UniProtKB - P10321 (HLAC_HUMAN)
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>sp|P10321|HLAC_HUMAN HLA class I histocompatibility antigen, C alpha chain OS=Homo sapiens OX=9606 GN=HLA-C PE=1 SV=3 MRVMAPRALLLLLSGGLALTETWACSHSMRYFDTAVSRPGRGEPRFISVGYVDDTQFVRF DSDAASPRGEPRAPWVEQEGPEYWDRETQKYKRQAQADRVSLRNLRGYYNQSEDGSHTLQ RMSGCDLGPDGRLLRGYDQSAYDGKDYIALNEDLRSWTAADTAAQITQRKLEAARAAEQL RAYLEGTCVEWLRRYLENGKETLQRAEPPKTHVTHHPLSDHEATLRCWALGFYPAEITLT WQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGQEQRYTCHMQHEGLQEPLTLSWEP SSQPTIPIMGIVAGLAVLVVLAVLGAVVTAMMCRRKSSGGKGGSCSQAACSNSAQGSDES LITCKAHelp videoAdd a publicationFeedback
Protein
HLA class I histocompatibility antigen, C alpha chain
Gene
HLA-C
Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:
Annotation score:5 out of 5
<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>Select a section on the left to see content.
<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni
Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity (PubMed:20972337, PubMed:24091323, PubMed:20439706, PubMed:11172028, PubMed:20104487, PubMed:28649982, PubMed:29312307). In complex with B2M/beta 2 microglobulin displays a restricted repertoire of self and viral peptides and acts as a dominant ligand for inhibitory and activating killer immunoglobulin receptors (KIRs) expressed on NK cells (PubMed:16141329). In an allogeneic setting, such as during pregnancy, mediates interaction of extravillous trophoblasts with KIR on uterine NK cells and regulate trophoblast invasion necessary for placentation and overall fetal growth (PubMed:20972337, PubMed:24091323). During viral infection, may present viral peptides with low affinity for KIRs, impeding KIR-mediated inhibition through peptide antagonism and favoring lysis of infected cells (PubMed:20439706). Presents a restricted repertoire of viral peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-C-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected cells, particularly in chronic viral infection settings such as HIV-1 or CMV infection (PubMed:11172028, PubMed:20104487, PubMed:28649982). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (By similarity). Typically presents intracellular peptide antigens of 9 amino acids that arise from cytosolic proteolysis via proteasome. Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9. Preferentially displays peptides having a restricted repertoire of hydrophobic or aromatic amino acids (Phe, Ile, Leu, Met, Val and Tyr) at the C-terminal anchor (PubMed:8265661, PubMed:25311805).By similarity
<p>Manually curated information which has been propagated from a related experimentally characterized protein.</p> <p><a href="/manual/evidences#ECO:0000250">More...</a></p> Manual assertion inferred from sequence similarity toi
10 Publications<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More...</a></p> Manual assertion based on experiment ini
- Ref.22"Allele-specific peptide ligand motifs of HLA-C molecules."
Falk K., Roetzschke O., Grahovac B., Schendel D., Stevanovic S., Gnau V., Jung G., Strominger J.L., Rammensee H.G.
Proc. Natl. Acad. Sci. U.S.A. 90:12005-12009(1993) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION. - Ref.24"The HIV-1 regulatory proteins Tat and Rev are frequently targeted by cytotoxic T lymphocytes derived from HIV-1-infected individuals."
HIV Controller Study Collaboration
Addo M.M., Altfeld M., Rosenberg E.S., Eldridge R.L., Philips M.N., Habeeb K., Khatri A., Brander C., Robbins G.K., Mazzara G.P., Goulder P.J., Walker B.D.
Proc. Natl. Acad. Sci. U.S.A. 98:1781-1786(2001) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (ALLELE C*05:01). - Ref.26"Recognition of peptide-MHC class I complexes by activating killer immunoglobulin-like receptors."
Stewart C.A., Laugier-Anfossi F., Vely F., Saulquin X., Riedmuller J., Tisserant A., Gauthier L., Romagne F., Ferracci G., Arosa F.A., Moretta A., Sun P.D., Ugolini S., Vivier E.
Proc. Natl. Acad. Sci. U.S.A. 102:13224-13229(2005) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH KIR2DL1; KIR2DL2; KIR2DL3 AND KIR2DS1. - Ref.29"Characterization of an HLA-C-restricted CTL response in chronic HIV infection."
Makadzange A.T., Gillespie G., Dong T., Kiama P., Bwayo J., Kimani J., Plummer F., Easterbrook P., Rowland-Jones S.L.
Eur. J. Immunol. 40:1036-1041(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (ALLELE C*04:01). - Ref.30"Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2."
Hiby S.E., Apps R., Sharkey A.M., Farrell L.E., Gardner L., Mulder A., Claas F.H., Walker J.J., Redman C.W., Redman C.C., Morgan L., Tower C., Regan L., Moore G.E., Carrington M., Moffett A.
J. Clin. Invest. 120:4102-4110(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH KIR2DL1 AND KIR2DS1. - Ref.31"Peptide antagonism as a mechanism for NK cell activation."
Fadda L., Borhis G., Ahmed P., Cheent K., Pageon S.V., Cazaly A., Stathopoulos S., Middleton D., Mulder A., Claas F.H., Elliott T., Davis D.M., Purbhoo M.A., Khakoo S.I.
Proc. Natl. Acad. Sci. U.S.A. 107:10160-10165(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (C*01:02), INTERACTION WITH KIR2DL2 AND KIR2DL3. - Ref.33"Maternal uterine NK cell-activating receptor KIR2DS1 enhances placentation."
Xiong S., Sharkey A.M., Kennedy P.R., Gardner L., Farrell L.E., Chazara O., Bauer J., Hiby S.E., Colucci F., Moffett A.
J. Clin. Invest. 123:4264-4272(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (ALLELE C*06:02). - Ref.35"Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule."
Rasmussen M., Harndahl M., Stryhn A., Boucherma R., Nielsen L.L., Lemonnier F.A., Nielsen M., Buus S.
J. Immunol. 193:4790-4802(2014) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION. - Ref.37"Cytomegalovirus-Specific T Cells Restricted by HLA-Cw*0702 Increase Markedly with Age and Dominate the CD8+ T-Cell Repertoire in Older People."
Hosie L., Pachnio A., Zuo J., Pearce H., Riddell S., Moss P.
Front. Immunol. 8:1776-1776(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (ALLELE C*07:02). - Ref.41"Structural and regulatory diversity shape HLA-C protein expression levels."
Kaur G., Gras S., Mobbs J.I., Vivian J.P., Cortes A., Barber T., Kuttikkatte S.B., Jensen L.T., Attfield K.E., Dendrou C.A., Carrington M., McVean G., Purcell A.W., Rossjohn J., Fugger L.
Nat. Commun. 8:15924-15924(2017) [PubMed] [Europe PMC] [Abstract]
ALLELE C*01:02: The peptide-bound form interacts with KIR2DL2 and KIR2DL3 inhibitory receptors on NK cells. The low affinity peptides compete with the high affinity peptides impeding KIR-mediated inhibition and favoring lysis of infected cells (PubMed:20439706). Presents to CD8-positive T cells a CMV epitope derived from UL83/pp65 (RCPEMISVL), an immediate-early antigen necessary for initiating viral replication (PubMed:12947002).2 Publications
Manual assertion based on experiment ini
- Ref.25"Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles."
Kondo E., Akatsuka Y., Kuzushima K., Tsujimura K., Asakura S., Tajima K., Kagami Y., Kodera Y., Tanimoto M., Morishima Y., Takahashi T.
