KLRD1
entrez
3824
canonical
uniprot
Q13241
canonical
ensembl
ENSG00000134539
resolver
ensp
ENSP00000310929
resolver
ensp
ENSP00000338130
resolver
ensp
ENSP00000371333
resolver
ensp
ENSP00000443584
resolver
ensp
ENSP00000533046
resolver
enst
ENST00000543777
resolver
genesymbol
KLRD1
resolver
genesymbol_syn
CD94
resolver
hgnc
HGNC:6378
resolver
uniprot
F6WZH4
resolver
uniprot
O43321
resolver
uniprot
O43773
resolver
uniprot
Q53ZY6
resolver
uniprot
Q9UBE3
resolver
uniprot
Q9UEQ0
resolver
uniprot_entry
F6WZH4_HUMAN
resolver
uniprot_entry
KLRD1_HUMAN
resolver
uniprot_entry
Q53ZY6_HUMAN
resolver
uniprot_sec
O43321
resolver
uniprot_sec
O43773
resolver
uniprot_sec
Q9UBE3
resolver
uniprot_sec
Q9UEQ0
resolver
amino_acid_sequence
MAVFKTTLWRLISGTLGIICLSLMSTLGILLKNSFTKLSIEPAFTPGPNIELQKDSDCCSCQEKWVGYRCNCYFISSEQKTWNESRHLCASQKSSLLQLQNTDELDFMSSSQQFYWIGLSYSEEHTAWLWENGSALSQYLFPSFETFNTKNCIAYNPNGNALDESCEDKNRYICKQQLI
uniprot
proteins
function
FUNCTION: Immune receptor involved in self-nonself discrimination. In complex with KLRC1 or KLRC2 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 and non-classical MHC class Ib molecules (PubMed:10023772, PubMed:18064301, PubMed:18083576, PubMed:37264229, PubMed:9486650, PubMed:9754572). Enables cytotoxic cells to monitor the expression of MHC class I molecules in healthy cells and to tolerate self (PubMed:12387742, PubMed:18064301, PubMed:9430220). Primarily functions as a ligand binding subunit as it lacks the capacity to signal. {ECO:0000269|PubMed:10023772, ECO:0000269|PubMed:12387742, ECO:0000269|PubMed:18064301, ECO:0000269|PubMed:18083576, ECO:0000269|PubMed:37264229, ECO:0000269|PubMed:9430220, ECO:0000269|PubMed:9486650, ECO:0000269|PubMed:9754572}.; FUNCTION: KLRD1-KLRC1 acts as an immune inhibitory receptor. 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). Upon HLA-E-peptide binding, transmits intracellular signals through KLRC1 immunoreceptor tyrosine-based inhibition motifs (ITIMs) by recruiting INPP5D/SHIP-1 and INPPL1/SHIP-2 tyrosine phosphatases to ITIMs, and ultimately opposing signals transmitted by activating receptors through dephosphorylation of proximal signaling molecules (PubMed:12165520, PubMed:9485206). {ECO:0000269|PubMed:12165520, ECO:0000269|PubMed:12387742, ECO:0000269|PubMed:18064301, ECO:0000269|PubMed:30503213, ECO:0000269|PubMed:30860984, ECO:0000269|PubMed:9430220, ECO:0000269|PubMed:9485206, ECO:0000269|PubMed:9486650}.; FUNCTION: KLRD1-KLRC2 acts as an immune activating receptor (PubMed:15940674, PubMed:9655483). On cytotoxic lymphocyte subsets recognizes HLA-E loaded with signal sequence-derived peptides from non-classical MHC class Ib HLA-G molecules, likely playing a role in the generation and effector functions of adaptive NK cells and in maternal-fetal tolerance during pregnancy (PubMed:30134159, PubMed:9754572). Regulates the effector functions of terminally differentiated cytotoxic lymphocyte subsets, and in particular may play a role in adaptive NK cell response to viral infection (PubMed:20952657, PubMed:21825173). Upon HLA-E-peptide binding, transmits intracellular signals via the adapter protein TYROBP/DAP12, triggering the phosphorylation of proximal signaling molecules and cell activation (PubMed:15940674, PubMed:9655483). {ECO:0000269|PubMed:15940674, ECO:0000269|PubMed:20952657, ECO:0000269|PubMed:21825173, ECO:0000269|PubMed:30134159, ECO:0000269|PubMed:9655483, ECO:0000269|PubMed:9754572}.; 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: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:32859121}.
uniprot
proteins
mass_dalton
20513
uniprot
proteins
mutagenesis
MUTAGEN 79; /note="Q->A: Has no impact on the affinity for HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 112; /note="Q->A: Abolishes binding to HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 114; /note="F->A: Abolishes binding to HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 146; /note="T->A: Has no impact on the affinity for HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 148; /note="N->A: Has no impact on the affinity for HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 158; /note="N->A: Has no impact on the affinity for HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 160; /note="N->A: Abolishes binding to HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 162; /note="L->A: Abolishes binding to HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 163; /note="D->A: Impairs binding to HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 164; /note="E->A: Impairs binding to HLA-E."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 168; /note="D->A: Reduces binding to HLA-E."; /evidence="ECO:0000269|PubMed:18083576
uniprot
proteins
pubmed
10023772
uniprot
proteins
pubmed
10428963
uniprot
proteins
pubmed
10669413
uniprot
proteins
pubmed
12165520
uniprot
proteins
pubmed
12387742
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15751767
uniprot
proteins
pubmed
15940674
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
18064301
uniprot
proteins
pubmed
18083576
uniprot
proteins
pubmed
18332182
uniprot
proteins
pubmed
18448674
uniprot
proteins
pubmed
20952657
uniprot
proteins
pubmed
21825173
uniprot
proteins
pubmed
23335510
uniprot
proteins
pubmed
30134159
uniprot
proteins
pubmed
30503213
uniprot
proteins
pubmed
30860984
uniprot
proteins
pubmed
32859121
uniprot
proteins
pubmed
37264229
uniprot
proteins
pubmed
7589107
uniprot
proteins
pubmed
9430220
uniprot
proteins
pubmed
9472066
uniprot
proteins
pubmed
9485206
uniprot
proteins
pubmed
9486650
uniprot
proteins
pubmed
9601951
uniprot
proteins
pubmed
9655483
uniprot
proteins
pubmed
9754572
uniprot
proteins
sequence_length
179
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20952657, ECO:0000269|PubMed:9485206}; Single-pass type II membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 11..31; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000255
uniprot
proteins