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TRPC7

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Target id: 492

Nomenclature: TRPC7

Family: Transient Receptor Potential channels (TRP)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 862 5q31.1 TRPC7 transient receptor potential cation channel subfamily C member 7 14
Mouse 6 1 862 13 B1 Trpc7 transient receptor potential cation channel, subfamily C, member 7 10
Rat 6 1 861 17p14 Trpc7 transient receptor potential cation channel, subfamily C, member 7 11
Previous and Unofficial Names Click here for help
TRP7 [10,14] | capacitative calcium channel TRPC7 | short transient receptor potential channel 7 | transient receptor potential cation channel
Database Links Click here for help
Alphafold Q9HCX4 (Hs), Q9WVC5 (Mm)
CATH/Gene3D 1.25.40.20
ChEMBL Target CHEMBL4105799 (Hs), CHEMBL4523502 (Mm)
Ensembl Gene ENSG00000069018 (Hs), ENSMUSG00000021541 (Mm), ENSRNOG00000012727 (Rn)
Entrez Gene 57113 (Hs), 26946 (Mm), 282822 (Rn)
Human Protein Atlas ENSG00000069018 (Hs)
KEGG Gene hsa:57113 (Hs), mmu:26946 (Mm), rno:282822 (Rn)
Pharos Q9HCX4 (Hs)
RefSeq Nucleotide NM_020389 (Hs), NM_012035 (Mm), NM_001191691 (Rn)
RefSeq Protein NP_065122 (Hs), NP_036165 (Mm), NP_001178620 (Rn)
UniProtKB Q9HCX4 (Hs), Q9WVC5 (Mm)
Wikipedia TRPC7 (Hs)
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
TRPC1 23
TRPC3 1
TRPC6 1
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
MxA 7
calmodulin 17
FKBP prolyl isomerase 1A 18
C-terminal tail-truncated TRPP2 9
Functional Characteristics Click here for help
γ = 25–75 pS; conducts mono and divalent cations with a preference for divalents (PCa/ PCs = 5.9); modest outward rectification (monovalent cation current recorded in the absence of extracellular divalents); monovalent cation current suppressed by extracellular Ca2+ and Mg2+
Ion Selectivity and Conductance Click here for help
Species:  Mouse
Rank order:  Ba2+ > Ca2+ > Na+ [25.0 - 50.0 pS] = Cs+
References:  17
Chemical activators (Human)
diacylglycerols

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Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
DOG Small molecule or natural product Click here for species-specific activity table Mm Agonist - - 1x10-4 -60.0 10
⤷ Conc range: 1x10-4 M [10]
Holding voltage: -60.0 mV
OAG Small molecule or natural product Click here for species-specific activity table Mm Agonist - - 1x10-4 -60.0 10
⤷ Conc range: 1x10-4 M [10]
Holding voltage: -60.0 mV
pyrazolopyrimidine 4n Small molecule or natural product Click here for species-specific activity table Hs Activation 6.1 pIC50 - - 13
⤷ pIC50 6.1 (IC50 8.9x10-7 M) [13]
OptoBI-1 Small molecule or natural product Click here for species-specific activity table Hs Activation - - - - 20
⤷ photoswitch activation; concentration range: 1-2x10-5M [20]
View species-specific activator tables
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
La3+ Click here for species-specific activity table Mm Antagonist - - 1x10-4 -60.0 10
⤷ Conc range: 1x10-4 M [10]
Holding voltage: -60.0 mV
SKF96365 Small molecule or natural product Click here for species-specific activity table Mm Antagonist - - 2.5x10-5 -60.0 10
⤷ Conc range: 2.5x10-5 M [10]
Holding voltage: -60.0 mV
SH045 Small molecule or natural product Click here for species-specific activity table Hs - ~6.7 – 7.7 pIC50 - - 3
⤷ pIC50 ~7.7 (IC50 ~2x10-8 M) [3]
pIC50 6.7 (IC50 2.2x10-7 M) [3]
Description: Measuring inhibition of calcium flux in HEK293 cells expressing hTRPC7, in a FLIPR assay.
SAR7334 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - 6.7 pIC50 - - 8
⤷ pIC50 6.7 (IC50 2.26x10-7 M) [8]
larixyl acetate Small molecule or natural product Click here for species-specific activity table Hs Inhibition ~6.3 pIC50 - - 21
⤷ pIC50 ~6.3 (IC50 ~5x10-7 M) [21]
BI 749327 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.3 pIC50 - - 6
⤷ pIC50 6.3 [6]
amiloride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs - - - - -
⤷
2-APB Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - - - - -
⤷
View species-specific channel blocker tables
Immunopharmacology Comments
Expressed on chicken B cells [12].
Tissue Distribution Click here for help
Kidney, intestine, pituitary gland, brain.
Species:  Human
Technique:  RT-PCR
References:  15
Heart, lung eye, brain, kidney, liver, testis, retina, iris, inner ear
Species:  Mouse
Technique:  RT-PCR, western blotting, immunohistochemistry
References:  4,10,19,22
Brain
Species:  Rat
Technique:  RT-PCR
References:  2
Functional Assays Click here for help
TRPC7 is activated by depletion of intracellular calcium stores.
Species:  Human
Tissue: 
Response measured:  Intracellular Ca2+ levels.
References:  14
Calcium imaging.
Species:  Rat
Tissue:  Myocardium.
Response measured:  Intracellular Ca2+ levels.
References:  16
TRPC7 is constitutively activated and enhanced by stimulation of G protein-coupled receptor.
Species:  Mouse
Tissue: 
Response measured:  Intracellular Ca2+ levels.
References:  10
Physiological Functions Click here for help
The broad physiological role of TRPC7 is not known. TRPC7 conducts Ca2+ in AT1-induced myocardial apoptosis via a calcineurin-dependent pathway.
Species:  Rat
Tissue:  Myocardium
References:  16
Knock out of TRPC7 in DT40 B-lymphocytes alters thapsigargin activated [Ca2+]i signals.
Species:  Chicken
Tissue:  Immortalized chicken B-lymphocyte cell line DT40
References:  5
In mouse, ablating the expression of both TRPC6 and TRPC7 eliminates the intrinsic light response of the M1 subtype of melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (M1-ipRGCs).
Species:  Mouse
Tissue:  Eye
References:  22