Blood 103:630-638(2004) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (ALLELES C*01:02; C*04:01; C*08:01; C*12:02 AND C*15:02). - Ref.31"Peptide antagonism as a mechanism for NK cell activation."
Fadda L., Borhis G., Ahmed P., Cheent K., Pageon S.V., Cazaly A., Stathopoulos S., Middleton D., Mulder A., Claas F.H., Elliott T., Davis D.M., Purbhoo M.A., Khakoo S.I.
Proc. Natl. Acad. Sci. U.S.A. 107:10160-10165(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (C*01:02), INTERACTION WITH KIR2DL2 AND KIR2DL3.
ALLELE C*04:01: Presents a conserved HIV-1 epitope derived from env (SFNCGGEFF) to memory CD8-positive T cells, eliciting very strong IFNG responses (PubMed:20104487). Presents CMV epitope derived from UL83/pp65 (QYDPVAALF) to CD8-positive T cells, triggering T cell cytotoxic response (PubMed:12947002).2 Publications
Manual assertion based on experiment ini
- Ref.25"Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles."
Kondo E., Akatsuka Y., Kuzushima K., Tsujimura K., Asakura S., Tajima K., Kagami Y., Kodera Y., Tanimoto M., Morishima Y., Takahashi T.
Blood 103:630-638(2004) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (ALLELES C*01:02; C*04:01; C*08:01; C*12:02 AND C*15:02). - Ref.29"Characterization of an HLA-C-restricted CTL response in chronic HIV infection."
Makadzange A.T., Gillespie G., Dong T., Kiama P., Bwayo J., Kimani J., Plummer F., Easterbrook P., Rowland-Jones S.L.
Eur. J. Immunol. 40:1036-1041(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (ALLELE C*04:01).
ALLELE C*05:01: Presents HIV-1 epitope derived from rev (SAEPVPLQL) to CD8-positive T cells, triggering T cell cytotoxic response.1 Publication
Manual assertion based on experiment ini
- Ref.24"The HIV-1 regulatory proteins Tat and Rev are frequently targeted by cytotoxic T lymphocytes derived from HIV-1-infected individuals."
HIV Controller Study Collaboration
Addo M.M., Altfeld M., Rosenberg E.S., Eldridge R.L., Philips M.N., Habeeb K., Khatri A., Brander C., Robbins G.K., Mazzara G.P., Goulder P.J., Walker B.D.
Proc. Natl. Acad. Sci. U.S.A. 98:1781-1786(2001) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (ALLELE C*05:01).
ALLELE C*06:02: In trophoblasts, interacts with KIR2DS2 on uterine NK cells and triggers NK cell activation, including secretion of cytokines such as GMCSF that enhances trophoblast migration.1 Publication
Manual assertion based on experiment ini
- Ref.33"Maternal uterine NK cell-activating receptor KIR2DS1 enhances placentation."
Xiong S., Sharkey A.M., Kennedy P.R., Gardner L., Farrell L.E., Chazara O., Bauer J., Hiby S.E., Colucci F., Moffett A.
J. Clin. Invest. 123:4264-4272(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (ALLELE C*06:02).
ALLELE C*07:02: Plays an important role in the control of chronic CMV infection. Presents immunodominant CMV epitopes derived from IE1 (LSEFCRVL and CRVLCCYVL) and UL28 (FRCPRRFCF), both antigens synthesized during immediate-early period of viral replication. Elicits a strong anti-viral CD8-positive T cell immune response that increases markedly with age.1 Publication
Manual assertion based on experiment ini
- Ref.37"Cytomegalovirus-Specific T Cells Restricted by HLA-Cw*0702 Increase Markedly with Age and Dominate the CD8+ T-Cell Repertoire in Older People."
Hosie L., Pachnio A., Zuo J., Pearce H., Riddell S., Moss P.
Front. Immunol. 8:1776-1776(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (ALLELE C*07:02).
ALLELE C*08:01: Presents viral epitopes derived from CMV UL83 (VVCAHELVC) and IAV M1 (GILGFVFTL), triggering CD8-positive T cell cytotoxic response.2 Publications
Manual assertion based on experiment ini
- Ref.25"Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles."
Kondo E., Akatsuka Y., Kuzushima K., Tsujimura K., Asakura S., Tajima K., Kagami Y., Kodera Y., Tanimoto M., Morishima Y., Takahashi T.
Blood 103:630-638(2004) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (ALLELES C*01:02; C*04:01; C*08:01; C*12:02 AND C*15:02). - Ref.40"The immunodominant influenza A virus M158-66 cytotoxic T lymphocyte epitope exhibits degenerate class I major histocompatibility complex restriction in humans."
Choo J.A., Liu J., Toh X., Grotenbreg G.M., Ren E.C.
J. Virol. 88:10613-10623(2014) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 26-298 (ALLELE C*08:01) IN COMPLEX WITH B2M AND PEPTIDE, FUNCTION (ALLELE C*08:01), DOMAIN, DISULFIDE BOND.
ALLELE C*12:02: Presents CMV epitope derived from UL83 (VAFTSHEHF) to CD8-positive T cells.1 Publication
Manual assertion based on experiment ini
- Ref.25"Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles."
Kondo E., Akatsuka Y., Kuzushima K., Tsujimura K., Asakura S., Tajima K., Kagami Y., Kodera Y., Tanimoto M., Morishima Y., Takahashi T.
Blood 103:630-638(2004) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (ALLELES C*01:02; C*04:01; C*08:01; C*12:02 AND C*15:02).
ALLELE C*15:02: Presents CMV epitope derived from UL83 CC (VVCAHELVC) to CD8-positive T cells, triggering T cell cytotoxic response.1 Publication
Manual assertion based on experiment ini
- Ref.25"Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles."
Kondo E., Akatsuka Y., Kuzushima K., Tsujimura K., Asakura S., Tajima K., Kagami Y., Kodera Y., Tanimoto M., Morishima Y., Takahashi T.
Blood 103:630-638(2004) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (ALLELES C*01:02; C*04:01; C*08:01; C*12:02 AND C*15:02).
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei | 87 | Self- and pathogen-derived peptide antigen1 Publication Manual assertion based on experiment ini
| 1 | |
| Binding sitei | 94 | Self- and pathogen-derived peptide antigen1 Publication Manual assertion based on experiment ini
| 1 | |
| Binding sitei | 101 | Self- and pathogen-derived peptide antigen1 Publication Manual assertion based on experiment ini
| 1 | |
| Binding sitei | 183 | Self- and pathogen-derived peptide antigen1 Publication Manual assertion based on experiment ini
| 1 | |
| Binding sitei | 195 | Self- and pathogen-derived peptide antigen1 Publication Manual assertion based on experiment ini
| 1 |
<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni
- peptide antigen binding Source: UniProtKB
<p>Inferred from Direct Assay</p>
<p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p>
<p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p>
Inferred from direct assayi
- "Multiple viral ligands naturally presented by different class I molecules in transporter antigen processing-deficient vaccinia virus-infected cells."
Lorente E., Infantes S., Barnea E., Beer I., Garcia R., Lasala F., Jimenez M., Vilches C., Lemonnier F.A., Admon A., Lopez D.
J. Virol. 86:527-541(2012) [PubMed] [Europe PMC] [Abstract]
- TAP binding Source: UniProtKBInferred from direct assayi
- "Allele-specific differences in the interaction of MHC class I molecules with transporters associated with antigen processing."
Neisig A., Wubbolts R., Zang X., Melief C., Neefjes J.
J. Immunol. 156:3196-3206(1996) [PubMed] [Europe PMC] [Abstract] - "Point mutations in the alpha 2 domain of HLA-A2.1 define a functionally relevant interaction with TAP."
