UniProt functional annotation for Q8VIM0



	UniProt functional annotation for Q8VIM0

UniProt code: Q8VIM0.

Organism: Mus musculus (Mouse).

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

Function: Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may be influenced by the cellular context and/or the respective ligand (PubMed:18006747). Regulates macrophage activation (PubMed:11823861). Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance (PubMed:14556006, PubMed:18006747). In CD8+ cells attenuates TCR-induced signaling, specifically by blocking NF-kappaB and NFAT promoter activities resulting in the loss of IL-2 secretion. The function may implicate its association with LCK proposed to impair phosphorylation of TCR subunits (By similarity). In contrast, shown to activate TCR-induced signaling in T-cells probably implicating ZAP70, LCP2, LCK and FYN (PubMed:21807895). Expressed on Treg cells can inhibit Th17 cell responses (By similarity). Receptor for LGALS9. Binding to LGALS9 is believed to result in suppression of T-cell responses; the resulting apoptosis of antigen-specific cells may implicate HAVCR2 phosphorylation and disruption of its association with BAG6 (PubMed:22863785). Binding to LGALS9 is proposed to be involved in innate immune response to intracellular pathogens. Expressed on Th1 cells interacts with LGALS9 expressed on Mycobacterium tuberculosis- infected macrophages to stimulate antibactericidal activity including IL-1 beta secretion and to restrict intracellular bacterial growth (PubMed:20937702). However, the function as receptor for LGALS9 has been challenged (By similarity). Also reported to enhance CD8+ T-cell responses to an acute infection such as by Listeria monocytogenes (PubMed:24567532). Receptor for phosphatidylserine (PtSer); PtSer- binding is calcium-dependent (PubMed:20083673). May recognize PtSer on apoptotic cells leading to their phagocytosis. Mediates the engulfment of apoptotic cells by dendritic cells (PubMed:19224762). Expressed on T-cells, promotes conjugation but not engulfment of apoptotic cells (PubMed:20083673). Expressed on dendritic cells (DCs) positively regulates innate immune response and in synergy with Toll-like receptors promotes secretion of TNF-alpha (PubMed:18006747). In tumor- imfiltrating DCs suppresses nucleic acid-mediated innate immune repsonse by interaction with HMGB1 and interfering with nucleic acid- sensing and trafficking of nucleid acids to endosomes (PubMed:22842346). Can enhance mast cell production of Th2 cytokines Il-4, IL-6 and IL-13 (PubMed:17620455). Expressed on natural killer (NK) cells acts as a coreceptor to enhance IFN-gamma production in response to LGALS9. In contrast, shown to suppress NK cell-mediated cytotoxicity (By similarity). Negatively regulates NK cell function in LPS-induced endotoxic shock (PubMed:25337993). {ECO:0000250|UniProtKB:Q8TDQ0, ECO:0000269|PubMed:11823861, ECO:0000269|PubMed:14556006, ECO:0000269|PubMed:17620455, ECO:0000269|PubMed:18006747, ECO:0000269|PubMed:19224762, ECO:0000269|PubMed:20083673, ECO:0000269|PubMed:20937702, ECO:0000269|PubMed:21807895, ECO:0000269|PubMed:22842346, ECO:0000269|PubMed:24567532, ECO:0000269|PubMed:25337993, ECO:0000305|PubMed:22863785}.

Subunit: Interacts with HMGB1; impairs HMGB1 binding to B-DNA and likely HMGB1-mediated innate immune response (PubMed:22842346). Interacts with BAG6 (PubMed:22863785). Interacts (phosphorylated) with PIK3R1 and PIK3R2. Interacts (not dependent on its phosphorylation status) with FYN (PubMed:21807895). Interacts (in basal state T-cells) with VAV1; AKT1/2, LCP2, ZAP70, SYK, PIK3R1, FYN, SH3BP2 and SH2D2A. Interacts (in activated T-cells) with LCK and PLCG (By similarity). {ECO:0000250|UniProtKB:Q8TDQ0, ECO:0000269|PubMed:21807895, ECO:0000269|PubMed:22842346, ECO:0000269|PubMed:22863785}.

Subcellular location: [Isoform 1]: Membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Cell junction {ECO:0000250|UniProtKB:Q8TDQ0}. Note=Localizes to the immunological synapse between CD8+ T-cells and target cells. {ECO:0000250|UniProtKB:Q8TDQ0}.

Subcellular location: [Isoform 2]: Secreted {ECO:0000269|PubMed:14556006}.

