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Details on Person UniProt:P04439-1 HLA-A
| Class:Id | ReferenceIsoform:9666226 |
|---|---|
| _chainChangeLog | signal peptide:1-24 for 9666226 added on Fri November 1 2019;chain:25-365 for 9666226 added on Fri November 1 2019 |
| _displayName | UniProt:P04439-1 HLA-A |
| _timestamp | 2026-02-20 22:33:02 |
| chain | signal peptide:1-24 chain:25-365 |
| checksum | DEDFCEC4450E0580 |
| comment | FUNCTION Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-A-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:10449296, PubMed:12138174, PubMed:12393434, PubMed:1402688, PubMed:15893615, PubMed:17189421, PubMed:19543285, PubMed:21498667, PubMed:24192765, PubMed:24395804, PubMed:2456340, PubMed:2784196, PubMed:28250417, PubMed:7504010, PubMed:7694806, PubMed:9862734). May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity (PubMed:25880248, PubMed:7506728, PubMed:7679507). 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 (PubMed:12796775, PubMed:18275829, PubMed:19542454, PubMed:28250417). Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome or via endopeptidase IDE/insulin-degrading enzyme (PubMed:17079320, PubMed:17189421, PubMed:20364150, PubMed:26929325, PubMed:27049119). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:7504010, PubMed:9862734).FUNCTION Allele A*01:01: Presents a restricted peptide repertoire including viral epitopes derived from IAV NP/nucleoprotein (CTELKLSDY), IAV PB1/polymerase basic protein 1 (VSDGGPNLY), HAdV-11 capsid L3/hexon protein (LTDLGQNLLY), SARS-CoV-2 3a/ORF3a (FTSDYYQLY) as well as tumor peptide antigens including MAGE1 (EADPTGHSY), MAGEA3 (EVDPIGHLY) and WT1 (TSEKRPFMCAY), all having in common a canonical motif with a negatively charged Asp or Glu residue at position 3 and a Tyr anchor residue at the C-terminus (PubMed:1402688, PubMed:17189421, PubMed:19177349, PubMed:20364150, PubMed:24395804, PubMed:25880248, PubMed:26758806, PubMed:30530481, PubMed:32887977, PubMed:7504010). A number of HLA-A*01:01-restricted peptides carry a post-translational modification with oxidation and N-terminal acetylation being the most frequent (PubMed:25880248). Fails to present highly immunogenic peptides from the EBV latent antigens (PubMed:18779413).FUNCTION Allele A*02:01: A major allele in human populations, presents immunodominant viral epitopes derived from IAV M/matrix protein 1 (GILGFVFTL), HIV-1 env (TLTSCNTSV), HIV-1 gag-pol (ILKEPVHGV), HTLV-1 Tax (LLFGYPVYV), HBV C/core antigen (FLPSDFFPS), HCMV UL83/pp65 (NLVPMVATV) as well as tumor peptide antigens including MAGEA4 (GVYDGREHTV), WT1 (RMFPNAPYL) and CTAG1A/NY-ESO-1 (SLLMWITQC), all having in common hydrophobic amino acids at position 2 and at the C-terminal anchors.FUNCTION Allele A*03:01: Presents viral epitopes derived from IAV NP (ILRGSVAHK), HIV-1 nef (QVPLRPMTYK), HIV-1 gag-pol (AIFQSSMTK), SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) as well as tumor peptide antigens including PMEL (LIYRRRLMK), NODAL (HAYIQSLLK), TRP-2 (RMYNMVPFF), all having in common hydrophobic amino acids at position 2 and Lys or Arg anchor residues at the C-terminus (PubMed:19543285, PubMed:21943705, PubMed:2456340, PubMed:32887977, PubMed:7504010, PubMed:7679507, PubMed:9862734). May also display spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein (PubMed:27049119).FUNCTION Allele A*11:01: Presents several immunodominant epitopes derived from HIV-1 gag-pol and HHV-4 EBNA4, containing the peptide motif with Val, Ile, Thr, Leu, Tyr or Phe at position 2 and Lys anchor residue at the C-terminus. Important in the control of HIV-1, EBV and HBV infections (PubMed:10449296). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) (PubMed:32887977).FUNCTION Allele A*23:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response.FUNCTION Allele A*24:02: Presents viral epitopes derived from HIV-1 nef (RYPLTFGWCF), EBV lytic- and latent-cycle antigens BRLF1 (TYPVLEEMF), BMLF1 (DYNFVKQLF) and LMP2 (IYVLVMLVL), SARS-CoV nucleocapsid/N (QFKDNVILL), as well as tumor peptide antigens including PRAME (LYVDSLFFL), all sharing a common signature motif, namely an aromatic residue Tyr or Phe at position 2 and a nonhydrophobic anchor residue Phe, Leu or Iso at the C-terminus (PubMed:12393434, PubMed:20844028, PubMed:24192765, PubMed:9047241). Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response (PubMed:17182537, PubMed:18502829).FUNCTION Allele A*26:01: Presents several epitopes derived from HIV-1 gag-pol (EVIPMFSAL, ETKLGKAGY) and env (LVSDGGPNLY), carrying as anchor residues preferentially Glu at position 1, Val or Thr at position 2 and Tyr at the C-terminus.FUNCTION Allele A*29:02: Presents peptides having a common motif, namely a Glu residue at position 2 and Tyr or Leu anchor residues at the C-terminus.FUNCTION Allele A*32:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response.FUNCTION Allele A*68:01: Presents viral epitopes derived from IAV NP (KTGGPIYKR) and HIV-1 tat (ITKGLGISYGR), having a common signature motif namely, Val or Thr at position 2 and positively charged residues Arg or Lys at the C-terminal anchor.FUNCTION Allele A*74:01: Presents immunodominant HIV-1 epitopes derived from gag-pol (GQMVHQAISPR, QIYPGIKVR) and rev (RQIHSISER), carrying an aliphatic residue at position 2 and Arg anchor residue at the C-terminus. May contribute to viral load control in chronic HIV-1 infection.SUBUNIT Heterotrimer that consists of an alpha chain HLA-A, a beta chain B2M and a peptide (peptide-HLA-A-B2M) (PubMed:11502003, PubMed:18275829, PubMed:19177349, PubMed:19542454, PubMed:21943705, PubMed:22245737, PubMed:24395804, PubMed:26758806, PubMed:28250417, PubMed:7504010, PubMed:7506728, PubMed:7679507, PubMed:7694806, PubMed:7935798, PubMed:8805302, PubMed:8906788, PubMed:9177355). Early in biogenesis, HLA-A-B2M dimer interacts with the components of the peptide-loading complex composed of TAPBP, TAP1-TAP2, TAPBPL, PDIA3/ERP57 and CALR (PubMed:21263072). Interacts with TAP1-TAP2 transporter via TAPBP; this interaction is obligatory for the loading of peptide epitopes delivered to the ER by TAP1-TAP2 transporter (PubMed:21263072, PubMed:8630735, PubMed:8805302). Interacts with TAPBPL; TAPBPL binds peptide-free HLA-A-B2M complexes or those loaded with low affinity peptides, likely facilitating peptide exchange for higher affinity peptides (PubMed:26869717, PubMed:35725941). Only optimally assembled peptide-HLA-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-A (via polymorphic alpha-1 and alpha-2 domains) interacts with antigen-specific TCR (via CDR3 domains) (PubMed:12796775, PubMed:18275829, PubMed:22245737). One HLA-A molecule (mainly via nonpolymorphic alpha-3 domain) interacts with one CD8A homodimer (via CDR-like loop); this interaction ensures peptide-HLA-A-B2M recognition by CD8-positive T cells only (PubMed:2784196, PubMed:9177355). Alleles A*23:01; A*24:02 and A*32:01 interact (via Bw4 motif) with KIR3DL1 on NK cells; this interaction is direct.SUBUNIT (Microbial infection) Interacts with HHV-8 MIR1 protein.SUBUNIT (Microbial infection) Interacts with HTLV-1 accessory protein p12I.INTERACTION Ubiquitous.INDUCTION Up-regulated by IFNG, and pro-inflammatory cytokines IL1B and TNF.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:19177349, PubMed:19542454, PubMed:20619457, PubMed:20844028, PubMed:21543847, PubMed:21943705, PubMed:22245737, PubMed:24395804, PubMed:26758806, PubMed:2784196, PubMed:28250417, PubMed:7694806, PubMed:8906788). Mediates the interaction with TAP1-TAP2 complex (PubMed:8805302).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-A allotypes contain functional VL9 peptides (VMAPRTLLL, VMAPRTLVL and VPAPRTLLL).PTM (Microbial infection) Polyubiquitinated in a post ER compartment by interaction with human herpesvirus 8 MIR1 protein. This targets the protein for rapid degradation via the ubiquitin system.PTM N-linked glycosylation at Asn-110.POLYMORPHISM Highly polymorphic. 