KLRC1
entrez
3821
canonical
uniprot
P26715
canonical
ensembl
ENSG00000134545
resolver
ensp
ENSP00000256965
resolver
ensp
ENSP00000352064
resolver
ensp
ENSP00000385304
resolver
ensp
ENSP00000438038
resolver
ensp
ENSP00000441432
resolver
genesymbol
KLRC1
resolver
genesymbol_syn
NKG2A
resolver
hgnc
HGNC:6374
resolver
uniprot_entry
NKG2A_HUMAN
resolver
amino_acid_sequence
MDNQGVIYSDLNLPPNPKRQQRKPKGNKNSILATEQEITYAELNLQKASQDFQGNDKTYHCKDLPSAPEKLIVGILGIICLILMASVVTIVVIPSTLIQRHNNSSLNTRTQKARHCGHCPEEWITYSNSCYYIGKERRTWEESLLACTSKNSSLLSIDNEEEMKFLSIISPSSWIGVFRNSSHHPWVTMNGLAFKHEIKDSDNAELNCAVLQVNRLKSAQCGSSIIYHCKHKL
uniprot
proteins
function
FUNCTION: Immune inhibitory receptor involved in self-nonself discrimination. In complex with KLRD1 on cytotoxic and regulatory lymphocyte subsets, recognizes non-classical major histocompatibility (MHC) class Ib molecule HLA-E loaded with self-peptides derived from the signal sequence of classical MHC class Ia molecules. Enables cytotoxic cells to monitor the expression of MHC class I molecules in healthy cells and to tolerate self (PubMed:18083576, PubMed:37264229, PubMed:9430220, PubMed:9486650). Upon HLA-E-peptide binding, transmits intracellular signals through two immunoreceptor tyrosine-based inhibition motifs (ITIMs) by recruiting INPP5D/SHP-1 and INPPL1/SHP-2 tyrosine phosphatases to ITIMs, and ultimately opposing signals transmitted by activating receptors through dephosphorylation of proximal signaling molecules (PubMed:12165520, PubMed:9485206). Key inhibitory receptor on natural killer (NK) cells that regulates their activation and effector functions (PubMed:30860984, PubMed:9430220, PubMed:9485206, PubMed:9486650). Dominantly counteracts T cell receptor signaling on a subset of memory/effector CD8-positive T cells as part of an antigen-driven response to avoid autoimmunity (PubMed:12387742). On intraepithelial CD8-positive gamma-delta regulatory T cells triggers TGFB1 secretion, which in turn limits the cytotoxic programming of intraepithelial CD8-positive alpha-beta T cells, distinguishing harmless from pathogenic antigens (PubMed:18064301). In HLA-E-rich tumor microenvironment, acts as an immune inhibitory checkpoint and may contribute to progressive loss of effector functions of NK cells and tumor-specific T cells, a state known as cell exhaustion (PubMed:30503213, PubMed:30860984). {ECO:0000269|PubMed:12165520, ECO:0000269|PubMed:12387742, ECO:0000269|PubMed:18064301, ECO:0000269|PubMed:18083576, ECO:0000269|PubMed:30503213, ECO:0000269|PubMed:30860984, ECO:0000269|PubMed:37264229, ECO:0000269|PubMed:9430220, ECO:0000269|PubMed:9485206, ECO:0000269|PubMed:9486650}.; FUNCTION: (Microbial infection) Viruses like human cytomegalovirus have evolved an escape mechanism whereby virus-induced down-regulation of host MHC class I molecules is coupled to the binding of viral peptides to HLA-E, restoring HLA-E expression and inducing HLA-E-dependent NK cell immune tolerance to infected cells. Recognizes HLA-E in complex with human cytomegalovirus UL40-derived peptide (VMAPRTLIL) and inhibits NK cell cytotoxicity. {ECO:0000269|PubMed:10669413, ECO:0000269|PubMed:23335510}.; FUNCTION: (Microbial infection) May recognize HLA-E in complex with HIV-1 gag/Capsid protein p24-derived peptide (AISPRTLNA) on infected cells and may inhibit NK cell cytotoxicity, a mechanism that allows HIV-1 to escape immune recognition. {ECO:0000269|PubMed:15751767}.; FUNCTION: (Microbial infection) Upon SARS-CoV-2 infection, may contribute to functional exhaustion of cytotoxic NK cells and CD8-positive T cells (PubMed:32203188, PubMed:32859121). On NK cells, may recognize HLA-E in complex with SARS-CoV-2 S/Spike protein S1-derived peptide (LQPRTFLL) expressed on the surface of lung epithelial cells, inducing NK cell exhaustion and dampening antiviral immune surveillance (PubMed:32859121). {ECO:0000269|PubMed:32203188, ECO:0000269|PubMed:32859121}.
uniprot
proteins
mass_dalton
26314
uniprot
proteins
mutagenesis
MUTAGEN 6; /note="V->A: Decreases interaction with INPP5D/SHIP-1; when associated A-38."; /evidence="ECO:0000269|PubMed:12165520"; MUTAGEN 8; /note="Y->F: Impairs phosphorylation, interaction with INPP5D/SHIP-1 and NK cell functional inhibition; when associated F-40."; /evidence="ECO:0000269|PubMed:12165520"; MUTAGEN 38; /note="I->A: Decreases interaction with INPP5D/SHIP-1; when associated A-6."; /evidence="ECO:0000269|PubMed:12165520"; MUTAGEN 40; /note="Y->F: Impairs phosphorylation, interaction with INPP5D/SHIP-1 and NK cell functional inhibition; when associated F-8."; /evidence="ECO:0000269|PubMed:12165520"; MUTAGEN 137; /note="R->A: Reduces binding to HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 163; /note="M->I: Has no impact on the affinity for HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 167..170; /note="SIIS->ASIL: Impairs binding to HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 172; /note="S->A: Has no impact on the affinity for HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 200; /note="D->A: Has no impact on the affinity for HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 202; /note="D->A: Has no impact on the affinity for HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 212; /note="Q->A: Reduces binding to HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 213; /note="V->A: Has no impact on the affinity for HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 215; /note="R->A: Reduces binding to HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 217; /note="K->A: Reduces binding to HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 220; /note="Q->A: Has little impact on affinity for HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 223; /note="S->A: Has no impact on affinity for HLA-E."; /evidence="ECO:0000269|PubMed:18083576
uniprot
proteins
post_translational_modification
PTM: Phosphorylated. {ECO:0000269|PubMed:12165520}.
uniprot
proteins
pubmed
10669413
uniprot
proteins
pubmed
12165520
uniprot
proteins
pubmed
12387742
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15751767
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
18064301
uniprot
proteins
pubmed
18083576
uniprot
proteins
pubmed
18332182
uniprot
proteins
pubmed
18448674
uniprot
proteins
pubmed
2007850
uniprot
proteins
pubmed
20952657
uniprot
proteins
pubmed
23335510
uniprot
proteins
pubmed
30503213
uniprot
proteins
pubmed
30860984
uniprot
proteins
pubmed
32203188
uniprot
proteins
pubmed
32859121
uniprot
proteins
pubmed
37264229
uniprot
proteins
pubmed
8753859
uniprot
proteins
pubmed
9430220
uniprot
proteins
pubmed
9485206
uniprot
proteins
pubmed
9486650
uniprot
proteins
pubmed
9598306
uniprot
proteins
sequence_length
233
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12165520, ECO:0000269|PubMed:20952657}; Single-pass type II membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 71..93; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000255
uniprot
proteins