Tchem TRPM2 Transient receptor potential cation channel subfamily M member 2

Protein Summary

Description

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). Isoform 2: Lacks cation channel activity. Does not mediate cation transport in response to oxidative stress or ADP-ribose. 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. 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]

Uniprot Accession IDs

• O94759
• D3DSL6
• Q5KTC2
• Q6J3P5
• Q96KN6
• Q96Q93

Gene Name

• TRPM2

Ensembl ID

• ENST00000300481
• ENSP00000300481
• ENSG00000142185
• ENST00000300482
• ENSP00000300482
• ENST00000397928
• ENSP00000381023

Symbol

• EREG1
• KNP3
• LTRPC2
• TRPC7
• KNP3
• EREG1
• TRPC7
• LTRPC2
• NUDT9H
• LTrpC-2
• NUDT9L1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.9
biological term	0.75
disease perturbation	0.74
ligand (chemical)	0.63
gene perturbation	0.61

Protein Classes

PANTHER Classes

Protein / Transporter / Ion Channel / Transient Receptor Potential Cation Channel Subfamily M Member 2

Protein / Receptor / Transient Receptor Potential Cation Channel Subfamily M Member 2

DTO Classes

Protein / Ion Channel / Transient Receptor Potential Calcium Channel (Trp-cc) Family / Ltrpc Subfamily / Trpm2 Sub-subfamily / Transient Receptor Potential Cation Channel Subfamily M Member 2

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 241.96   (req: < 5)

Gene RIFs: 140   (req: <= 3)

Antibodies: 265   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 241.96   (req: >= 5)

Gene RIFs: 140   (req: > 3)

Antibodies: 265   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 24

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 24

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2