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HLA-E major histocompatibility complex, class I, E [ Homo sapiens (human) ]

Gene ID: 3133, updated on 20-Apr-2020

Summary

Official Symbol
HLA-Eprovided by HGNC
Official Full Name
major histocompatibility complex, class I, Eprovided by HGNC
Primary source
HGNC:HGNC:4962
See related
Ensembl:ENSG00000204592 MIM:143010
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
QA1; HLA-6.2
Summary
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]
Expression
Ubiquitous expression in spleen (RPKM 452.2), lung (RPKM 398.4) and 24 other tissues See more
Orthologs

Genomic context

See HLA-E in Genome Data Viewer
Location:
6p22.1
Exon count:
8
Annotation release Status Assembly Chr Location
109.20200228 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (30489508..30494194)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (30457183..30461982)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene SUCLA2 pseudogene 1 Neighboring gene RAN pseudogene 1 Neighboring gene long intergenic non-protein coding RNA 2569 Neighboring gene G protein nucleolar 1 (putative) Neighboring gene proline rich 3

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.
NHGRI GWA Catalog
Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
NHGRI GWA Catalog
Common variants conferring risk of schizophrenia.
NHGRI GWA Catalog
Genetic predictors of medically refractory ulcerative colitis.
NHGRI GWA Catalog
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.
NHGRI GWA Catalog
Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis.
NHGRI GWA Catalog
Genome-wide association study implicates HLA-C*01:02 as a risk factor at the major histocompatibility complex locus in schizophrenia.
NHGRI GWA Catalog
Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder.
NHGRI GWA Catalog
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
NHGRI GWA Catalog
Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci.
NHGRI GWA Catalog
Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region.
NHGRI GWA Catalog
Genome-wide association study of ulcerative colitis in Koreans suggests extensive overlapping of genetic susceptibility with Caucasians.
NHGRI GWA Catalog
GWAS meta analysis identifies TSNARE1 as a novel Schizophrenia / Bipolar susceptibility locus.
NHGRI GWA Catalog
HLA-Cw*1202-B*5201-DRB1*1502 haplotype increases risk for ulcerative colitis but reduces risk for Crohn's disease.
NHGRI GWA Catalog
Identification of independent risk loci for Graves' disease within the MHC in the Japanese population.
NHGRI GWA Catalog
Identification of nine novel loci associated with white blood cell subtypes in a Japanese population.
NHGRI GWA Catalog
Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.
NHGRI GWA Catalog
Multiple genetic loci for bone mineral density and fractures.
NHGRI GWA Catalog
Novel risk loci for rheumatoid arthritis in Han Chinese and congruence with risk variants in Europeans.
NHGRI GWA Catalog
Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia.
NHGRI GWA Catalog
Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Treatment of CD4+ T cells with HIV-1 gp120 significantly increases CD4 association with CD3, CD45RA, CD45RB, CD59, CD38, CD26 and HLA class I, and decreases that with CD45RC PubMed
env Conformational changes in HIV-1 gp120, including an enhanced expression of the V3 loop of gp120 and of epitopes that are exposed upon CD4 binding, are consistent with the formation of a multimolecular complex between HLA class I and gp120/160 PubMed
env The presence of HLA-C and HLA-E molecules on HIV-infected cells facilitates evasion of NK-mediated killing of anti-gp120-coated HIV-infected cells PubMed
Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 interacts with HLA-E; predicted interaction to be involved in antigenicity/immunity and virus egress PubMed
env HIV-1 gp160-derived peptide p18 presented by H-2Dd class I major histocompatibility complex molecules is processed by angiotensin-1 converting enzyme (ACE) prior to T cell stimulation by the peptide p18 PubMed
Envelope transmembrane glycoprotein gp41 env HIV-1 gp41 selectively enhances MHC class I, ICAM-1, IFN-alpha, IFN-beta, and IFN-omega expression in H9 cells PubMed
env Soluble HIV-1 gp41 enhancement effects on MHC class I and II antigen expression can be inhibited by soluble gp41-binding proteins of 45, 49 and 62 kD from human B cells PubMed
env Soluble HIV-1 gp41 can selectively enhance MHC class I and II expression on human B cells, but does not increase expression of other cell surface antigens such as CD21 and CD54 (ICAM-1) PubMed
Nef nef HIV-1 Nef downregulates the expression of MHC-I at the surface of lymphoid, monocytic and epithelial cells, causing MHC-I molecules to be rapidly internalized, accumulated in endosomal vesicles and degraded PubMed
nef Double (W13A/V16R) and triple (W13A/V16R/M20A) substitution mutants of HIV-1 Nef fail to downregulate MHC-I PubMed
nef HIV-1 Nef-mediated downregulation of MHC-I requires Nef motif EEEE(65)-dependent binding to the sorting protein PACS-2, which targets Nef to the paranuclear region and enables Nef PXXP(75) to bind and activate a trans-Golgi network localized Src kinase PubMed
nef A methionine residue at amino acid 20 in the alpha-helix domain is required for the ability of HIV-1 Nef to downregulate MHC-I expression but not for the downregulation of CD4 PubMed
nef Four glutamic acids from position 62 to 65 in the SH3 domain of HIV-1 Nef bind to the cytoplasmic tail at position 320Y of MHC-I, and are required for the Nef-mediated downregulation of MHC-I from the cell surface PubMed
nef HIV-1 Nef-induced downregulation of MHC-I expression and MHC-I targeting to the trans-Golgi network (TGN) require the binding of Nef to PACS-1, a molecule that controls the TGN localization of the cellular protein furin PubMed
nef HIV-1 Nef downregulates expression of MHC-I by blocking transport of MHC-I molecules to the cell surface through a mechanism that requires phosphoinositide 3-kinase (PI 3-kinase) activity PubMed
nef Amino acid residue Y320 in the MHC-I cytoplasmic domain and residues E62-65 and P78 in HIV-1 Nef are required for interaction with the mu subunit of AP-1 PubMed
nef Interaction of HIV-1 Nef with the mu subunit of AP adaptor complexes requires the recognition of tyrosine-based sorting signals, which likely facilitates the connection between MHC I and the clathrin-dependent sorting machinery PubMed
nef MHC-I is found in the Rab7(+) vesicles and is targeted for degradation via the activity of the Nef-interacting protein, beta-COP PubMed
nef Deletion of the 19 N-terminal amino acids including the myristoylation signal from HIV-1 Nef inhibits both MHC-I and CD4 downregulation while preserving most CTL, T-helper and B-cell epitopes PubMed
Tat tat HIV-1 Tat upregulates MHC class I in monocyte-derived dendritic cells and CD8(+) T cells, thereby driving T cell-mediated immune responses PubMed
tat HIV-1 Tat represses the MHC class I gene promoter by binding to and repressing TAFII250, a component of the general transcription factor TFIID, suggesting a mechanism for HIV-1 to downregulate MHC class I expression and avoid immune surveillance PubMed
Vpu vpu HLA class I-associated immune responses have minor effects on Vpu variability, suggesting that Vpu conformation and function are preserved through many possible combinations of primary and secondary polymorphisms PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • DKFZp686P19218