Lewis J.W., Neisig A., Neefjes J., Elliott T.
Curr. Biol. 6:873-883(1996) [PubMed] [Europe PMC] [Abstract]
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent Source: UniProtKBInferred from direct assayi
- "Multiple viral ligands naturally presented by different class I molecules in transporter antigen processing-deficient vaccinia virus-infected cells."
Lorente E., Infantes S., Barnea E., Beer I., Garcia R., Lasala F., Jimenez M., Vilches C., Lemonnier F.A., Admon A., Lopez D.
J. Virol. 86:527-541(2012) [PubMed] [Europe PMC] [Abstract]
- antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent Source: Reactome
- antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent Source: Reactome
- antigen processing and presentation of peptide antigen via MHC class I Source: Reactome
- immune response Source: UniProtKB
<p>Non-traceable Author Statement</p>
<p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p>
<p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#nas">GO evidence code guide</a></p>
Non-traceable author statementi
- Ref.5"The molecular basis for reactivity of anti-Cw1 and anti-Cw3 alloantisera with HLA-B46 haplotypes."
Zemmour J., Gumperz J.E., Hildebrand W.H., Ward F.E., Marsh S.G.E., Williams R.C., Parham P.
Tissue Antigens 39:249-257(1992) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELES C*01:02; C*03:02 AND C*08:01). - "Complete nucleotide sequence of a unique HLA class I C locus product expressed on the human choriocarcinoma cell line BeWo."
Ellis S.A., Strachan T., Palmer M.S., McMichael A.J.
J. Immunol. 142:3281-3285(1989) [PubMed] [Europe PMC] [Abstract] - Ref.13"The structure and expression of genes encoding serologically undetected HLA-C locus antigens."
Takiguchi M., Nishimura I., Hayashi H., Karaki S., Kariyone A., Kano K.
J. Immunol. 143:1372-1378(1989) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE C*12:02). - "Cloning and analysis of HLA class I cDNA encoding a new HLA-C specificity Cx52."
Takata H., Inoko H., Ando A., Haranaka M., Watanabe B., Tsuji K., Iri H.
Immunogenetics 28:265-270(1988) [PubMed] [Europe PMC] [Abstract]
- interferon-gamma-mediated signaling pathway Source: Reactome
- neutrophil degranulation Source: Reactome
- regulation of immune response Source: Reactome
- type I interferon signaling pathway Source: Reactome
- viral process Source: UniProtKB-KW
<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi
| Biological process | Adaptive immunity, Host-virus interaction, Immunity, Innate immunity |
Enzyme and pathway databases
Reactome - a knowledgebase of biological pathways and processes More...Reactomei | R-HSA-1236974 ER-Phagosome pathway R-HSA-1236977 Endosomal/Vacuolar pathway R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell R-HSA-2172127 DAP12 interactions R-HSA-6798695 Neutrophil degranulation R-HSA-877300 Interferon gamma signaling R-HSA-909733 Interferon alpha/beta signaling R-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC |
<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi
| <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi | Recommended name: HLA class I histocompatibility antigen, C alpha chainShort name: HLA-C Alternative name(s): HLA-Cw Human leukocyte antigen C |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi | |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>Organismi | Homo sapiens (Human) |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri | 9606 [NCBI] |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineagei | cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi |
|
Organism-specific databases
Human Gene Nomenclature Database More...HGNCi | HGNC:4933 HLA-C |
neXtProt; the human protein knowledge platform More...neXtProti | NX_P10321 |
<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication
<p>Manually curated information which has been inferred by a curator based on his/her scientific knowledge or on the scientific content of an article.</p> <p><a href="/manual/evidences#ECO:0000305">More...</a></p> Manual assertion inferred by curator fromi
- Ref.27"N-linked glycosylation selectively regulates the generic folding of HLA-Cw1."
Martayan A., Sibilio L., Setini A., Lo Monaco E., Tremante E., Fruci D., Colonna M., Giacomini P.
J. Biol. Chem. 283:16469-16476(2008) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH THE PEPTIDE LOADING COMPLEX, MUTAGENESIS OF SER-112, GLYCOSYLATION AT ASN-110, SUBCELLULAR LOCATION.
- Endoplasmic reticulum membrane 1 Publication
Plasma membrane
- Cell membrane 3 Publications
Manual assertion based on experiment ini
- Ref.27"N-linked glycosylation selectively regulates the generic folding of HLA-Cw1."
Martayan A., Sibilio L., Setini A., Lo Monaco E., Tremante E., Fruci D., Colonna M., Giacomini P.
J. Biol. Chem. 283:16469-16476(2008) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH THE PEPTIDE LOADING COMPLEX, MUTAGENESIS OF SER-112, GLYCOSYLATION AT ASN-110, SUBCELLULAR LOCATION. - Ref.30"Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2."
Hiby S.E., Apps R., Sharkey A.M., Farrell L.E., Gardner L., Mulder A., Claas F.H., Walker J.J., Redman C.W., Redman C.C., Morgan L., Tower C., Regan L., Moore G.E., Carrington M., Moffett A.
J. Clin. Invest. 120:4102-4110(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH KIR2DL1 AND KIR2DS1. - Ref.41"Structural and regulatory diversity shape HLA-C protein expression levels."
Kaur G., Gras S., Mobbs J.I., Vivian J.P., Cortes A., Barber T., Kuttikkatte S.B., Jensen L.T., Attfield K.E., Dendrou C.A., Carrington M., McVean G., Purcell A.W., Rossjohn J., Fugger L.
Nat. Commun. 8:15924-15924(2017) [PubMed] [Europe PMC] [Abstract]
- Cell membrane 3 Publications
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKBInferred from direct assayi
- "Receptor-mediated ER export of human MHC class I molecules is regulated by the C-terminal single amino acid."
Cho S., Ryoo J., Jun Y., Ahn K.
Traffic 12:42-55(2011) [PubMed] [Europe PMC] [Abstract]
- integral component of lumenal side of endoplasmic reticulum membrane Source: Reactome
- endoplasmic reticulum Source: UniProtKBInferred from direct assayi
Endosome
- early endosome membrane Source: Reactome
- recycling endosome membrane Source: Reactome
Extracellular region or secreted
- extracellular exosome Source: UniProtKBInferred from high throughput direct assayi
- "MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis."
Buschow S.I., van Balkom B.W., Aalberts M., Heck A.J., Wauben M., Stoorvogel W.
Immunol. Cell Biol. 88:851-856(2010) [PubMed] [Europe PMC] [Abstract]
- extracellular exosome Source: UniProtKBInferred from high throughput direct assayi
Golgi apparatus
- Golgi apparatus Source: UniProtKBInferred from direct assayi
- "Receptor-mediated ER export of human MHC class I molecules is regulated by the C-terminal single amino acid."
Cho S., Ryoo J., Jun Y., Ahn K.
Traffic 12:42-55(2011) [PubMed] [Europe PMC] [Abstract]
- Golgi membrane Source: Reactome
- Golgi apparatus Source: UniProtKBInferred from direct assayi
Plasma Membrane
- integral component of plasma membrane Source: UniProtKBNon-traceable author statementi
- Ref.5"The molecular basis for reactivity of anti-Cw1 and anti-Cw3 alloantisera with HLA-B46 haplotypes."
Zemmour J., Gumperz J.E., Hildebrand W.H., Ward F.E., Marsh S.G.E., Williams R.C., Parham P.
Tissue Antigens 39:249-257(1992) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELES C*01:02; C*03:02 AND C*08:01). - "Complete nucleotide sequence of a unique HLA class I C locus product expressed on the human choriocarcinoma cell line BeWo."
