TRPC4

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]

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
Gene location (Human) Chr. Chromosome 13 (human)[1] Band 13q13.3 Start 37,636,636 bp[1] End 37,870,425 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 C|3 25.43 cM Start 54,156,035 bp[2] End 54,318,471 bp[2]
RNA expression pattern 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 • GO:0001948 protein binding • calcium channel activity Cellular component • integral component of membrane • calcium channel complex • membrane • intercellular junction • cortical cytoskeleton • cell membrane • cell surface • basolateral plasma membrane • caveola • membrane raft • integral component of plasma membrane • macromolecular 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
Species	Human	Mouse
Entrez	7223	22066
Ensembl	ENSG00000133107	ENSMUSG00000027748
UniProt	Q9UBN4	Q9QUQ5
RefSeq (mRNA)	NM_001135955 NM_001135956 NM_001135957 NM_001135958 NM_003306 NM_016179 NM_001354799 NM_001354806 NM_001372055	NM_001253682 NM_001253683 NM_016984
RefSeq (protein)	NP_001129427 NP_001129428 NP_001129429 NP_001129430 NP_003297 NP_057263 NP_001341728 NP_001341735 NP_001358984	NP_001240611 NP_001240612 NP_058680
Location (UCSC)	Chr 13: 37.64 – 37.87 Mb	Chr 3: 54.16 – 54.32 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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 is 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]

See also

• TRPC

References

1. GRCh38: Ensembl release 89: ENSG00000133107 - Ensembl, May 2017
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.
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.
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.
7. "Entrez Gene: transient receptor potential cation channel, subfamily C, member 4".
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. doi:10.1371/journal.pone.0000573. PMC 1892805. PMID 17593972.
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.
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.
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.
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.
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.
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. doi:10.1016/S0014-5793(00)02362-0. PMID 11163362.
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.
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. doi:10.1073/pnas.102596199. PMC 124253. PMID 12032305.

Further reading

• Islam, Md. Shahidul (January 2011). Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology. 704. Berlin: Springer. p. 700. ISBN 978-94-007-0264-6.
• Clapham DE, Julius D, Montell C, Schultz G (2006). "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.
• Cavalié A (2007). "Ionic channels formed by TRPC4". Handb Exp Pharmacol. Handbook of Experimental Pharmacology. 179 (179): 93–108. doi:10.1007/978-3-540-34891-7_5. ISBN 978-3-540-34889-4. PMID 17217052.

External links

• TRPC4+protein,+human at the US 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.