HLA-C Gene (Protein Coding)

Major Histocompatibility Complex, Class I, C

GCID:: GC06M031272

GIFtS:: 44

Genes Participants

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 h... See more...

Aliases for HLA-C Gene

Major Histocompatibility Complex, Class I, C ² ³ ⁵
HLA Class I Histocompatibility Antigen, C Alpha Chain ³ ⁴
HLAC ³ ⁴
Major Histocompatibility Antigen HLA-C ³
MHC Class I Antigen Heavy Chain HLA-C ³
Human Leukocyte Antigen-C Alpha Chain ³
Psoriasis Susceptibility 1 ²
Human Leukocyte Antigen C ⁴

HLA-C Alpha Chain ³
HLA-C Antigen ³
HLA-JY3 ³
D6S204 ³
PSORS1 ³
HLA-Cw ⁴
HLC-C ³
MHC ³

External Ids for HLA-C Gene

HGNC: 4933
Entrez Gene: 3107
Ensembl: ENSG00000204525
OMIM: 142840
UniProtKB: P10321

Previous HGNC Symbols for HLA-C Gene

HLA-JY3
D6S204
PSORS1

Previous GeneCards Identifiers for HLA-C Gene

GC06M031290
GC06M031007
GC06M031341
GC06M031344
GC06M031236

Search aliases for HLA-C gene in PubMed and other databases

Summaries for HLA-C Gene

Entrez Gene Summary for HLA-C Gene

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]

CIViC Summary for HLA-C Gene

GeneCards Summary for HLA-C Gene

HLA-C (Major Histocompatibility Complex, Class I, C) is a Protein Coding gene. Diseases associated with HLA-C include Psoriasis 1 and Human Immunodeficiency Virus Type 1. Among its related pathways are Innate Immune System and Human cytomegalovirus infection. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and TAP binding. An important paralog of this gene is HLA-B.

UniProtKB/Swiss-Prot Summary for HLA-C Gene

Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity (PubMed:20972337, PubMed:24091323, PubMed:20439706, PubMed:11172028, PubMed:20104487, PubMed:28649982, PubMed:29312307). In complex with B2M/beta 2 microglobulin displays a restricted repertoire of self and viral peptides and acts as a dominant ligand for inhibitory and activating killer immunoglobulin receptors (KIRs) expressed on NK cells (PubMed:16141329). In an allogeneic setting, such as during pregnancy, mediates interaction of extravillous trophoblasts with KIR on uterine NK cells and regulate trophoblast invasion necessary for placentation and overall fetal growth (PubMed:20972337, PubMed:24091323). During viral infection, may present viral peptides with low affinity for KIRs, impeding KIR-mediated inhibition through peptide antagonism and favoring lysis of infected cells (PubMed:20439706). Presents a restricted repertoire of viral peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-C-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected cells, particularly in chronic viral infection settings such as HIV-1 or CMV infection (PubMed:11172028, PubMed:20104487, PubMed:28649982). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (By similarity). Typically presents intracellular peptide antigens of 9 amino acids that arise from cytosolic proteolysis via proteasome. Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9. Preferentially displays peptides having a restricted repertoire of hydrophobic or aromatic amino acids (Phe, Ile, Leu, Met, Val and Tyr) at the C-terminal anchor (PubMed:8265661, PubMed:25311805).
- HLAC_HUMAN,P10321
ALLELE C*01:02: The peptide-bound form interacts with KIR2DL2 and KIR2DL3 inhibitory receptors on NK cells. The low affinity peptides compete with the high affinity peptides impeding KIR-mediated inhibition and favoring lysis of infected cells (PubMed:20439706). Presents to CD8-positive T cells a CMV epitope derived from UL83/pp65 (RCPEMISVL), an immediate-early antigen necessary for initiating viral replication (PubMed:12947002).
- HLAC_HUMAN,P10321
ALLELE C*04:01: Presents a conserved HIV-1 epitope derived from env (SFNCGGEFF) to memory CD8-positive T cells, eliciting very strong IFNG responses (PubMed:20104487). Presents CMV epitope derived from UL83/pp65 (QYDPVAALF) to CD8-positive T cells, triggering T cell cytotoxic response (PubMed:12947002).
- HLAC_HUMAN,P10321
ALLELE C*05:01: Presents HIV-1 epitope derived from rev (SAEPVPLQL) to CD8-positive T cells, triggering T cell cytotoxic response.
- HLAC_HUMAN,P10321
ALLELE C*06:02: In trophoblasts, interacts with KIR2DS2 on uterine NK cells and triggers NK cell activation, including secretion of cytokines such as GMCSF that enhances trophoblast migration.
- HLAC_HUMAN,P10321
ALLELE C*07:02: Plays an important role in the control of chronic CMV infection. Presents immunodominant CMV epitopes derived from IE1 (LSEFCRVL and CRVLCCYVL) and UL28 (FRCPRRFCF), both antigens synthesized during immediate-early period of viral replication. Elicits a strong anti-viral CD8-positive T cell immune response that increases markedly with age.
- HLAC_HUMAN,P10321
ALLELE C*08:01: Presents viral epitopes derived from CMV UL83 (VVCAHELVC) and IAV M1 (GILGFVFTL), triggering CD8-positive T cell cytotoxic response.
- HLAC_HUMAN,P10321
ALLELE C*12:02: Presents CMV epitope derived from UL83 (VAFTSHEHF) to CD8-positive T cells.
- HLAC_HUMAN,P10321
ALLELE C*15:02: Presents CMV epitope derived from UL83 CC (VVCAHELVC) to CD8-positive T cells, triggering T cell cytotoxic response.
- HLAC_HUMAN,P10321

