UniProt functional annotation for P04439



	UniProt functional annotation for P04439

UniProt codes: P04439, P01892, P05534, P13746.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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:2456340, PubMed:2784196, PubMed:1402688, PubMed:7504010, PubMed:9862734, PubMed:10449296, PubMed:12138174, PubMed:12393434, PubMed:15893615, PubMed:17189421, PubMed:19543285, PubMed:21498667, PubMed:24192765, PubMed:7694806, PubMed:24395804, PubMed:28250417). 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:17189421, PubMed:20364150, PubMed:17079320, 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). {ECO:0000269|PubMed:10449296, ECO:0000269|PubMed:12138174, ECO:0000269|PubMed:12393434, ECO:0000269|PubMed:12796775, ECO:0000269|PubMed:1402688, ECO:0000269|PubMed:15893615, ECO:0000269|PubMed:17079320, ECO:0000269|PubMed:17189421, ECO:0000269|PubMed:18275829, ECO:0000269|PubMed:19542454, ECO:0000269|PubMed:19543285, ECO:0000269|PubMed:20364150, ECO:0000269|PubMed:21498667, ECO:0000269|PubMed:24192765, ECO:0000269|PubMed:24395804, ECO:0000269|PubMed:2456340, ECO:0000269|PubMed:25880248, ECO:0000269|PubMed:26929325, ECO:0000269|PubMed:27049119, ECO:0000269|PubMed:2784196, ECO:0000269|PubMed:28250417, ECO:0000269|PubMed:7504010, ECO:0000269|PubMed:7506728, ECO:0000269|PubMed:7679507, ECO:0000269|PubMed:7694806, ECO:0000269|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:7504010, PubMed:17189421, PubMed:20364150, PubMed:25880248, PubMed:30530481, PubMed:19177349, PubMed:24395804, PubMed:26758806, PubMed:32887977). 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). {ECO:0000269|PubMed:1402688, ECO:0000269|PubMed:17189421, ECO:0000269|PubMed:18779413, ECO:0000269|PubMed:19177349, ECO:0000269|PubMed:20364150, ECO:0000269|PubMed:24395804, ECO:0000269|PubMed:25880248, ECO:0000269|PubMed:26758806, ECO:0000269|PubMed:30530481, ECO:0000269|PubMed:7504010}.

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. {ECO:0000269|PubMed:11502003, ECO:0000269|PubMed:12138174, ECO:0000269|PubMed:12796775, ECO:0000269|PubMed:17079320, ECO:0000269|PubMed:18275829, ECO:0000269|PubMed:19542454, ECO:0000269|PubMed:20619457, ECO:0000269|PubMed:22245737, ECO:0000269|PubMed:26929325, ECO:0000269|PubMed:2784196, ECO:0000269|PubMed:28250417, ECO:0000269|PubMed:7694806, ECO:0000269|PubMed:7935798, ECO:0000269|PubMed:8630735, ECO:0000269|PubMed:8805302, ECO:0000269|PubMed:8906788, ECO:0000269|PubMed:9177355}.

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:7504010, PubMed:7679507, PubMed:9862734, PubMed:19543285, PubMed:21943705, PubMed:2456340, PubMed:32887977). 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). {ECO:0000269|PubMed:19543285, ECO:0000269|PubMed:21943705, ECO:0000269|PubMed:2456340, ECO:0000269|PubMed:27049119, ECO:0000269|PubMed:7504010, ECO:0000269|PubMed:7679507, ECO:0000269|PubMed:9862734}.

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). {ECO:0000269|PubMed:10449296, ECO:0000269|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. {ECO:0000269|PubMed:17182537}.

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:9047241, PubMed:12393434, PubMed:24192765, PubMed:20844028). 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). {ECO:0000269|PubMed:12393434, ECO:0000269|PubMed:17182537, ECO:0000269|PubMed:18502829, ECO:0000269|PubMed:20844028, ECO:0000269|PubMed:24192765, ECO:0000269|PubMed:9047241}.

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. {ECO:0000269|PubMed:15893615}.

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. {ECO:0000269|PubMed:8622959}.

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. {ECO:0000269|PubMed:17182537}.

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. {ECO:0000269|PubMed:1448153, ECO:0000269|PubMed:1448154, ECO:0000269|PubMed:2784196}.

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. {ECO:0000269|PubMed:21498667}.

