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TRPC6

Family: Transient Receptor Potential channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Ion Selectivity and Conductance
Activators
Pore Blockers
Tissue Distribution
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
References
Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 931 11q21-q22 TRPC6 transient receptor potential cation channel, subfamily C, member 6 5
Mouse 6 1 930 9 A1 Trpc6 transient receptor potential cation channel, subfamily C, member 6 2
Rat 6 1 930 8q11 Trpc6 transient receptor potential cation channel, subfamily C, member 6 11
Previous and Unofficial Names
TRP6
Trrp6
short transient receptor potential channel 6
transient receptor potential cation channel, subfamily C, member 6
transient receptor protein 6
mtrp6
AV025995
Database Links
Ensembl ENSG00000137672 (Hs), ENSMUSG00000031997 (Mm), ENSRNOG00000006324 (Rn)
Entrez Gene 7225 (Hs), 22068 (Mm), 89823 (Rn)
GeneCards TRPC6 (Hs)
GenitoUrinary Development Molecular Anatomy Project Trpc6 (Mm)
HomoloGene 37944 (Hs)
Human Protein Reference Database 04710 (Hs)
InterPro Q9Y210 (Hs), Q61143 (Mm)
KEGG Gene hsa:7225 (Hs), mmu:22068 (Mm), rno:89823 (Rn)
OMIM 603652 (Hs)
Orphanet Gene ORPHA120298 (Hs)
PharmGKB Gene PA37011 (Hs)
PhosphoSitePlus Q9Y210 (Hs), Q61143 (Mm), Q99N78 (Rn)
Protein Ontology (PRO) PRO:000016696 (Hs)
RefSeq Nucleotide NM_004621 (Hs), NM_013838 (Mm), NM_053559 (Rn)
RefSeq Protein NP_004612 (Hs), NP_038866 (Mm), NP_446011 (Rn)
TreeFam ENSG00000137672 (Hs), ENSMUSG00000031997 (Mm), ENSRNOG00000006324 (Rn)
UniGene Hs. 159003 (Hs)
UniProt Q9Y210 (Hs), Q61143 (Mm)
Wikipedia TRPC6
Transient Receptor Potential channels
Search for 3D structures on the PDB
Search by keyword: Transient Receptor Potential channels TRPC6 Search by accession number: Q61143, Q9Y210
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
TRPC7 3
TRPC3 3
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
calmodulin 1
FKBP12 13
Ion Selectivity and Conductance
Species:  Human
Rank order:  Ca2+ > Cs+ > Na+
References:  5
Ion Selectivity and Conductance Comments
Slope conductance of 35pS in symmetrical 120mM Cs+ [5].
Voltage Dependence
Not Determined
Other chemical activators (Human)
diacylglycerols
Physical activators (Human)
membrane stretch (likely indirect)
Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
OAG Hs - - 1x10-4 -60.0 5
SLG Hs - - 1x10-4 -60.0 5
SAG Hs - - 1x10-5 -60.0 5
Pore Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
Gd3+ Mm 5.7 pIC50 - -60.0 7
La3+ Mm 5.4 pIC50 - -60.0 7
SKF96365 Mm 5.4 pIC50 - -60.0 7
amiloride Mm 3.9 pIC50 - -60.0 7
Cd2+ Mm 3.6 pIC50 - -60.0 7

