam07654  74 DEYTCRVEHEGL 85

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DR; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DR. HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. HLA-DR is also involved in several autoimmune conditions, disease susceptibility, and disease resistance including seronegative-rheumatoid arthritis, penicillamine-induced myasthenia, schizophrenia, Goodpasture syndrome, systemic lupus erythematosus, Alzheimers, tuberculoid leprosy, and Hashimoto's thyroiditis. HLA-DR molecules are upregulated in response to signaling. HLA-DR is an alphabeta heterodimer cell surface receptor, each subunit of which contains two extracellular domains, a membrane-spanning domain, and a cytoplasmic tail. Both alpha and beta chains are anchored in the membrane. The DR beta chain is encoded by 4 loci, however no more than 3 functional loci are present in a single individual, and no more than two on a single chromosome. Sometimes an individual may only possess 2 copies of the same locus, DRB1*. The HLA-DRB1 locus is ubiquitous and encodes a very large number of functionally variable gene products (HLA-DR1 to HLA-DR17). The HLA-DRB3 locus encodes the HLA-DR52 specificity, is moderately variable and is variably associated with certain HLA-DRB1 types. The HLA-DRB4 locus encodes the HLA-DR53 specificity, has some variation, and is associated with certain HLA-DRB1 types. The HLA-DRB5 locus encodes the HLA-DR51 specificity, which is typically invariable, and is linked to the HLA-DR2 types. Three genetically distinct isotypes of class II MHC molecules are found in humans (HLA-DR, HLA-DQ, and HLA-DP), and two in mice (I-E and I-A). MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 302 PKIQLHLANKDPLPS---LVCSIAGYYPLDVGVTWIR---EELGGIpaqVSgasfSSLRQStmGTYSISSTVMADPGP-T 374
Cdd:cd21000     4 PKVTVYPAKTQPLQHhnlLVCSVNGFYPGSIEVRWFRngqEEKAGV---VS----TGLIQN--GDWTFQTLVMLETVPrS 74

                          90       100
                  ....*....|....*....|..
gi 1720417551 375 GATYTCQVAHVSLEEPLTTSMR 396
Cdd:cd21000    75 GEVYTCQVEHPSVTSPLTVEWR 96

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 1720417551 192 TSETQTLNHLLGSSVSLHCSFSmaPGLDLTGVEWRLQHKGSGQLVYSWKTGQGQAKR-----KGATLEPEELLRAGNASL 266
Cdd:cd20984     1 TVTAKHLAGNIGEDGILSCTFT--PDIKLSDIVIQWLKEGDSGLVHEFKEGKDELSRqspmfRGRTSLFADQVHVGNASL 78

                          90       100
                  ....*....|....*....|
gi 1720417551 267 TLPNLTLKDEGNYICQISTS 286
Cdd:cd20984    79 RLKNVQLTDAGTYLCIISNS 98

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 1720417551 201 LLGSSVSLHCSFSMAPGLDLTGVEWRLQHKGSGQLVYSWKTGQGQAKRKGA------TLEPEELLRaGNASLTLPNLTLK 274
Cdd:cd20934    10 LVGTDATLRCSFSPEPGFSLAQLSVFWQLTDTKQLVHSFTESQDQGRDQGSayanrtALFPDLLAQ-GNASLRLQRVRVA 88

                          90       100
                  ....*....|....*....|....*..
gi 1720417551 275 DEGNYICQISTSLYQAQQIMpLNILAP 301
Cdd:cd20934    89 DEGSYTCFVSVQDFGSAAVS-LQVAAP 114

