======= HAVCR2 =======
== Gene Information ==
* **Official Symbol**: HAVCR2
* **Official Name**: hepatitis A virus cellular receptor 2
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=84868|84868]]
* **UniProt**: [[https://www.uniprot.org/uniprot/Q8TDQ0|Q8TDQ0]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=HAVCR2&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20HAVCR2|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/606652|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: The protein encoded by this gene belongs to the immunoglobulin superfamily, and TIM family of proteins. CD4-positive T helper lymphocytes can be divided into types 1 (Th1) and 2 (Th2) on the basis of their cytokine secretion patterns. Th1 cells are involved in cell-mediated immunity to intracellular pathogens and delayed-type hypersensitivity reactions, whereas, Th2 cells are involved in the control of extracellular helminthic infections and the promotion of atopic and allergic diseases. This protein is a Th1-specific cell surface protein that regulates macrophage activation, and inhibits Th1-mediated auto- and alloimmune responses, and promotes immunological tolerance. [provided by RefSeq, Sep 2011].
* **UniProt Summary**: 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:24825777). Regulates macrophage activation (PubMed:11823861). Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance (PubMed:14556005). 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, and/or LGALS9- dependent recruitment of PTPRC to the immunological synapse (PubMed:24337741, PubMed:26492563). In contrast, shown to activate TCR-induced signaling in T-cells probably implicating ZAP70, LCP2, LCK and FYN (By similarity). Expressed on Treg cells can inhibit Th17 cell responses (PubMed:24838857). Receptor for LGALS9 (PubMed:16286920, PubMed:24337741). 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. 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 (By similarity). However, the function as receptor for LGALS9 has been challenged (PubMed:23555261). Also reported to enhance CD8+ T-cell responses to an acute infection such as by Listeria monocytogenes (By similarity). Receptor for phosphatidylserine (PtSer); PtSer-binding is calcium-dependent. May recognize PtSer on apoptotic cells leading to their phagocytosis. Mediates the engulfment of apoptotic cells by dendritic cells. Expressed on T-cells, promotes conjugation but not engulfment of apoptotic cells. Expressed on dendritic cells (DCs) positively regulates innate immune response and in synergy with Toll-like receptors promotes secretion of TNF-alpha. 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 (By similarity). Expressed on natural killer (NK) cells acts as a coreceptor to enhance IFN-gamma production in response to LGALS9 (PubMed:22323453). In contrast, shown to suppress NK cell-mediated cytotoxicity (PubMed:22383801). Negatively regulates NK cell function in LPS-induced endotoxic shock (By similarity). {ECO:0000250|UniProtKB:Q8VIM0, ECO:0000269|PubMed:11823861, ECO:0000269|PubMed:14556005, ECO:0000269|PubMed:16286920, ECO:0000269|PubMed:22323453, ECO:0000269|PubMed:23555261, ECO:0000269|PubMed:24838857, ECO:0000269|PubMed:26492563, ECO:0000305|PubMed:24825777}.
|V-set|
|negative regulation of interleukin-3 production|
|negative regulation of macrophage colony-stimulating factor production|
|negative regulation of granulocyte colony-stimulating factor production|
|negative regulation of immunological synapse formation|
|negative regulation of response to tumor cell|
|negative regulation of natural killer cell mediated immune response to tumor cell|
|regulation of interleukin-3 production|
|negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target|
|negative regulation of immune response to tumor cell|
|natural killer cell tolerance induction|
|regulation of immunological synapse formation|
|regulation of tolerance induction dependent upon immune response|
|negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell|
|negative regulation of myeloid dendritic cell activation|
|regulation of granulocyte colony-stimulating factor production|
|toll-like receptor 7 signaling pathway|
|regulation of macrophage colony-stimulating factor production|
|regulation of myeloid dendritic cell activation|
|negative regulation of interferon-alpha production|
|regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell|
|negative regulation of defense response to bacterium|
|negative regulation of T-helper 1 type immune response|
|regulation of natural killer cell mediated cytotoxicity directed against tumor cell target|
|negative regulation of natural killer cell activation|
|regulation of natural killer cell mediated immune response to tumor cell|
|positive regulation of defense response to bacterium|
|toll-like receptor 3 signaling pathway|
|macrophage activation involved in immune response|
|tolerance induction|
|negative regulation of natural killer cell mediated cytotoxicity|
|regulation of immune response to tumor cell|
|regulation of response to tumor cell|
|negative regulation of natural killer cell mediated immunity|
|toll-like receptor 9 signaling pathway|
|regulation of tolerance induction|
|negative regulation of leukocyte mediated cytotoxicity|
|regulation of defense response to bacterium|
|positive regulation of tumor necrosis factor secretion|
|negative regulation of cell killing|
|positive regulation of interleukin-4 production|
|negative regulation of interleukin-2 production|
|positive regulation of macrophage activation|
|regulation of interleukin-4 production|
|regulation of T-helper 1 type immune response|
|regulation of interferon-alpha production|
|regulation of tumor necrosis factor secretion|
|regulation of natural killer cell activation|
|negative regulation of interferon-gamma production|
|immunological synapse|
|mediator complex|
|negative regulation of lymphocyte mediated immunity|
|negative regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|negative regulation of interleukin-6 production|
|regulation of natural killer cell mediated cytotoxicity|
|negative regulation of adaptive immune response|
|regulation of natural killer cell mediated immunity|
|negative regulation of type I interferon production|
|negative regulation of leukocyte mediated immunity|
|macrophage activation|
|regulation of macrophage activation|
|regulation of interleukin-2 production|
|negative regulation of innate immune response|
|positive regulation of chemokine production|
|positive regulation of interleukin-1 production|
|negative regulation of tumor necrosis factor production|
|negative regulation of T cell proliferation|
|negative regulation of tumor necrosis factor superfamily cytokine production|
