TRPC4

Protein and coding gene in humans

TRPC4
Identifiers
AliasesTRPC4, HTRP-4, HTRP4, TRP4, transient receptor potential cation channel subfamily C member 4
External IDsOMIM: 603651; MGI: 109525; HomoloGene: 22955; GeneCards: TRPC4; OMA:TRPC4 - orthologs
Gene location (Human)
Chromosome 13 (human)
Chr.Chromosome 13 (human)[1]
Chromosome 13 (human)
Genomic location for TRPC4
Genomic location for TRPC4
Band13q13.3Start37,632,063 bp[1]
End37,869,802 bp[1]
Gene location (Mouse)
Chromosome 3 (mouse)
Chr.Chromosome 3 (mouse)[2]
Chromosome 3 (mouse)
Genomic location for TRPC4
Genomic location for TRPC4
Band3 C|3 25.43 cMStart54,063,456 bp[2]
End54,225,892 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • stromal cell of endometrium

  • smooth muscle tissue

  • right coronary artery

  • myometrium

  • left coronary artery

  • prostate

  • gallbladder

  • popliteal artery

  • seminal vesicula

  • islet of Langerhans
Top expressed in
  • subiculum

  • Region I of hippocampus proper

  • dentate gyrus

  • hippocampus proper

  • barrel cortex

  • secondary oocyte

  • habenula

  • ventromedial nucleus

  • paraventricular nucleus of hypothalamus

  • arcuate nucleus
More reference expression data
BioGPS


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
SpeciesHumanMouse
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: 37.63 – 37.87 MbChr 3: 54.06 – 54.23 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000133107 – Ensembl, May 2017
  2. ^ a b c 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. S2CID 17936350.
  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. Bibcode:2007PLoSO...2..573F. doi:10.1371/journal.pone.0000573. PMC 1892805. PMID 17593972.
  9. ^ 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.
  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. S2CID 20930490.
  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. S2CID 44945442.
  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. ^ 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.

Further reading

  • Islam, Md. Shahidul (January 2011). Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology. Vol. 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. S2CID 17936350.
  • Cavalié A (2007). "Ionic channels formed by TRPC4". Transient Receptor Potential (TRP) Channels. Handbook of Experimental Pharmacology. Vol. 179. pp. 93–108. doi:10.1007/978-3-540-34891-7_5. ISBN 978-3-540-34889-4. PMID 17217052.

External links

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

  • v
  • t
  • e
Ligand-gated
Voltage-gated
Constitutively active
Proton-gated
Voltage-gated
Calcium-activated
Inward-rectifier
Tandem pore domain
Voltage-gated
Miscellaneous
Cl−: Chloride channel
H+: Proton channel
M+: CNG cation channel
M+: TRP cation channel
H2O (+ solutes): Porin
Cytoplasm: Gap junction
By gating mechanism
Ion channel class
see also disorders
  • v
  • t
  • e
TRP channel modulators
TRPA
Activators
Blockers
TRPC
Activators
Blockers
TRPM
Activators
Blockers
TRPML
Activators
Blockers
TRPP
Activators
Blockers
TRPV
Activators
Blockers
See also: Receptor/signaling modulators • Ion channel modulators