Gene Wiki entry for HLA-C Gene

Additional gene information for HLA-C Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HLA-C Gene

Genomics for HLA-C Gene

GeneHancer (GH) Regulatory Elements for HLA-C Gene

Promoters and enhancers for HLA-C Gene

GeneHancer (GH) Identifier	GH Type	GH Score	GH Sources	Gene Association Score	Total Score	TSS distance (kb)	Number of Genes Away	Size (kb)	Transcription Factor Binding Sites
GH06J031269	Promoter/Enhancer	2	EPDnew FANTOM5 Ensembl ENCODE dbSUPER	613.5	+0.5	477	4.7	HNRNPK ZNF217 POLR2G SP1 CTCF ZIC2 ZBTB10 POLR2A CLOCK FOS	HLA-C piR-38512-004 piR-48456 PSORS1C3 PPT2 TNXB LSM2 PSORS1C2 HCG18 TCF19
GH06J031352	Promoter/Enhancer	2.2	EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER	41.9	-84.1	-84056	7	ZBTB40 SP1 ZBTB10 POLR2A FOS RELA RCOR1 NFYB ZNF266 KLF9	HLA-B ENSG00000271581 MIR6891 NONHSAG043472.2 lnc-HLA-C-2 piR-47864 HLA-C DDX39B MICA LY6G5B
GH06J031307	Promoter/Enhancer	1.2	FANTOM5 Ensembl ENCODE	59.7	-36.3	-36265	1.6	ZNF217 ZFX NFYB EZH2 POLR2A HCFC1 SIN3A MYC PBX2 YY1	LINC02571 ENSG00000229836 NONHSAG045731.2 lnc-HLA-C-4 HLA-C PSORS1C3 PSORS1C2 HLA-B ENSG00000272221 MUCL3
GH06J031399	Promoter/Enhancer	2.3	EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER	27.2	-129.5	-129465	7.2	ZNF217 CTCF SIN3A NRF1 USF1 POLR2G SP1 GTF2E2 JUND PHF8	MICA ENSG00000199332 HCP5 MICA-AS1 ENSG00000272221 HLA-C MICB DDX39B LSM2 RPL3P2
GH06J031196	Promoter/Enhancer	1.9	Ensembl ENCODE CraniofacialAtlas dbSUPER	27.6	+74.0	73959	3.6	RXRA ZNF217 CTCF SIN3A NRF1 POLR2G USF1 NCOR1 BCLAF1 GTF2E2	ENSG00000272501 HCG27 GQ472773-002 KC312698 PSORS1C3 POU5F1 PSORS1C2 PRRT1 HLA-C GNL1

- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HLA-C on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HLA-C

Top Transcription factor binding sites by QIAGEN in the HLA-C gene promoter:

AP-1
AP-2gamma
ARP-1
ATF-2
ATF6
c-Jun
CUTL1
POU2F1
USF-1
USF1

Genomic Locations for HLA-C Gene

chr6:31,268,749-31,272,136: (GRCh38/hg38)

Size:: 3,388 bases
Orientation:: Minus strand

chr6:31,236,526-31,239,907: (GRCh37/hg19)

Size:: 3,382 bases
Orientation:: Minus strand

Genomic View for HLA-C Gene

Genes around HLA-C on UCSC Golden Path with GeneCards custom track

Cytogenetic band:

6p21.33 by HGNC
6p21.33 by Entrez Gene
6p21.33 by Ensembl

HLA-C Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)

Genomic Location for HLA-C Gene — Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for HLA-C Gene

Proteins for HLA-C Gene

Protein details for HLA-C Gene (UniProtKB/Swiss-Prot)
Protein Symbol:

P10321-HLAC_HUMAN

Recommended name:

HLA class I histocompatibility antigen, C alpha chain

Protein Accession:

P10321

Secondary Accessions:
- O02863
- O02864
- O02865
- O02866
- O02958
- O19505
- O19652
- O19676
- O62879
- O62882
- O62883
- O62888
- O78060
- O78061
- O78062
- O78063
- O78067
- O78068
- O78069
- O78072
- O78083
- O78090
- O78091
- O78149
- O78165
- O78166
- O78178
- O78202
- O78203
- O78211
- O78214
- P04222
- P30499
- P30500
- P30501
- P30502
- P30503
- P30504
- P30505
- P30506
- P30507
- P30508
- P30509
- P30510
- P79498
- Q07000
- Q29631
- Q29641
- Q29643
- Q29652
- Q29743
- Q29768
- Q29862
- Q29864
- Q29865
- Q29867
- Q29921
- Q29959
- Q29960
- Q29963
- Q29986
- Q29989
- Q29990
- Q29991
- Q29992
- Q29993
- Q30192
- Q31605
- Q31627
- Q860R1
- Q860R2
- Q95463
- Q95603
- Q95604
- Q99528
- Q9BD28
- Q9GIK4
- Q9GIK8
- Q9GJ33
- Q9MY30
- Q9MY31
- Q9MY35
- Q9MY49
- Q9MY74
- Q9MYI3
- Q9TNN7
- Q9TNZ8
- Q9TPS4
- Q9TPV8
- Q9TPX2
- Q9TQB4
- Q9TQJ5
- Q9TQP9
- Q9UM32
- Q9UM33
- Q9UM42
- Q9UQS9
Protein attributes for HLA-C Gene
Size:

366 amino acids

Molecular mass:

40649 Da
Quaternary structure:
Heterotrimer that consists of an alpha chain HLA-C, a beta chain B2M and a peptide (peptide-HLA-C-B2M) (PubMed:28649982, PubMed:10850706, PubMed:24990997). Early in biogenesis, HLA-C-B2M dimer interacts with the components of the peptide-loading complex composed of TAPBP, TAP1-TAP2, TAPBPL, PDIA3/ERP57 and CALR (PubMed:18420581). Interacts with TAP1-TAP2 transporter via TAPBP; this interaction is obligatory for the loading of peptide epitopes delivered to the endoplasmic reticulum (ER) by TAP1-TAP2 transporter (By similarity). Being very selective in the peptide binding, forms a stable interaction with TAP1-TAP2, often leading to the accumulation of free heavy chains in the ER (PubMed:18420581). Only optimally assembled peptide-HLA-C-B2M trimer translocates to the surface of antigen-presenting cells, where it interacts with TCR and CD8 coreceptor on the surface of T cells. HLA-C (via polymorphic alpha-1 and alpha-2 domains) interacts with antigen-specific TCR (via CDR3 domains) (By similarity). One HLA-C molecule (mainly via nonpolymorphic alpha-3 domain) interacts with one CD8A homodimer (via CDR-like loop); this interaction insures peptide-HLA-C-B2M recognition by CD8-positive T cells only (By similarity). The peptide-HLA-C-B2M complex also interacts with KIRs. HLA-C type 1 (C1, with Asn104), including HLA-C*02, C*04, C*05, C*06 and C*15, interact with KIR2DL1 and KIR2DS1, and HLA-C type 2 (C2, with Lys104), including HLA-C*01, C*03, C*07 and C*08, interact with KIR2DL2 and KIR2DL3 (PubMed:20972337, PubMed:24091323, PubMed:16141329, PubMed:20439706, PubMed:11323700, PubMed:10850706).