|positive regulation of interferon-gamma production|
|maternal process involved in female pregnancy|
|negative regulation of mononuclear cell proliferation|
|negative regulation of lymphocyte proliferation|
|regulation of leukocyte mediated cytotoxicity|
|positive regulation of NIK/NF-kappaB signaling|
|regulation of chemokine production|
|negative regulation of leukocyte proliferation|
|negative regulation of NF-kappaB transcription factor activity|
|positive regulation of tumor necrosis factor production|
|positive regulation of tumor necrosis factor superfamily cytokine production|
|negative regulation of response to biotic stimulus|
|defense response to Gram-positive bacterium|
|positive regulation of T cell proliferation|
|regulation of interleukin-1 production|
|toll-like receptor signaling pathway|
|regulation of interferon-gamma production|
|regulation of cell killing|
|regulation of NIK/NF-kappaB signaling|
|negative regulation of T cell activation|
|negative regulation of immune effector process|
|negative regulation of leukocyte cell-cell adhesion|
|regulation of type I interferon production|
|pattern recognition receptor signaling pathway|
|positive regulation of lymphocyte proliferation|
|positive regulation of mononuclear cell proliferation|
|positive regulation of leukocyte proliferation|
|positive regulation of cytokine secretion|
|regulation of interleukin-6 production|
|regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|negative regulation of lymphocyte activation|
|negative regulation of immune response|
|regulation of tumor necrosis factor production|
|regulation of lymphocyte mediated immunity|
|regulation of tumor necrosis factor superfamily cytokine production|
|regulation of T cell proliferation|
|regulation of adaptive immune response|
|negative regulation of DNA-binding transcription factor activity|
|negative regulation of leukocyte activation|
|negative regulation of cell-cell adhesion|
|female pregnancy|
|cellular response to lipopolysaccharide|
|cellular response to molecule of bacterial origin|
|negative regulation of cell activation|
|positive regulation of T cell activation|
|regulation of cytokine secretion|
|regulation of leukocyte mediated immunity|
|negative regulation of defense response|
|regulation of lymphocyte proliferation|
|regulation of mononuclear cell proliferation|
|positive regulation of ERK1 and ERK2 cascade|
|multi-multicellular organism process|
|cellular response to biotic stimulus|
|negative regulation of multi-organism process|
|positive regulation of leukocyte cell-cell adhesion|
|regulation of leukocyte proliferation|
|innate immune response-activating signal transduction|
|positive regulation of cell-cell adhesion|
|early endosome|
|activation of innate immune response|
|positive regulation of protein secretion|
|negative regulation of cell adhesion|
|negative regulation of cytokine production|
|positive regulation of peptide secretion|
|regulation of ERK1 and ERK2 cascade|
|regulation of leukocyte cell-cell adhesion|
|response to lipopolysaccharide|
|regulation of T cell activation|
|response to molecule of bacterial origin|
|defense response to bacterium|
|positive regulation of innate immune response|
|positive regulation of lymphocyte activation|
|positive regulation of response to biotic stimulus|
|negative regulation of response to external stimulus|
|regulation of cell-cell adhesion|
|positive regulation of cell adhesion|
|positive regulation of secretion by cell|
|positive regulation of leukocyte activation|
|positive regulation of cell activation|
|positive regulation of protein transport|
|regulation of DNA-binding transcription factor activity|
|positive regulation of secretion|
|negative regulation of immune system process|
|positive regulation of cytokine production|
|regulation of innate immune response|
|positive regulation of establishment of protein localization|
|regulation of protein secretion|
|regulation of immune effector process|
|positive regulation of defense response|
|regulation of peptide secretion|
|inflammatory response|
|positive regulation of multi-organism process|
|regulation of lymphocyte activation|
|cellular response to lipid|
|regulation of response to biotic stimulus|
|myeloid cell activation involved in immune response|
|positive regulation of MAPK cascade|
|cell junction|
|immune response-activating signal transduction|
|myeloid leukocyte activation|
|immune response-regulating signaling pathway|
|positive regulation of response to external stimulus|
|regulation of leukocyte activation|
|adaptive immune response|
|cell surface|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|activation of immune response|
|regulation of cell activation|
|immune system development|
|negative regulation of cell population proliferation|
|regulation of cell adhesion|
|response to bacterium|
|regulation of cytokine production|
|regulation of protein transport|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of MAPK cascade|
|regulation of defense response|
|innate immune response|
|regulation of multi-organism process|
|regulation of secretion|
|multicellular organismal reproductive process|
|multicellular organism reproduction|
|response to lipid|
|positive regulation of immune response|
|positive regulation of cell population proliferation|
|leukocyte activation|
|defense response to other organism|
|positive regulation of transport|
|multi-organism reproductive process|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|regulation of protein localization|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|cell activation|
|immune effector process|
|regulation of response to external stimulus|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|negative regulation of molecular function|
|regulation of immune response|
|positive regulation of immune system process|
|negative regulation of multicellular organismal process|
|positive regulation of protein modification process|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|defense response|
|reproductive process|
|reproduction|
|regulation of protein phosphorylation|
|regulation of response to stress|
|response to oxygen-containing compound|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|positive regulation of signal transduction|
|regulation of immune system process|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|positive regulation of multicellular organismal process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|regulation of transport|
|immune response|
\\
=== CRISPR Data ===
No hits were found.
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 12836
* **Expression level (log2 read counts)**: 2.42
{{:chemogenomics:nalm6 dist.png?nolink |}}