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UniProtKB - P04439 (HLAA_HUMAN)

Entry version 197 (17 Jun 2020)
Sequence version 2 (22 Aug 2003)
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Protein

HLA class I histocompatibility antigen, A alpha chain

Gene

HLA-A

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>

<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. 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).26 Publications
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) 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). 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).10 Publications
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.17 Publications
Allele A*03:01: Presents viral epitopes derived from IAV NP (ILRGSVAHK), HIV-1 nef (QVPLRPMTYK), HIV-1 gag-pol (AIFQSSMTK) 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). 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).7 Publications
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.1 Publication
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.1 Publication
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).6 Publications
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.1 Publication
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.1 Publication
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.1 Publication
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.3 Publications
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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<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 sitei31Pathogen-derived peptide antigen1 Publication1
Binding sitei97Pathogen-derived peptide antigen1 Publication1
Binding sitei108Pathogen-derived peptide antigen1 Publication1
Binding sitei140Self-peptide antigen1 Publication1
Binding sitei167Pathogen-derived peptide antigen1 Publication1
Binding sitei170Pathogen-derived peptide antigen1 Publication1
Binding sitei183Self- and pathogen-derived peptide antigen2 Publications1
Binding sitei195Pathogen-derived peptide antigen1 Publication1

<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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<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 processAdaptive 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-164940 Nef mediated downregulation of MHC class I complex cell surface expression
R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-6798695 Neutrophil degranulation
R-HSA-877300 Interferon gamma signaling
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-909733 Interferon alpha/beta signaling
R-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC

Protein family/group databases

Transport Classification Database

More...TCDBi		9.A.75.1.2 the mhc ii receptor (mhc2r) family

<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, A alpha chain
Alternative name(s):
Human leukocyte antigen A
Short name:
HLA-A
<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
Name:HLA-AImported
Synonyms:HLAA
<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>OrganismiHomo 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 identifieri9606 [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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 6

Organism-specific databases

Eukaryotic Pathogen Database Resources

More...EuPathDBi		HostDB:ENSG00000206503.11

Human Gene Nomenclature Database

More...HGNCi		HGNC:4931 HLA-A

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		142800 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P04439

<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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<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 domaini25 – 308ExtracellularSequence analysisAdd BLAST284
<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>Transmembranei309 – 332HelicalSequence analysisAdd BLAST24
Topological domaini333 – 365CytoplasmicSequence analysisAdd BLAST33

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

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).4 Publications
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).2 Publications
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.1 Publication
Allele A*29:02 is associated with increased susceptibility to birdshot chorioretinopathy (BSCR). May aberrantly present retinal autoantigens and induce autoimmune uveitis.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<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>Mutagenesisi110N → Q: Impairs the recruitment of HLA-A*02 in the peptide-loading complex. 1 Publication1
Mutagenesisi156S → C: Impairs the maturation of a peptide-receptive HLA-A*02-B2M complex. 1 Publication1
Mutagenesisi158T → K: Impairs binding to TAP1-TAP2 transporter, resulting in impaired presentation of intracellular peptides. 2 Publications1

Organism-specific databases

MalaCards human disease database

More...MalaCardsi		HLA-A
MIMi126200 phenotype
222100 phenotype

Open Targets

More...OpenTargetsi		ENSG00000206503

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		179 Birdshot chorioretinopathy
414750 Phenytoin or carbamazepine toxicity

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA35055

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P04439 Tbio

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL2632
CHEMBL4295692

Drug and drug target database

More...DrugBanki		DB02740 3-Indolebutyric Acid
DB11294 Coccidioides immitis spherule
DB06226 Nelipepimut-S

<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 keyPosition(s)DescriptionActionsGraphical viewLength
<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 peptidei1 – 241 PublicationAdd BLAST24
<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_000001881525 – 365HLA class I histocompatibility antigen, A alpha chainAdd BLAST341

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<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 residuei83SulfotyrosineSequence analysis1
<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>Glycosylationi110N-linked (GlcNAc...) asparagine1 Publication1
<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 bondi125 ↔ 188PROSITE-ProRule annotation8 Publications
Disulfide bondi227 ↔ 283PROSITE-ProRule annotation8 Publications
Modified residuei343PhosphoserineCombined sources1
Modified residuei344PhosphotyrosineCombined sources1
Modified residuei349PhosphoserineCombined sources1
Modified residuei350PhosphoserineCombined sources1
Modified residuei352PhosphoserineCombined sources1
Modified residuei356PhosphoserineCombined sources1
Modified residuei359PhosphoserineCombined sources1

<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

(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.1 Publication
N-linked glycosylation at Asn-110.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Sulfation, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		P04439

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P04439

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P04439

MaxQB - The MaxQuant DataBase

More...MaxQBi		P04439

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P04439

PeptideAtlas

More...PeptideAtlasi		P04439

PRoteomics IDEntifications database

More...PRIDEi		P04439

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		51505
51506
51714
51843
52596
52597
52979
52980
53320
53321
53322
53564
54669
54670
54671
54672
54673
54674
54675
54676
54707
58716

PTM databases

GlyConnect protein glycosylation platform

More...GlyConnecti		1315
1316
1317
1318
1319
1320
1321
1322
1323
1324
1325
1326
1327
1328
1329

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P04439

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P04439

SwissPalm database of S-palmitoylation events

More...SwissPalmi		P04439

<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.Curated

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Up-regulated by IFNG, and proinflammatory cytokines IL1B and TNF.2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000206503 Expressed in mononuclear cell and 238 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P04439 baseline and differential

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000206503 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-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.

