Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person UniProt:P10321 HLA-C
| Class:Id | ReferenceGeneProduct:49109 |
|---|---|
| _chainChangeLog | signal peptide:1-24 added on Fri February 6 2015;chain:25-366 added on Fri February 6 2015 |
| _displayName | UniProt:P10321 HLA-C |
| _timestamp | 2024-11-03 19:51:33 |
| chain | signal peptide:1-24 chain:25-366 |
| checksum | 59C23D95FD1D0BC8 |
| comment | FUNCTION Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity (PubMed:11172028, PubMed:20104487, PubMed:20439706, PubMed:20972337, PubMed:24091323, 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:25311805, PubMed:8265661).FUNCTION 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).FUNCTION 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).FUNCTION ALLELE C*05:01: Presents HIV-1 epitope derived from rev (SAEPVPLQL) to CD8-positive T cells, triggering T cell cytotoxic response.FUNCTION 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.FUNCTION 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.FUNCTION ALLELE C*08:01: Presents viral epitopes derived from CMV UL83 (VVCAHELVC) and IAV M1 (GILGFVFTL), triggering CD8-positive T cell cytotoxic response.FUNCTION ALLELE C*12:02: Presents CMV epitope derived from UL83 (VAFTSHEHF) to CD8-positive T cells.FUNCTION ALLELE C*15:02: Presents CMV epitope derived from UL83 CC (VVCAHELVC) to CD8-positive T cells, triggering T cell cytotoxic response.SUBUNIT Heterotrimer that consists of an alpha chain HLA-C, a beta chain B2M and a peptide (peptide-HLA-C-B2M) (PubMed:10850706, PubMed:24990997, PubMed:28649982). 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 ensures 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:10850706, PubMed:11323700, PubMed:16141329, PubMed:20439706, PubMed:20972337, PubMed:24091323).SUBUNIT (Microbial infection) Interacts with HTLV-1 p12I accessory protein.INTERACTION Ubiquitous. Highly expressed in fetal extravillous trophoblasts in the decidua basalis (at protein level).DOMAIN The alpha-1 domain is a structural part of the peptide-binding cleft.DOMAIN The alpha-2 domain is a structural part of the peptide-binding cleft (PubMed:10850706, PubMed:24990997, PubMed:28649982). Mediates the interaction with TAP1-TAP2 complex.DOMAIN The alpha-3 Ig-like domain mediates the interaction with CD8 coreceptor.DOMAIN The VL9 peptide/epitope (VMAPRT[V/L][L/V/I/F]L) derived from the signal sequence is loaded onto HLA-E and enables HLA-E expression at the plasma membrane. Distinct VL9 peptides presented by HLA-E variably affect its recognition by KLRD1-KLRC1 or KLRD1-KLRC2 receptors on NK cells, setting NK cell activation threshold. Common HLA-C allotypes contain functional VL9 peptides (VMAPRTLIL and VMAPRTLLL). VL9 peptides (VMAPRTALL and VMAPRQALL) derived from HLA-C*07, C*17 and C*18 allotypes display low affinity for HLA-E and fail to drive NK cell activation.PTM 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.POLYMORPHISM 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. Allelic variations of HLA-C signal peptide regulate HLA-E recognition by KLRD1-KLRC1 and KLRD1-KLRC2 receptors in viral infection and tumorigenesis by affecting its processing and by changing the affinity of HLA-E-VL9 complex for KLRD1-KLRC1 and KLRD1-KLRC2 receptors.DISEASE Disease susceptibility is associated with variants 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.MISCELLANEOUS A transcript of allele C*16:01. This isoform lacks the transmembrane domain and is predicted to be a secreted protein. |
| description | recommendedName: HLA class I histocompatibility antigen, C alpha chain shortName: HLA-C alternativeName: HLA-Cw alternativeName: Human leukocyte antigen C |
| geneName | HLA-C HLAC |
| identifier | P10321 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Adaptive immunity Alternative splicing Cell membrane Disulfide bond Endoplasmic reticulum Glycoprotein Host-virus interaction Immunity Innate immunity Membrane MHC I Phosphoprotein Proteomics identification Reference proteome Signal Transmembrane Transmembrane helix |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | HLA-C |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8962164] ENSEMBL:ENSG00000204525 HLA-C [Homo sapiens] |
| secondaryIdentifier | HLAC_HUMAN O02863 O02864 O02865 O02866 O02958 O19505 O19652 O19676 O62879 O62882 O62883 O62888 O78060 O78061 O78062 O78063 O78067 O78068 O78069 O78072 O78083 O78090 O78091 O78149 O78165 O78166 O78178 O78202 O78203 O78211 O78214 P04222 P30499 P30500 P30501 P30502 P30503 P30504 P30505 P30506 P30507 P30508 P30509 P30510 P79498 Q07000 Q29631 Q29641 Q29643 Q29652 Q29743 Q29768 Q29862 Q29864 Q29865 Q29867 Q29921 Q29959 Q29960 Q29963 Q29986 Q29989 Q29990 Q29991 Q29992 Q29993 Q30192 Q31605 Q31627 Q860R1 Q860R2 Q95463 Q95603 Q95604 Q99528 Q9BD28 Q9GIK4 Q9GIK8 Q9GJ33 Q9MY30 Q9MY31 Q9MY35 Q9MY49 Q9MY74 Q9MYI3 Q9TNN7 Q9TNZ8 Q9TPS4 Q9TPV8 Q9TPX2 Q9TQB4 Q9TQJ5 Q9TQP9 Q9UM32 Q9UM33 Q9UM42 Q9UQS9 |
| sequenceLength | 366 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:9666228] UniProt:P10321-1 HLA-C [Homo sapiens] [ReferenceIsoform:9666229] UniProt:P10321-2 HLA-C [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:199595] HLA class I histocompatibility antigen, Cw-7 alpha chain precursor [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:983044] HLA class I histocompatibility antigen, Cw-7 alpha chain precursor [lumenal side of endoplasmic reticulum membrane] [Homo sapiens] [EntityWithAccessionedSequence:983354] HLA class I histocompatibility antigen, Cw-7 alpha chain precursor [ER to Golgi transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:983387] HLA class I histocompatibility antigen, Cw-7 alpha chain precursor [Golgi membrane] [Homo sapiens] [EntityWithAccessionedSequence:1236760] HLA class I histocompatibility antigen, Cw-7 alpha chain precursor [phagocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:1236799] HLA class I histocompatibility antigen, Cw-7 alpha chain precursor [early endosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:6803292] HLA class I histocompatibility antigen, Cw-7 alpha chain precursor [secretory granule membrane] [Homo sapiens] [EntityWithAccessionedSequence:8863915] HLA class I histocompatibility antigen, Cw-7 alpha chain precursor [recycling endosome membrane] [Homo sapiens] |
| (referenceSequence) | [GroupModifiedResidue:9985191] N4-(N-acetylamino)glucosyl-L-asparagine (N-(α-Glc-(1→3)-α-Man-(1→2)-α-Man-(1→2)-α-Man-(1→3)-(α-Man-(1→2)-α-Man-(1→3)-(α-Man-(1→2)-α-Man-(1→6))-α-Man-(1→6))-β-Man-(1→4)-β-GlcNAc-(1→4)-β-GlcNAc)-L-Asn residue) at 110 |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:P10321 HLA-C (49109)
