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

Gene ID: 3135, updated on 5-Apr-2020

Summary

Official Symbol
HLA-Gprovided by HGNC
Official Full Name
major histocompatibility complex, class I, Gprovided by HGNC
Primary source
HGNC:HGNC:4964
See related
Ensembl:ENSG00000204632 MIM:142871
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
MHC-G
Summary
HLA-G 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-G is expressed on fetal derived placental cells. 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 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]
Expression
Broad expression in placenta (RPKM 29.5), colon (RPKM 14.0) and 15 other tissues See more

Genomic context

See HLA-G in Genome Data Viewer
Location:
6p22.1
Exon count:
9
Annotation release Status Assembly Chr Location
109.20200228 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (29826979..29831130)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (29794756..29798899)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene ribosomal protein L7a pseudogene 7 Neighboring gene MHC class I polypeptide-related sequence G (pseudogene) Neighboring gene HLA complex group 4 pseudogene 8 Neighboring gene HCGVIII-2 pseudogene Neighboring gene uncharacterized LOC105375010 Neighboring gene MHC class I polypeptide-related sequence F (pseudogene)

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

Associated conditions

Description Tests
Asthma, susceptibility to
MedGen: C1869116 OMIM: 600807 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study.
NHGRI GWA Catalog
A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci.
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
Envelope surface glycoprotein gp160, precursor 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 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
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 HIV-1 gp41 selectively enhances MHC class I, ICAM-1, IFN-alpha, IFN-beta, and IFN-omega expression in H9 cells 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 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 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 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 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 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
nef HLA-G, which is mainly expressed in placental tissues and in thymic epithelial cells, resists Nef-induced cell surface downregulation as a result of its short intracytoplasmic domain PubMed
Tat tat HIV-1 Tat 47-59 peptide downregulates gene expression of HLA-G histocompatibility antigen, class I, G (HLA-G) in U-937 macrophages PubMed
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

Gene Ontology Provided by GOA

Function Evidence Code Pubs
CD8 receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
identical protein 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 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IDA
Inferred from Direct Assay
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
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 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
 
cellular defense response TAS
Traceable Author Statement
more info
PubMed 
immune response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
immune response-inhibiting cell surface receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
interferon-gamma-mediated signaling pathway TAS
Traceable Author Statement
more info
 
negative regulation of G0 to G1 transition IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of T cell mediated cytotoxicity IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of T cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of angiogenesis IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of dendritic cell differentiation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of immune response IC
Inferred by Curator
more info
PubMed 
negative regulation of natural killer cell mediated cytotoxicity IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of natural killer cell mediated cytotoxicity IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of protein kinase B signaling IDA
Inferred from Direct Assay
more info
PubMed 
peripheral B cell tolerance induction 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 tolerance induction IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of cellular senescence IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of endothelial cell apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interleukin-12 production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of macrophage cytokine 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 regulatory T cell differentiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of tolerance induction IMP
Inferred from Mutant Phenotype
more info
PubMed 
protection from natural killer cell mediated cytotoxicity IDA
Inferred from Direct Assay
more info
PubMed 
protein homotrimerization IDA
Inferred from Direct Assay
more info
PubMed 
regulation of immune response TAS
Traceable Author Statement
more info
 
type I interferon signaling pathway TAS
Traceable Author Statement
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 IEA
Inferred from Electronic Annotation
more info
 
cis-Golgi network membrane IDA
Inferred from Direct Assay
more info
PubMed 
early endosome 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 space IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
filopodium membrane IEA
Inferred from Electronic Annotation
more info
 
integral component of lumenal side of endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
 
membrane HDA PubMed 
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 G
Names
HLA G antigen
HLA-G histocompatibility antigen, class I, G
MHC class I antigen G
MHC class Ib antigen
b2 microglobulin
mutant MHC class I antigen
mutant 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.

Genomic

  1. NG_029039.1 RefSeqGene

    Range
    5001..9144
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001363567.1NP_001350496.1  HLA class I histocompatibility antigen, alpha chain G isoform 1 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1).
    Source sequence(s)
    AL645929
    Consensus CDS
    CCDS87380.1
    Related
    ENSP00000366024.2, ENST00000376828.6
    Conserved Domains (2) summary
    cd07698
    Location:212303
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    pfam00129
    Location:30208
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
  2. NM_002127.5NP_002118.1  HLA class I histocompatibility antigen, alpha chain G isoform 2 precursor

    See identical proteins and their annotated locations for NP_002118.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.
    Source sequence(s)
    AL551999, AL645929, DC397107, X17273
    Consensus CDS
    CCDS4668.1
    UniProtKB/Swiss-Prot
    P17693
    UniProtKB/TrEMBL
    Q6DU14
    Related
    ENSP00000412927.1, ENST00000428701.5
    Conserved Domains (2) summary
    cd07698
    Location:207298
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    pfam00129
    Location:25203
    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
    29826979..29831130
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017010817.1XP_016866306.1  HLA class I histocompatibility antigen, alpha chain G isoform X3

    UniProtKB/TrEMBL
    Q31611
    Related
    ENSP00000366014.3, ENST00000376818.7
    Conserved Domains (2) summary
    cd07698
    Location:116206
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    cl08246
    Location:25114
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
  2. XM_017010818.1XP_016866307.1  HLA class I histocompatibility antigen, alpha chain G isoform X3

    UniProtKB/TrEMBL
    Q31611
    Conserved Domains (2) summary
    cd07698
    Location:116206
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    cl08246
    Location:25114
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
  3. XM_024446420.1XP_024302188.1  HLA class I histocompatibility antigen, alpha chain G isoform X2

    Conserved Domains (2) summary
    cd07698
    Location:207298
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    pfam00129
    Location:25203
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2

Reference GRCh38.p13 ALT_REF_LOCI_1

Genomic

  1. NT_167244.2 Reference GRCh38.p13 ALT_REF_LOCI_1

    Range
    1092591..1096748
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_2

Genomic

  1. NT_113891.3 Reference GRCh38.p13 ALT_REF_LOCI_2

    Range
    1310541..1314698
    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
    1089792..1093935
    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
    1089466..1093608
    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
    1089450..1093593
    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
    1089745..1093902
    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
    1133010..1137167
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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