Explore drug-target interactions for this set of compounds using iPHACE

Tissue Distribution
Heart, lung, kidney, muscle, intestine, stomach, pancreas, prostate, bone, brain.
Species:  Human
Technique:  RT-PCR
References:  10
Testes, lung, spleen, epididymis, ovary, brain.
Species:  Mouse
Technique:  RT-PCR
References:  6
Brain, kidney, heart, lung, adrenal gland.
Species:  Rat
Technique:  RT-PCR
References:  8
Functional Assays
Cation influx in response to DAG generated by receptor-mediated activation of PLC-β and PLC-γ.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  Cation influx, using calcium imaging and patch clamp.
References:  5
Physiological Functions
TRPC6 is essential for proper regulation of podocyte structure and function.
Species:  Human
Tissue:  Kidney.
References:  9,12
Physiological Consequences of Altering Gene Expression
The trpc6 knockout mouse has increased vascular smooth muscle contractility.
Species:  Mouse
Tissue:  Vascular smooth muscle
Technique: 
References:  4
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpc6tm1Lbi Trpc6tm1Lbi/Trpc6tm1Lbi
involves: 129S/SvEv * C57BL/6J		 MGI:109523  MP:0005595 abnormal vascular smooth muscle physiology PMID: 16055711 
Trpc6tm1Lbi Trpc6tm1Lbi/Trpc6tm1Lbi
involves: 129S/SvEv * C57BL/6J		 MGI:109523  MP:0000250 abnormal vasoconstriction PMID: 16055711 
Trpc6tm1Lbi Trpc6tm1Lbi/Trpc6tm1Lbi
involves: 129S/SvEv * C57BL/6J		 MGI:109523  MP:0002842 increased systemic arterial blood pressure PMID: 16055711 
Trpc6tm1Lbi Trpc6tm1Lbi/Trpc6tm1Lbi
involves: 129S/SvEv * C57BL/6J		 MGI:109523  MP:0003025 increased vasoconstriction PMID: 16055711 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Focal segmental glomerulosis (FSGS)
OMIM:  603965
Orphanet:  93213
References:  9,12
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human R895C 9,12
Missense Human S270T 9,12
Missense Human N143S 9,12
Truncation Human K874X 9,12

REFERENCES

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1. Boulay, G. (2002) Ca(2+)-calmodulin regulates receptor-operated Ca(2+) entry activity of TRPC6 in HEK-293 cells. Cell Calcium, 32 (4): 201-7. [PMID:12379180]

2. Boulay, G; Zhu, X; Peyton, M; Jiang, M; Hurst, R; Stefani, E; Birnbaumer, L. (1997) Cloning and expression of a novel mammalian homolog of Drosophila transient receptor potential (Trp) involved in calcium entry secondary to activation of receptors coupled by the Gq class of G protein. J. Biol. Chem., 272 (47): 29672-80. [PMID:9368034]

3. 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]

4. Dietrich, A; Mederos Y Schnitzler, M; Gollasch, M; Gross, V; Storch, U; Dubrovska, G; Obst, M; Yildirim, E; Salanova, B; Kalwa, H; Essin, K; Pinkenburg, O; Luft, FC; Gudermann, T; Birnbaumer, L. (2005) Increased vascular smooth muscle contractility in TRPC6-/- mice. Mol. Cell. Biol., 25 (16): 6980-9. [PMID:16055711]

5. 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]

6. 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]

7. Inoue, R; Okada, T; Onoue, H; Hara, Y; Shimizu, S; Naitoh, S; Ito, Y; Mori, Y. (2001) The transient receptor potential protein homologue TRP6 is the essential component of vascular alpha(1)-adrenoceptor-activated Ca(2+)-permeable cation channel. Circ. Res., 88 (3): 325-32. [PMID:11179201]

8. Mizuno, N; Kitayama, S; Saishin, Y; Shimada, S; Morita, K; Mitsuhata, C; Kurihara, H; Dohi, T. (1999) Molecular cloning and characterization of rat trp homologues from brain. Brain Res. Mol. Brain Res., 64 (1): 41-51. [PMID:9889314]

9. Reiser, J; Polu, KR; Moller, CC; Kenlan, P; Altintas, MM; Wei, C; Faul, C; Herbert, S; Villegas, I; Avila-Casado, C; McGee, M; Sugimoto, H; Brown, D; Kalluri, R; Mundel, P; Smith, PL; Clapham, DE; Pollak, MR. (2005) TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nat. Genet., 37 (7): 739-44. [PMID:15924139]

10. 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]

11. Soboloff, J; Spassova, M; Xu, W; He, LP; Cuesta, N; Gill, DL. (2005) Role of endogenous TRPC6 channels in Ca2+ signal generation in A7r5 smooth muscle cells. J. Biol. Chem., 280 (48): 39786-94. [PMID:16204251]

12. 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. (2005) A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science, 308 (5729): 1801-4. [PMID:15879175]

13. 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]

To cite this database page, please use the following:

David E. Clapham, Bernd Nilius, Grzegorz Owsianik.
Transient Receptor Potential channels: TRPC6. Last modified on 07/05/2012. Accessed on 18/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=491.


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