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

Gene ID: 3107, updated on 30-Jun-2015
Official Symbol
HLA-Cprovided by HGNC
Official Full Name
major histocompatibility complex, class I, Cprovided by HGNC
Primary source
HGNC:HGNC:4933
See related
Ensembl:ENSG00000204525; HPRD:00829; MIM:142840; Vega:OTTHUMG00000031154
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
HLC-C; D6S204; PSORS1; HLA-JY3
Summary
HLA-C 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 endoplasmic reticulum lumen. They are expressed in nearly all 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 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. Over one hundred HLA-C alleles have been described [provided by RefSeq, Jul 2008]
Orthologs
See HLA-C in Epigenomics, MapViewer
Location:
6p21.3
Exon count:
8
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 6 NC_000006.12 (31268749..31272136, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (31236526..31239913, complement)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene psoriasis susceptibility 1 candidate 3 (non-protein coding) Neighboring gene HLA complex group 27 (non-protein coding) Neighboring gene ubiquitin specific peptidase 8 pseudogene 1 Neighboring gene ribosomal protein L3 pseudogene 2

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Congenital human immunodeficiency virus
MedGen: C1836230 OMIM: 609423 GeneReviews: Not available
Compare labs
Psoriasis susceptibility 1
MedGen: C1867449 OMIM: 177900 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci.
NHGRI GWA Catalog
A genome-wide association study for coronary artery disease identifies a novel susceptibility locus in the major histocompatibility complex.
NHGRI GWA Catalog
A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.
NHGRI GWA Catalog
A genome-wide association study identifies protein quantitative trait loci (pQTLs).
NHGRI GWA Catalog
A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.
NHGRI GWA Catalog
A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci.
NHGRI GWA Catalog
A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients.
NHGRI GWA Catalog
Association study of common genetic variants and HIV-1 acquisition in 6,300 infected cases and 7,200 controls.
NHGRI GWA Catalog
Common genetic variation and the control of HIV-1 in humans.
NHGRI GWA Catalog
Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis.
NHGRI GWA Catalog
Genetic variants at 6p21.33 are associated with susceptibility to follicular lymphoma.
NHGRI GWA Catalog
Genome-wide association analysis of blood biomarkers in chronic obstructive pulmonary disease.
NHGRI GWA Catalog
Genome-wide association study for levels of total serum IgE identifies HLA-C in a Japanese population.
NHGRI GWA Catalog
Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects.
NHGRI GWA Catalog
Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC.
NHGRI GWA Catalog
Genome-wide association study identified the human leukocyte antigen region as a novel locus for plasma beta-2 microglobulin.
NHGRI GWA Catalog
Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2.
NHGRI GWA Catalog
Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population.
NHGRI GWA Catalog
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.
NHGRI GWA Catalog
Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways.
NHGRI GWA Catalog
Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02).
NHGRI GWA Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog
Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene.
NHGRI GWA Catalog
Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization.
NHGRI GWA Catalog
Multiple loci are associated with white blood cell phenotypes.
NHGRI GWA Catalog
New loci associated with chronic hepatitis B virus infection in Han Chinese.
NHGRI GWA Catalog
Novel associations for hypothyroidism include known autoimmune risk loci.
NHGRI GWA Catalog
The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.
NHGRI GWA Catalog