Subunit: Heterotrimer that consists of an alpha chain HLA-A, a beta chain B2M and a peptide (peptide-HLA-A-B2M) (PubMed:7504010, PubMed:7679507, PubMed:21943705, PubMed:19177349, PubMed:24395804, PubMed:26758806, PubMed:7504010, PubMed:7506728, PubMed:8805302, PubMed:7694806, PubMed:7935798, PubMed:9177355, PubMed:18275829, PubMed:22245737, PubMed:28250417, PubMed:11502003, PubMed:8906788, PubMed:19542454). 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:8805302, PubMed:8630735, PubMed:21263072). 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). 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:22245737, PubMed:12796775, PubMed:18275829). One HLA-A molecule (mainly via nonpolymorphic alpha-3 domain) interacts with one CD8A homodimer (via CDR-like loop); this interaction insures peptide- HLA-A-B2M recognition by CD8-positive T cells only (PubMed:9177355, PubMed:2784196). Alleles A*23:01; A*24:02 and A*32:01 interact (via Bw4 motif) with KIR3DL1 on NK cells; this interaction is direct. {ECO:0000269|PubMed:11502003, ECO:0000269|PubMed:12796775, ECO:0000269|PubMed:17182537, ECO:0000269|PubMed:18275829, ECO:0000269|PubMed:18502829, ECO:0000269|PubMed:19177349, ECO:0000269|PubMed:21263072, ECO:0000269|PubMed:21943705, ECO:0000269|PubMed:22245737, ECO:0000269|PubMed:24395804, ECO:0000269|PubMed:26758806, ECO:0000269|PubMed:26869717, ECO:0000269|PubMed:2784196, ECO:0000269|PubMed:28250417, ECO:0000269|PubMed:7504010, ECO:0000269|PubMed:7506728, ECO:0000269|PubMed:7679507, ECO:0000269|PubMed:7694806, ECO:0000269|PubMed:7935798, ECO:0000269|PubMed:8630735, ECO:0000269|PubMed:8805302, ECO:0000269|PubMed:9177355}.

Subunit: (Microbial infection) Interacts with HHV-8 MIR1 protein. {ECO:0000269|PubMed:12006494}.

Subunit: (Microbial infection) Interacts with HTLV-1 accessory protein p12I. {ECO:0000269|PubMed:11390610}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:21263072, ECO:0000269|PubMed:25880248, ECO:0000269|PubMed:8805302}; Single-pass type I membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000305|PubMed:8805302}; Single-pass type I membrane protein {ECO:0000255}.

Tissue specificity: Ubiquitous. {ECO:0000305}.

Induction: Up-regulated by IFNG, and proinflammatory cytokines IL1B and TNF. {ECO:0000269|PubMed:21263072, ECO:0000269|PubMed:22245737}.

Domain: The alpha-1 domain is a structural part of the peptide-binding cleft. {ECO:0000269|PubMed:19177349, ECO:0000269|PubMed:19542454, ECO:0000269|PubMed:20619457, ECO:0000269|PubMed:20844028, ECO:0000269|PubMed:21943705, ECO:0000269|PubMed:22245737, ECO:0000269|PubMed:24395804, ECO:0000269|PubMed:26758806, ECO:0000269|PubMed:2784196, ECO:0000269|PubMed:7694806, ECO:0000269|PubMed:8906788}.

Domain: The alpha-2 domain is a structural part of the peptide-binding cleft (PubMed:21543847, PubMed:21943705, PubMed:19177349, PubMed:26758806, PubMed:24395804, PubMed:7694806, PubMed:8906788, PubMed:2784196, PubMed:28250417, PubMed:22245737, PubMed:19542454, PubMed:20619457, PubMed:20844028). Mediates the interaction with TAP1- TAP2 complex (PubMed:8805302). {ECO:0000269|PubMed:19177349, ECO:0000269|PubMed:19542454, ECO:0000269|PubMed:20619457, ECO:0000269|PubMed:20844028, ECO:0000269|PubMed:21543847, ECO:0000269|PubMed:21943705, ECO:0000269|PubMed:22245737, ECO:0000269|PubMed:24395804, ECO:0000269|PubMed:26758806, ECO:0000269|PubMed:2784196, ECO:0000269|PubMed:28250417, ECO:0000269|PubMed:7694806, ECO:0000269|PubMed:8805302, ECO:0000269|PubMed:8906788}.