Ellis S.A., Strachan T., Palmer M.S., McMichael A.J.
J. Immunol. 142:3281-3285(1989) [PubMed] [Europe PMC] [Abstract] - Ref.13"The structure and expression of genes encoding serologically undetected HLA-C locus antigens."
Takiguchi M., Nishimura I., Hayashi H., Karaki S., Kariyone A., Kano K.
J. Immunol. 143:1372-1378(1989) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE C*12:02). - "Cloning and analysis of HLA class I cDNA encoding a new HLA-C specificity Cx52."
Takata H., Inoko H., Ando A., Haranaka M., Watanabe B., Tsuji K., Iri H.
Immunogenetics 28:265-270(1988) [PubMed] [Europe PMC] [Abstract]
- MHC class I protein complex Source: UniProtKBInferred from direct assayi
- "Multiple viral ligands naturally presented by different class I molecules in transporter antigen processing-deficient vaccinia virus-infected cells."
Lorente E., Infantes S., Barnea E., Beer I., Garcia R., Lasala F., Jimenez M., Vilches C., Lemonnier F.A., Admon A., Lopez D.
J. Virol. 86:527-541(2012) [PubMed] [Europe PMC] [Abstract]
- plasma membrane Source: Reactome
- integral component of plasma membrane Source: UniProtKBNon-traceable author statementi
Other locations
- cell surface Source: UniProtKBInferred from direct assayi
- "Multiple viral ligands naturally presented by different class I molecules in transporter antigen processing-deficient vaccinia virus-infected cells."
Lorente E., Infantes S., Barnea E., Beer I., Garcia R., Lasala F., Jimenez M., Vilches C., Lemonnier F.A., Admon A., Lopez D.
J. Virol. 86:527-541(2012) [PubMed] [Europe PMC] [Abstract] - "HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer."
Llano M., Lee N., Navarro F., Garcia P., Albar J.P., Geraghty D.E., Lopez-Botet M.
Eur. J. Immunol. 28:2854-2863(1998) [PubMed] [Europe PMC] [Abstract]
- ER to Golgi transport vesicle membrane Source: Reactome
- membrane Source: UniProtKBInferred from high throughput direct assayi
- "Defining the membrane proteome of NK cells."
Ghosh D., Lippert D., Krokhin O., Cortens J.P., Wilkins J.A.
J Mass Spectrom 45:1-25(2010) [PubMed] [Europe PMC] [Abstract]
- phagocytic vesicle membrane Source: Reactome
- secretory granule membrane Source: Reactome
- cell surface Source: UniProtKBInferred from direct assayi
Topology
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini | 25 – 308 | ExtracellularSequence analysisAdd BLAST | 284 | |
| <p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei | 309 – 333 | HelicalSequence analysisAdd BLAST | 25 | |
| Topological domaini | 334 – 366 | CytoplasmicSequence analysisAdd BLAST | 33 |
Keywords - Cellular componenti
Cell membrane, Endoplasmic reticulum, Membrane, MHC I<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi
<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei
Psoriasis 1 (PSORS1)1 PublicationManual assertion based on experiment ini
- Ref.44"Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene."
Nair R.P., Stuart P.E., Nistor I., Hiremagalore R., Chia N.V.C., Jenisch S., Weichenthal M., Abecasis G.R., Lim H.W., Christophers E., Voorhees J.J., Elder J.T.
Am. J. Hum. Genet. 78:827-851(2006) [PubMed] [Europe PMC] [Abstract]Cited for: INVOLVEMENT IN PSORS1 (ALLELE C*06:02).
Ref.44
"Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene."
Nair R.P., Stuart P.E., Nistor I., Hiremagalore R., Chia N.V.C., Jenisch S., Weichenthal M., Abecasis G.R., Lim H.W., Christophers E., Voorhees J.J., Elder J.T.
Am. J. Hum. Genet. 78:827-851(2006) [PubMed] [Europe PMC] [Abstract]
Nair R.P., Stuart P.E., Nistor I., Hiremagalore R., Chia N.V.C., Jenisch S., Weichenthal M., Abecasis G.R., Lim H.W., Christophers E., Voorhees J.J., Elder J.T.
Am. J. Hum. Genet. 78:827-851(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PSORS1 (ALLELE C*06:02).
Disease susceptibility is associated with variations affecting the gene represented in this entry. Allele C*06:02 presents a melanocyte autoantigen ADAMTSL5 (VRSRRCLRL) to Valpha3S1/Vbeta13S1 TCR on CD8-positive T cells, and may trigger an autoimmune response against melanocytes.1 Publication
Manual assertion based on experiment ini
- Ref.45"Melanocyte antigen triggers autoimmunity in human psoriasis."
Arakawa A., Siewert K., Stoehr J., Besgen P., Kim S.M., Ruehl G., Nickel J., Vollmer S., Thomas P., Krebs S., Pinkert S., Spannagl M., Held K., Kammerbauer C., Besch R., Dornmair K., Prinz J.C.
J. Exp. Med. 212:2203-2212(2015) [PubMed] [Europe PMC] [Abstract]Cited for: INVOLVEMENT IN PSORS1 (ALLELE C*06:02).
Disease descriptionA common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis.
Related information in OMIMMutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi | 112 | S → G: Impairs N-linked glycosylation resulting in impaired interaction with CANX and CALR chaperones as well as TAPBPL. 1 Publication Manual assertion based on experiment ini
| 1 |
Organism-specific databases
MalaCards human disease database More...MalaCardsi | HLA-C |
Online Mendelian Inheritance in Man (OMIM) More...MIMi | 177900 phenotype |
Open Targets More...OpenTargetsi | ENSG00000204525 |
Orphanet; a database dedicated to information on rare diseases and orphan drugs More...Orphaneti | 99860 Precursor B-cell acute lymphoblastic leukemia |
The Pharmacogenetics and Pharmacogenomics Knowledge Base More...PharmGKBi | PA35057 |
Miscellaneous databases
Pharos NIH Druggable Genome Knowledgebase More...Pharosi | P10321 Tbio |
<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei | 1 – 24 | Sequence analysisAdd BLAST | 24 | |
| <p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_0000018868 | 25 – 366 | HLA class I histocompatibility antigen, C alpha chainAdd BLAST | 342 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi | 110 | N-linked (GlcNAc...) asparagine1 Publication Manual assertion based on experiment ini
| 1 | |
| <p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi | 125 ↔ 188 | PROSITE-ProRule annotation <p>Manual validated information which has been generated by the UniProtKB automatic annotation system.</p> <p><a href="/manual/evidences#ECO:0000255">More...</a></p> Manual assertion according to rulesi 2 PublicationsManual assertion based on experiment ini
| ||
| Disulfide bondi | 227 ↔ 283 | PROSITE-ProRule annotation Manual assertion according to rulesi 2 PublicationsManual assertion based on experiment ini
| ||
| <p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei | 357 | PhosphoserineBy similarity Manual assertion inferred from sequence similarity toi | 1 | |
| Modified residuei | 360 | PhosphoserineBy similarity Manual assertion inferred from sequence similarity toi | 1 |
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi
N-linked glycosylation at Asn-110 is required for efficient interaction with CANX and CALR chaperones and appropriate HLA-C-B2M folded conformers prior to peptide loading.2 Publications
Manual assertion based on experiment ini
- Ref.27"N-linked glycosylation selectively regulates the generic folding of HLA-Cw1."
Martayan A., Sibilio L., Setini A., Lo Monaco E., Tremante E., Fruci D., Colonna M., Giacomini P.
J. Biol. Chem. 283:16469-16476(2008) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH THE PEPTIDE LOADING COMPLEX, MUTAGENESIS OF SER-112, GLYCOSYLATION AT ASN-110, SUBCELLULAR LOCATION. - Ref.28"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-110.