References

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1. 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]

2. Facemire CS, Mohler PJ, Arendshorst WJ. (2004) Expression and relative abundance of short transient receptor potential channels in the rat renal microcirculation. Am J Physiol Renal Physiol, 286 (3): F546-51. [PMID:14678949]

3. 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]

4. 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]

5. Lievremont JP, Numaga T, Vazquez G, Lemonnier L, Hara Y, Mori E, Trebak M, Moss SE, Bird GS, Mori Y et al.. (2005) The role of canonical transient receptor potential 7 in B-cell receptor-activated channels. J Biol Chem, 280 (42): 35346-51. [PMID:16123040]

6. Lin BL, Matera D, Doerner JF, Zheng N, Del Camino D, Mishra S, Bian H, Zeveleva S, Zhen X, Blair NT et al.. (2019) In vivo selective inhibition of TRPC6 by antagonist BI 749327 ameliorates fibrosis and dysfunction in cardiac and renal disease. Proc Natl Acad Sci U S A, 116 (20): 10156-10161. [PMID:31028142]

7. 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]

8. 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]

9. 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]

10. Okada T, Inoue R, Yamazaki K, Maeda A, Kurosaki T, Yamakuni T, Tanaka I, Shimizu S, Ikenaka K, Imoto K et al.. (1999) Molecular and functional characterization of a novel mouse transient receptor potential protein homologue TRP7. Ca(2+)-permeable cation channel that is constitutively activated and enhanced by stimulation of G protein-coupled receptor. J Biol Chem, 274 (39): 27359-70. [PMID:10488066]

11. Onohara N, Nishida M, Inoue R, Kobayashi H, Sumimoto H, Sato Y, Mori Y, Nagao T, Kurose H. (2006) TRPC3 and TRPC6 are essential for angiotensin II-induced cardiac hypertrophy. EMBO J, 25 (22): 5305-16. [PMID:17082763]

12. 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]

13. 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]

14. Riccio A, Mattei C, Kelsell RE, Medhurst AD, Calver AR, Randall AD, Davis JB, Benham CD, Pangalos MN. (2002) Cloning and functional expression of human short TRP7, a candidate protein for store-operated Ca2+ influx. J Biol Chem, 277 (14): 12302-9. [PMID:11805119]

15. 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]

16. Satoh S, Tanaka H, Ueda Y, Oyama J, Sugano M, Sumimoto H, Mori Y, Makino N. (2007) Transient receptor potential (TRP) protein 7 acts as a G protein-activated Ca2+ channel mediating angiotensin II-induced myocardial apoptosis. Mol Cell Biochem, 294 (1-2): 205-15. [PMID:16838106]

17. Shi J, Mori E, Mori Y, Mori M, Li J, Ito Y, Inoue R. (2004) Multiple regulation by calcium of murine homologues of transient receptor potential proteins TRPC6 and TRPC7 expressed in HEK293 cells. J Physiol (Lond.), 561 (Pt 2): 415-32. [PMID:15579537]

18. 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]

19. 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]

20. Tiapko O, Shrestha N, Lindinger S, Guedes de la Cruz G, Graziani A, Klec C, Butorac C, Graier WF, Kubista H, Freichel M et al.. (2019) Lipid-independent control of endothelial and neuronal TRPC3 channels by light. Chem Sci, 10 (9): 2837-2842. [PMID:30997005]

21. Urban N, Wang L, Kwiek S, Rademann J, Kuebler WM, Schaefer M. (2016) Identification and Validation of Larixyl Acetate as a Potent TRPC6 Inhibitor. Mol Pharmacol, 89 (1): 197-213. [PMID:26500253]

22. Xue T, Do MT, Riccio A, Jiang Z, Hsieh J, Wang HC, Merbs SL, Welsbie DS, Yoshioka T, Weissgerber P et al.. (2011) Melanopsin signalling in mammalian iris and retina. Nature, 479 (7371): 67-73. [PMID:22051675]

23. 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]

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