UniProt functional annotation for O54709



	UniProt functional annotation for O54709

UniProt code: O54709.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

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 RAET1A, RAET1B, RAET1C, RAET1D, RAET1E, H60 and MULT1. {ECO:0000269|PubMed:10894171, ECO:0000269|PubMed:11248803, ECO:0000269|PubMed:11557981, ECO:0000269|PubMed:11567106, ECO:0000269|PubMed:12150888, ECO:0000269|PubMed:12370332, ECO:0000269|PubMed:12426564, ECO:0000269|PubMed:12426565, ECO:0000269|PubMed:15189740, ECO:0000269|PubMed:16086018, ECO:0000269|PubMed:18394936, ECO:0000269|PubMed:19631564, ECO:0000269|PubMed:21898152, ECO:0000269|PubMed:23298206}.

Subunit: Homodimer; disulfide-linked. Heterohexamer composed of two subunits of KLRK1 and four subunits of HCST/DAP10 (By similarity). Isoform 1 (via transmembrane domain) interacts with HCST/DAP10; the interaction is required for KLRK1 cell surface expression on activated CD8(+) T-cells, but is dispensable on activated TYROBP-expressing NK cells. Isoform 2 (via transmembrane domain) interacts with HCST/DAP10 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface expression and induces NK cell-mediated cytotoxicity. Isoform 2 (via transmembrane domain) interacts with TYROBP (via transmembrane domain); the interaction is required for KLRK1 NK cell surface expression and induce NK cell-mediated cytotoxicity and cytokine secretion. Isoform 1 does not interact with TYROBP. Interacts with CEACAM1; recruits PTPN6 that dephosphorylates VAV1 (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P26718, ECO:0000269|PubMed:11825567, ECO:0000269|PubMed:12426564, ECO:0000269|PubMed:12426565, ECO:0000269|PubMed:15294961}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:12426565, ECO:0000269|PubMed:15294961}; Single-pass type II membrane protein {ECO:0000269|PubMed:12426565, ECO:0000269|PubMed:15294961}. Note=Colocalized with HCST and TYROBP on the cell surface.

Tissue specificity: Expressed in natural killer (NK) cells, activated CD8(+) alpha-beta and gamma-delta T-cells and natural killer T (NKT) cells (at protein level). May be expressed on dendritic cell (DC). Isoform 1 is strongly expressed in natural killer (NK) cells. Isoform 2 is weakly expressed in natural killer (NK) cells. Isoform 1 and isoform 2 are expressed in stimulated, but not in unstimulated, CD8(+) T-cells and macrophages. {ECO:0000269|PubMed:11248803, ECO:0000269|PubMed:11567106, ECO:0000269|PubMed:12150888, ECO:0000269|PubMed:15048723}.

Developmental stage: Expressed in NK cells from the thymus at 15 dpc (at protein level). {ECO:0000269|PubMed:12150888}.

Induction: Up-regulated in activated CD8(+) T-cells. Up-regulated upon lipopolysaccharide (LPS) and interferon treatments in macrophages. Up- regulated in CD8(+) T-cell infiltring pancreatic islets of prediabetic nonobese diabetic (NOD) mice (at protein level). Isoform 1 and isoform 2 are up-regulated upon T-cell receptor (TCR) stimulation in CD8(+) T- cells. Isoform 1 is modestly up-regulated upon lipopolysaccharide (LPS) in macrophages. Isoform 2 is up-regulated upon lipopolysaccharide (LPS) in macrophages. Isoform 2 is up-regulated upon poly(I:C) and interleukin IL2 in natural killer (NK) cells. {ECO:0000269|PubMed:12150888, ECO:0000269|PubMed:15189740}.

Disease: Note=Involved in autoreactive CD8(+) T-cell-mediated development of autoimmune diabetes. {ECO:0000269|PubMed:15189740}.

Disruption phenotype: Mice display no visible phenotype. According to PubMed:18394936, show normal development of NK cells, B and T cells but display enhanced formation of aggressive tumors. According to PubMed:19631564, exhibit developmental perturbation in size of NK cell subpopulations, increased proliferation, faster maturation and increased sensitivity to apoptosis of immature NK cells, and lower cytolytic response to KLRK1-sensitive tumor targets. {ECO:0000269|PubMed:18394936, ECO:0000269|PubMed:19631564}.