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
Encyclopedia of Proteome Dynamics More...EPDi | P10321 |
MassIVE - Mass Spectrometry Interactive Virtual Environment More...MassIVEi | P10321 |
MaxQB - The MaxQuant DataBase More...MaxQBi | P10321 |
PaxDb, a database of protein abundance averages across all three domains of life More...PaxDbi | P10321 |
PeptideAtlas More...PeptideAtlasi | P10321 |
PRoteomics IDEntifications database More...PRIDEi | P10321 |
ProteomicsDB: a multi-organism proteome resource More...ProteomicsDBi | 51687 52599 54698 54699 54700 54701 54702 54703 58493 61274 61277 61278 61279 75736 83917 |
PTM databases
GlyConnect protein glycosylation platform More...GlyConnecti | 1352 1353 1354 1355 1356 1357 1358 1359 1360 1361 1362 1363 1364 |
iPTMnet integrated resource for PTMs in systems biology context More...iPTMneti | P10321 |
MetOSite database of methionine sulfoxide sites More...MetOSitei | P10321 |
Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat. More...PhosphoSitePlusi | P10321 |
SwissPalm database of S-palmitoylation events More...SwissPalmi | P10321 |
<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni
<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi
Ubiquitous. Highly expressed in fetal extravillous trophoblasts in the decidua basalis (at protein level).1 Publication
Manual assertion based on experiment ini
- Ref.30"Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2."
Hiby S.E., Apps R., Sharkey A.M., Farrell L.E., Gardner L., Mulder A., Claas F.H., Walker J.J., Redman C.W., Redman C.C., Morgan L., Tower C., Regan L., Moore G.E., Carrington M., Moffett A.
J. Clin. Invest. 120:4102-4110(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH KIR2DL1 AND KIR2DS1.
Gene expression databases
Bgee dataBase for Gene Expression Evolution More...Bgeei | ENSG00000204525 Expressed in mononuclear cell and 233 other tissues |
ExpressionAtlas, Differential and Baseline Expression More...ExpressionAtlasi | P10321 baseline and differential |
Organism-specific databases
Human Protein Atlas More...HPAi | ENSG00000204525 Low tissue specificity |
<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni
<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei
Heterotrimer that consists of an alpha chain HLA-C, a beta chain B2M and a peptide (peptide-HLA-C-B2M) (PubMed:28649982, PubMed:10850706, PubMed:24990997). Early in biogenesis, HLA-C-B2M dimer interacts with the components of the peptide-loading complex composed of TAPBP, TAP1-TAP2, TAPBPL, PDIA3/ERP57 and CALR (PubMed:18420581).
Interacts with TAP1-TAP2 transporter via TAPBP; this interaction is obligatory for the loading of peptide epitopes delivered to the endoplasmic reticulum (ER) by TAP1-TAP2 transporter (By similarity). Being very selective in the peptide binding, forms a stable interaction with TAP1-TAP2, often leading to the accumulation of free heavy chains in the ER (PubMed:18420581). Only optimally assembled peptide-HLA-C-B2M trimer translocates to the surface of antigen-presenting cells, where it interacts with TCR and CD8 coreceptor on the surface of T cells. HLA-C (via polymorphic alpha-1 and alpha-2 domains) interacts with antigen-specific TCR (via CDR3 domains) (By similarity). One HLA-C molecule (mainly via nonpolymorphic alpha-3 domain) interacts with one CD8A homodimer (via CDR-like loop); this interaction insures peptide-HLA-C-B2M recognition by CD8-positive T cells only (By similarity). The peptide-HLA-C-B2M complex also interacts with KIRs. HLA-C type 1 (C1, with Asn104), including HLA-C*02, C*04, C*05, C*06 and C*15, interact with KIR2DL1 and KIR2DS1, and HLA-C type 2 (C2, with Lys104), including HLA-C*01, C*03, C*07 and C*08, interact with KIR2DL2 and KIR2DL3 (PubMed:20972337, PubMed:24091323, PubMed:16141329, PubMed:20439706, PubMed:11323700, PubMed:10850706).
By similarityManual assertion inferred from sequence similarity toi
9 PublicationsManual assertion based on experiment ini
- Ref.26"Recognition of peptide-MHC class I complexes by activating killer immunoglobulin-like receptors."
Stewart C.A., Laugier-Anfossi F., Vely F., Saulquin X., Riedmuller J., Tisserant A., Gauthier L., Romagne F., Ferracci G., Arosa F.A., Moretta A., Sun P.D., Ugolini S., Vivier E.
Proc. Natl. Acad. Sci. U.S.A. 102:13224-13229(2005) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH KIR2DL1; KIR2DL2; KIR2DL3 AND KIR2DS1. - Ref.27"N-linked glycosylation selectively regulates the generic folding of HLA-Cw1."
Martayan A., Sibilio L., Setini A., Lo Monaco E., Tremante E., Fruci D., Colonna M., Giacomini P.
J. Biol. Chem. 283:16469-16476(2008) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH THE PEPTIDE LOADING COMPLEX, MUTAGENESIS OF SER-112, GLYCOSYLATION AT ASN-110, SUBCELLULAR LOCATION. - Ref.30"Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2."
Hiby S.E., Apps R., Sharkey A.M., Farrell L.E., Gardner L., Mulder A., Claas F.H., Walker J.J., Redman C.W., Redman C.C., Morgan L., Tower C., Regan L., Moore G.E., Carrington M., Moffett A.
J. Clin. Invest. 120:4102-4110(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH KIR2DL1 AND KIR2DS1. - Ref.31"Peptide antagonism as a mechanism for NK cell activation."
Fadda L., Borhis G., Ahmed P., Cheent K., Pageon S.V., Cazaly A., Stathopoulos S., Middleton D., Mulder A., Claas F.H., Elliott T., Davis D.M., Purbhoo M.A., Khakoo S.I.
Proc. Natl. Acad. Sci. U.S.A. 107:10160-10165(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (C*01:02), INTERACTION WITH KIR2DL2 AND KIR2DL3. - Ref.33"Maternal uterine NK cell-activating receptor KIR2DS1 enhances placentation."
Xiong S., Sharkey A.M., Kennedy P.R., Gardner L., Farrell L.E., Chazara O., Bauer J., Hiby S.E., Colucci F., Moffett A.
J. Clin. Invest. 123:4264-4272(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (ALLELE C*06:02). - Ref.38"Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand."
Boyington J.C., Motyka S.A., Schuck P., Brooks A.G., Sun P.D.
Nature 405:537-543(2000) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 25-302 (ALLELE C*03:04) IN COMPLEX WITH B2M PEPTIDE AND KIR2DL2, DISULFIDE BONDS, DOMAIN. - Ref.39"Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex."
Fan Q.R., Long E.O., Wiley D.C.
Nat. Immunol. 2:452-460(2001) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 25-299 (ALLELE C*04:01) IN COMPLEX WITH B2M PEPTIDE AND KIR2DL1. - Ref.40"The immunodominant influenza A virus M158-66 cytotoxic T lymphocyte epitope exhibits degenerate class I major histocompatibility complex restriction in humans."
Choo J.A., Liu J., Toh X., Grotenbreg G.M., Ren E.C.
J. Virol. 88:10613-10623(2014) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 26-298 (ALLELE C*08:01) IN COMPLEX WITH B2M AND PEPTIDE, FUNCTION (ALLELE C*08:01), DOMAIN, DISULFIDE BOND. - Ref.41"Structural and regulatory diversity shape HLA-C protein expression levels."
