TRPM2 [The Human Chemical-Genetic Interaction Map Project]

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======= TRPM2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: TRPM2
  * **<color #00a2e8>Official Name</color>**: transient receptor potential cation channel subfamily M member 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=7226|7226]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O94759|O94759]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=TRPM2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20TRPM2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/603749|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene forms a tetrameric cation channel that is permeable to calcium, sodium, and potassium and is regulated by free intracellular ADP-ribose. The encoded protein is activated by oxidative stress and confers susceptibility to cell death. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. Additional transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2016]. COMPLETENESS: complete on the 3' end. 
  * **<color #00a2e8>UniProt Summary</color>**:  Isoform 1: Nonselective, voltage-independent cation channel that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels (PubMed:11960981, PubMed:12594222, PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:20660597, PubMed:27383051, PubMed:27068538). Extracellular calcium passes through the channel and increases channel activity by binding to the cytoplasmic domain and stabilizing the channel in an open conformation (PubMed:19171771). Also contributes to Ca(2+) release from intracellular stores in response to ADP-ribose (PubMed:19454650). Plays a role in numerous processes that involve signaling via intracellular Ca(2+) levels (Probable). Besides, mediates the release of lysosomal Zn(2+) stores in response to reactive oxygen species, leading to increased cytosolic Zn(2+) levels (PubMed:25562606, PubMed:27068538). Activated by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Activated by intracellular ADP-ribose, beta-NAD (NAD(+)) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (PubMed:11960981, PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:27383051, PubMed:27068538). The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2'-phosphate (PubMed:20650899, PubMed:25918360). Activation by ADP-ribose and beta-NAD is strongly increased by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Likewise, reactive oxygen species lower the threshold for activation by moderate heat (37 degrees Celsius) (PubMed:22493272). Plays a role in mediating behavorial and physiological responses to moderate heat and thereby contributes to body temperature homeostasis. Plays a role in insulin secretion, a process that requires increased cytoplasmic Ca(2+) levels (By similarity). Required for normal IFNG and cytokine secretion and normal innate immune immunity in response to bacterial infection. Required for normal phagocytosis and cytokine release by macrophages exposed to zymosan (in vitro). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca(2+) levels (By similarity). Plays a role in the regulation of the reorganization of the actin cytoskeleton and filopodia formation in response to reactive oxygen species via its role in increasing cytoplasmic Ca(2+) and Zn(2+) levels (PubMed:27068538). Confers susceptibility to cell death following oxidative stress (PubMed:12594222, PubMed:25562606). {ECO:0000250|UniProtKB:Q91YD4, ECO:0000269|PubMed:11385575, ECO:0000269|PubMed:11509734, ECO:0000269|PubMed:11804595, ECO:0000269|PubMed:11960981, ECO:0000269|PubMed:12594222, ECO:0000269|PubMed:15561722, ECO:0000269|PubMed:16601673, ECO:0000269|PubMed:19171771, ECO:0000269|PubMed:19454650, ECO:0000269|PubMed:20650899, ECO:0000269|PubMed:20660597, ECO:0000269|PubMed:22493272, ECO:0000269|PubMed:25562606, ECO:0000269|PubMed:25918360, ECO:0000269|PubMed:27068538, ECO:0000269|PubMed:27383051, ECO:0000305}. Isoform 3: Lacks cation channel activity and negatively regulates the channel activity of isoform 1. Negatively regulates susceptibility to cell death in reposponse to oxidative stress. {ECO:0000269|PubMed:12594222}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Ion trans|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|mono-ADP-D-ribose binding|
|ligand-gated calcium channel activity|
|cellular response to temperature stimulus|
|ADP-ribose diphosphatase activity|
|calcium ion import across plasma membrane|
|sodium channel activity|
|calcium ion import into cytosol|
|cellular response to purine-containing compound|
|calcium-release channel activity|
|cation channel activity|
|dendritic cell chemotaxis|
|dendritic cell migration|
|zinc ion transmembrane transport|
|calcium-mediated signaling using intracellular calcium source|
|zinc ion transport|
|temperature homeostasis|
|dendritic cell differentiation|
|regulation of actin cytoskeleton reorganization|
|calcium ion import|
|regulation of filopodium assembly|
|calcium channel activity|
|release of sequestered calcium ion into cytosol|