Tissue specificity: Expressed in T-helper type 1 lymphocytes. Not expressed by naive T-cells but up-regulated as they differentiate into T-helper-1 cells. Also expressed by differentiated type 1 CD8+ cytotoxic T-cells. Expressed on peritoneal exudate macrophages, monocytes, and splenic dendritic cells (DCs). Expression on natural killer (NK) cells is inversely associated with IFN-gamma production during the initial 24 h of LPS-induced endotoxic shock. Expressed on mast cells. {ECO:0000269|PubMed:11823861, ECO:0000269|PubMed:14556006, ECO:0000269|PubMed:17620455, ECO:0000269|PubMed:19224762, ECO:0000269|PubMed:24567532, ECO:0000269|PubMed:25337993}.

Domain: The Ig-like V-type (immunoglobulin-like) domain mediates binding to PtSer involving a Ca(2+) ion. {ECO:0000269|PubMed:20083673}.

Ptm: Phosphorylated on tyrosine residues; modestly increased after TCR/CD28 stimulation. Can be phosphorylated in the cytoplasmatic domain by FYN (PubMed:21807895). Phosphorylation at Tyr-256 is increased by stimulation with ligand LGALS9 (By similarity). {ECO:0000250|UniProtKB:Q8TDQ0, ECO:0000269|PubMed:21807895}.

Ptm: N-glycosylated. {ECO:0000269|PubMed:21807895}.

Polymorphism: Polymorphic differences between BALB/c and HBA alleles in the Ig-like V-type domain are the reason for distinct binding affinities for PtSer. The HBA2 allele binds PtSer approximately 50% less than BALB/c. {ECO:0000269|PubMed:20083673}.

Miscellaneous: Belongs to the T-cell and airway phenotype regulator (Tapr) locus, a single chromosomal region that confers reduced T-helper type 2 responsiveness and protects against airway hyperactivity (AHR), the hallmark of human asthma.

Miscellaneous: In vivo administration of antibody to HAVCR2 enhances the clinical and pathological severity of experimental autoimmune encephalomyelitis (EAE), a Th1-dependent autoimmune disease and increases the number and activation level of macrophages.

Miscellaneous: Endogenous expression on dendritic cells is proposed to act as a negative regulator of chemotherapy-induced antitumor responses. {ECO:0000269|PubMed:22842346}.

Similarity: Belongs to the immunoglobulin superfamily. TIM family. {ECO:0000305}.

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:		Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may be influenced by the cellular context and/or the respective ligand (PubMed:18006747). Regulates macrophage activation (PubMed:11823861). Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance (PubMed:14556006, PubMed:18006747). In CD8+ cells attenuates TCR-induced signaling, specifically by blocking NF-kappaB and NFAT promoter activities resulting in the loss of IL-2 secretion. The function may implicate its association with LCK proposed to impair phosphorylation of TCR subunits (By similarity). In contrast, shown to activate TCR-induced signaling in T-cells probably implicating ZAP70, LCP2, LCK and FYN (PubMed:21807895). Expressed on Treg cells can inhibit Th17 cell responses (By similarity). Receptor for LGALS9. Binding to LGALS9 is believed to result in suppression of T-cell responses; the resulting apoptosis of antigen-specific cells may implicate HAVCR2 phosphorylation and disruption of its association with BAG6 (PubMed:22863785). Binding to LGALS9 is proposed to be involved in innate immune response to intracellular pathogens. Expressed on Th1 cells interacts with LGALS9 expressed on Mycobacterium tuberculosis- infected macrophages to stimulate antibactericidal activity including IL-1 beta secretion and to restrict intracellular bacterial growth (PubMed:20937702). However, the function as receptor for LGALS9 has been challenged (By similarity). Also reported to enhance CD8+ T-cell responses to an acute infection such as by Listeria monocytogenes (PubMed:24567532). Receptor for phosphatidylserine (PtSer); PtSer- binding is calcium-dependent (PubMed:20083673). May recognize PtSer on apoptotic cells leading to their phagocytosis. Mediates the engulfment of apoptotic cells by dendritic cells (PubMed:19224762). Expressed on T-cells, promotes conjugation but not engulfment of apoptotic cells (PubMed:20083673). Expressed on dendritic cells (DCs) positively regulates innate immune response and in synergy with Toll-like receptors promotes secretion of TNF-alpha (PubMed:18006747). In tumor- imfiltrating DCs suppresses nucleic acid-mediated innate immune repsonse by interaction with HMGB1 and interfering with nucleic acid- sensing and trafficking of nucleid acids to endosomes (PubMed:22842346). Can enhance mast cell production of Th2 cytokines Il-4, IL-6 and IL-13 (PubMed:17620455). Expressed on natural killer (NK) cells acts as a coreceptor to enhance IFN-gamma production in response to LGALS9. In contrast, shown to suppress NK cell-mediated cytotoxicity (By similarity). Negatively regulates NK cell function in LPS-induced endotoxic shock (PubMed:25337993). {ECO:0000250\|UniProtKB:Q8TDQ0, ECO:0000269\|PubMed:11823861, ECO:0000269\|PubMed:14556006, ECO:0000269\|PubMed:17620455, ECO:0000269\|PubMed:18006747, ECO:0000269\|PubMed:19224762, ECO:0000269\|PubMed:20083673, ECO:0000269\|PubMed:20937702, ECO:0000269\|PubMed:21807895, ECO:0000269\|PubMed:22842346, ECO:0000269\|PubMed:24567532, ECO:0000269\|PubMed:25337993, ECO:0000305\|PubMed:22863785}.


