UniProt functional annotation for P26718



	UniProt functional annotation for P26718

UniProt code: P26718.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Functions as an activating and costimulatory receptor involved in immunosurveillance upon binding to various cellular stress- inducible ligands displayed at the surface of autologous tumor cells and virus-infected cells. Provides both stimulatory and costimulatory innate immune responses on activated killer (NK) cells, leading to cytotoxic activity. Acts as a costimulatory receptor for T-cell receptor (TCR) in CD8(+) T-cell-mediated adaptive immune responses by amplifying T-cell activation. Stimulates perforin-mediated elimination of ligand-expressing tumor cells. Signaling involves calcium influx, culminating in the expression of TNF-alpha. Participates in NK cell- mediated bone marrow graft rejection. May play a regulatory role in differentiation and survival of NK cells. Binds to ligands belonging to various subfamilies of MHC class I-related glycoproteins including MICA, MICB, RAET1E, RAET1G, RAET1L/ULBP6, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4. {ECO:0000269|PubMed:10426994, ECO:0000269|PubMed:11224526, ECO:0000269|PubMed:11777960, ECO:0000269|PubMed:15240696, ECO:0000269|PubMed:19658097, ECO:0000269|PubMed:21898152, ECO:0000269|PubMed:23298206, ECO:0000269|PubMed:28559451}.

Subunit: Homodimer; disulfide-linked. Heterohexamer composed of two subunits of KLRK1 and four subunits of HCST/DAP10. Interacts (via transmembrane domain) with HCST/DAP10 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface and induces NK cell- mediated cytotoxicity. Does not interact with TYROBP. Interacts with CEACAM1; recruits PTPN6 that dephosphorylates VAV1 (PubMed:23696226). {ECO:0000269|PubMed:10426993, ECO:0000269|PubMed:10426994, ECO:0000269|PubMed:11015446, ECO:0000269|PubMed:11754823, ECO:0000269|PubMed:15294961, ECO:0000269|PubMed:15894612, ECO:0000269|PubMed:23696226}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:10426994, ECO:0000269|PubMed:11015446, ECO:0000269|PubMed:15294961}; Single-pass type II membrane protein {ECO:0000269|PubMed:10426994, ECO:0000269|PubMed:11015446, ECO:0000269|PubMed:15294961}. Note=Colocalized with HCST on the cell surface.

Tissue specificity: Expressed in natural killer (NK) cells, CD8(+) alpha-beta and gamma-delta T-cells. Expressed on essentially all CD56+CD3- NK cells from freshly isolated PBMC. Expressed in interferon- producing killer dendritic cells (IKDCs). {ECO:0000269|PubMed:10426993, ECO:0000269|PubMed:15294961, ECO:0000269|PubMed:16444266}.

Induction: Up-regulated by interleukin IL15 in primary NK cells. {ECO:0000269|PubMed:11777960}.

Miscellaneous: Is not capable of signal transduction by itself, but operates through the adapter protein HCST (PubMed:10426994 and PubMed:15894612). Some families of ligands for human and mouse KLRK1 receptors have been characterized being very similar in structure and highly likely to be orthologs. In humans, an additional distinct subfamily of ligands (MICA and MICB) differs structurally, having an extra MHC alpha 3-like domain (PubMed:23298206). {ECO:0000305|PubMed:23298206}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Functions as an activating and costimulatory receptor involved in immunosurveillance upon binding to various cellular stress- inducible ligands displayed at the surface of autologous tumor cells and virus-infected cells. Provides both stimulatory and costimulatory innate immune responses on activated killer (NK) cells, leading to cytotoxic activity. Acts as a costimulatory receptor for T-cell receptor (TCR) in CD8(+) T-cell-mediated adaptive immune responses by amplifying T-cell activation. Stimulates perforin-mediated elimination of ligand-expressing tumor cells. Signaling involves calcium influx, culminating in the expression of TNF-alpha. Participates in NK cell- mediated bone marrow graft rejection. May play a regulatory role in differentiation and survival of NK cells. Binds to ligands belonging to various subfamilies of MHC class I-related glycoproteins including MICA, MICB, RAET1E, RAET1G, RAET1L/ULBP6, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4. {ECO:0000269\|PubMed:10426994, ECO:0000269\|PubMed:11224526, ECO:0000269\|PubMed:11777960, ECO:0000269\|PubMed:15240696, ECO:0000269\|PubMed:19658097, ECO:0000269\|PubMed:21898152, ECO:0000269\|PubMed:23298206, ECO:0000269\|PubMed:28559451}.


Subunit:		Homodimer; disulfide-linked. Heterohexamer composed of two subunits of KLRK1 and four subunits of HCST/DAP10. Interacts (via transmembrane domain) with HCST/DAP10 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface and induces NK cell- mediated cytotoxicity. Does not interact with TYROBP. Interacts with CEACAM1; recruits PTPN6 that dephosphorylates VAV1 (PubMed:23696226). {ECO:0000269\|PubMed:10426993, ECO:0000269\|PubMed:10426994, ECO:0000269\|PubMed:11015446, ECO:0000269\|PubMed:11754823, ECO:0000269\|PubMed:15294961, ECO:0000269\|PubMed:15894612, ECO:0000269\|PubMed:23696226}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:10426994, ECO:0000269\|PubMed:11015446, ECO:0000269\|PubMed:15294961}; Single-pass type II membrane protein {ECO:0000269\|PubMed:10426994, ECO:0000269\|PubMed:11015446, ECO:0000269\|PubMed:15294961}. Note=Colocalized with HCST on the cell surface.
Tissue specificity:		Expressed in natural killer (NK) cells, CD8(+) alpha-beta and gamma-delta T-cells. Expressed on essentially all CD56+CD3- NK cells from freshly isolated PBMC. Expressed in interferon- producing killer dendritic cells (IKDCs). {ECO:0000269\|PubMed:10426993, ECO:0000269\|PubMed:15294961, ECO:0000269\|PubMed:16444266}.
Induction:		Up-regulated by interleukin IL15 in primary NK cells. {ECO:0000269\|PubMed:11777960}.
Miscellaneous:		Is not capable of signal transduction by itself, but operates through the adapter protein HCST (PubMed:10426994 and PubMed:15894612). Some families of ligands for human and mouse KLRK1 receptors have been characterized being very similar in structure and highly likely to be orthologs. In humans, an additional distinct subfamily of ligands (MICA and MICB) differs structurally, having an extra MHC alpha 3-like domain (PubMed:23298206). {ECO:0000305\|PubMed:23298206}.