Kaur G., Gras S., Mobbs J.I., Vivian J.P., Cortes A., Barber T., Kuttikkatte S.B., Jensen L.T., Attfield K.E., Dendrou C.A., Carrington M., McVean G., Purcell A.W., Rossjohn J., Fugger L.
Nat. Commun. 8:15924-15924(2017) [PubMed] [Europe PMC] [Abstract]
(Microbial infection) Interacts with HTLV-1 p12I accessory protein.
1 PublicationManual assertion based on experiment ini
- Ref.23"Free major histocompatibility complex class I heavy chain is preferentially targeted for degradation by human T-cell leukemia/lymphotropic virus type 1 p12(I) protein."
Johnson J.M., Nicot C., Fullen J., Ciminale V., Casareto L., Mulloy J.C., Jacobson S., Franchini G.
J. Virol. 75:6086-6094(2001) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH HTLV-1 ACCESSORY PROTEIN P12I (MICROBIAL INFECTION).
<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi
Show more detailsHide detailsP10321
GO - Molecular functioni
- TAP binding Source: UniProtKBInferred from direct assayi
- "Allele-specific differences in the interaction of MHC class I molecules with transporters associated with antigen processing."
Neisig A., Wubbolts R., Zang X., Melief C., Neefjes J.
J. Immunol. 156:3196-3206(1996) [PubMed] [Europe PMC] [Abstract] - "Point mutations in the alpha 2 domain of HLA-A2.1 define a functionally relevant interaction with TAP."
Lewis J.W., Neisig A., Neefjes J., Elliott T.
Curr. Biol. 6:873-883(1996) [PubMed] [Europe PMC] [Abstract]
Protein-protein interaction databases
The Biological General Repository for Interaction Datasets (BioGrid) More...BioGridi | 109352, 122 interactors |
Protein interaction database and analysis system More...IntActi | P10321, 85 interactors |
Molecular INTeraction database More...MINTi | P10321 |
<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsHide details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/structure%5Fsection">'Structure'</a> section is used to indicate the positions of experimentally determined beta strands within the protein sequence.<p><a href='/help/strand' target='_top'>More...</a></p>Beta strandi | 28 – 36 | Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More...</a></p> Manual assertion inferred from combination of experimental and computational evidencei | 9 | |
| Beta strandi | 41 – 43 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 45 – 52 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 8 | |
| Beta strandi | 55 – 61 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 7 | |
| Beta strandi | 64 – 66 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 70 – 73 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| <p>This subsection of the <a href="http://www.uniprot.org/help/structure%5Fsection">'Structure'</a> section is used to indicate the positions of experimentally determined helical regions within the protein sequence.<p><a href='/help/helix' target='_top'>More...</a></p>Helixi | 74 – 77 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Helixi | 81 – 109 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 29 | |
| Beta strandi | 113 – 115 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 118 – 127 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 10 | |
| Beta strandi | 131 – 142 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 12 | |
| Beta strandi | 145 – 150 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 6 | |
| Beta strandi | 157 – 159 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Helixi | 162 – 173 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 12 | |
| Helixi | 176 – 185 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 10 | |
| Helixi | 187 – 198 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 12 | |
| Helixi | 200 – 203 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 210 – 219 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 10 | |
| Beta strandi | 222 – 235 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 14 | |
| Beta strandi | 238 – 243 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 6 | |
| Helixi | 249 – 251 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 252 – 254 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 261 – 263 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 265 – 274 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 10 | |
| Helixi | 278 – 280 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 281 – 286 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 6 | |
| Beta strandi | 290 – 292 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 294 – 296 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 |
3D structure databases
SWISS-MODEL Repository - a database of annotated 3D protein structure models More...SMRi | P10321 |
Database of comparative protein structure models More...ModBasei | Search... |
Protein Data Bank in Europe - Knowledge Base More...PDBe-KBi | Search... |
<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini | 209 – 297 | Ig-like C1-typeAdd BLAST | 89 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni | 25 – 114 | Alpha-1Sequence analysisAdd BLAST | 90 | |
| Regioni | 115 – 206 | Alpha-2Sequence analysisAdd BLAST | 92 | |
| Regioni | 207 – 298 | Alpha-3Sequence analysisAdd BLAST | 92 | |
| Regioni | 299 – 308 | Connecting peptide | 10 |
<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini
The alpha-1 domain is a structural part of the peptide-binding cleft.1 Publication
Manual assertion based on experiment ini
- Ref.41"Structural and regulatory diversity shape HLA-C protein expression levels."
Kaur G., Gras S., Mobbs J.I., Vivian J.P., Cortes A., Barber T., Kuttikkatte S.B., Jensen L.T., Attfield K.E., Dendrou C.A., Carrington M., McVean G., Purcell A.W., Rossjohn J., Fugger L.
Nat. Commun. 8:15924-15924(2017) [PubMed] [Europe PMC] [Abstract]
The alpha-2 domain is a structural part of the peptide-binding cleft (PubMed:28649982, PubMed:10850706, PubMed:24990997). Mediates the interaction with TAP1-TAP2 complex.3 Publications
Manual assertion based on experiment ini
- Ref.38"Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand."
Boyington J.C., Motyka S.A., Schuck P., Brooks A.G., Sun P.D.
Nature 405:537-543(2000) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 25-302 (ALLELE C*03:04) IN COMPLEX WITH B2M PEPTIDE AND KIR2DL2, DISULFIDE BONDS, DOMAIN. - Ref.40"The immunodominant influenza A virus M158-66 cytotoxic T lymphocyte epitope exhibits degenerate class I major histocompatibility complex restriction in humans."
Choo J.A., Liu J., Toh X., Grotenbreg G.M., Ren E.C.
J. Virol. 88:10613-10623(2014) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 26-298 (ALLELE C*08:01) IN COMPLEX WITH B2M AND PEPTIDE, FUNCTION (ALLELE C*08:01), DOMAIN, DISULFIDE BOND. - Ref.41"Structural and regulatory diversity shape HLA-C protein expression levels."
Kaur G., Gras S., Mobbs J.I., Vivian J.P., Cortes A., Barber T., Kuttikkatte S.B., Jensen L.T., Attfield K.E., Dendrou C.A., Carrington M., McVean G., Purcell A.W., Rossjohn J., Fugger L.
Nat. Commun. 8:15924-15924(2017) [PubMed] [Europe PMC] [Abstract]
The alpha-3 Ig-like domain mediates the interaction with CD8 coreceptor.By similarity
Manual assertion inferred from sequence similarity toi
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
Ensembl GeneTree More...GeneTreei | ENSGT00980000198488 |
KEGG Orthology (KO) More...KOi | K06751 |
Database of Orthologous Groups More...OrthoDBi | 1390181at2759 |
Database for complete collections of gene phylogenies More...PhylomeDBi | P10321 |
TreeFam database of animal gene trees More...TreeFami | TF336617 |
Family and domain databases
Gene3D Structural and Functional Annotation of Protein Families More...Gene3Di | 2.60.40.10, 1 hit 3.30.500.10, 1 hit |
Integrated resource of protein families, domains and functional sites More...InterProi | View protein in InterPro IPR007110 Ig-like_dom IPR036179 Ig-like_dom_sf IPR013783 Ig-like_fold IPR003597 Ig_C1-set IPR011161 MHC_I-like_Ag-recog IPR037055 MHC_I-like_Ag-recog_sf IPR011162 MHC_I/II-like_Ag-recog IPR001039 MHC_I_a_a1/a2 IPR010579 MHC_I_a_C |
Pfam protein domain database More...Pfami | View protein in Pfam PF07654 C1-set, 1 hit PF00129 MHC_I, 1 hit PF06623 MHC_I_C, 1 hit |
Protein Motif fingerprint database; a protein domain database More...PRINTSi | PR01638 MHCCLASSI |
Simple Modular Architecture Research Tool; a protein domain database More...SMARTi | View protein in SMART SM00407 IGc1, 1 hit |
Superfamily database of structural and functional annotation More...SUPFAMi | SSF48726 SSF48726, 1 hit SSF54452 SSF54452, 1 hit |
<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i
<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.