Domain: The alpha-3 Ig-like domain mediates the interaction with CD8 coreceptor. {ECO:0000269|PubMed:2784196}.

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. {ECO:0000269|PubMed:12006494}.

Ptm: N-linked glycosylation at Asn-110. {ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:21263072}.

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). Allele A*31:01 is associated with carbamazepine-induced hypersensitivity reactions among subjects of Northern European ancestry [MIM:608579] (PubMed:21428769). {ECO:0000269|PubMed:21428769, ECO:0000269|PubMed:28650991}.

Disease: Note=Alleles A*02:01 and A*24:02 are associated with increased susceptibility to diabetes mellitus, insulin-dependent (IDDM) (PubMed:22245737, PubMed:18802479, PubMed:16731854, 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:22245737, PubMed:18802479). 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). {ECO:0000269|PubMed:16731854, ECO:0000269|PubMed:18802479, ECO:0000269|PubMed:22245737, ECO:0000269|PubMed:22522618}.

Disease: Note=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). {ECO:0000269|PubMed:10746785, ECO:0000269|PubMed:18953350}.

Disease: Note=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. {ECO:0000269|PubMed:30872678}.

Disease: Note=Allele A*29:02 is associated with increased susceptibility to birdshot chorioretinopathy (BSCR). May aberrantly present retinal autoantigens and induce autoimmune uveitis. {ECO:0000269|PubMed:1728143}.

Similarity: Belongs to the MHC class I family. {ECO:0000305}.

Sequence caution: Sequence=CAA25162.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305|PubMed:6609814};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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:2456340, PubMed:2784196, PubMed:1402688, PubMed:7504010, PubMed:9862734, PubMed:10449296, PubMed:12138174, PubMed:12393434, PubMed:15893615, PubMed:17189421, PubMed:19543285, PubMed:21498667, PubMed:24192765, PubMed:7694806, PubMed:24395804, PubMed:28250417). 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:17189421, PubMed:20364150, PubMed:17079320, 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). {ECO:0000269\|PubMed:10449296, ECO:0000269\|PubMed:12138174, ECO:0000269\|PubMed:12393434, ECO:0000269\|PubMed:12796775, ECO:0000269\|PubMed:1402688, ECO:0000269\|PubMed:15893615, ECO:0000269\|PubMed:17079320, ECO:0000269\|PubMed:17189421, ECO:0000269\|PubMed:18275829, ECO:0000269\|PubMed:19542454, ECO:0000269\|PubMed:19543285, ECO:0000269\|PubMed:20364150, ECO:0000269\|PubMed:21498667, ECO:0000269\|PubMed:24192765, ECO:0000269\|PubMed:24395804, ECO:0000269\|PubMed:2456340, ECO:0000269\|PubMed:25880248, ECO:0000269\|PubMed:26929325, ECO:0000269\|PubMed:27049119, ECO:0000269\|PubMed:2784196, ECO:0000269\|PubMed:28250417, ECO:0000269\|PubMed:7504010, ECO:0000269\|PubMed:7506728, ECO:0000269\|PubMed:7679507, ECO:0000269\|PubMed:7694806, ECO:0000269\|PubMed:9862734}.



Function:		Allele A01:01: 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:7504010, PubMed:17189421, PubMed:20364150, PubMed:25880248, PubMed:30530481, PubMed:19177349, PubMed:24395804, PubMed:26758806, PubMed:32887977). A number of HLA-A01:01-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). {ECO:0000269\|PubMed:1402688, ECO:0000269\|PubMed:17189421, ECO:0000269\|PubMed:18779413, ECO:0000269\|PubMed:19177349, ECO:0000269\|PubMed:20364150, ECO:0000269\|PubMed:24395804, ECO:0000269\|PubMed:25880248, ECO:0000269\|PubMed:26758806, ECO:0000269\|PubMed:30530481, ECO:0000269\|PubMed:7504010}.



