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Gene and Protein Information | |||||||
Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 6 | 1 | 836 | 4q27 | TRPC3 | transient receptor potential cation channel subfamily C member 3 | 38 |
Mouse | 6 | 1 | 836 | 3 17.93 cM | Trpc3 | transient receptor potential cation channel, subfamily C, member 3 | 23 |
Rat | 6 | 1 | 836 | 2q25 | Trpc3 | transient receptor potential cation channel, subfamily C, member 3 | 24 |
Previous and Unofficial Names | |
TRP3 [38] | short transient receptor potential channel 3 | transient receptor protein 3 | trp-related protein 3 | transient receptor potential cation channel |
Database Links | |
Alphafold | Q13507 (Hs), Q9QZC1 (Mm), Q9JMI9 (Rn) |
CATH/Gene3D | 1.25.40.20 |
ChEMBL Target | CHEMBL2417348 (Hs), CHEMBL4739706 (Mm), CHEMBL4105916 (Rn) |
Ensembl Gene | ENSG00000138741 (Hs), ENSMUSG00000027716 (Mm), ENSRNOG00000016070 (Rn) |
Entrez Gene | 7222 (Hs), 22065 (Mm), 60395 (Rn) |
Human Protein Atlas | ENSG00000138741 (Hs) |
KEGG Gene | hsa:7222 (Hs), mmu:22065 (Mm), rno:60395 (Rn) |
OMIM | 602345 (Hs) |
Pharos | Q13507 (Hs) |
RefSeq Nucleotide | NM_001130698 (Hs), NM_019510 (Mm), NM_021771 (Rn) |
RefSeq Protein | NP_001124170 (Hs), NP_062383 (Mm), NP_068539 (Rn) |
UniProtKB | Q13507 (Hs), Q9QZC1 (Mm), Q9JMI9 (Rn) |
Wikipedia | TRPC3 (Hs) |
Associated Proteins | ||||||||||||||||||||||||||||||||||||||
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Ion Selectivity and Conductance | ||||||
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Ion Selectivity and Conductance Comments | ||||||
Non-selective cation channel. |
Chemical activators (Human) |
diacylglycerols |
Download all structure-activity data for this target as a CSV file
Activators | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Channel Blockers | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Immunopharmacology Comments |
Expressed on B cells, T cells, neutrophils and monocytes/macrophages [25]. |
Cell Type Associations | ||||||
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Tissue Distribution | ||||||||
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Functional Assays | ||||||||||
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Physiological Functions | ||||||||
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Phenotypes, Alleles and Disease Models | Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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1. Adebiyi A, Zhao G, Narayanan D, Thomas-Gatewood CM, Bannister JP, Jaggar JH. (2010) Isoform-selective physical coupling of TRPC3 channels to IP3 receptors in smooth muscle cells regulates arterial contractility. Circ Res, 106 (10): 1603-12. [PMID:20378853]
2. Balzer M, Lintschinger B, Groschner K. (1999) Evidence for a role of Trp proteins in the oxidative stress-induced membrane conductances of porcine aortic endothelial cells. Cardiovasc Res, 42 (2): 543-9. [PMID:10533589]
3. Bandyopadhyay BC, Swaim WD, Liu X, Redman RS, Patterson RL, Ambudkar IS. (2005) Apical localization of a functional TRPC3/TRPC6-Ca2+-signaling complex in polarized epithelial cells. Role in apical Ca2+ influx. J Biol Chem, 280 (13): 12908-16. [PMID:15623527]
4. Becker EB, Oliver PL, Glitsch MD, Banks GT, Achilli F, Hardy A, Nolan PM, Fisher EM, Davies KE. (2009) A point mutation in TRPC3 causes abnormal Purkinje cell development and cerebellar ataxia in moonwalker mice. Proc Natl Acad Sci USA, 106 (16): 6706-11. [PMID:19351902]
5. Dietrich A, Kalwa H, Rost BR, Gudermann T. (2005) The diacylgylcerol-sensitive TRPC3/6/7 subfamily of cation channels: functional characterization and physiological relevance. Pflugers Arch, 451 (1): 72-80. [PMID:15971081]