<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.
This entry describes 2 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basketAdded to basketThis entry has 2 described isoforms and 45 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: P10321-1) [UniParc]FASTAAdd to basketAdded to basket
This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
« Hide
Show »10 20 30 40 50
MRVMAPRALL LLLSGGLALT ETWACSHSMR YFDTAVSRPG RGEPRFISVG
60 70 80 90 100
YVDDTQFVRF DSDAASPRGE PRAPWVEQEG PEYWDRETQK YKRQAQADRV
110 120 130 140 150
SLRNLRGYYN QSEDGSHTLQ RMSGCDLGPD GRLLRGYDQS AYDGKDYIAL
160 170 180 190 200
NEDLRSWTAA DTAAQITQRK LEAARAAEQL RAYLEGTCVE WLRRYLENGK
210 220 230 240 250
ETLQRAEPPK THVTHHPLSD HEATLRCWAL GFYPAEITLT WQRDGEDQTQ
260 270 280 290 300
DTELVETRPA GDGTFQKWAA VVVPSGQEQR YTCHMQHEGL QEPLTLSWEP
310 320 330 340 350
SSQPTIPIMG IVAGLAVLVV LAVLGAVVTA MMCRRKSSGG KGGSCSQAAC
360
SNSAQGSDES LITCKA
Length:366
Mass (Da):40,649
Last modified:December 20, 2005 - v3
<p>The checksum is a form of redundancy check that is calculated
from the sequence. It is useful for tracking sequence updates.</p>
<p>It should be noted that while, in theory, two different sequences could
have the same checksum value, the likelihood that this would happen
is extremely low.</p>
<p>However UniProtKB may contain entries with identical sequences in case
of multiple genes (paralogs).</p>
<p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64)
using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1.
The algorithm is described in the ISO 3309 standard.
</p>
<p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br />
<strong>Cyclic redundancy and other checksums</strong><br />
<a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p>
Checksum:i59C23D95FD1D0BC8
Isoform 2 (identifier: P10321-2) [UniParc]FASTAAdd to basketAdded to basket
The sequence of this isoform differs from the canonical sequence as follows:
153-157: DLRSW → HLRSC
297-338: SWEPSSQPTIPIMGIVAGLAVLVVLAVLGAVVTAMMCRRKSS → RW
« Hide
10 20 30 40 50
MRVMAPRALL LLLSGGLALT ETWACSHSMR YFDTAVSRPG RGEPRFISVG
60 70 80 90 100
YVDDTQFVRF DSDAASPRGE PRAPWVEQEG PEYWDRETQK YKRQAQADRV
110 120 130 140 150
SLRNLRGYYN QSEDGSHTLQ RMSGCDLGPD GRLLRGYDQS AYDGKDYIAL
160 170 180 190 200
NEHLRSCTAA DTAAQITQRK LEAARAAEQL RAYLEGTCVE WLRRYLENGK
210 220 230 240 250
ETLQRAEPPK THVTHHPLSD HEATLRCWAL GFYPAEITLT WQRDGEDQTQ
260 270 280 290 300
DTELVETRPA GDGTFQKWAA VVVPSGQEQR YTCHMQHEGL QEPLTLRWGG
310 320
KGGSCSQAAC SNSAQGSDES LITCKA
Note: A transcript of allele C*16:01. This isoform lacks the transmembrane domain and is predicted to be a secreted protein.1 Publication
Show »Manual assertion inferred by curator fromi
- Ref.1"Three new class I HLA alleles: structure of mRNAs and alternative mechanisms of processing."
Cianetti L., Testa U., Scotto L., la Valle R., Simeone A., Boccoli G., Giannella G., Peschle C., Boncinelli E.
Immunogenetics 29:80-91(1989) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE C*16:01), ALTERNATIVE SPLICING.
<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi
There are 45 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket| Entry | Entry name | Protein names | Gene names | Length | Annotation | ||
|---|---|---|---|---|---|---|---|
| Q5QT33 | Q5QT33_HUMAN | HLA class I antigen HLA class I antigen (HLA class I histocompatibility antigen) (HLA class I histocompatibility antigen C alpha chain) (HLA class I histocompatibility antigen Cw-1 alpha chain) (HLA class I histocompatibility antigen, C alpha chain) (HLA-C alpha chain) (MHC class I antigen) (MHC class I protein) | HLA-C HLA-Cw, HLAC | 366 | Annotation score: Annotation score:2 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| O78179 | O78179_HUMAN | HLA class I histocompatibility anti... HLA class I histocompatibility antigen, C alpha chain (HLA-C protein) (MHC class I antigen) (MHC class I protein) | HLA-C HLA-Cw | 366 | Annotation score: Annotation score:2 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| Q53YP1 | Q53YP1_HUMAN | HLA class I histocompatibility anti... HLA class I histocompatibility antigen (HLA class I histocompatibility antigen C alpha chain) (HLA class I histocompatibility antigen, C alpha chain) (MHC class I antigen) | HLA-C HLA-Cw | 366 | Annotation score: Annotation score:2 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| Q5RIP0 | Q5RIP0_HUMAN | HLA class I histocompatibility anti... HLA class I histocompatibility antigen C alpha chain (HLA class I histocompatibility antigen, C alpha chain) (MHC class I antigen) (MHC class I histocompatibility antigen) | HLA-C HLA-Cw | 366 | Annotation score: Annotation score:2 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| A0A140T9J9 | A0A140T9J9_HUMAN | HLA class I histocompatibility anti... HLA class I histocompatibility antigen, C alpha chain | HLA-C | 372 | Annotation score: Annotation score:2 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| A0A0G2JH50 | A0A0G2JH50_HUMAN | HLA class I histocompatibility anti... HLA class I histocompatibility antigen, C alpha chain | HLA-C | 372 | Annotation score: Annotation score:2 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| O19617 | O19617_HUMAN | HLA class I antigen HLA class I antigen (HLA class I histocompatibility antigen) (HLA class I histocompatibility antigen, C alpha chain) (HLA-C protein) (MHC class I antigen) (MHC class I histocompatibility antigen) (MHC class I protein) (Major histocompatibility complex, class I, C) | HLA-C HLA-Cw | 366 | Annotation score: Annotation score:2 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| A0A1W2PRU9 | A0A1W2PRU9_HUMAN | HLA class I histocompatibility anti... HLA class I histocompatibility antigen, C alpha chain | HLA-C | 244 | Annotation score: Annotation score:2 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| A2AEA2 | A2AEA2_HUMAN | HLA class I histocompatibility anti... HLA class I histocompatibility antigen, C alpha chain | HLA-C | 372 | Annotation score: Annotation score:2 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| A0A1W2PNZ7 | A0A1W2PNZ7_HUMAN | HLA class I histocompatibility anti... HLA class I histocompatibility antigen, C alpha chain | HLA-C | 244 | Annotation score: Annotation score:2 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| There are more potential isoformsShow all | |||||||
<p>This subsection of the 'Sequence' section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement%5Fin%5Fdisease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi
Displays lower polymorphism than HLA-A and HLA-B. Polymorphic residues encode for alpha-1 and alpha-2 domains of the peptide-binding cleft, where they contribute to variations in peptide binding and TCR recognition among different alleles. The human population is estimated to have millions of HLA-C alleles. But only 14 common HLA-C alleles are considered core alleles, representing all functionally significant variation (polymorphism) in alpha-1 and alpha-2 domains. These are: C*01:02; C*02:02; C*03:02; C*04:01; C*05:01; C*06:02; C*07:01; C*07:04; C*08:01; C*12:02; C*14:02; C*15:02; C*16:01 and C*17:01. Among these, C*01:02; C*02:02; C*03:02; C*08:01; C*12:02; C*14:02 and C*15:02, were likely passed by introgression from archaic to modern humans. Functional alleles of more recent origin (non-core) were derived by recombination (PubMed:28650991). The sequence shown is that of C*07:02. The sequences of core alleles and common representative alleles of serologically distinct allele groups are described as variants of C*07:02.Curated1 Publication
Manual assertion based on experiment ini
- Ref.46"Distinguishing functional polymorphism from random variation in the sequences of >10,000 HLA-A, -B and -C alleles."
