TRPC4

TRPC4
Identifiers
Aliases	TRPC4, HTRP-4, HTRP4, TRP4, transient receptor potential cation channel subfamily C member 4
External IDs	OMIM: 603651; MGI: 109525; HomoloGene: 22955; GeneCards: TRPC4; OMA:TRPC4 - orthologs
Gene location (Human)
Chr.	Chromosome 13 (human)
End	37,869,802 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	54,225,892 bp
RNA expression pattern
	Top expressed in
	stromal cell of endometrium; ; decidua; ; smooth muscle tissue; ; testicle; ; body of uterus; ; right coronary artery; ; myometrium; ; left coronary artery; ; prostate; ; gallbladder;
	Top expressed in
	lateral septal nucleus; ; subiculum; ; Region I of hippocampus proper; ; CA3 field; ; dentate gyrus; ; anterior amygdaloid area; ; hippocampus proper; ; dentate gyrus of hippocampal formation granule cell; ; barrel cortex; ; secondary oocyte;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	beta-catenin binding; store-operated calcium channel activity; cadherin binding; inositol 1,4,5 trisphosphate binding; ion channel activity; protein binding; calcium channel activity;
Cellular component	integral component of membrane; calcium channel complex; membrane; cell-cell junction; cortical cytoskeleton; plasma membrane; cell surface; basolateral plasma membrane; caveola; membrane raft; integral component of plasma membrane; protein-containing complex; cation channel complex;
Biological process	regulation of cytosolic calcium ion concentration; calcium ion import; oligodendrocyte differentiation; ion transport; calcium ion transmembrane transport; manganese ion transport; gamma-aminobutyric acid secretion; calcium ion transport; transmembrane transport;
	Sources:Amigo / QuickGO
Orthologs
	7223
	22066
	ENSG00000133107
	ENSMUSG00000027748
	Q9UBN4
	Q9QUQ5
NM_001135955; NM_001135956; NM_001135957; NM_001135958; NM_003306;
	NM_016179; NM_001354799; NM_001354806; NM_001372055
	NM_001253682; NM_001253683; NM_016984
NP_001129427; NP_001129428; NP_001129429; NP_001129430; NP_003297;
	NP_057263; NP_001341728; NP_001341735; NP_001358984
	NP_001240611; NP_001240612; NP_058680
	Wikidata
View/Edit Human	View/Edit Mouse

The short transient receptor potential channel 4 (TrpC4), also known as Trp-related protein 4, is a protein that in humans is encoded by the TRPC4 gene.^[5]^[6]

Function

TrpC4 is a member of the transient receptor potential cation channels. This protein forms a non-selective calcium-permeable cation channel that is activated by Gαi-coupled receptors, Gαq-coupled receptors and tyrosine kinases, and plays a role in multiple processes including endothelial permeability, vasodilation, neurotransmitter release and cell proliferation.^[7]

Tissue distribution

The nonselective cation channel TrpC4 has been shown to be present in high abundance in the cortico-limbic regions of the brain.^[8] In addition, TRPC4 mRNA is present in midbrain dopaminergic neurons in the ventral tegmental area and the substantia nigra.^[9]

Roles

Deletion of the trpc4 gene decreases levels of sociability in a social exploration task. These results suggest that TRPC4 may play a role in regulating social anxiety in a number of different disorders.^[10] However deletion of the trpc4 gene had no impact on basic or complex strategic learning.^[11] Given that the trpc4 gene is expressed in a select population of midbrain dopamine neurons, it has been proposed that it may have an important role in dopamine related processes including addiction and attention.^[9]

Clinical significance

Single nucleotide polymorphisms in this gene may be associated with generalized epilepsy with photosensitivity.^[12]

Interactions

TRPC4 has been shown to interact with ITPR1,^[13]^[14] TRPC1,^[15]^[16] and TRPC5.^[16]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000133107 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000027748 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Zhu X, Jiang M, Peyton M, Boulay G, Hurst R, Stefani E, Birnbaumer L (May 1996). "trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry". Cell. 85 (5): 661–71. doi:10.1016/S0092-8674(00)81233-7. PMID 8646775.
^ 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". Pharmacol. Rev. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100. S2CID 17936350.
^ "Entrez Gene: transient receptor potential cation channel, subfamily C, member 4".
^ Fowler MA, Sidiropoulou K, Ozkan ED, Phillips CW, Cooper DC (2007). "Corticolimbic expression of TRPC4 and TRPC5 channels in the rodent brain". PLOS ONE. 2 (6): e573. Bibcode:2007PLoSO...2..573F. doi:10.1371/journal.pone.0000573. PMC 1892805. PMID 17593972.
^ ^a ^b Cooper D, Illig K, Varnell A, Ostertag E, Klipec W (2011). "TRPC4 ion channel protein is selectively expressed in a subpopulation of dopamine neurons in the ventral tegmental area". Nature Precedings. arXiv:1204.0142. doi:10.1038/npre.2011.6577.1. S2CID 19188350.
^ Cooper D, Rasmus K, Wang J-G, Varnell A, Ostertag E (2011). "Sociability is decreased following deletion of the trpc4 gene". Nature Precedings. doi:10.1038/npre.2011.6367.1.
^ Cooper D, Collins M, Drish A, Swenson L, Ostertag E, Klipec W, Nguyen P, Deeney B, Williamson C, Wenzel K, Stumme J (2012). "Deletion of the trpc4 gene and its role in simple and complex strategic learning". Nature Precedings. doi:10.1038/npre.2012.6929.1.
^ von Spiczak S, Muhle H, Helbig I, de Kovel CG, Hampe J, Gaus V, Koeleman BP, Lindhout D, Schreiber S, Sander T, Stephani U (September 2010). "Association study of TRPC4 as a candidate gene for generalized epilepsy with photosensitivity". Neuromolecular Med. 12 (3): 292–9. doi:10.1007/s12017-010-8122-x. hdl:11858/00-001M-0000-0029-429E-D. PMID 20574736. S2CID 20930490.
^ Yuan JP, Kiselyov K, Shin DM, Chen J, Shcheynikov N, Kang SH, Dehoff MH, Schwarz MK, Seeburg PH, Muallem S, Worley PF (September 2003). "Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors". Cell. 114 (6): 777–89. doi:10.1016/S0092-8674(03)00716-5. PMID 14505576.
^ Mery L, Magnino F, Schmidt K, Krause KH, Dufour JF (January 2001). "Alternative splice variants of hTrp4 differentially interact with the C-terminal portion of the inositol 1,4,5-trisphosphate receptors". FEBS Lett. 487 (3): 377–83. Bibcode:2001FEBSL.487..377M. doi:10.1016/S0014-5793(00)02362-0. PMID 11163362. S2CID 44945442.
^ Strübing C, Krapivinsky G, Krapivinsky L, Clapham DE (October 2003). "Formation of novel TRPC channels by complex subunit interactions in embryonic brain". J. Biol. Chem. 278 (40): 39014–9. doi:10.1074/jbc.M306705200. PMID 12857742.
^ ^a ^b Hofmann T, Schaefer M, Schultz G, Gudermann T (May 2002). "Subunit composition of mammalian transient receptor potential channels in living cells". Proc. Natl. Acad. Sci. U.S.A. 99 (11): 7461–6. Bibcode:2002PNAS...99.7461H. doi:10.1073/pnas.102596199. PMC 124253. PMID 12032305.