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. {ECO:0000269\|PubMed:11502003, ECO:0000269\|PubMed:12138174, ECO:0000269\|PubMed:12796775, ECO:0000269\|PubMed:17079320, ECO:0000269\|PubMed:18275829, ECO:0000269\|PubMed:19542454, ECO:0000269\|PubMed:20619457, ECO:0000269\|PubMed:22245737, ECO:0000269\|PubMed:26929325, ECO:0000269\|PubMed:2784196, ECO:0000269\|PubMed:28250417, ECO:0000269\|PubMed:7694806, ECO:0000269\|PubMed:7935798, ECO:0000269\|PubMed:8630735, ECO:0000269\|PubMed:8805302, ECO:0000269\|PubMed:8906788, ECO:0000269\|PubMed:9177355}.



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:7504010, PubMed:7679507, PubMed:9862734, PubMed:19543285, PubMed:21943705, PubMed:2456340, PubMed:32887977). 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). {ECO:0000269\|PubMed:19543285, ECO:0000269\|PubMed:21943705, ECO:0000269\|PubMed:2456340, ECO:0000269\|PubMed:27049119, ECO:0000269\|PubMed:7504010, ECO:0000269\|PubMed:7679507, ECO:0000269\|PubMed:9862734}.



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). {ECO:0000269\|PubMed:10449296, ECO:0000269\|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. {ECO:0000269\|PubMed:17182537}.



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:9047241, PubMed:12393434, PubMed:24192765, PubMed:20844028). 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). {ECO:0000269\|PubMed:12393434, ECO:0000269\|PubMed:17182537, ECO:0000269\|PubMed:18502829, ECO:0000269\|PubMed:20844028, ECO:0000269\|PubMed:24192765, ECO:0000269\|PubMed:9047241}.



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. {ECO:0000269\|PubMed:15893615}.



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. {ECO:0000269\|PubMed:8622959}.



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. {ECO:0000269\|PubMed:17182537}.



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. {ECO:0000269\|PubMed:1448153, ECO:0000269\|PubMed:1448154, ECO:0000269\|PubMed:2784196}.



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. {ECO:0000269\|PubMed:21498667}.