Robinson J., Guethlein L.A., Cereb N., Yang S.Y., Norman P.J., Marsh S.G.E., Parham P.
PLoS Genet. 13:E1006862-E1006862(2017) [PubMed] [Europe PMC] [Abstract]Cited for: POLYMORPHISM.
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_082408 | 7 | R → Q in allele C*17:01. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082409 | 8 | A → T in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02 and allele C*16:01. 13 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082410 | 10 | L → I in allele C*01:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02 and allele C*16:01. 12 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082411 | 16 | G → A in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*17:01. 15 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082412 | 20 | T → I in allele C*17:01. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082413 | 25 | C → G in allele C*03:02, allele C*03:04, allele C*04:01 and allele C*17:01. 7 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082414 | 30 | R → K in allele C*01:02. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082415 | 33 | D → F in allele C*01:02; requires 2 nucleotide substitutions. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082416 | 33 | D → S in allele C*04:01 and allele C*14:02; requires 2 nucleotide substitutions. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082417 | 33 | D → Y in allele C*02:02, allele C*03:02, allele C*03:04, allele C*05:01, allele C*08:01, allele C*12:02, allele C*15:02, allele C*16:01 and allele C*17:01. 13 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082418 | 35 | A → S in allele C*01:02, allele C*04:01 and allele C*14:02. 5 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082419 | 38 | R → W in allele C*04:01. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082420 | 40 | G → S in allele C*02:02. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082421 | 45 | R → H in allele C*02:02, allele C*03:02, allele C*03:04 and allele C*15:02. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082422 | 48 | S → A in allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*17:01. 14 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082423 | 59 | R → Q in allele C*05:01 and C*08:01. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082424 | 73 | A → E in allele C*04:01. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082425 | 90 | K → N in allele C*07:01, C*15:02. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082426 | 97 | A → T in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*05:01, allele C*08:01, allele C*14:02, allele C*15:02 and allele C*16:01. 9 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082427 | 101 | S → N in allele C*02:02, allele C*04:01, allele C*05:01, allele C*06:02, allele C*15:02, allele C*17:01 and allele C*18:01. 11 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082428 | 104 | N → K in allele C*02:02, allele C*04:01, allele C*05:01, allele C*06:02, allele C*15:02, allele C*17:01 and allele C*18:01. 11 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082429 | 114 | D → A in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*05:01, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*17:01. 12 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082430 | 118 | T → I in allele C*03:02, allele C*03:04 and allele C*15:02. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082431 | 119 | L → F in allele C*07:04. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082432 | 119 | L → I in allele C*03:04, allele C*15:02 and allele C*17:01. 5 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082433 | 121 | R → W in allele C*01:02, allele C*06:02, allele C*14:02 and allele C*16:01. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082434 | 123 | S → C in allele C*01:02. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082435 | 123 | S → F in allele C*04:01, allele C*14:02 and allele C*18:01. 5 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082436 | 123 | S → Y in allele C*07:01, allele C*02:02, allele C*03:02, allele C*03:04, allele C*05:01, allele C*06:02, allele C*07:04, allele C*08:01, allele C*12:02, allele C*15:02, allele C*16:01 and allele C*17:01. 14 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082437 | 127 | L → V in allele C*03:02 and allele C*03:04. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082438 | 137 | Y → H in allele C*15:02. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082439 | 138 | D → N in allele C*04:01, allele C*05:01, allele C*08:01, allele C*17:01 and allele C*18:01. 9 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082440 | 140 | S → F in allele C*04:01, allele C*05:01, allele C*07:04, allele C*08:01, allele C*17:01 and allele C*18:01. 10 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082441 | 140 | S → L in allele C*15:02. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082442 | 140 | S → Y in alleles C*01:02, C*03:04. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082443 | 162 | T → K in allele C*05:01. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082444 | 167 | T → S in allele C*17:01. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082445 | 171 | L → W in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*18:01. 14 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082446 | 176 | A → E in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*12:02, allele C*14:02, allele C*15:02, allele C*17:01 and allele C*18:01. 15 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082447 | 176 | A → T in allele C*08:01. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082448 | 180 | L → D in allele C*07:04; requires 2 nucleotide substitutions. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082449 | 180 | L → Q in allele C*16:01. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082450 | 180 | L → R in allele C*01:02, allele C*04:01, allele C*05:01, allele C*14:02 and allele C*18:01. 8 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082451 | 180 | L → W in allele C*02:02, allele C*06:02 and allele C*12:02. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082452 | 187 | T → E in alleles C*02:02 and allele C*17:01; requires 2 nucleotide substitutions. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082453 | 187 | T → L in allele C*03:02 and allele C*03:04; requires 2 nucleotide substitutions. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082454 | 194 | R → G in allele C*17:01. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082455 | 197 | E → K in allele C*03:02 and allele C*03:04. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082456 | 201 | E → K in allele C*05:01, allele C*07:04 and allele C*08:01. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082457 | 208 | P → H in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*18:01. 14 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082458 | 208 | P → R in allele C*17:01. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082459 | 217 | P → L in allele C*16:01. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082460 | 218 | L → V in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01, allele C*17:01 and allele C*18:01. 16 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082461 | 235 | A → T in allele C*02:02. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082462 | 243 | R → W in alleles C*01:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*14:02 and allele C*18:01. 7 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082463 | 272 | V → M in allele C*01:02. Combined sources Manual assertion inferred from combination of experimental and computational evidencei
Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082464 | 277 | Q → E in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*18:01. 14 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082465 | 285 | M → V in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01, allele C*17:01 and allele C*18:01. 16 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082466 | 291 | Q → P in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*18:01. 14 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082467 | 294 | L → C in allele C*17:01; requires 2 nucleotide substitutions. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082468 | 297 | S → R in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01, allele C*17:01 and allele C*18:01. 16 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082469 | 299 | E → G in alleles C*05:01 and allele C*08:01. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082470 | 299 | E → K in allele C*04:01, allele C*17:01 and allele C*18:01. 6 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082471 | 308 – 319 | IMGIV…LAVLV → NLGIVSGPAVLAVLAVLA in allele C*17:01. 2 Publications Manual assertion based on experiment ini
| 12 | |
| Natural variantiVAR_082472 | 309 | M → V in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01 and allele C*18:01. 14 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082473 | 319 | V → A in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02 and allele C*16:01. 13 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082474 | 327 | V → M in allele C*04:01. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082475 | 328 | V → M in allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02 and allele C*15:02. 7 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_082476 | 329 | T → A in allele C*01:02, allele C*02:02, allele C*03:02, allele C*03:04, allele C*04:01, allele C*05:01, allele C*06:02, allele C*08:01, allele C*12:02, allele C*14:02, allele C*15:02, allele C*16:01, allele C*17:01 and allele C*18:01. 16 Publications Manual assertion based on experiment ini
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