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DQ and I-A; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of human histocompatibility antigen (HLA) DQ and mouse I-A. Three genetically distinct isotypes of class II MHC molecules are found in humans (HLA-DR, HLA-DQ, and HLA-DP), and two in mice (I-E and I-A). I-A and I-E have the same basic features insofar as peptide loading and presentation, they differ in that each interacts with distinctly different sets of peptides, and in the incidence of deletion of their genes. A structural understanding of the similarities and differences between I-A and I-E may help with understanding their roles in peptide presentation and T cell activation. Mouse I-Ag7 has a genetic susceptibility to autoimmune diabetes due to its small, uncharged amino acid residue at position 57 of their beta chain which results in the absence of a salt bridge between beta 57 and Arg alpha 76, which is adjacent to the P9 pocket of the peptide-binding groove. Human HLA-DR, -DQ, and -DP are about 70% similar to each other. HLA-DQ (DQ) is a cell surface receptor protein found on antigen presenting cells. It is an alphabeta heterodimer of type MHC class II. The alpha and beta chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromosome band 6p21.3. A person often produces two alpha-chain and two beta chain variants and thus 4 isoforms of DQ. HLA-DQ is involved in the autoimmune diseases celiac disease and diabetes mellitus type. DQ is one of several antigens involved in rejection of organ transplants. DQ2 is encoded by the HLA-DQB1*02 allele group. DQ6 is encoded by the HLA-DQB1*06 allele group. DQ2 beta-chains combine with alpha-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively. DQ6 beta-chains combine with alpha-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. For DQ6, however, cis-isoform pairing only occurs with DQ1 alpha-chains. There are many haplotypes of DQ6. Susceptibility to Leptospirosis infection was found associated with undifferentiated DQ6. DQ8 is determined by the antibody recognition of beta8 and this generally detects the gene product of DQB1*0302. DQ8 is commonly linked to autoimmune disease in the human population. DQ8 is the second most predominant isoform linked to celiac disease and the DQ most linked to Type 1 diabetes. DQ8 increases the risk for rheumatoid arthritis and is linked to the primary risk locus for RA, HLA-DR4. DR4 also plays an important role in Type 1 diabetes. DQ8 is a split antigen of the DQ3 broad antigen. MHC class II molecules play a key role in the initiation of the antigen-specific immune response. They are expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice, and induced in nonprofessional APCs, such as keratinocyctes; they are expressed on the surface of activated human T cells and on T cells from other species. MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes; these peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC, and bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 317 LVCSIAGYYPLDVGVTWIR---EELGGIpaqVSgasfSSLRQSTMGTYSIssTVMADPGPT-GATYTCQVAHVSLEEPLT 392
Cdd:cd21001    22 LVCSVTDFYPGQIKVRWFRndqEETAGV---VS----TPLIRNGDWTFQI--LVMLEMTPQrGDVYTCHVEHPSLQSPIT 92

                  ....
gi 1720417551 393 TSMR 396
Cdd:cd21001    93 VEWR 96

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 1720417551 189 FQVTSETQTLNHLLGSSVSLHCSFSmaPGLDLTGVEWRLQHKGSGQLVYSWKTGQGQAKR-----KGATlepeELLRA-- 261
Cdd:cd05713     1 FSVIGPTEPILALVGEDAELPCHLS--PKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEqmpeyRGRT----ELLKDai 74

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1720417551 262 --GNASLTLPNLTLKDEGNYICQISTSLYQAQQIMPLNI 298
Cdd:cd05713    75 aeGSVALRIHNVRPSDEGQYTCFFRSGSFYEEATLELKV 113

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 191 VTSETQTLNHLLGSSVSLHCSFSMAPGLdlTGVEWRLQHKGSG-QLVYSWKTGQGQAKRKGATLEPEELLRAGNASLTLP 269
Cdd:cd00099     1 VTQSPRSLSVQEGESVTLSCEVSSSFSS--TYIYWYRQKPGQGpEFLIYLSSSKGKTKGGVPGRFSGSRDGTSSFSLTIS 78

                          90       100
                  ....*....|....*....|....
gi 1720417551 270 NLTLKDEGNYICQISTSLYQAQQI 293
Cdd:cd00099    79 NLQPEDSGTYYCAVSESGGTDKLT 102

Immunoglobulin variable (IgV) domain of B7-H6; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H6 (also known as NCR3LG1). B7-H6 contains one IgV domain and one IgC domain (IgV-IgC) and belongs to the B7-family, which consists of structurally related cell-surface protein ligands which bind to receptors on lymphocytes that regulate immune responses. B7-H6 is a ligand of NKp30, which is a member of CD28 family and an activating receptor of natural killer (NK) cells. The expression of NKp30 has been found in most of NK cells, which is involved in the process of tumor cell killing and interaction with antigen presenting cells (APCs) such as dendritic cells. Studies showed that NK cells eliminate B7-H6-expressing tumor cells either directly via cytotoxicity or indirectly by cytokine secretion. For instance, chimeric NKp30-expressing T cells responded to B7-H6(+) tumor cells and those T cells produced IFN-gamma and killed B7-H6-expressing tumor cells in vivo. B7-H6 mRNA is not found in normal cells, while high expression of B7-H6 is found in certain type tumor cells, such as lymphoma, leukemia, ovarian cancer, brain tumors, breast cancers, and various sarcomas. Since B7-H6 can bind NKp30 to exert anti-tumor effects by NK cells, which are able to recognize the difference between cancer cells and normal cells, B7-H6 may serve as a promising target for cancer immunotherapy.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 202 LGSSVSLHCSFSMAPGLDLT--GVEWRLQHKGSGQ--LVYSWKTGQGQAKRKGATLEPEELlRAGNASLTLPNLTLKDEG 277
Cdd:cd20981    15 LNDNVTIFCNIFYSQPLNITsmGITWFRKSLTFDKevKVFEFFGDHQKAFRPGAIVSPWRL-KSGDASLQLPGVQLEEAG 93