Protein interactions

Protein Gene Interaction Pubs
Asp asp Antisense reading frame-derived cryptic epitopes from the env gene are inhibited by the HLA-I alleles in CD8+ T-cells PubMed
asp Antisense reading frame-derived cryptic epitopes from the gag, pol, and nef genes are inhibited by the predicted HLA-I alleles, and presented by HIV-1-infected CD8+ T-cells PubMed
Envelope surface glycoprotein gp120 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
env HLA-C positive cells co-expressing HIV-1 gp120/gp41 fuse more rapidly and produce larger syncytia than HLA-C negative cells 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 A highly conserved region of HIV-1 gp120 (amino acids 376 to 383) is recognized by an HLA-C molecule, Cw4 PubMed
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
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 HLA-C positive cells co-expressing HIV-1 gp120/gp41 fuse more rapidly and produce larger syncytia than HLA-C negative 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
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 clones from acute controllers display a lesser ability to downregulate CD4 and HLA class I from the cell surface, and a reduced ability to enhance virion infectivity compared to those from acute progressors PubMed
nef HIV-1 Nef clones obtained from chronic patients infected with HIV-1 subtypes A, B, C or D show a functional hierarchy of subtype B > A/D > C for Nef-mediated HLA class I downregulation PubMed
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 HIV-1 Nef clones, isolated from plasma of elite controllers (EC) and chronic progressors (CP), show significantly lower HLA class I downregulation activity in EC than that in CP PubMed
nef Protective HLA alleles have a true preference for HIV-1 Gag protein, while non-protective HLA alleles preferentially interact with HIV-1 Nef PubMed
nef The HIV-1 Nef highly conserved valine-glycine-phenylalanine amino acid triplet (VGF) motif, which links the acidic cluster and the proline-rich motif, is important for downregulation of CXCR4 and MHC-I PubMed
nef HLA-A2 molecules with HLA-A cytoplasmic domains are more downregulated by HIV-1 Nef than those with HLA-B domains. There is no downregulation of HLA-A2 with HLA-C cytoplasmic domains by Nef PubMed
nef Asp327 and Tyr320 of MHC-I, Asp123 of Nef, and Arg225, Arg393, Lys396, Arg211, and Arg246 of mu 1 are involved in a crucial three-way electrostatic network, which results in the Nef-MHC-I CD-mu 1 complex formation PubMed
nef HIV-1 Nef with A84D, Y135F, and G140R mutation impairs to its ability to downregulate MHC-I 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 In promonocytic cells, Nef/Hck recruits the ZAP-70 homolog Syk to downregulate MHC-I PubMed
nef Nef/Hck complex recruits and phosphorylates the tyrosine kinase ZAP-70, which binds class I PI3K to trigger MHC-I downregulation in primary CD4+ T cells 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
Pr55(Gag) gag HIV-1 Gag peptides (Gag144-152, Gag163-171 and Gag295-304) enhance binding of KIR2DL2 to HLA-C03:04 and result in inhibition of KIR2DL2+ primary NK cells PubMed
gag Protective HLA alleles have a true preference for HIV-1 Gag protein, while non-protective HLA alleles preferentially interact with HIV-1 Nef PubMed
gag HIV-1 Gag virus-like particles efficiently activate human monocyte-derived dendritic cells (MDDC) and induce MDDC maturation with an associated increase in the surface expression of CD80, CD86 and MHC classes I and II PubMed
gag The PTAP L-domains in the p6 domain of HIV-1 Gag regulates ubiquitination of Gag which controls MHC-I presentation and gag processing in the DRiP pathway. PubMed
gag HLA-C/HIV-1 Gag209-218 peptide complexes bind KIR2DL2, which results in functional inhibition of primary NK cells PubMed
gag Specific HIV-1 residues in Vpr, Gag, and Rev and HLA alleles (particularly B and C) confer susceptibility to the CTL response in HIV-1 infected patients PubMed
gag Targeting HIV-1 Gag into the defective ribosomal product pathway enhances MHC class I antigen presentation and CD8+ T cell activation PubMed
Rev rev Specific HIV-1 residues in Vpr, Gag, and Rev and HLA alleles (particularly B and C) confer susceptibility to the CTL response in HIV-1 infected patients PubMed
Tat tat Four mutations (C27S, K51T, R55L, and G79A) on HIV-1 Tat result in the loss of the deleterious effects of Tat on the expression of MHC I, IL-2, and CD25 genes compared with wild-type Tat in Jurkat cells 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
Vpr vpr Specific HIV-1 residues in Vpr, Gag, and Rev and HLA alleles (particularly B and C) confer susceptibility to the CTL response in HIV-1 infected patients PubMed
Vpu vpu Using antibodies specific to MHC class I A, B, and C molecules (clone W6/32), HIV-1 Vpu protein has been shown to downregulate the expression of MHC class I molecules on the surface of HIV-1 infected cells PubMed
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

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • FLJ27082

Gene Ontology Provided by GOA

Function Evidence Code Pubs
TAP binding IDA
Inferred from Direct Assay
more info
PubMed 
peptide antigen binding IDA
Inferred from Direct Assay
more info
PubMed 
peptide antigen binding ISS
Inferred from Sequence or Structural Similarity
more info
 
