HLA-E
HLA class I histocompatibility antigen, alpha chain E
Also known as: HLAE_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P13747
- Gene
- HLA-E
- Ensembl
- ENSG00000204592
- Chromosome
- 6
- Canonical length
- 358 aa
- Protein class
- Plasma proteins, Predicted membrane proteins, Predicted secreted proteins
- Subcellular location
- Vesicles,Plasma membrane
- Secretome location
- Secreted to blood
OverviewNCBI Gene
HLA-E 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. HLA-E binds a restricted subset of peptides derived from the leader peptides of other class I molecules. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one 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. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
358 residues, UniProt reviewed canonical sequence.
>P13747|HLA-E
1 MVDGTLLLLL SEALALTQTW AGSHSLKYFH TSVSRPGRGE PRFISVGYVD DTQFVRFDND
61 AASPRMVPRA PWMEQEGSEY WDRETRSARD TAQIFRVNLR TLRGYYNQSE AGSHTLQWMH
121 GCELGPDGRF LRGYEQFAYD GKDYLTLNED LRSWTAVDTA AQISEQKSND ASEAEHQRAY
181 LEDTCVEWLH KYLEKGKETL LHLEPPKTHV THHPISDHEA TLRCWALGFY PAEITLTWQQ
241 DGEGHTQDTE LVETRPAGDG TFQKWAAVVV PSGEEQRYTC HVQHEGLPEP VTLRWKPASQ
301 PTIPIVGIIA GLVLLGSVVS GAVVAAVIWR KKSSGGKGGS YSKAEWSDSA QGSESHSLLocalizationUniProt · AlphaFold · HPA
Whether an antibody against HLA-E 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
- 1,118 nTPM
Expression across tissuesHPA
Tissue
- lung: 1,118 nTPM
- spleen: 984 nTPM
- adipose tissue: 713 nTPM
- breast: 572 nTPM
- skin: 503 nTPM
- small intestine: 416 nTPM
Single-cell type
- platelets: 272 nCPM
- neutrophils: 207 nCPM
- microglia: 149 nCPM
- plasma cells: 121 nCPM
- nk-cells: 96 nCPM
- vascular endothelial cells: 93 nCPM
Immune cell
- neutrophil: 1,925 nTPM
- total PBMC: 1,442 nTPM
- eosinophil: 1,155 nTPM
- basophil: 1,142 nTPM
- gdT-cell: 724 nTPM
- memory CD8 T-cell: 709 nTPM
Brain region
- midbrain: 63 nTPM
- medulla oblongata: 34 nTPM
- pons: 33 nTPM
- white matter: 29 nTPM
- hypothalamus: 28 nTPM
- thalamus: 25 nTPM
ReferencesPubMed · IEDB
Publications for HLA-E 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.
Reference: AutoantibodyPubMed
2 publications
- Antibodies to HLA-E in nonalloimmunized males: pattern of HLA-Ia reactivity of anti-HLA-E-positive sera.
2010 · J Immunol · RCR 1.4 · 46 citations - Augmentation of anti-HLA-E antibodies with concomitant HLA-Ia reactivity in IFNγ-treated autologous melanoma cell vaccine recipients.
2012 · J Immunotoxicol · RCR 0.3 · 12 citations
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. 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)
- 0.61
- gnomAD pLI
- 0.04
- gnomAD missense Z
- 1.98
- DepMap mean gene effect
- -0.13
- DepMap dependency class
- selective
OntologyGO
Biological processes
- adaptive immune response
- antibacterial humoral response
- 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 Ib
- CD8-positive, alpha-beta T cell activation
- defense response to Gram-positive bacterium
- immune response
- innate immune response
- natural killer cell tolerance induction
- negative regulation of natural killer cell activation
- negative regulation of natural killer cell mediated cytotoxicity
- negative regulation of T cell proliferation
- positive regulation of CD8-positive, alpha-beta T cell activation
- positive regulation of CD8-positive, alpha-beta T cell proliferation
- positive regulation of immunoglobulin production
- positive regulation of interleukin-13 production
- positive regulation of interleukin-4 production
- positive regulation of natural killer cell activation
- positive regulation of natural killer cell cytokine production
- positive regulation of natural killer cell mediated cytotoxicity
- positive regulation of natural killer cell mediated immunity
- positive regulation of natural killer cell proliferation
- positive regulation of T cell mediated cytotoxicity
- positive regulation of TRAIL production
- positive regulation of tumor necrosis factor production
- protection from natural killer cell mediated cytotoxicity
- positive regulation of antibody-dependent cellular cytotoxicity
- regulation of natural killer cell mediated immunity
Molecular functions
- beta-2-microglobulin binding
- MHC class I protein binding
- natural killer cell lectin-like receptor binding
- peptide antigen binding
- receptor ligand activity
- signaling receptor binding
- T cell receptor binding
Cellular components
- cell surface
- early endosome membrane
- ER to Golgi transport vesicle membrane
- external side of plasma membrane
- extracellular exosome
- extracellular space
- Golgi membrane
- lumenal side of endoplasmic reticulum membrane
- MHC class I protein complex
- MHC class Ib 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
InteractionsUniProt · HPA
Protein binding partners of HLA-E in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads HLA-E as an antibody target. Whether an autoantibody or antibody against HLA-E could matter depends on whether native HLA-E is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
HLA-E is annotated at the cell surface, where native HLA-E is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label HLA-E as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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