                          90
                  ....*....|....
gi 1720417551 278 NYICQISTSLYQAQ 291
Cdd:cd20981    94 EYRCEVVVTPLKAQ 107

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 1720417551 197 TLNHLLGSSVSLHCSF-SMAPGLDLTGVEWRLQHKGSGQLVYSWKTGQGQAkrkgATLEP----EELLRAGN-----ASL 266
Cdd:cd05715     8 ELNVLNGSDVRLTCTFtSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKGKP----YILKVgrfkDRVSWAGNpskkdASI 83

                          90
                  ....*....|....*..
gi 1720417551 267 TLPNLTLKDEGNYICQI 283
Cdd:cd05715    84 VISNLQFSDNGTYTCDV 100

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 1720417551 201 LLGSSVSLHCSFSmaPGLDLTgVEWrlQHKGSGQLVYSWKTG------QGQAKRKGATLEPEELLRaGNASLTLPNLTLK 274
Cdd:cd16091    10 LLSEDCILPCSFT--PGSEVV-IHW--YKQDSDIKVHSYYYGkdqlesQDQRYRNRTSLFKDQISN-GNASLLLRRVQLQ 83

                          90
                  ....*....|.
gi 1720417551 275 DEGNYICQIST 285
Cdd:cd16091    84 DEGRYKCYTST 94

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DP; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DP. HLA class II histocompatibility antigen, DP(W2) beta chain is a protein that in humans is encoded by the HLA-DPB1 gene. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. MHC class II molecules are encoded by three different loci, HLA-DR, -DQ, and -DP, which are about 70% similar to each other. HLA-DP is an alphabeta heterodimer cell-surface receptor. Each DP subunit (alpha-subunit, beta-subunit) is composed of a alpha-helical N-terminal domain, an IgG-like beta sheet, a membrane spanning domain, and a cytoplasmic domain. The alpha-helical domain forms the sides of the peptide binding groove. The beta sheet regions form the base of the binding groove and the bulk of the molecule as well as the inter-subunit (non-covalent) binding region. Individuals carrying the MHCII allele, HLA-DP2, are at risk for chronic beryllium disease (CBD), a debilitating inflammatory lung condition caused by the reaction of CD4 T cells to inhaled beryllium. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 301 PPKIQLHLANKDPLPS---LVCSIAGYYPLDVGVTWIR---EELGGIpaqvsgASFSSLRQstmGTYSISSTVMADPGP- 373
Cdd:cd21003     3 QPKVNVSPSKKGPLQHhnlLVCHVTDFYPGNIQVRWFLngqEETAGV------VSTNLIHN---GDWTFQILVMLEMTPq 73

                          90       100
                  ....*....|....*....|...
gi 1720417551 374 TGATYTCQVAHVSLEEPLTTSMR 396
Cdd:cd21003    74 QGDVYTCQVEHPSLDSPVTVEWK 96

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin heavy epsilon and gamma chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin constant-1 set domain of epsilon and gamma chains. It belongs to a family composed of the first immunoglobulin constant-1 set domain of alpha, delta, epsilon, gamma, and mu heavy chains. This domain is found on the Fab antigen-binding fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns. This group belongs to the C1-set of IgSF domains, which are classical Ig-like domains resembling the antibody constant domain. C1-set domains are found almost exclusively in molecules involved in the immune system, such as in immunoglobulin light and heavy chains, in the major histocompatibility complex (MHC) class I and II complex molecules, and in various T-cell receptors.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720417551 316 SLVCSIAGYYPLDVGVTWIREELGGipaqvSGASFSSLRQSTmGTYSISS--TVMADPGPTgATYTCQVAH 384
Cdd:cd21817    20 TLGCLVTGYFPEPVTVTWNSGSLTS-----GVKTFPAVLQSS-GLYTTSSqvTVPSSSWGS-QTFTCNVEH 83