22 Publications

(Microbial infection) Interacts with HHV-8 MIR1 protein.

1 Publication

(Microbial infection) Interacts with HTLV-1 accessory protein p12I.

1 Publication

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		109350, 112 interactors

Protein interaction database and analysis system

More...IntActi		P04439, 79 interactors

Molecular INTeraction database

More...MINTi		P04439

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P04439

<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

1365
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P04439

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 keyPosition(s)DescriptionActionsGraphical viewLength
<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>Domaini209 – 295Ig-like C1-typeSequence analysisAdd BLAST87

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<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>Regioni25 – 114Alpha-1Sequence analysisAdd BLAST90
Regioni115 – 206Alpha-2Sequence analysisAdd BLAST92
Regioni207 – 298Alpha-3Sequence analysisAdd BLAST92
Regioni299 – 308Connecting peptideSequence analysis10

<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.11 Publications
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).14 Publications
The alpha-3 Ig-like domain mediates the interaction with CD8 coreceptor.1 Publication

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the MHC class I family.Curated

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic 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		P04439

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
IPR003006 Ig/MHC_CS
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 basket

This entry has 2 described isoforms and 31 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P04439-1) [UniParc]FASTAAdd 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
        10         20         30         40         50
MAVMAPRTLL LLLSGALALT QTWAGSHSMR YFFTSVSRPG RGEPRFIAVG 
        60         70         80         90        100
YVDDTQFVRF DSDAASQRME PRAPWIEQEG PEYWDQETRN VKAQSQTDRV 
       110        120        130        140        150
DLGTLRGYYN QSEAGSHTIQ IMYGCDVGSD GRFLRGYRQD AYDGKDYIAL 
       160        170        180        190        200
NEDLRSWTAA DMAAQITKRK WEAAHEAEQL RAYLDGTCVE WLRRYLENGK 
       210        220        230        240        250
ETLQRTDPPK THMTHHPISD HEATLRCWAL GFYPAEITLT WQRDGEDQTQ 
       260        270        280        290        300
DTELVETRPA GDGTFQKWAA VVVPSGEEQR YTCHVQHEGL PKPLTLRWEL 
       310        320        330        340        350
SSQPTIPIVG IIAGLVLLGA VITGAVVAAV MWRRKSSDRK GGSYTQAASS 
       360 
DSAQGSDVSL TACKV
Length:365
Mass (Da):40,841
Last modified:August 22, 2003 - v2
<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:iDEDFCEC4450E0580
GO
Isoform 2 (identifier: P04439-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     176-187: EAEQLRAYLDGT → AAEQQRAYLEGR
     337-337: S → SGGEGVK

Show »
Length:371
Mass (Da):41,394
Checksum:i55F09DFBB5F35C89
GO

<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 31 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5SUL5Q5SUL5_HUMAN
HLA class I histocompatibility anti...
HLA-A HLA, HLA-A*0101
365Annotation 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>
Q5SPM2Q5SPM2_HUMAN
HLA class I heavy chain
HLA-A HLA, HLA-A26
365Annotation 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>
B0UXQ0B0UXQ0_HUMAN
HLA class I histocompatibility anti...
HLA-A HLA
365Annotation 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>
Q53Z42Q53Z42_HUMAN
HLA class I antigen
HLA-A HLA
365Annotation 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>
Q5RJ27Q5RJ27_HUMAN
HLA class I histocompatibility anti...
HLA-A HLA
365Annotation 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>
Q5SRN5Q5SRN5_HUMAN
HLA class I histocompatibility anti...
HLA-A
371Annotation 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>
A0A140T9X5A0A140T9X5_HUMAN
HLA class I histocompatibility anti...
HLA-A
371Annotation 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>
A0A140T913A0A140T913_HUMAN
HLA class I histocompatibility anti...
HLA-A
371Annotation 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>
A0A140T8Y4A0A140T8Y4_HUMAN
HLA class I histocompatibility anti...
HLA-A
371Annotation 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>
A0A0G2JPD3A0A0G2JPD3_HUMAN
HLA class I histocompatibility anti...
HLA-A
394Annotation 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 reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence CAA25162 differs from that shown. Reason: Erroneous gene model prediction.1 Publication