Miscellaneous: Is not capable of signal transduction by itself; isoform 1 operates either through the signaling adapter protein HCST and isoform 2 through both HCST and TYROBP signaling adapter proteins (PubMed:12426564). Some families of ligands for mouse and human 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:12426564, ECO:0000305|PubMed:23298206}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



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 RAET1A, RAET1B, RAET1C, RAET1D, RAET1E, H60 and MULT1. {ECO:0000269\|PubMed:10894171, ECO:0000269\|PubMed:11248803, ECO:0000269\|PubMed:11557981, ECO:0000269\|PubMed:11567106, ECO:0000269\|PubMed:12150888, ECO:0000269\|PubMed:12370332, ECO:0000269\|PubMed:12426564, ECO:0000269\|PubMed:12426565, ECO:0000269\|PubMed:15189740, ECO:0000269\|PubMed:16086018, ECO:0000269\|PubMed:18394936, ECO:0000269\|PubMed:19631564, ECO:0000269\|PubMed:21898152, ECO:0000269\|PubMed:23298206}.


Subunit:		Homodimer; disulfide-linked. Heterohexamer composed of two subunits of KLRK1 and four subunits of HCST/DAP10 (By similarity). Isoform 1 (via transmembrane domain) interacts with HCST/DAP10; the interaction is required for KLRK1 cell surface expression on activated CD8(+) T-cells, but is dispensable on activated TYROBP-expressing NK cells. Isoform 2 (via transmembrane domain) interacts with HCST/DAP10 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface expression and induces NK cell-mediated cytotoxicity. Isoform 2 (via transmembrane domain) interacts with TYROBP (via transmembrane domain); the interaction is required for KLRK1 NK cell surface expression and induce NK cell-mediated cytotoxicity and cytokine secretion. Isoform 1 does not interact with TYROBP. Interacts with CEACAM1; recruits PTPN6 that dephosphorylates VAV1 (By similarity). {ECO:0000250, ECO:0000250\|UniProtKB:P26718, ECO:0000269\|PubMed:11825567, ECO:0000269\|PubMed:12426564, ECO:0000269\|PubMed:12426565, ECO:0000269\|PubMed:15294961}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:12426565, ECO:0000269\|PubMed:15294961}; Single-pass type II membrane protein {ECO:0000269\|PubMed:12426565, ECO:0000269\|PubMed:15294961}. Note=Colocalized with HCST and TYROBP on the cell surface.
Tissue specificity:		Expressed in natural killer (NK) cells, activated CD8(+) alpha-beta and gamma-delta T-cells and natural killer T (NKT) cells (at protein level). May be expressed on dendritic cell (DC). Isoform 1 is strongly expressed in natural killer (NK) cells. Isoform 2 is weakly expressed in natural killer (NK) cells. Isoform 1 and isoform 2 are expressed in stimulated, but not in unstimulated, CD8(+) T-cells and macrophages. {ECO:0000269\|PubMed:11248803, ECO:0000269\|PubMed:11567106, ECO:0000269\|PubMed:12150888, ECO:0000269\|PubMed:15048723}.
Developmental stage:		Expressed in NK cells from the thymus at 15 dpc (at protein level). {ECO:0000269\|PubMed:12150888}.
Induction:		Up-regulated in activated CD8(+) T-cells. Up-regulated upon lipopolysaccharide (LPS) and interferon treatments in macrophages. Up- regulated in CD8(+) T-cell infiltring pancreatic islets of prediabetic nonobese diabetic (NOD) mice (at protein level). Isoform 1 and isoform 2 are up-regulated upon T-cell receptor (TCR) stimulation in CD8(+) T- cells. Isoform 1 is modestly up-regulated upon lipopolysaccharide (LPS) in macrophages. Isoform 2 is up-regulated upon lipopolysaccharide (LPS) in macrophages. Isoform 2 is up-regulated upon poly(I:C) and interleukin IL2 in natural killer (NK) cells. {ECO:0000269\|PubMed:12150888, ECO:0000269\|PubMed:15189740}.
Disease:		Note=Involved in autoreactive CD8(+) T-cell-mediated development of autoimmune diabetes. {ECO:0000269\|PubMed:15189740}.
Disruption phenotype:		Mice display no visible phenotype. According to PubMed:18394936, show normal development of NK cells, B and T cells but display enhanced formation of aggressive tumors. According to PubMed:19631564, exhibit developmental perturbation in size of NK cell subpopulations, increased proliferation, faster maturation and increased sensitivity to apoptosis of immature NK cells, and lower cytolytic response to KLRK1-sensitive tumor targets. {ECO:0000269\|PubMed:18394936, ECO:0000269\|PubMed:19631564}.
Miscellaneous:		Is not capable of signal transduction by itself; isoform 1 operates either through the signaling adapter protein HCST and isoform 2 through both HCST and TYROBP signaling adapter proteins (PubMed:12426564). Some families of ligands for mouse and human 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:12426564, ECO:0000305\|PubMed:23298206}.