First immunoglobulin (Ig) variable (V) domain of rat MRC OX-2 antigen, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of rat MRC OX-2 antigen (also known as CD200) and similar proteins. MRC OX-2 is a membrane glycoprotein expressed in a variety of lymphoid and non-lymphoid cells in rats. It has a similar broad distribution pattern in humans. MRC OX-2 may regulate myeloid cell activity. The protein has an extracellular portion containing two Ig-like domains, a transmembrane portion, and a cytoplasmic portion.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 187 VEFQVTSETQTLnhllGSSVSLHCSFSMApgLDLTGVEW-RLQHKGSGQLV-YSWKTG---QGQAKRKgATLEPEELlra 261
Cdd:cd05846     1 VVVHTGDTRAVL----GGNATLSCNLTLP--EEVLQVTWqKIKASSPENIVtYSKKYGvkiQPSYVRR-ISFTSSGL--- 70

                          90       100
                  ....*....|....*....|....
gi 1720417551 262 GNASLTLPNLTLKDEGNYICQIST 285
Cdd:cd05846    71 NSTSITIWNVTLEDEGCYKCLFNT 94

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of the major histocompatibility complex (MHC) class II alpha chain. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are also expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 301 PPKIQLHLanKDPL----P-SLVCSIAGYYPLDVGVTWIREelgGIPAQ--VSGASFSSLRQSTMGTYSISSTVmadpgP 373
Cdd:cd05767     2 PPEVTVFP--KSPVelgePnTLICFVDNFFPPVINVTWLRN---GQPVTdgVSETVFLPREDHSFRKFSYLPFT-----P 71

                          90       100
                  ....*....|....*....|
gi 1720417551 374 T-GATYTCQVAHVSLEEPLT 392
Cdd:cd05767    72 SeGDIYDCRVEHWGLEEPLL 91

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 1720417551 202 LGSSVSLHCSFSMAP-----GLDLTGVEWRLQHKGSGQL------------VYSWKTGQGQAKrkgATLEPEellRAGNA 264
Cdd:cd05714    11 LGGNVTLPCKFYRDPtafgsGIHKIRIKWTKLTSDSGYLkevdvlvamgnvVYHKKTYGGRVS---VPLKPG---SDSDA 84

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1720417551 265 SLTLPNLTLKDEGNYICQISTSLYQAQQIMPLNI 298
Cdd:cd05714    85 SLVITDLTASDYGLYRCEVIEGIEDDQDVVALDV 118

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, delta, epsilon, gamma, and mu chains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin constant-1 set domain of alpha, delta, epsilon, gamma, and mu heavy chains. This domain is found on the Fab antigen-binding fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns. This group belongs to the C1-set of IgSF domains, which are classical Ig-like domains resembling the antibody constant domain. C1-set domains are found almost exclusively in molecules involved in the immune system, such as in immunoglobulin light and heavy chains, in the major histocompatibility complex (MHC) class I and II complex molecules, and in various T-cell receptors.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 317 LVCSIAGYYPLDVGVTWIREELGGIPAQVSGasFSSLRQSTmGTYSISS--TVMADPGPTGATYTCQVAH 384
Cdd:cd04985    21 LGCLISDYFPESITVSWQKNTNSITSGFTRT--FPVVLRSG-GDYSCSSqlTVPLQEWNSGEVYKCQVQH 87

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) F; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen alpha chain F (HLA-F). HLA-F, encoded by the HLA-F gene in humans, belongs to the non-classical HLA class I heavy chain paralogs. This class I molecule mainly exists as a heterodimer associated with the invariant light chain beta-2-microglobulin. HLA-F molecules can interact with both activating and inhibitory receptors on immune cells, such as NK cells, and can present a diverse panel of peptides. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 301 PPKIQL-HLANKDPLPSLVCSIAGYYPLDVGVTWIREElggiPAQVSGASFSSLRQSTMGTYSISSTVMAdPGPTGATYT 379
Cdd:cd21023     5 PPKAHVaHHPISDHEATLRCWALGFYPAEITLTWQRDG----EEQTQDTELVETRPAGDGTFQKWAAVVV-PPGEEQRYT 79

                          90
                  ....*....|..
gi 1720417551 380 CQVAHVSLEEPL 391
Cdd:cd21023    80 CHVQHEGLPQPL 91

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 190 QVTSETQTLNHLLGSSVSLHCSFSmapgldltgvewrlqhkGSGQLVYSWKTGqGQAKRKGATLEPEELLraGNASLTLP 269
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEAT-----------------GSPPPTITWYKN-GEPISSGSTRSRSLSG--SNSTLTIS 62