Subunit:		Heterotrimer that consists of an alpha chain HLA-A, a beta chain B2M and a peptide (peptide-HLA-A-B2M) (PubMed:7504010, PubMed:7679507, PubMed:21943705, PubMed:19177349, PubMed:24395804, PubMed:26758806, PubMed:7504010, PubMed:7506728, PubMed:8805302, PubMed:7694806, PubMed:7935798, PubMed:9177355, PubMed:18275829, PubMed:22245737, PubMed:28250417, PubMed:11502003, PubMed:8906788, PubMed:19542454). 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:8805302, PubMed:8630735, PubMed:21263072). 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). 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:22245737, PubMed:12796775, PubMed:18275829). One HLA-A molecule (mainly via nonpolymorphic alpha-3 domain) interacts with one CD8A homodimer (via CDR-like loop); this interaction insures peptide- HLA-A-B2M recognition by CD8-positive T cells only (PubMed:9177355, PubMed:2784196). Alleles A23:01; A24:02 and A*32:01 interact (via Bw4 motif) with KIR3DL1 on NK cells; this interaction is direct. {ECO:0000269\|PubMed:11502003, ECO:0000269\|PubMed:12796775, ECO:0000269\|PubMed:17182537, ECO:0000269\|PubMed:18275829, ECO:0000269\|PubMed:18502829, ECO:0000269\|PubMed:19177349, ECO:0000269\|PubMed:21263072, ECO:0000269\|PubMed:21943705, ECO:0000269\|PubMed:22245737, ECO:0000269\|PubMed:24395804, ECO:0000269\|PubMed:26758806, ECO:0000269\|PubMed:26869717, ECO:0000269\|PubMed:2784196, ECO:0000269\|PubMed:28250417, ECO:0000269\|PubMed:7504010, ECO:0000269\|PubMed:7506728, ECO:0000269\|PubMed:7679507, ECO:0000269\|PubMed:7694806, ECO:0000269\|PubMed:7935798, ECO:0000269\|PubMed:8630735, ECO:0000269\|PubMed:8805302, ECO:0000269\|PubMed:9177355}.
Subunit:		(Microbial infection) Interacts with HHV-8 MIR1 protein. {ECO:0000269\|PubMed:12006494}.
Subunit:		(Microbial infection) Interacts with HTLV-1 accessory protein p12I. {ECO:0000269\|PubMed:11390610}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:21263072, ECO:0000269\|PubMed:25880248, ECO:0000269\|PubMed:8805302}; Single-pass type I membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000305\|PubMed:8805302}; Single-pass type I membrane protein {ECO:0000255}.
Tissue specificity:		Ubiquitous. {ECO:0000305}.
Induction:		Up-regulated by IFNG, and proinflammatory cytokines IL1B and TNF. {ECO:0000269\|PubMed:21263072, ECO:0000269\|PubMed:22245737}.
Domain:		The alpha-1 domain is a structural part of the peptide-binding cleft. {ECO:0000269\|PubMed:19177349, ECO:0000269\|PubMed:19542454, ECO:0000269\|PubMed:20619457, ECO:0000269\|PubMed:20844028, ECO:0000269\|PubMed:21943705, ECO:0000269\|PubMed:22245737, ECO:0000269\|PubMed:24395804, ECO:0000269\|PubMed:26758806, ECO:0000269\|PubMed:2784196, ECO:0000269\|PubMed:7694806, ECO:0000269\|PubMed:8906788}.
Domain:		The alpha-2 domain is a structural part of the peptide-binding cleft (PubMed:21543847, PubMed:21943705, PubMed:19177349, PubMed:26758806, PubMed:24395804, PubMed:7694806, PubMed:8906788, PubMed:2784196, PubMed:28250417, PubMed:22245737, PubMed:19542454, PubMed:20619457, PubMed:20844028). Mediates the interaction with TAP1- TAP2 complex (PubMed:8805302). {ECO:0000269\|PubMed:19177349, ECO:0000269\|PubMed:19542454, ECO:0000269\|PubMed:20619457, ECO:0000269\|PubMed:20844028, ECO:0000269\|PubMed:21543847, ECO:0000269\|PubMed:21943705, ECO:0000269\|PubMed:22245737, ECO:0000269\|PubMed:24395804, ECO:0000269\|PubMed:26758806, ECO:0000269\|PubMed:2784196, ECO:0000269\|PubMed:28250417, ECO:0000269\|PubMed:7694806, ECO:0000269\|PubMed:8805302, ECO:0000269\|PubMed:8906788}.
Domain:		The alpha-3 Ig-like domain mediates the interaction with CD8 coreceptor. {ECO:0000269\|PubMed:2784196}.
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. {ECO:0000269\|PubMed:12006494}.
Ptm:		N-linked glycosylation at Asn-110. {ECO:0000269\|PubMed:19159218, ECO:0000269\|PubMed:21263072}.
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: A01:01; A02:01; A02:05; A03:01; A11:01; A24:02; A26:01; A29:02; A30:01; A74:01 and A80:01. Among these, A02:01; A11:01; A24:02 and A26:01, 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 A03:01. The sequences of core alleles and common representative alleles of serologically distinct allele groups are described as variants of A03:01 (PubMed:28650991). Allele A31:01 is associated with carbamazepine-induced hypersensitivity reactions among subjects of Northern European ancestry [MIM:608579] (PubMed:21428769). {ECO:0000269\|PubMed:21428769, ECO:0000269\|PubMed:28650991}.
Disease:		Note=Alleles A02:01 and A24:02 are associated with increased susceptibility to diabetes mellitus, insulin-dependent (IDDM) (PubMed:22245737, PubMed:18802479, PubMed:16731854, PubMed:22522618). In a glucose-dependent way, allele A02:01 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:22245737, PubMed:18802479). Allele A24:02 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). {ECO:0000269\|PubMed:16731854, ECO:0000269\|PubMed:18802479, ECO:0000269\|PubMed:22245737, ECO:0000269\|PubMed:22522618}.
Disease:		Note=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). {ECO:0000269\|PubMed:10746785, ECO:0000269\|PubMed:18953350}.
Disease:		Note=Allele A26:01 is associated with increased susceptibility to Behcet disease (BD) in the Northeast Asian population. Especially in the HLA-B51-negative BD populations, HLA- A*26 is significantly associated with the onset of BD. {ECO:0000269\|PubMed:30872678}.
Disease:		Note=Allele A*29:02 is associated with increased susceptibility to birdshot chorioretinopathy (BSCR). May aberrantly present retinal autoantigens and induce autoimmune uveitis. {ECO:0000269\|PubMed:1728143}.
Similarity:		Belongs to the MHC class I family. {ECO:0000305}.
Sequence caution:		Sequence=CAA25162.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305\|PubMed:6609814};