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

    Gene ID: 3133, updated on 9-Dec-2024

    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; AllianceGenome:HGNC:4962
    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See HLA-E in Genome Data Viewer
    Location:
    6p22.1
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (30489509..30494194)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (30353696..30358381)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (30457286..30461971)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene SUCLA2 pseudogene 1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:30443157-30443780 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:30457579-30458127 Neighboring gene RAN pseudogene 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:30481847-30482624 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:30485727-30486226 Neighboring gene long intergenic non-protein coding RNA 2569 Neighboring gene G protein nucleolar 1 (putative) Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:30523544-30524109 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:30524110-30524674

    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

    EBI GWAS Catalog

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

    Clone Names

    • DKFZp686P19218

    Gene Ontology Provided by GOA

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

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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
      E2G051, P13747, Q30169, Q6DU44, Q9BT83, Q9GIY7, Q9GIY8
      UniProtKB/TrEMBL
      A0A0F7WBW2, A0A4E9D3W4, A0A4E9E4P1, A0A5C0C6I5, Q6DU50, S5RFZ0
      Related
      ENSP00000365817.4, ENST00000376630.5
      Conserved Domains (2) summary
      pfam00129
      Location:22200
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
      cd21024
      Location:201295
      IgC1_MHC_Ib_HLA-E; Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) E; member of the C1-set of Ig superfamily (IgSF) domains

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      30489509..30494194
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017010807.2XP_016866296.1  HLA class I histocompatibility antigen, alpha chain E isoform X1

      UniProtKB/TrEMBL
      B4DL31

    Reference GRCh38.p14 ALT_REF_LOCI_2

    Genomic

    1. NT_113891.3 Reference GRCh38.p14 ALT_REF_LOCI_2

      Range
      1969211..1973929
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054329806.1XP_054185781.1  HLA class I histocompatibility antigen, alpha chain E isoform X1

      UniProtKB/TrEMBL
      B4DL31

    Reference GRCh38.p14 ALT_REF_LOCI_3

    Genomic

    1. NT_167245.2 Reference GRCh38.p14 ALT_REF_LOCI_3

      Range
      1745308..1750026
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054330294.1XP_054186269.1  HLA class I histocompatibility antigen, alpha chain E isoform X1

      UniProtKB/TrEMBL
      B4DL31

    Reference GRCh38.p14 ALT_REF_LOCI_4

    Genomic

    1. NT_167246.2 Reference GRCh38.p14 ALT_REF_LOCI_4

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

    mRNA and Protein(s)

    1. XM_054330589.1XP_054186564.1  HLA class I histocompatibility antigen, alpha chain E isoform X1

      UniProtKB/TrEMBL
      B4DL31

    Reference GRCh38.p14 ALT_REF_LOCI_5

    Genomic

    1. NT_167247.2 Reference GRCh38.p14 ALT_REF_LOCI_5

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

    mRNA and Protein(s)

    1. XM_054330818.1XP_054186793.1  HLA class I histocompatibility antigen, alpha chain E isoform X1

      UniProtKB/TrEMBL
      B4DL31

    Reference GRCh38.p14 ALT_REF_LOCI_6

    Genomic

    1. NT_167248.2 Reference GRCh38.p14 ALT_REF_LOCI_6

      Range
      1744572..1749290
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054331061.1XP_054187036.1  HLA class I histocompatibility antigen, alpha chain E isoform X1

      UniProtKB/TrEMBL
      B4DL31

    Reference GRCh38.p14 ALT_REF_LOCI_7

    Genomic

    1. NT_167249.2 Reference GRCh38.p14 ALT_REF_LOCI_7

      Range
      1790245..1794963
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054331330.1XP_054187305.1  HLA class I histocompatibility antigen, alpha chain E isoform X1

      UniProtKB/TrEMBL
      B4DL31

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      30353696..30358381
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)