TRPM2

Transient receptor potential cation channel, subfamily M, member 2

Identifiers

TRPM2 ; EREG1; KNP3; LTRPC2; NUDT9H; NUDT9L1; TRPC7

External IDs

OMIM: 603749 MGI: 1351901 HomoloGene: 20709 IUPHAR: 494 ChEMBL: 1250402 GeneCards: TRPM2 Gene

3.6.1.13

Gene ontology
Molecular function	• calcium channel activity • sodium channel activity • manganese ion transmembrane transporter activity • ADP-ribose diphosphatase activity
Cellular component	• plasma membrane • integral component of plasma membrane
Biological process	• calcium ion transport • metabolic process • response to hydroperoxide • ion transmembrane transport • sodium ion transmembrane transport • transmembrane transport • calcium ion transmembrane transport • manganese ion transmembrane transport
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 21:
44.35 – 44.44 Mb

Chr 10:
77.91 – 77.97 Mb

PubMed search

Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a protein that in humans is encoded by the TRPM2 gene.

Function

The TRPM2 gene is highly expressed in the brain and was implicated by both genetic linkage studies in families^[1] and then by case control or trio allelic association studies in the genetic aetiology of bipolar affective disorder (Manic Depression).^[2]^[3]

The physiological role of TRPM2 is not well understood. It was shown to be involved in insulin secretion.^[4]^[5] In the immune cells it mediates parts of the responses to TNF-alpha.^[6] A role has been suggested for TRPM2 in activation of NLRP3 inflammasome, the dysregulation of which is strongly associated with a number of auto inflammatory and metabolic diseases, such as gout, obesity and diabetes.^[7] In the brain it is involved in the toxicity of amyloid beta, a protein associated with Alzheimer's disease.^[8]

Structure

The protein encoded by this gene is a non-selective calcium-permeable cation channel and is part of the Transient Receptor Potential ion channel super family. The closest relative is the cold and menthol activated TRPM8 ion channel. While TRPM2 is not cold sensitive it is activated by heat.^[4] The TRPM2 ion channel is activated by free intracellular ADP-ribose in synergy with free intracellular calcium.^[9] ADP-Ribose is produced to by the enzyme PARP in response to oxidative stress and confers susceptibility to cell death. Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.^[10]

References

↑ Gurling H (1998). "Chromosome 21 workshop". Psychiatric Genetics 8 (2): 109–13. doi:10.1097/00041444-199800820-00015. PMID 9686433.
↑ McQuillin A, Bass NJ, Kalsi G, Lawrence J, Puri V, Choudhury K, Detera-Wadleigh SD, Curtis D, Gurling HM (Feb 2006). "Fine mapping of a susceptibility locus for bipolar and genetically related unipolar affective disorders, to a region containing the C21ORF29 and TRPM2 genes on chromosome 21q22.3". Molecular Psychiatry 11 (2): 134–42. doi:10.1038/sj.mp.4001759. PMID 16205735.
↑ Xu C, Macciardi F, Li PP, Yoon IS, Cooke RG, Hughes B, Parikh SV, McIntyre RS, Kennedy JL, Warsh JJ (Jan 2006). "Association of the putative susceptibility gene, transient receptor potential protein melastatin type 2, with bipolar disorder". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 141B (1): 36–43. doi:10.1002/ajmg.b.30239. PMID 16252251.
1 2 Togashi K, Hara Y, Tominaga T, Higashi T, Konishi Y, Mori Y, Tominaga M (May 2006). "TRPM2 activation by cyclic ADP-ribose at body temperature is involved in insulin secretion". The EMBO Journal 25 (9): 1804–15. doi:10.1038/sj.emboj.7601083. PMC 1456947. PMID 16601673.
↑ Bari MR, Akbar S, Eweida M, Kühn FJ, Gustafsson AJ, Lückhoff A, Islam MS (Sep 2009). "H2O2-induced Ca2+ influx and its inhibition by N-(p-amylcinnamoyl) anthranilic acid in the beta-cells: involvement of TRPM2 channels". Journal of Cellular and Molecular Medicine 13 (9B): 3260–7. doi:10.1111/j.1582-4934.2009.00737.x. PMC 4516483. PMID 19382906.
↑ Yamamoto S, Shimizu S, Kiyonaka S, Takahashi N, Wajima T, Hara Y, Negoro T, Hiroi T, Kiuchi Y, Okada T, Kaneko S, Lange I, Fleig A, Penner R, Nishi M, Takeshima H, Mori Y (Jul 2008). "TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration". Nature Medicine 14 (7): 738–47. doi:10.1038/nm1758. PMC 2789807. PMID 18542050.
↑ Zhong Z, Zhai Y, Liang S, Mori Y, Han R, Sutterwala FS, Qiao L (2013). "TRPM2 links oxidative stress to NLRP3 inflammasome activation". Nature Communications 4: 1611. doi:10.1038/ncomms2608. PMC 3605705. PMID 23511475.
↑ Miller BA (Jan 2006). "The role of TRP channels in oxidative stress-induced cell death". The Journal of Membrane Biology 209 (1): 31–41. doi:10.1007/s00232-005-0839-3. PMID 16685599.
↑ Csanády L, Törocsik B (Feb 2009). "Four Ca2+ ions activate TRPM2 channels by binding in deep crevices near the pore but intracellularly of the gate". The Journal of General Physiology 133 (2): 189–203. doi:10.1085/jgp.200810109. PMC 2638199. PMID 19171771.
↑ "Entrez Gene: TRPM2 transient receptor potential cation channel, subfamily M, member 2".

External links

TRPM2 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3

Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ

Proton-gated	Amiloride-sensitive cation channel 1 2 3 4

Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1

Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1

Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18

Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker gene

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B

H⁺: Proton channel	HVCN1

M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4

M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6

H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family

Cytoplasm: Gap junction	Connexin: A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4) Innexin

By gating mechanism

Ion channel class	Ligand-gated Light-gated Voltage-gated Stretch-activated

see also disorders

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TRPM2

Function

Structure

See also

References

Further reading

External links