(Microbial infection) Interacts with HTLV-1 p12I accessory protein.
Miscellaneous:
[Isoform 2]: A transcript of allele C*16:01. This isoform lacks the transmembrane domain and is predicted to be a secreted protein.
Three dimensional structures from OCA and Proteopedia for HLA-C Gene
- 1EFX (3D)
- 1IM9 (3D)
- 1QQD (3D)
- 3BZF (3D)
- 4NT6 (3D)
- 5VGD (3D)
Alternative splice isoforms for HLA-C Gene
UniProtKB/Swiss-Prot:
P10321-1

P10321-2

neXtProt entry for HLA-C Gene

Protein Expression for HLA-C Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for HLA-C Gene

N-linked glycosylation at Asn-110 is required for efficient interaction with CANX and CALR chaperones and appropriate HLA-C-B2M folded conformers prior to peptide loading.
- P10321-HLAC_HUMAN
Glycosylation at Asn110
- NX_P10321 (NX_P10321-1)
Ubiquitination at Lys210
- NX_P10321 (NX_P10321-1)
Glycosylation from GlyConnect
- HLAC_HUMAN (1352, 1353, 1354, 1355, 1356, 1357, 1358, 1359, 1360, 1361, 1362, 1363, 1364)

Other Protein References for HLA-C Gene

ENSEMBL proteins:

REFSEQ proteins:

Antibody Products

Creative Diagnostics

Creative Biolabs

BioLegend HLA-C Antibody

Novus Biologicals Antibodies for HLA-C

Invitrogen Antibodies for HLA-C (AFLGC-HLA-C)

Biorbyt antibodies for HLA-C
- orb110316

Boster Bio Antibodies for HLA-C
- PB9377

Santa Cruz Biotechnology (SCBT) Antibodies for HLA-C

Browse Sino Biological Antibodies

Protein Products

Creative Biomart Recombinant Human HLA 293 Cell Lysate, Recombinant Human major histocompatibility complex, class I, C, His-tagged, and Recombinant Human HLA-C Protein, His-tagged

OriGene Purified Proteins for HLA-C
Search Origene for MassSpec and Protein Over-expression Lysates for HLA-C
Origene Custom Protein Services for HLA-C

Novus Biologicals proteins and lysates for HLA-C

ProSpec Recombinant Proteins for HLA-C

antibodies-online: Show 34 available HLA-C Proteins ranked by validation data
Compare Top HLA-C Proteins

Search for HLA-C Proteins at ProSci

Assay Products

antibodies-online: Show 4 available HLA-C Elisa Kits ranked by validation data
Compare Top HLA-C Elisa Kits
Quality Products:

Browse Boster Bio ELISA Kits

Browse Sino Biological Assays

No data available for DME Specific Peptides for HLA-C Gene

Domains & Families for HLA-C Gene

Gene Families for HLA-C Gene

HGNC:

Human Protein Atlas (HPA):

Plasma proteins
Predicted intracellular proteins
Predicted membrane proteins

Protein Domains for HLA-C Gene

Blocks:

MHC class I signature
Immunoglobulin C-type
MHC_I, C-terminal

InterPro:

ProtoNet:

P10321

Suggested Antigen Peptide Sequences for HLA-C Gene

GenScript: Design optimal peptide antigens:

MHC class I antigen Cw*1 (1C01_HUMAN)
MHC class I antigen Cw*2 (1C02_HUMAN)
MHC class I antigen Cw*3 (1C03_HUMAN)
MHC class I antigen Cw*4 (1C04_HUMAN)
MHC class I antigen Cw*5 (1C05_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P10321

UniProtKB/Swiss-Prot:

HLAC_HUMAN :

The alpha-1 domain is a structural part of the peptide-binding cleft.

Domain:

The alpha-1 domain is a structural part of the peptide-binding cleft.
The alpha-2 domain is a structural part of the peptide-binding cleft (PubMed:28649982, PubMed:10850706, PubMed:24990997). Mediates the interaction with TAP1-TAP2 complex.
The alpha-3 Ig-like domain mediates the interaction with CD8 coreceptor.