HLA-C

Protein identityUniProt · HPA

UniProt accession

P10321

Gene

HLA-C

Ensembl

ENSG00000204525

Chromosome

6

Canonical length

366 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI 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. About 6000 HLA-C alleles have been described. The HLA system plays an important role in the occurrence and outcome of infectious diseases, including those caused by the malaria parasite, the human immunodeficiency virus (HIV), and the severe acute respiratory syndrome coronavirus (SARS-CoV). The structural spike and the nucleocapsid proteins of the novel coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), are reported to contain multiple Class I epitopes with predicted HLA restrictions. Individual HLA genetic variation may help explain different immune responses to a virus across a population.[provided by RefSeq, Aug 2020]

Canonical amino-acid sequenceUniProt

366 residues, UniProt reviewed canonical sequence.

>P10321|HLA-C
     1  MRVMAPRALL LLLSGGLALT ETWACSHSMR YFDTAVSRPG RGEPRFISVG YVDDTQFVRF
    61  DSDAASPRGE PRAPWVEQEG PEYWDRETQK YKRQAQADRV SLRNLRGYYN QSEDGSHTLQ
   121  RMSGCDLGPD GRLLRGYDQS AYDGKDYIAL NEDLRSWTAA DTAAQITQRK LEAARAAEQL
   181  RAYLEGTCVE WLRRYLENGK ETLQRAEPPK THVTHHPLSD HEATLRCWAL GFYPAEITLT
   241  WQRDGEDQTQ DTELVETRPA GDGTFQKWAA VVVPSGQEQR YTCHMQHEGL QEPLTLSWEP
   301  SSQPTIPIMG IVAGLAVLVV LAVLGAVVTA MMCRRKSSGG KGGSCSQAAC SNSAQGSDES
   361  LITCKA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HLA-C can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.38

Highest tissue expression

1,378 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HLA-C.

Disease | AllUniProt

Conditions HLA-C is implicated in, by any mechanism.

• Psoriasis 1 (PSORS1) MIM:177900

Disease | ImmuneIEDB

Conditions an epitope on HLA-C was assayed in.

• viral infectious disease T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.02

gnomAD pLI

0

gnomAD missense Z

0.13

DepMap mean gene effect

-0.15

DepMap dependency class

selective

OntologyGO

Biological processes

• adaptive immune response
• antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent
• antigen processing and presentation of endogenous peptide antigen via MHC class Ib
• immune response
• innate immune response
• positive regulation of natural killer cell mediated cytotoxicity
• positive regulation of T cell mediated cytotoxicity

Molecular functions

• peptide antigen binding
• receptor ligand activity
• signaling receptor binding
• TAP binding

Cellular components

• cell surface
• early endosome membrane
• endoplasmic reticulum
• ER to Golgi transport vesicle membrane
• external side of plasma membrane
• extracellular exosome
• extracellular space
• Golgi apparatus
• Golgi membrane
• lumenal side of endoplasmic reticulum membrane
• membrane
• MHC class I protein complex
• phagocytic vesicle membrane
• plasma membrane
• recycling endosome membrane
• secretory granule membrane

Protein domainsUniProt · Pfam · InterPro

• MHC class I alpha chain, alpha1 alpha2 domains
• Immunoglobulin C1-set
• Immunoglobulin-like domain
• MHC class I, alpha chain, C-terminal
• MHC class I-like antigen recognition-like
• MHC classes I/II-like antigen recognition protein
• Immunoglobulin-like fold
• Immunoglobulin-like domain superfamily
• MHC class I-like antigen recognition-like superfamily
• Antigen-presenting and immune regulatory MHC class I-related
• Class I Histocompatibility antigen, domains alpha 1 and 2
• MHC_I C-terminus
• Immunoglobulin C1-set domain

KeywordsUniProt

• Adaptive immunity
• Cell membrane
• Disulfide bond
• Endoplasmic reticulum
• Glycoprotein
• Host-virus interaction
• Immunity
• Innate immunity
• Membrane
• MHC I
• Phosphoprotein
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of HLA-C in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CALR
• TAP1-TAP2
• TAPBPL
• TCR
• AURKB
• CLEC4E
• HLA-A
• HLA-B
• HSPA5
• KIR2DL1
• KIR2DL3
• RAB3B
• ROR2
• TMEM106B