6. Gilliam JC, Wensel TG. (2011) TRP channel gene expression in the mouse retina. Vision Res, 51 (23-24): 2440-52. [PMID:22037305]
7. Halaszovich CR, Zitt C, Jungling E, Luckhoff A. (2000) Inhibition of TRP3 channels by lanthanides. Block from the cytosolic side of the plasma membrane. J Biol Chem, 275 (48): 37423-8. [PMID:10970899]
8. Hartmann J, Dragicevic E, Adelsberger H, Henning HA, Sumser M, Abramowitz J, Blum R, Dietrich A, Freichel M, Flockerzi V et al.. (2008) TRPC3 channels are required for synaptic transmission and motor coordination. Neuron, 59 (3): 392-8. [PMID:18701065]
9. He LP, Hewavitharana T, Soboloff J, Spassova MA, Gill DL. (2005) A functional link between store-operated and TRPC channels revealed by the 3,5-bis(trifluoromethyl)pyrazole derivative, BTP2. J Biol Chem, 280 (12): 10997-1006. [PMID:15647288]
10. Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G. (1999) Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature, 397 (6716): 259-63. [PMID:9930701]
11. Häfner S, Burg F, Kannler M, Urban N, Mayer P, Dietrich A, Trauner D, Broichhagen J, Schaefer M. (2018) A (+)-Larixol Congener with High Affinity and Subtype Selectivity toward TRPC6. ChemMedChem, 13 (10): 1028-1035. [PMID:29522264]
12. Inada H, Iida T, Tominaga M. (2006) Different expression patterns of TRP genes in murine B and T lymphocytes. Biochem Biophys Res Commun, 350 (3): 762-7. [PMID:17027915]
13. Jang Y, Lee Y, Kim SM, Yang YD, Jung J, Oh U. (2012) Quantitative analysis of TRP channel genes in mouse organs. Arch Pharm Res, 35 (10): 1823-30. [PMID:23139135]
14. Kato AS, Knierman MD, Siuda ER, Isaac JT, Nisenbaum ES, Bredt DS. (2012) Glutamate receptor δ2 associates with metabotropic glutamate receptor 1 (mGluR1), protein kinase Cγ, and canonical transient receptor potential 3 and regulates mGluR1-mediated synaptic transmission in cerebellar Purkinje neurons. J Neurosci, 32 (44): 15296-308. [PMID:23115168]
15. Kiyonaka S, Kato K, Nishida M, Mio K, Numaga T, Sawaguchi Y, Yoshida T, Wakamori M, Mori E, Numata T et al.. (2009) Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound. Proc Natl Acad Sci USA, 106 (13): 5400-5. [PMID:19289841]
16. Li HS, Xu XZ, Montell C. (1999) Activation of a TRPC3-dependent cation current through the neurotrophin BDNF. Neuron, 24 (1): 261-73. [PMID:10677043]
17. Li Y, Jia YC, Cui K, Li N, Zheng ZY, Wang YZ, Yuan XB. (2005) Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factor. Nature, 434 (7035): 894-8. [PMID:15758952]
18. Lievremont JP, Bird GS, Putney Jr JW. (2005) Mechanism of inhibition of TRPC cation channels by 2-aminoethoxydiphenylborane. Mol Pharmacol, 68 (3): 758-62. [PMID:15933213]
19. Lussier MP, Cayouette S, Lepage PK, Bernier CL, Francoeur N, St-Hilaire M, Pinard M, Boulay G. (2005) MxA, a member of the dynamin superfamily, interacts with the ankyrin-like repeat domain of TRPC. J Biol Chem, 280 (19): 19393-400. [PMID:15757897]
20. Maier T, Follmann M, Hessler G, Kleemann HW, Hachtel S, Fuchs B, Weissmann N, Linz W, Schmidt T, Löhn M et al.. (2015) Discovery and pharmacological characterization of a novel potent inhibitor of diacylglycerol-sensitive TRPC cation channels. Br J Pharmacol, 172 (14): 3650-60. [PMID:25847402]
21. Miehe S, Crause P, Schmidt T, Löhn M, Kleemann HW, Licher T, Dittrich W, Rütten H, Strübing C. (2012) Inhibition of diacylglycerol-sensitive TRPC channels by synthetic and natural steroids. PLoS ONE, 7 (4): e35393. [PMID:22530015]
22. Miyagi K, Kiyonaka S, Yamada K, Miki T, Mori E, Kato K, Numata T, Sawaguchi Y, Numaga T, Kimura T et al.. (2009) A pathogenic C terminus-truncated polycystin-2 mutant enhances receptor-activated Ca2+ entry via association with TRPC3 and TRPC7. J Biol Chem, 284 (49): 34400-12. [PMID:19812035]