|negative regulation of sequestering of calcium ion|
|ficolin-1-rich granule membrane|
|calcium ion transmembrane import into cytosol|
|cellular response to hydrogen peroxide|
|calcium ion transport into cytosol|
|tertiary granule membrane|
|inorganic cation import across plasma membrane|
|inorganic ion import across plasma membrane|
|hydrolase activity|
|cellular response to calcium ion|
|cytosolic calcium ion transport|
|sodium ion transmembrane transport|
|specific granule membrane|
|protein homotetramerization|
|import across plasma membrane|
|cell projection|
|cellular response to antibiotic|
|response to hydrogen peroxide|
|transition metal ion transport|
|regulation of sequestering of calcium ion|
|cellular response to reactive oxygen species|
|perikaryon|
|cytoplasmic vesicle membrane|
|leukocyte chemotaxis|
|calcium-mediated signaling|
|protein tetramerization|
|response to calcium ion|
|response to purine-containing compound|
|sodium ion transport|
|response to temperature stimulus|
|cellular response to metal ion|
|response to reactive oxygen species|
|calcium ion transmembrane transport|
|regulation of plasma membrane bounded cell projection assembly|
|regulation of cell projection assembly|
|cell chemotaxis|
|cellular response to toxic substance|
|cellular response to inorganic substance|
|cellular response to oxidative stress|
|calcium ion transport|
|lysosome|
|positive regulation of cytosolic calcium ion concentration|
|divalent metal ion transport|
|lysosomal membrane|
|divalent inorganic cation transport|
|response to antibiotic|
|multicellular organismal homeostasis|
|regulation of cytosolic calcium ion concentration|
|leukocyte differentiation|
|second-messenger-mediated signaling|
|protein homooligomerization|
|regulation of actin cytoskeleton organization|
|response to metal ion|
|leukocyte migration|
|response to oxidative stress|
|regulation of actin filament-based process|
|monovalent inorganic cation transport|
|cellular response to drug|
|cellular calcium ion homeostasis|
|calcium ion homeostasis|
|cellular divalent inorganic cation homeostasis|
|neutrophil degranulation|
|divalent inorganic cation homeostasis|
|neutrophil activation involved in immune response|
|neutrophil mediated immunity|
|neutrophil activation|
|granulocyte activation|
|response to toxic substance|
|leukocyte degranulation|
|myeloid leukocyte mediated immunity|
|protein complex oligomerization|
|myeloid cell activation involved in immune response|
|response to inorganic substance|
|regulation of cytoskeleton organization|
|cellular response to organic cyclic compound|
|chemotaxis|
|taxis|
|cellular metal ion homeostasis|
|hemopoiesis|
|inorganic cation transmembrane transport|
|myeloid leukocyte activation|
|cellular response to organonitrogen compound|
|hematopoietic or lymphoid organ development|
|cation transmembrane transport|
|metal ion homeostasis|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|cellular cation homeostasis|
|metal ion transport|
|cellular ion homeostasis|
|inorganic ion transmembrane transport|
|immune system development|
|cellular response to nitrogen compound|
|import into cell|
|regulation of plasma membrane bounded cell projection organization|
|regulated exocytosis|
|cation homeostasis|
|regulation of cell projection organization|
|inorganic ion homeostasis|
|calcium ion binding|
|cellular chemical homeostasis|
|leukocyte mediated immunity|
|ion homeostasis|
|exocytosis|
|cation transport|
|cellular homeostasis|
|response to organic cyclic compound|
|leukocyte activation|
|ion transmembrane transport|
|regulation of cellular component biogenesis|
|cell migration|
|response to organonitrogen compound|
|secretion by cell|
|response to drug|
|export from cell|
|cellular response to oxygen-containing compound|
|cell activation|
|localization of cell|
|cell motility|
|response to nitrogen compound|
|immune effector process|
|chemical homeostasis|
|secretion|
|response to abiotic stimulus|
|cellular response to endogenous stimulus|
|transmembrane transport|
|regulation of organelle organization|
|locomotion|
|ion transport|
|integral component of plasma membrane|
|response to endogenous stimulus|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|homeostatic process|
|intracellular signal transduction|
|cellular response to stress|
|establishment of localization in cell|
|protein-containing complex subunit organization|
|immune response|
|vesicle-mediated transport|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp271|CCT251545 0.2μM R06 exp271]]|-1.88|
|[[:results:exp165|RO-3306 3 to 4μM on day4 R04 exp165]]|-1.75|
|[[:results:exp16|DABN 2μM R00 exp16]]|1.92|
|[[:results:exp335|Aminopterin 0.005μM R07 exp335]]|2.19|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
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|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 6191
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 8.27 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='TRPM2 Expression in NALM6 Cells: 8.27'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>