HLA-A

Protein identityUniProt · HPA

UniProt accession

P04439

Gene

HLA-A

Ensembl

ENSG00000206503

Chromosome

6

Canonical length

365 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Subcellular location

Golgi apparatus,Plasma membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

HLA-A belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen so that they can be recognized by cytotoxic T cells. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. More than 6000 HLA-A alleles have been described. The HLA system plays an important role in the occurrence and outcome of infectious diseases, including those caused by the malaria parasite, the human immunodeficiency virus (HIV), and the severe acute respiratory syndrome coronavirus (SARS-CoV). The structural spike and the nucleocapsid proteins of the novel coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), are reported to contain multiple Class I epitopes with predicted HLA restrictions. Individual HLA genetic variation may help explain different immune responses to a virus across a population.[provided by RefSeq, Aug 2020]

Canonical amino-acid sequenceUniProt

365 residues, UniProt reviewed canonical sequence.

>P04439|HLA-A
     1  MAVMAPRTLL LLLSGALALT QTWAGSHSMR YFFTSVSRPG RGEPRFIAVG YVDDTQFVRF
    61  DSDAASQRME PRAPWIEQEG PEYWDQETRN VKAQSQTDRV DLGTLRGYYN QSEAGSHTIQ
   121  IMYGCDVGSD GRFLRGYRQD AYDGKDYIAL NEDLRSWTAA DMAAQITKRK WEAAHEAEQL
   181  RAYLDGTCVE WLRRYLENGK ETLQRTDPPK THMTHHPISD HEATLRCWAL GFYPAEITLT
   241  WQRDGEDQTQ DTELVETRPA GDGTFQKWAA VVVPSGEEQR YTCHVQHEGL PKPLTLRWEL
   301  SSQPTIPIVG IIAGLVLLGA VITGAVVAAV MWRRKSSDRK GGSYTQAASS DSAQGSDVSL
   361  TACKV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HLA-A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.37

Highest tissue expression

1,420 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HLA-A.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 131 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Susceptibility to severe COVID-19

ReferencesPubMed · IEDB

Publications for HLA-A from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.75

gnomAD pLI

0

gnomAD missense Z

-0.1

DepMap mean gene effect

-0.18

DepMap dependency class

selective

OntologyGO

Biological processes

• antibacterial humoral response
• antigen processing and presentation of endogenous peptide antigen via MHC class I
• antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent
• antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent
• antigen processing and presentation of endogenous peptide antigen via MHC class Ib
• antigen processing and presentation of exogenous peptide antigen via MHC class I
• CD8-positive, alpha-beta T cell activation
• defense response to Gram-positive bacterium
• detection of bacterium
• immune response
• innate immune response
• peptide antigen assembly with MHC class I protein complex
• positive regulation of CD8-positive, alpha-beta T cell activation
• positive regulation of CD8-positive, alpha-beta T cell proliferation
• positive regulation of memory T cell activation
• positive regulation of T cell cytokine production
• positive regulation of T cell mediated cytotoxicity
• positive regulation of type II interferon production
• protection from natural killer cell mediated cytotoxicity
• T cell mediated cytotoxicity
• T cell mediated cytotoxicity directed against tumor cell target
• T cell receptor signaling pathway

Molecular functions

• beta-2-microglobulin binding
• CD8 receptor binding
• peptide antigen binding
• RNA binding
• signaling receptor binding
• T cell receptor binding
• TAP binding
• TAP complex binding

Cellular components

• cell surface
• early endosome membrane
• endoplasmic reticulum
• endoplasmic reticulum exit site
• endoplasmic reticulum membrane
• ER to Golgi transport vesicle membrane
• external side of plasma membrane
• extracellular exosome
• extracellular space
• Golgi apparatus
• Golgi medial cisterna
• Golgi membrane
• lumenal side of endoplasmic reticulum membrane
• membrane
• MHC class I peptide loading complex
• MHC class I protein complex
• phagocytic vesicle membrane
• plasma membrane
• recycling endosome membrane

Protein domainsUniProt · Pfam · InterPro

• MHC class I alpha chain, alpha1 alpha2 domains
• Immunoglobulin/major histocompatibility complex, conserved site
• Immunoglobulin C1-set
• Immunoglobulin-like domain
• MHC class I, alpha chain, C-terminal
• MHC class I-like antigen recognition-like
• MHC classes I/II-like antigen recognition protein
• Immunoglobulin-like fold
• Immunoglobulin-like domain superfamily
• MHC class I-like antigen recognition-like superfamily
• Antigen-presenting and immune regulatory MHC class I-related
• Class I Histocompatibility antigen, domains alpha 1 and 2
• MHC_I C-terminus
• Immunoglobulin C1-set domain

KeywordsUniProt

• Adaptive immunity
• Cell membrane
• Disulfide bond
• Endoplasmic reticulum
• Glycoprotein
• Host-virus interaction
• Immunity
• Immunoglobulin domain
• Innate immunity
• Membrane
• MHC I
• Phosphoprotein
• Signal
• Sulfation
• Transmembrane
• Transmembrane helix
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of HLA-A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CALR
• TAP1-TAP2
• TAPBPL
• TCR
• B2M
• HLA-C