Gene Ontology Provided by GOA

Function Evidence Code Pubs
MHC class I protein binding IDA
Inferred from Direct Assay
more info
PubMed 
T cell receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
beta-2-microglobulin binding IDA
Inferred from Direct Assay
more info
PubMed 
beta-2-microglobulin binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
natural killer cell lectin-like receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
peptide antigen binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
peptide antigen binding IDA
Inferred from Direct Assay
more info
PubMed 
peptide antigen binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
signaling receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
signaling receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
CD8-positive, alpha-beta T cell activation IDA
Inferred from Direct Assay
more info
PubMed 
adaptive immune response IDA
Inferred from Direct Assay
more info
PubMed 
antibacterial humoral response IDA
Inferred from Direct Assay
more info
PubMed 
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
antigen processing and presentation of endogenous peptide antigen via MHC class Ib IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
antigen processing and presentation of endogenous peptide antigen via MHC class Ib IDA
Inferred from Direct Assay
more info
PubMed 
antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent TAS
Traceable Author Statement
more info
 
antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent TAS
Traceable Author Statement
more info
 
antigen processing and presentation of exogenous peptide antigen via MHC class Ib IDA
Inferred from Direct Assay
more info
PubMed 
antigen processing and presentation of peptide antigen via MHC class I IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
antigen processing and presentation of peptide antigen via MHC class I TAS
Traceable Author Statement
more info
 
defense response to Gram-positive bacterium IDA
Inferred from Direct Assay
more info
PubMed 
immune response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
innate immune response TAS
Traceable Author Statement
more info
 
interferon-gamma-mediated signaling pathway TAS
Traceable Author Statement
more info
 
natural killer cell tolerance induction IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of natural killer cell mediated cytotoxicity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of CD8-positive, alpha-beta T cell activation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of CD8-positive, alpha-beta T cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of T cell mediated cytotoxicity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of T cell mediated cytotoxicity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of TRAIL production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of antibody-dependent cellular cytotoxicity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of immunoglobulin secretion IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interleukin-13 production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interleukin-4 production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of natural killer cell cytokine production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of natural killer cell mediated cytotoxicity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of natural killer cell mediated immunity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of natural killer cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of tumor necrosis factor production IDA
Inferred from Direct Assay
more info
PubMed 
protection from natural killer cell mediated cytotoxicity IDA
Inferred from Direct Assay
more info
PubMed 
regulation of immune response TAS
Traceable Author Statement
more info
 
regulation of natural killer cell mediated immunity IDA
Inferred from Direct Assay
more info
PubMed 
type I interferon signaling pathway TAS
Traceable Author Statement
more info
 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
ER to Golgi transport vesicle membrane TAS
Traceable Author Statement
more info
 
Golgi membrane TAS
Traceable Author Statement
more info
 
MHC class I protein complex IDA
Inferred from Direct Assay
more info
PubMed 
MHC class Ib protein complex IDA
Inferred from Direct Assay
more info
PubMed 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
early endosome membrane TAS
Traceable Author Statement
more info
 
external side of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
extracellular exosome HDA PubMed 
extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
integral component of lumenal side of endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
 
phagocytic vesicle membrane TAS
Traceable Author Statement
more info
 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
recycling endosome membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
HLA class I histocompatibility antigen, alpha chain E
Names
MHC class I antigen E
MHC class Ib antigen

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_005516.6NP_005507.3  HLA class I histocompatibility antigen, alpha chain E precursor

    See identical proteins and their annotated locations for NP_005507.3

    Status: REVIEWED

    Source sequence(s)
    AK292391, BC002578, CA439575, X56841
    Consensus CDS
    CCDS34379.1
    UniProtKB/Swiss-Prot
    P13747
    UniProtKB/TrEMBL
    A8K8M6, O19682, Q6DU44
    Related
    ENSP00000365817.4, ENST00000376630.5
    Conserved Domains (2) summary
    cd07698
    Location:204295
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    pfam00129
    Location:23200
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p13 Primary Assembly

    Range
    30489508..30494194
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017010809.2XP_016866298.1  HLA class I histocompatibility antigen, alpha chain E isoform X2

  2. XM_017010808.1XP_016866297.1  HLA class I histocompatibility antigen, alpha chain E isoform X1

  3. XM_017010807.1XP_016866296.1  HLA class I histocompatibility antigen, alpha chain E isoform X1

Reference GRCh38.p13 ALT_REF_LOCI_2

Genomic

  1. NT_113891.3 Reference GRCh38.p13 ALT_REF_LOCI_2

    Range
    1969244..1973929
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_3

Genomic

  1. NT_167245.2 Reference GRCh38.p13 ALT_REF_LOCI_3

    Range
    1745341..1750026
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_4

Genomic

  1. NT_167246.2 Reference GRCh38.p13 ALT_REF_LOCI_4

    Range
    1799744..1804429
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_5

Genomic

  1. NT_167247.2 Reference GRCh38.p13 ALT_REF_LOCI_5

    Range
    1833565..1838250
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_6

Genomic

  1. NT_167248.2 Reference GRCh38.p13 ALT_REF_LOCI_6

    Range
    1744605..1749290
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_7

Genomic

  1. NT_167249.2 Reference GRCh38.p13 ALT_REF_LOCI_7

    Range
    1790278..1794963
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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