External links

TRPC4+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000133107 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000027748 – 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.

[pmid8646775-5] Zhu X, Jiang M, Peyton M, Boulay G, Hurst R, Stefani E, Birnbaumer L (May 1996). "trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry". Cell. 85 (5): 661–71. doi:10.1016/S0092-8674(00)81233-7. PMID 8646775.

[pmid16382100-6] 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". Pharmacol. Rev. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100. S2CID 17936350.

[entrez-7] "Entrez Gene: transient receptor potential cation channel, subfamily C, member 4".

[pmid17593972-8] Fowler MA, Sidiropoulou K, Ozkan ED, Phillips CW, Cooper DC (2007). "Corticolimbic expression of TRPC4 and TRPC5 channels in the rodent brain". PLOS ONE. 2 (6): e573. Bibcode:2007PLoSO...2..573F. doi:10.1371/journal.pone.0000573. PMC 1892805. PMID 17593972.

[Cooper_2011_b-9] Cooper D, Illig K, Varnell A, Ostertag E, Klipec W (2011). "TRPC4 ion channel protein is selectively expressed in a subpopulation of dopamine neurons in the ventral tegmental area". Nature Precedings. arXiv:1204.0142. doi:10.1038/npre.2011.6577.1. S2CID 19188350.

[Copper_2011-10] Cooper D, Rasmus K, Wang J-G, Varnell A, Ostertag E (2011). "Sociability is decreased following deletion of the trpc4 gene". Nature Precedings. doi:10.1038/npre.2011.6367.1.

[Cooper_2012-11] Cooper D, Collins M, Drish A, Swenson L, Ostertag E, Klipec W, Nguyen P, Deeney B, Williamson C, Wenzel K, Stumme J (2012). "Deletion of the trpc4 gene and its role in simple and complex strategic learning". Nature Precedings. doi:10.1038/npre.2012.6929.1.

[pmid20574736-12] von Spiczak S, Muhle H, Helbig I, de Kovel CG, Hampe J, Gaus V, Koeleman BP, Lindhout D, Schreiber S, Sander T, Stephani U (September 2010). "Association study of TRPC4 as a candidate gene for generalized epilepsy with photosensitivity". Neuromolecular Med. 12 (3): 292–9. doi:10.1007/s12017-010-8122-x. hdl:11858/00-001M-0000-0029-429E-D. PMID 20574736. S2CID 20930490.

[pmid14505576-13] Yuan JP, Kiselyov K, Shin DM, Chen J, Shcheynikov N, Kang SH, Dehoff MH, Schwarz MK, Seeburg PH, Muallem S, Worley PF (September 2003). "Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors". Cell. 114 (6): 777–89. doi:10.1016/S0092-8674(03)00716-5. PMID 14505576.

[pmid11163362-14] Mery L, Magnino F, Schmidt K, Krause KH, Dufour JF (January 2001). "Alternative splice variants of hTrp4 differentially interact with the C-terminal portion of the inositol 1,4,5-trisphosphate receptors". FEBS Lett. 487 (3): 377–83. Bibcode:2001FEBSL.487..377M. doi:10.1016/S0014-5793(00)02362-0. PMID 11163362. S2CID 44945442.

[pmid12857742-15] Strübing C, Krapivinsky G, Krapivinsky L, Clapham DE (October 2003). "Formation of novel TRPC channels by complex subunit interactions in embryonic brain". J. Biol. Chem. 278 (40): 39014–9. doi:10.1074/jbc.M306705200. PMID 12857742.

[pmid12032305-16] Hofmann T, Schaefer M, Schultz G, Gudermann T (May 2002). "Subunit composition of mammalian transient receptor potential channels in living cells". Proc. Natl. Acad. Sci. U.S.A. 99 (11): 7461–6. Bibcode:2002PNAS...99.7461H. doi:10.1073/pnas.102596199. PMC 124253. PMID 12032305.

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