23. Mori Y, Takada N, Okada T, Wakamori M, Imoto K, Wanifuchi H, Oka H, Oba A, Ikenaka K, Kurosaki T. (1998) Differential distribution of TRP Ca2+ channel isoforms in mouse brain. Neuroreport, 9 (3): 507-15. [PMID:9512398]
24. Ohki G, Miyoshi T, Murata M, Ishibashi K, Imai M, Suzuki M. (2000) A calcium-activated cation current by an alternatively spliced form of Trp3 in the heart. J Biol Chem, 275 (50): 39055-60. [PMID:10984475]
25. Parenti A, De Logu F, Geppetti P, Benemei S. (2016) What is the evidence for the role of TRP channels in inflammatory and immune cells?. Br J Pharmacol, 173 (6): 953-69. [PMID:26603538]
26. Qu C, Ding M, Zhu Y, Lu Y, Du J, Miller M, Tian J, Zhu J, Xu J, Wen M et al.. (2017) Pyrazolopyrimidines as Potent Stimulators for Transient Receptor Potential Canonical 3/6/7 Channels. J Med Chem, 60 (11): 4680-4692. [PMID:28395140]
27. Riccio A, Medhurst AD, Mattei C, Kelsell RE, Calver AR, Randall AD, Benham CD, Pangalos MN. (2002) mRNA distribution analysis of human TRPC family in CNS and peripheral tissues. Brain Res Mol Brain Res, 109 (1-2): 95-104. [PMID:12531519]
28. Richter JM, Schaefer M, Hill K. (2014) Clemizole hydrochloride is a novel and potent inhibitor of transient receptor potential channel TRPC5. Mol Pharmacol, 86 (5): 514-21. [PMID:25140002]
29. Rosker C, Graziani A, Lukas M, Eder P, Zhu MX, Romanin C, Groschner K. (2004) Ca(2+) signaling by TRPC3 involves Na(+) entry and local coupling to the Na(+)/Ca(2+) exchanger. J Biol Chem, 279 (14): 13696-704. [PMID:14736881]
30. Schleifer H, Doleschal B, Lichtenegger M, Oppenrieder R, Derler I, Frischauf I, Glasnov TN, Kappe CO, Romanin C, Groschner K. (2012) Novel pyrazole compounds for pharmacological discrimination between receptor-operated and store-operated Ca(2+) entry pathways. Br J Pharmacol, 167 (8): 1712-22. [PMID:22862290]
31. Seo K, Rainer PP, Shalkey Hahn V, Lee DI, Jo SH, Andersen A, Liu T, Xu X, Willette RN, Lepore JJ et al.. (2014) Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy. Proc Natl Acad Sci USA, 111 (4): 1551-6. [PMID:24453217]
32. Sinkins WG, Goel M, Estacion M, Schilling WP. (2004) Association of immunophilins with mammalian TRPC channels. J Biol Chem, 279 (33): 34521-9. [PMID:15199065]
33. Takumida M, Anniko M. (2009) Expression of canonical transient receptor potential channel (TRPC) 1-7 in the mouse inner ear. Acta Otolaryngol, 129 (12): 1351-8. [PMID:19922081]
34. Washburn DG, Holt DA, Dodson J, McAtee JJ, Terrell LR, Barton L, Manns S, Waszkiewicz A, Pritchard C, Gillie DJ et al.. (2013) The discovery of potent blockers of the canonical transient receptor channels, TRPC3 and TRPC6, based on an anilino-thiazole pharmacophore. Bioorg Med Chem Lett, 23 (17): 4979-84. [PMID:23886683]
35. Xu X, Lozinskaya I, Costell M, Lin Z, Ball JA, Bernard R, Behm DJ, Marino JP, Schnackenberg CG. (2013) Characterization of Small Molecule TRPC3 and TRPC6 agonist and Antagonists. Biophys J, 104 (2): 454a Meeting abstract. DOI: 10.1016/j.bpj.2012.11.2513
36. Yuan JP, Zeng W, Huang GN, Worley PF, Muallem S. (2007) STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels. Nat Cell Biol, 9 (6): 636-45. [PMID:17486119]
37. Zagranichnaya TK, Wu X, Villereal ML. (2005) Endogenous TRPC1, TRPC3, and TRPC7 proteins combine to form native store-operated channels in HEK-293 cells. J Biol Chem, 280 (33): 29559-69. [PMID:15972814]
38. Zhu X, Jiang M, Peyton M, Boulay G, Hurst R, Stefani E, Birnbaumer L. (1996) trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry. Cell, 85 (5): 661-71. [PMID:8646775]
39. Zitt C, Obukhov AG, Strübing C, Zobel A, Kalkbrenner F, Lückhoff A, Schultz G. (1997) Expression of TRPC3 in Chinese hamster ovary cells results in calcium-activated cation currents not related to store depletion. J Cell Biol, 138 (6): 1333-41. [PMID:9298988]