Component Evidence Code Pubs
ER to Golgi transport vesicle membrane TAS
Traceable Author Statement
more info
 
Golgi apparatus IDA
Inferred from Direct Assay
more info
PubMed 
Golgi apparatus ISS
Inferred from Sequence or Structural Similarity
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 I protein complex ISS
Inferred from Sequence or Structural Similarity
more info
 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
cell surface ISS
Inferred from Sequence or Structural Similarity
more info
 
early endosome membrane TAS
Traceable Author Statement
more info
 
endoplasmic reticulum IDA
Inferred from Direct Assay
more info
PubMed 
endoplasmic reticulum ISS
Inferred from Sequence or Structural Similarity
more info
 
extracellular exosome IDA
Inferred from Direct Assay
more info
PubMed 
extracellular region IEA
Inferred from Electronic Annotation
more info
 
integral component of lumenal side of endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
 
integral component of plasma membrane NAS
Non-traceable Author Statement
more info
PubMed 
phagocytic vesicle membrane TAS
Traceable Author Statement
more info
 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
 
plasma membrane TAS
Traceable Author Statement
more info
 
Preferred Names
HLA class I histocompatibility antigen, Cw-1 alpha chain
Names
HLA class I histocompatibility antigen, C alpha chain
MHC class I antigen heavy chain HLA-C
human leukocyte antigen-C alpha chain
major histocompatibility antigen HLA-C

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_029422.2 RefSeqGene

    Range
    4996..8383
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001243042.1NP_001229971.1  HLA class I histocompatibility antigen, Cw-1 alpha chain precursor

    See identical proteins and their annotated locations for NP_001229971.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) represents the C*07:01:01:01 allele of the HLA-C gene, as represented in the alternate locus group ALT_REF_LOCI_2 of the reference genome.
    Source sequence(s)
    AL662833
    UniProtKB/TrEMBL
    O19617
    Conserved Domains (2) summary
    cd07698
    Location:207299
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    pfam00129
    Location:26203
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
  2. NM_002117.5NP_002108.4  HLA class I histocompatibility antigen, Cw-1 alpha chain precursor

    See identical proteins and their annotated locations for NP_002108.4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the C*07:02:01 allele of the HLA-C gene, as represented in the assembled chromosome 6 in the primary assembly of the reference genome.
    Source sequence(s)
    AL671883, BC007814
    Consensus CDS
    CCDS34393.1
    UniProtKB/Swiss-Prot
    P10321
    UniProtKB/TrEMBL
    Q6R739
    UniProtKB/TrEMBL
    Q95HC2
    Related
    ENSP00000365402, OTTHUMP00000029213, ENST00000376228, OTTHUMT00000076281
    Conserved Domains (2) summary
    cd07698
    Location:207299
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    pfam00129
    Location:26203
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107

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

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p2 Primary Assembly

    Range
    31268749..31272136
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p2 ALT_REF_LOCI_2

Genomic

  1. NT_113891.3 Reference GRCh38.p2 ALT_REF_LOCI_2

    Range
    2749675..2753062
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p2 ALT_REF_LOCI_3

Genomic

  1. NT_167245.2 Reference GRCh38.p2 ALT_REF_LOCI_3

    Range
    2526549..2529926
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p2 ALT_REF_LOCI_4

Genomic

  1. NT_167246.2 Reference GRCh38.p2 ALT_REF_LOCI_4

    Range
    2577801..2581178
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p2 ALT_REF_LOCI_5

Genomic

  1. NT_167247.2 Reference GRCh38.p2 ALT_REF_LOCI_5

    Range
    2611478..2614855
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p2 ALT_REF_LOCI_6

Genomic

  1. NT_167248.2 Reference GRCh38.p2 ALT_REF_LOCI_6

    Range
    2524181..2527558
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p2 ALT_REF_LOCI_7

Genomic

  1. NT_167249.2 Reference GRCh38.p2 ALT_REF_LOCI_7

    Range
    2570707..2574084
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018917.2 Alternate CHM1_1.1

    Range
    31239250..31242627
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)