                          90
                  ....*....|....*
gi 1720417551 270 NLTLKDEGNYICQIS 284
Cdd:pfam13927  63 NVTRSDAGTYTCVAS 77

Class I major histocompatibility complex (MHC) beta-2-microglobulin; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain in beta-2-microglobulin (beta2m). Beta2m is the non-covalently bound light chain of the human class I major histocompatibility complex (MHC-I). Beta2m is structured as a beta-sandwich domain composed of two facing beta-sheets (four stranded and three stranded), that is typical of the C-type immunoglobulin superfamily. This structure is stabilized by an intramolecular disulfide bridge connecting two Cys residues in the facing beta-sheets. In vivo, MHC-I continuously exposes beta2m on the cell surface, where it may be released to plasmatic fluids, transported to the kidneys, degraded, and finally excreted.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 301 PPKIQL---HLANKDPLPSLVCSIAGYYPLDVGvtwIREELGGIP---AQVSGASFSSlrqstmgTYSISSTVMADPGPT 374
Cdd:cd05770     2 TPKVQVysrFPAENGKPNVLNCYVSGFHPPDIE---IRLLKNGVKiedVEQSDLSFSK-------DWTFYLLKYTEFTPT 71

                          90       100
                  ....*....|....*....|...
gi 1720417551 375 -GATYTCQVAHVSLEEPLTTSMR 396
Cdd:cd05770    72 kGDEYACRVRHNTLSEPKIYKWD 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 1720417551 203 GSSVSLHCSFSMAPG----LDltgVEWRLQHKGSGQ---LVYSwktgqgqAKRKGATLEPEELLR--------AGNASLT 267
Cdd:cd20960    15 GENVTLPCHHQLGLEdqgtLD---IEWLLLPSDKVEkvvITYS-------GDRVYNHYYPALKGRvaftsndlSGDASLN 84

                          90
                  ....*....|....*....
gi 1720417551 268 LPNLTLKDEGNYICQISTS 286
Cdd:cd20960    85 ISNLKLSDTGTYQCKVKKA 103

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) B and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) B and similar proteins. The classical class I molecules (HLA-A, -B, and -C) are responsible for the presentation of endogenous antigen to CD8+ T cells. The receptor is a heterodimer, and is composed of a heavy alpha chain and smaller beta chain. The alpha chain is encoded by a variant HLA-B gene, and the beta chain (beta-2-microglobulin) is an invariant beta-2-microglobulin molecule. The beta-2-microglobulin protein is coded for by a separate region of the human genome. Human leukocyte antigen (HLA) B*3501 (B35) is a common human allele involved in mediating protective immunity against HIV. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 301 PPKIQL-HLANKDPLPSLVCSIAGYYPLDVGVTWIREElggiPAQVSGASFSSLRQSTMGTYSISSTVMAdPGPTGATYT 379
Cdd:cd21026     5 PPKTHVtHHPISDHEATLRCWALGFYPAEITLTWQRDG----EDQTQDTELVETRPAGDRTFQKWAAVVV-PSGEEQRYT 79

                          90
                  ....*....|...
gi 1720417551 380 CQVAHVSLEEPLT 392
Cdd:cd21026    80 CHVQHEGLPKPLT 92

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of Qa-2; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of QA-2. Qa-2 is a nonclassical MHC Ib antigen, which has been implicated in both innate and adaptive immune responses, as well as embryonic development. Qa-2 has an unusual peptide binding specificity in that it requires two dominant C-terminal anchor residues and is capable of associating with a substantially more diverse array of peptide sequences than other nonclassical MHC. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720417551 301 PPKIQL-HLANKDPLPSLVCSIAGYYPLDVGVTWireELGGiPAQVSGASFSSLRQSTMGTYSISSTVMADPGPTgATYT 379
Cdd:cd21014     4 PPKAHVtHHPRSYGAVTLRCWALGFYPADITLTW---QLNG-EELTQDMELVETRPAGDGTFQKWASVVVPLGKE-QNYT 78

                          90
                  ....*....|...
gi 1720417551 380 CQVAHVSLEEPLT 392
Cdd:cd21014    79 CHVNHEGLPEPLT 91

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 1720417551 206 VSLHCSFSmapgldltgvewrlqhkGSGQLVYSWKtgqgqakRKGATLEPEELLR----AGNASLTLPNLTLKDEGNYIC 281
Cdd:cd00096     1 VTLTCSAS-----------------GNPPPTITWY-------KNGKPLPPSSRDSrrseLGNGTLTISNVTLEDSGTYTC 56