Subunit:		Interacts with HMGB1; impairs HMGB1 binding to B-DNA and likely HMGB1-mediated innate immune response (PubMed:22842346). Interacts with BAG6 (PubMed:22863785). Interacts (phosphorylated) with PIK3R1 and PIK3R2. Interacts (not dependent on its phosphorylation status) with FYN (PubMed:21807895). Interacts (in basal state T-cells) with VAV1; AKT1/2, LCP2, ZAP70, SYK, PIK3R1, FYN, SH3BP2 and SH2D2A. Interacts (in activated T-cells) with LCK and PLCG (By similarity). {ECO:0000250\|UniProtKB:Q8TDQ0, ECO:0000269\|PubMed:21807895, ECO:0000269\|PubMed:22842346, ECO:0000269\|PubMed:22863785}.
Subcellular location:		[Isoform 1]: Membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Cell junction {ECO:0000250\|UniProtKB:Q8TDQ0}. Note=Localizes to the immunological synapse between CD8+ T-cells and target cells. {ECO:0000250\|UniProtKB:Q8TDQ0}.
Subcellular location:		[Isoform 2]: Secreted {ECO:0000269\|PubMed:14556006}.
Tissue specificity:		Expressed in T-helper type 1 lymphocytes. Not expressed by naive T-cells but up-regulated as they differentiate into T-helper-1 cells. Also expressed by differentiated type 1 CD8+ cytotoxic T-cells. Expressed on peritoneal exudate macrophages, monocytes, and splenic dendritic cells (DCs). Expression on natural killer (NK) cells is inversely associated with IFN-gamma production during the initial 24 h of LPS-induced endotoxic shock. Expressed on mast cells. {ECO:0000269\|PubMed:11823861, ECO:0000269\|PubMed:14556006, ECO:0000269\|PubMed:17620455, ECO:0000269\|PubMed:19224762, ECO:0000269\|PubMed:24567532, ECO:0000269\|PubMed:25337993}.
Domain:		The Ig-like V-type (immunoglobulin-like) domain mediates binding to PtSer involving a Ca(2+) ion. {ECO:0000269\|PubMed:20083673}.
Ptm:		Phosphorylated on tyrosine residues; modestly increased after TCR/CD28 stimulation. Can be phosphorylated in the cytoplasmatic domain by FYN (PubMed:21807895). Phosphorylation at Tyr-256 is increased by stimulation with ligand LGALS9 (By similarity). {ECO:0000250\|UniProtKB:Q8TDQ0, ECO:0000269\|PubMed:21807895}.
Ptm:		N-glycosylated. {ECO:0000269\|PubMed:21807895}.
Polymorphism:		Polymorphic differences between BALB/c and HBA alleles in the Ig-like V-type domain are the reason for distinct binding affinities for PtSer. The HBA2 allele binds PtSer approximately 50% less than BALB/c. {ECO:0000269\|PubMed:20083673}.
Miscellaneous:		Belongs to the T-cell and airway phenotype regulator (Tapr) locus, a single chromosomal region that confers reduced T-helper type 2 responsiveness and protects against airway hyperactivity (AHR), the hallmark of human asthma.
Miscellaneous:		In vivo administration of antibody to HAVCR2 enhances the clinical and pathological severity of experimental autoimmune encephalomyelitis (EAE), a Th1-dependent autoimmune disease and increases the number and activation level of macrophages.
Miscellaneous:		Endogenous expression on dendritic cells is proposed to act as a negative regulator of chemotherapy-induced antitumor responses. {ECO:0000269\|PubMed:22842346}.
Similarity:		Belongs to the immunoglobulin superfamily. TIM family. {ECO:0000305}.