<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

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 [MIMi:608579] (PubMed:21428769).2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<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_0823153V → I in allele A*34:01. 1 Publication1
Natural variantiVAR_0823165A → P in allele A*80:01. 2 Publications1
Natural variantiVAR_08231710L → V in allele A*02:01, allele A*02:05, allele A*23:01, allele A*24:02, allele A*25:01, allele A*26:01, allele A*34:01, allele A*43:01, allele A*66:01, allele A*68:01 and allele A*69:01. 10 Publications1
Natural variantiVAR_08231814S → L in allele A*29:02, allele A*31:01, allele A*32:01, allele A*33:01 and allele A*74:01. 7 Publications1
Natural variantiVAR_08231923W → R in allele A*74:01. 1 Publication1
Natural variantiVAR_08232033F → S in allele A*23:01, allele A*24:02 and allele A*30:01. 4 PublicationsCorresponds to variant dbSNP:rs2075684Ensembl.1
Natural variantiVAR_08232133F → T in allele A*29:02, allele A*31:01 and allele A*33:01; requires 2 nucleotide substitutions. 4 Publications1
Natural variantiVAR_08232233F → Y in allele A*02:05, allele A*11:01, allele A*25:01, allele A*26:01, allele A*34:01, allele A*43:01, allele A*66:01, allele A*68:01 and allele A*69:01. 9 PublicationsCorresponds to variant dbSNP:rs2075684Ensembl.1
Natural variantiVAR_08232341R → S in allele A*30:01. 2 PublicationsCorresponds to variant dbSNP:rs1059423Ensembl.1
Natural variantiVAR_08232455T → S in allele A*80:01. 2 Publications1
Natural variantiVAR_08232559R → Q in allele A*80:01. 2 Publications1
Natural variantiVAR_08232667Q → R in allele A*02:05. 1 PublicationCorresponds to variant dbSNP:rs41559117Ensembl.1
Natural variantiVAR_08232768R → K in alleles A*01:01 and allele A*36:01. 4 Publications1
Natural variantiVAR_08232880G → E in allele A*80:01. 2 Publications1
Natural variantiVAR_08232980G → R in allele A*30:01 and allele A*31:01. 4 PublicationsCorresponds to variant dbSNP:rs1059449Ensembl.1
Natural variantiVAR_08233086Q → E in allele A*23:01, allele 24:02 and allele A*80:01. 4 Publications1
Natural variantiVAR_08233186Q → G in allele A*02:01 and allele A*02:05; requires 2 nucleotide substitutions. 4 Publications1
Natural variantiVAR_08233286Q → L in alleles A*29:02 and allele A*43:01. 2 Publications1
Natural variantiVAR_08233386Q → R in allele A*25:01, allele A*26:01, allele A*33:01, allele A*34:01, allele A*66:01, allele A*68:01 and allele A*69:01. 6 Publications1
Natural variantiVAR_08233487E → N in alleles A*25:01, allele A*26:01, allele A*33:01, allele A*34:01, allele A*66:01, allele A*68:01 and allele A*69:01; requires 2 nucleotide substitutions. 6 Publications1
Natural variantiVAR_08233587E → Q in allele A*29:02 and allele A*43:01. 2 Publications1
Natural variantiVAR_08233689R → G in allele A*23:01 and allele 24:02. 2 PublicationsCorresponds to variant dbSNP:rs199474430Ensembl.1
Natural variantiVAR_08233790N → K in allele A*02:01, allele A*02:05, allele A*23:01, allele 24:02 and allele A*34:01. 7 PublicationsCorresponds to variant dbSNP:rs199474436Ensembl.1
Natural variantiVAR_08233891V → M in allele A*01:01 and allele A*36:01. 4 Publications1
Natural variantiVAR_08233994Q → H in allele A*01:01, allele A*02:01, allele A*02:05, allele A*23:01, allele 24:02, allele A*25:01, allele A*26:01, allele A*31:01, allele A*32:01, allele A*33:01, allele A*36:01, allele A*43:01, allele A*74:01 and allele A*80:01. 19 PublicationsCorresponds to variant dbSNP:rs78306866Ensembl.1
Natural variantiVAR_08234097T → I in allele A*31:01 and allele A*33:01. 3 PublicationsCorresponds to variant dbSNP:rs199474457Ensembl.1
Natural variantiVAR_08234198D → H in allele A*02:01 and allele A*02:05. 4 Publications1
Natural variantiVAR_08234298D → N in allele A*80:01. 2 Publications1
Natural variantiVAR_082343100V → A in allele A*01:01, allele A*26:01, allele A*29:02, allele A*36:01, allele A*43:01 and allele A*80:01. 9 Publications1
Natural variantiVAR_082344100V → E in allele A*23:01, allele A*24:02, allele A*25:01 and allele A*32:01. 5 PublicationsCorresponds to variant dbSNP:rs1071742Ensembl.1
Natural variantiVAR_082345101D → N Allele A*01:01, allele A*23:01, allele A*24:02, allele A*26:01, allele A*29:02, allele A*36:01, allele A*43:01 and allele A*80:01. 11 Publications