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TRPC1

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Target not currently curated in GtoImmuPdb

Target id: 486

Nomenclature: TRPC1

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 1 793 3q23 TRPC1 transient receptor potential cation channel subfamily C member 1 22
Mouse 6 1 793 9 50.2 cM Trpc1 transient receptor potential cation channel, subfamily C, member 1
Rat 6 1 759 8q31 Trpc1 transient receptor potential cation channel, subfamily C, member 1 18
Previous and Unofficial Names Click here for help
TRP1 | short transient receptor potential channel 1 | transient receptor potential cation channel
Database Links Click here for help
Alphafold P48995 (Hs), Q61056 (Mm), Q9QX01 (Rn)
CATH/Gene3D 1.25.40.20
ChEMBL Target CHEMBL4296083 (Hs), CHEMBL4523661 (Hs), CHEMBL4523660 (Hs)
Ensembl Gene ENSG00000144935 (Hs), ENSMUSG00000032839 (Mm), ENSRNOG00000054902 (Rn)
Entrez Gene 7220 (Hs), 22063 (Mm), 89821 (Rn)
Human Protein Atlas ENSG00000144935 (Hs)
KEGG Gene hsa:7220 (Hs), mmu:22063 (Mm), rno:89821 (Rn)
OMIM 602343 (Hs)
Pharos P48995 (Hs)
RefSeq Nucleotide NM_003304 (Hs), NM_011643 (Mm), NM_053558 (Rn)
RefSeq Protein NP_003295 (Hs), NP_035773 (Mm), NP_446010 (Rn)
UniProtKB P48995 (Hs), Q61056 (Mm), Q9QX01 (Rn)
Wikipedia TRPC1 (Hs)
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
TRPC5 15
TRPC3 16
TRPC4 15
TRPP2 9,20
TRPV6 13
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
STIM1 7
IP3R 19
Homer 19
calmodulin 14
D2 receptor 6
caveolin-1 17
α1 syntrophin 12
Functional Characteristics Click here for help
It is not yet clear that TRPC1 forms a homomer. It does form heteromers with TRPC4 and TRPC5
Ion Selectivity and Conductance Click here for help
Species:  Human
Rank order:  Ca2+ [5.0 pS] = Cs+ [5.0 pS] = Na+ [5.0 pS]
References:  15
Chemical activators (Human)
NO-mediated cysteine S-nitrosylation
Physical activators (Human)
membrane stretch (likely direct)

Download all structure-activity data for this target as a CSV file go icon to follow link

Activator Comments
The precise activation pathway of TRPC1 containing channels remains controversial, as do the interaction partners. There is evidence that TRPC1 is involved in store-operated calcium entry, via interactions with STIM1 (reviewed in [2]), yet other researchers see no effect [4]. Recent work suggests TRPC1 may form a channel on endoplasmic and/or sarcoplasmic reticulum membranes [1,3].

When complexed with TRPC4 or TRPC5, TRPC1 is activated as a result of stimulation of Gq signalling pathways. The precise mechanism is unclear.

