TRPC6

Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of the same name. TRPC6 is a transient receptor potential channel of the classical TRPC subfamily. It has been associated with depression and anxiety (see below), as well as with focal segmental glomerulosclerosis (FSGS).[5]

TRPC6
Identifiers
Aliases	TRPC6, FSGS2, TRP6, transient receptor potential cation channel subfamily C member 6
External IDs	OMIM: 603652 MGI: 109523 HomoloGene: 37944 GeneCards: TRPC6
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q22.1 Start 101,451,564 bp[1] End 101,872,562 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 A1|9 2.46 cM Start 8,544,142 bp[2] End 8,680,741 bp[2]
Gene ontology Molecular function • actinin binding • store-operated calcium channel activity • clathrin binding • inositol 1,4,5 trisphosphate binding • ion channel activity • GO:0001948 protein binding • actin binding • calcium channel activity • cation channel activity • protein homodimerization activity • ATPase binding Cellular component • cytoplasm • integral component of membrane • membrane • cell membrane • integral component of plasma membrane • slit diaphragm • cation channel complex Biological process • regulation of cytosolic calcium ion concentration • positive regulation of cytosolic calcium ion concentration • aging • cation transport • ion transport • single fertilization • platelet activation • positive regulation of ion transmembrane transporter activity • negative regulation of dendrite morphogenesis • positive regulation of peptidyl-threonine phosphorylation • calcium ion transmembrane transport • positive regulation of neuron differentiation • neuron differentiation • manganese ion transport • cellular response to hypoxia • calcium ion transport • cellular response to hydrogen peroxide • positive regulation of calcium ion transport • transmembrane transport Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7225	22068
Ensembl	ENSG00000137672	ENSMUSG00000031997
UniProt	Q9Y210	Q61143
RefSeq (mRNA)	NM_004621	NM_001282086 NM_001282087 NM_013838
RefSeq (protein)	NP_004612	NP_001269015 NP_001269016 NP_038866
Location (UCSC)	Chr 11: 101.45 – 101.87 Mb	Chr 9: 8.54 – 8.68 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Interactions

TRPC6 has been shown to interact with:

• FYN,[6]
• TRPC2,[7] and
• TRPC3.[8]

Ligands

Two of the primary active constituents responsible for the antidepressant and anxiolytic benefits of Hypericum perforatum, also known as St. John's Wort, are hyperforin and adhyperforin.[9][10] These compounds are inhibitors of the reuptake of serotonin, norepinephrine, dopamine, γ-aminobutyric acid, and glutamate, and they are reported to exert these effects by binding to and activating TRPC6.[10][11] Recent results with hyperforin have cast doubt on these findings as similar currents are seen upon Hyperforin treatment regardless of the presence of TRPC6.[12]

References

1. GRCh38: Ensembl release 89: ENSG00000137672 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031997 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Winn MP, Conlon PJ, Lynn KL, Farrington MK, Creazzo T, Hawkins AF, Daskalakis N, Kwan SY, Ebersviller S, Burchette JL, Pericak-Vance MA, Howell DN, Vance JM, Rosenberg PB (June 2005). "A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis". Science. 308 (5729): 1801–4. doi:10.1126/science.1106215. PMID 15879175.
6. Hisatsune C, Kuroda Y, Nakamura K, Inoue T, Nakamura T, Michikawa T, Mizutani A, Mikoshiba K (April 2004). "Regulation of TRPC6 channel activity by tyrosine phosphorylation". The Journal of Biological Chemistry. 279 (18): 18887–94. doi:10.1074/jbc.M311274200. PMID 14761972.
7. Chu X, Tong Q, Cheung JY, Wozney J, Conrad K, Mazack V, Zhang W, Stahl R, Barber DL, Miller BA (March 2004). "Interaction of TRPC2 and TRPC6 in erythropoietin modulation of calcium influx". The Journal of Biological Chemistry. 279 (11): 10514–22. doi:10.1074/jbc.M308478200. PMID 14699131.
8. Hofmann T, Schaefer M, Schultz G, Gudermann T (May 2002). "Subunit composition of mammalian transient receptor potential channels in living cells". Proceedings of the National Academy of Sciences of the United States of America. 99 (11): 7461–6. doi:10.1073/pnas.102596199. PMC 124253. PMID 12032305.
9. Müller WE, Singer A, Wonnemann M (July 2001). "Hyperforin--antidepressant activity by a novel mechanism of action". Pharmacopsychiatry. 34 Suppl 1: S98-102. doi:10.1055/s-2001-15512. PMID 11518085.
10. Chatterjee SS, Bhattacharya SK, Wonnemann M, Singer A, Müller WE (1998). "Hyperforin as a possible antidepressant component of hypericum extracts". Life Sciences. 63 (6): 499–510. doi:10.1016/S0024-3205(98)00299-9. PMID 9718074.
11. Leuner K, Kazanski V, Müller M, Essin K, Henke B, Gollasch M, Harteneck C, Müller WE (December 2007). "Hyperforin--a key constituent of St. John's wort specifically activates TRPC6 channels". FASEB Journal. 21 (14): 4101–11. doi:10.1096/fj.07-8110com. PMID 17666455.
12. Sell TS, Belkacemi T, Flockerzi V, Beck A (December 2014). "Protonophore properties of hyperforin are essential for its pharmacological activity". Scientific Reports. 4: 7500. doi:10.1038/srep07500. PMC 4266863. PMID 25511254.

Further reading

• Heiner I, Eisfeld J, Lückhoff A (2004). "Role and regulation of TRP channels in neutrophil granulocytes". Cell Calcium. 33 (5–6): 533–40. doi:10.1016/S0143-4160(03)00058-7. PMID 12765698.
• Walz G (September 2005). "Slit or pore? A mutation of the ion channel TRPC6 causes FSGS". Nephrology, Dialysis, Transplantation. 20 (9): 1777–9. doi:10.1093/ndt/gfh961. PMID 15998650.
• Clapham DE, Julius D, Montell C, Schultz G (December 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacological Reviews. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100.
• Schlöndorff JS, Pollak MR (December 2006). "TRPC6 in glomerular health and disease: what we know and what we believe". Seminars in Cell & Developmental Biology. 17 (6): 667–74. doi:10.1016/j.semcdb.2006.11.003. PMC 2705932. PMID 17116414.
• Dietrich A, Gudermann T (2007). "TRPC6". Handbook of Experimental Pharmacology. Handbook of Experimental Pharmacology. 179 (179): 125–41. doi:10.1007/978-3-540-34891-7_7. ISBN 978-3-540-34889-4. PMID 17217054.

External links

• TRPC6+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)