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-A alleles. But only 11 common HLA-A alleles are considered core alleles, representing all functionally significant variation (polymorphism) in alpha-1 and alpha-2 domains. These are: A*01:01; A*02:01; A*02:05; A*03:01; A*11:01; A*24:02; A*26:01; A*29:02; A*30:01; A*74:01 and A*80:01. Among these, A*02:01; A*11:01; A*24:02 and A*26:01, 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 A*03:01. The sequences of core alleles and common representative alleles of serologically distinct allele groups are described as variants of A*03:01 (PubMed:28650991). Allelic variations of HLA-A 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 (PubMed:37264229). Allele A*31:01 is associated with carbamazepine-induced hypersensitivity reactions among subjects of Northern European ancestry [MIM:608579] (PubMed:21428769).DISEASE Alleles A*02:01 and A*24:02 are associated with increased susceptibility to diabetes mellitus, insulin-dependent (IDDM) (PubMed:16731854, PubMed:18802479, PubMed:22245737, PubMed:22522618). In a glucose-dependent way, allele A*02:01 may aberrantly present the signal peptide of preproinsulin (ALWGPDPAAA) on the surface of pancreatic beta cells to autoreactive CD8-positive T cells, potentially driving T-cell mediated cytotoxicity in pancreatic islets (PubMed:18802479, PubMed:22245737). Allele A*24:02 may present the signal peptide of preproinsulin (LWMRLLPLL) and contribute to acute pancreatic beta-cell destruction and early onset of IDDM (PubMed:16731854, PubMed:22522618).DISEASE Allele A*03:01 is associated with increased susceptibility to multiple sclerosis (MS), an autoimmune disease of the central nervous system (PubMed:10746785). May contribute to the initiation phase of the disease by presenting myelin PLP1 self-peptide (KLIETYFSK) to autoreactive CD8-positive T cells capable of initiating the first autoimmune attacks (PubMed:18953350).DISEASE Allele A*26:01 is associated with increased susceptibility to Behcet disease (BD) in the Northeast Asian population. Especially in the HLA-B*51-negative BD populations, HLA-A*26 is significantly associated with the onset of BD.DISEASE Allele A*29:02 is associated with increased susceptibility to birdshot chorioretinopathy (BSCR). May aberrantly present retinal autoantigens and induce autoimmune uveitis.SIMILARITY Belongs to the MHC class I family. |
| created | [InstanceEdit:9666080] Weiser, JD |
| description | recommendedName: HLA class I histocompatibility antigen, A alpha chain alternativeName: Human leukocyte antigen A shortName: HLA-A |
| geneName | HLA-A HLAA |
| identifier | P04439 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Adaptive immunity Alternative splicing Cell membrane Direct protein sequencing Disulfide bond Endoplasmic reticulum Glycoprotein Host-virus interaction Immunity Immunoglobulin domain Innate immunity Membrane MHC I Phosphoprotein Proteomics identification Reference proteome Signal Sulfation Transmembrane Transmembrane helix Ubl conjugation |
| 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 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | HLA-A |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8962512] ENSEMBL:ENSG00000206503 HLA-A [Homo sapiens] |
| secondaryIdentifier | HLAA_HUMAN B1PKZ3 O02939 O02954 O02955 O02963 O19509 O19546 O19598 O19605 O19606 O19619 O19647 O19673 O19687 O19695 O19756 O19794 O19795 O43906 O43907 O46874 O62921 O62924 O77937 O77938 O77964 O78073 O78171 O98009 O98010 O98011 O98137 P01891 P01892 P05534 P06338 P10313 P10314 P10315 P10316 P13746 P16188 P16189 P16190 P18462 P30443 P30444 P30445 P30446 P30447 P30448 P30449 P30450 P30451 P30452 P30453 P30454 P30455 P30456 P30457 P30458 P30459 P30512 P30514 P79505 P79562 P79563 Q09160 Q29680 Q29747 Q29835 Q29837 Q29838 Q29899 Q29908 Q29909 Q29910 Q30208 Q31623 Q5S3G1 Q65A82 Q8MHM1 Q8MHN9 Q95352 Q95355 Q95362 Q95377 Q95380 Q95IZ5 Q9BCN0 Q9BD15 Q9BD19 Q9GJE6 Q9GJE7 Q9GJE8 Q9MW42 Q9MY89 Q9MYA3 Q9MYA5 Q9MYC4 Q9MYE6 Q9MYE9 Q9MYG4 Q9MYG5 Q9MYI5 Q9TP25 Q9TPQ3 Q9TPR8 Q9TPX8 Q9TPX9 Q9TPY0 Q9TQ24 Q9TQE8 Q9TQE9 Q9TQF1 Q9TQF5 Q9TQF8 Q9TQF9 Q9TQG0 Q9TQG5 Q9TQG7 Q9TQH5 Q9TQI3 Q9TQK5 Q9TQM6 Q9TQN5 Q9TQP5 Q9TQP6 Q9TQP7 Q9UIN1 Q9UIN2 Q9UIP7 Q9UQU3 Q9UQU6 Q9UQU7 |
| sequenceLength | 365 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | P04439-1 |
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No pathways have been reviewed or authored by UniProt:P04439-1 HLA-A (9666226)