Low concentrations of La3+ or Gd3+ enhance TRPC1/4 or C1/5 currents. TRPC1 does not appear to be a mechanically sensitive channel [5].
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 Hs Antagonist - - 1x10-4 -70.0 15
⤷ Conc range: 1x10-4 M [15]
Holding voltage: -70.0 mV
Gd3+ Click here for species-specific activity table Hs Antagonist - - 2x10-5 -70.0 22
⤷ Conc range: 2x10-5 M [22]
Holding voltage: -70.0 mV
2-APB Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist - - - -70.0 15
⤷ [15]
Holding voltage: -70.0 mV
SKF96365 Small molecule or natural product Click here for species-specific activity table Hs - - - - -
⤷
GsMTx-4 Peptide Click here for species-specific activity table Hs - - - - -
⤷
Tissue Distribution Click here for help
Brain (CA3 hippocampus, cerebellar Purkinje neurones).
Species:  Rat
Technique:  Immunohistochemistry
References:  15
Heart, brain, lung, liver > spleen, kidney, testes.
Species:  Rat
Technique:  Northern Blot.
References:  18
Functional Assays Click here for help
Enhances store-operated calcium entry.
Species:  Human
Tissue:  Tranfected COS cells.
Response measured:  Ca2+ levels by fluorescence videomicroscopy.
References:  21
Generates a non-selective cation current in heterologously-expressing cells, activated by G protein-coupled receptors or perhaps by membrane stretch.
Species:  Human
Tissue:  Heterologous expression, Xenopus oocytes.
Response measured:  Cation current.
References:  11,22
Physiological Functions Click here for help
Contributes to slow excitatory postsynaptic potential activated by metabotropic glutamate receptors in cerebellar Purkinje neurones.
Species:  Rat
Tissue:  Cerebellar Purkinje neurones.
References:  8
May form channel in skeletal muscle sarcoplasmic reticulum.
Species:  Mouse
Tissue:  Skeletal muscle
References:  3
May contribute to relaxation of mouse aorta.
Species:  Mouse
Tissue:  Aortic endothelial and smooth muscle cells.
References:  10
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpc1tm1Lbi Trpc1tm1Lbi/Trpc1tm1Lbi
involves: 129S/SvEv		 MGI:109528  MP:0005310 abnormal salivary gland physiology PMID: 17956991 
Trpc1tm1Lbi Trpc1tm1Lbi/Trpc1tm1Lbi
involves: 129S/SvEv		 MGI:109528  MP:0000623 decreased salivation PMID: 17956991 
Trpc1tm1Lbi Trpc1tm1Lbi/Trpc1tm1Lbi
involves: 129S/SvEv * C57BL/6J		 MGI:109528  MP:0001264 increased body size PMID: 17647013 
Trpc1tm1Lbi Trpc1tm1Lbi/Trpc1tm1Lbi
involves: 129S/SvEv * C57BL/6J		 MGI:109528  MP:0001260 increased body weight PMID: 17647013 

References

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1. Alfonso S, Benito O, Alicia S, Angélica Z, Patricia G, Diana K, Vaca L, Luis V. (2008) Regulation of the cellular localization and function of human transient receptor potential channel 1 by other members of the TRPC family. Cell Calcium, 43 (4): 375-87. [PMID:17850866]

2. Ambudkar IS, Ong HL, Liu X, Bandyopadhyay BC, Bandyopadhyay B, Cheng KT. (2007) TRPC1: the link between functionally distinct store-operated calcium channels. Cell Calcium, 42 (2): 213-23. [PMID:17350680]

3. Berbey C, Weiss N, Legrand C, Allard B. (2009) Transient receptor potential canonical type 1 (TRPC1) operates as a sarcoplasmic reticulum calcium leak channel in skeletal muscle. J Biol Chem, 284 (52): 36387-94. [PMID:19875453]

4. DeHaven WI, Jones BF, Petranka JG, Smyth JT, Tomita T, Bird GS, Putney Jr JW. (2009) TRPC channels function independently of STIM1 and Orai1. J Physiol (Lond.), 587 (Pt 10): 2275-98. [PMID:19332491]

5. Gottlieb P, Folgering J, Maroto R, Raso A, Wood TG, Kurosky A, Bowman C, Bichet D, Patel A, Sachs F et al.. (2008) Revisiting TRPC1 and TRPC6 mechanosensitivity. Pflugers Arch, 455 (6): 1097-103. [PMID:17957383]

6. Hannan MA, Kabbani N, Paspalas CD, Levenson R. (2008) Interaction with dopamine D2 receptor enhances expression of transient receptor potential channel 1 at the cell surface. Biochim Biophys Acta, 1778 (4): 974-82. [PMID:18261457]

7. Huang GN, Zeng W, Kim JY, Yuan JP, Han L, Muallem S, Worley PF. (2006) STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels. Nat Cell Biol, 8 (9): 1003-10. [PMID:16906149]

8. Kim SJ, Kim YS, Yuan JP, Petralia RS, Worley PF, Linden DJ. (2003) Activation of the TRPC1 cation channel by metabotropic glutamate receptor mGluR1. Nature, 426 (6964): 285-91. [PMID:14614461]

9. Kobori T, Smith GD, Sandford R, Edwardson JM. (2009) The transient receptor potential channels TRPP2 and TRPC1 form a heterotetramer with a 2:2 stoichiometry and an alternating subunit arrangement. J Biol Chem, 284 (51): 35507-13. [PMID:19850920]

10. Kochukov MY, Balasubramanian A, Noel RC, Marrelli SP. (2013) Role of TRPC1 and TRPC3 channels in contraction and relaxation of mouse thoracic aorta. J Vasc Res, 50 (1): 11-20. [PMID:23095462]

11. Maroto R, Raso A, Wood TG, Kurosky A, Martinac B, Hamill OP. (2005) TRPC1 forms the stretch-activated cation channel in vertebrate cells. Nat Cell Biol, 7 (2): 179-85. [PMID:15665854]

12. Sabourin J, Lamiche C, Vandebrouck A, Magaud C, Rivet J, Cognard C, Bourmeyster N, Constantin B. (2009) Regulation of TRPC1 and TRPC4 cation channels requires an alpha1-syntrophin-dependent complex in skeletal mouse myotubes. J Biol Chem, 284 (52): 36248-61. [PMID:19812031]

13. Schindl R, Fritsch R, Jardin I, Frischauf I, Kahr H, Muik M, Riedl MC, Groschner K, Romanin C. (2012) Canonical transient receptor potential (TRPC) 1 acts as a negative regulator for vanilloid TRPV6-mediated Ca2+ influx. J Biol Chem, 287 (42): 35612-20. [PMID:22932896]

14. Singh BB, Liu X, Tang J, Zhu MX, Ambudkar IS. (2002) Calmodulin regulates Ca(2+)-dependent feedback inhibition of store-operated Ca(2+) influx by interaction with a site in the C terminus of TrpC1. Mol Cell, 9 (4): 739-50. [PMID:11983166]

15. Strübing C, Krapivinsky G, Krapivinsky L, Clapham DE. (2001) TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron, 29 (3): 645-55. [PMID:11301024]

16. Strübing C, Krapivinsky G, Krapivinsky L, Clapham DE. (2003) Formation of novel TRPC channels by complex subunit interactions in embryonic brain. J Biol Chem, 278 (40): 39014-9. [PMID:12857742]

17. Sundivakkam PC, Kwiatek AM, Sharma TT, Minshall RD, Malik AB, Tiruppathi C. (2009) Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells. Am J Physiol, Cell Physiol, 296 (3): C403-13. [PMID:19052258]

18. Wang W, O'Connell B, Dykeman R, Sakai T, Delporte C, Swaim W, Zhu X, Birnbaumer L, Ambudkar IS. (1999) Cloning of Trp1beta isoform from rat brain: immunodetection and localization of the endogenous Trp1 protein. Am J Physiol, 276 (4 Pt 1): C969-79. [PMID:10199829]

19. Yuan JP, Kiselyov K, Shin DM, Chen J, Shcheynikov N, Kang SH, Dehoff MH, Schwarz MK, Seeburg PH, Muallem S et al.. (2003) Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. Cell, 114 (6): 777-89. [PMID:14505576]

20. Zhang P, Luo Y, Chasan B, González-Perrett S, Montalbetti N, Timpanaro GA, Cantero Mdel R, Ramos AJ, Goldmann WH, Zhou J et al.. (2009) The multimeric structure of polycystin-2 (TRPP2): structural-functional correlates of homo- and hetero-multimers with TRPC1. Hum Mol Genet, 18 (7): 1238-51. [PMID:19193631]

21. 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]

22. Zitt C, Zobel A, Obukhov AG, Harteneck C, Kalkbrenner F, Lückhoff A, Schultz G. (1996) Cloning and functional expression of a human Ca2+-permeable cation channel activated by calcium store depletion. Neuron, 16 (6): 1189-96. [PMID:8663995]

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