TRPV4

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Transient receptor potential cation channel, subfamily V, member 4
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols TRPV4 ; CMT2C; HMSN2C; OTRPC4; SMAL; SPSMA; SSQTL1; TRP12; VRL2; VROAC
External IDs OMIM605427 MGI1926945 HomoloGene11003 IUPHAR: TRPV4 ChEMBL: 3119 GeneCards: TRPV4 Gene
RNA expression pattern
PBB GE TRPV4 219516 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 59341 63873
Ensembl ENSG00000111199 ENSMUSG00000014158
UniProt Q9HBA0 Q9EPK8
RefSeq (mRNA) NM_001177428 NM_022017
RefSeq (protein) NP_001170899 NP_071300
Location (UCSC) Chr 12:
110.22 – 110.27 Mb
Chr 5:
114.62 – 114.66 Mb
PubMed search [1] [2]

Transient receptor potential cation channel subfamily V member 4 is a protein that in humans is encoded by the TRPV4 gene.[1][1][2][2][3]

This gene encodes TRPV4, a member of the OSM9-like transient receptor potential channel (OTRPC) subfamily in the transient receptor potential (TRP) superfamily of ion channels.[3][4][5] The encoded protein is a Ca2+-permeable, nonselective cation channel that is thought to be involved in the regulation of systemic osmotic pressure.[6] Two transcript variants encoding different isoforms have been found for this gene.[7]

Mutations in the TRPV4 gene are associated with a vast range of disorders, including brachyolmia type 3, congenital distal spinal muscular atrophy, scapuloperoneal spinal muscular atrophy and subtype 2C of Charcot–Marie–Tooth disease.[8]

Pharmacology[edit]

A number of TRPV4 agonists and antagonists have been identified in the past ten years.[9] The discovery of unselective modulators (e.g. antagonist Ruthenium Red) was followed by the apparition of more potent (agonist 4aPDD)[10] or selective (antagonist RN-1734)[11] compounds, including some with bioavailability suitable for in vivo pharmacology studies such as agonist GSK1016790A[12] (with ~10 fold selectivity vs TRPV1) and antagonist HC-067047[13] (with ~5 fold selectivity vs hERG and ~10 fold selectivity vs TRPM8).

Interactions[edit]

TRPV4 has been shown to interact with MAP7[14] and LYN.[15]

Function in sunburn pain[edit]

Wolfgang Liedtke, M.D., Ph.D., associate professor of neurology and neurobiology at Duke University School of Medicine reported in the Proceedings of the National Academy of Sciences (PNAS) that studies on genetically engineered mouse model missing TRPV4 only in the cells of the epidermis and on mouse cell cultures have led to the conclusion that exposure to UVB rays caused calcium to flow into the skin cells, but only when the TRPV4 ion channel was present; the influx of calcium ions brings in another molecule called endothelin, which triggers TRPV4 to send more calcium into the cells. Endothelin is known to cause pain and to evoke itching in humans. Could Discovery Lead to End of Sunburn Pain? (Science Daily)

See also[edit]

References[edit]

  1. ^ a b Strotmann R, Harteneck C, Nunnenmacher K, Schultz G, Plant TD (Dec 2000). "OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity". Nat Cell Biol 2 (10): 695–702. doi:10.1038/35036318. PMID 11025659. 
  2. ^ a b Liedtke W, Choe Y, Marti-Renom MA, Bell AM, Denis CS, Sali A, Hudspeth AJ, Friedman JM, Heller S (Nov 2000). "Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor". Cell 103 (3): 525–35. doi:10.1016/S0092-8674(00)00143-4. PMC 2211528. PMID 11081638. 
  3. ^ a b Clapham DE, Julius D, Montell C, Schultz G (Dec 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. 
  4. ^ Harteneck C, Plant TD, Schultz G (April 2000). "From worm to man: three subfamilies of TRP channels". Trends Neurosci. 23 (4): 159–66. doi:10.1016/S0166-2236(99)01532-5. PMID 10717675. 
  5. ^ Plant TD, Strotmann R (2007). "TRPV4". Handb Exp Pharmacol 179 (179): 189–205. doi:10.1007/978-3-540-34891-7_11. PMID 17217058. 
  6. ^ Harteneck C, Reiter B (February 2007). "TRP channels activated by extracellular hypo-osmoticity in epithelia". Biochem. Soc. Trans. 35 (Pt 1): 91–5. doi:10.1042/BST0350091. PMID 17233610. 
  7. ^ "Entrez Gene: TRPV4 transient receptor potential cation channel, subfamily V, member 4". 
  8. ^ Online 'Mendelian Inheritance in Man' (OMIM) 605427
  9. ^ Vincent F, Duncton MA (2011). "TRPV4 agonists and antagonists". Curr Top Med Chem 11 (17): 2216–26. PMID 21671873. 
  10. ^ Watanabe H, Davis JB, Smart D, et al. (April 2002). "Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives". J. Biol. Chem. 277 (16): 13569–77. doi:10.1074/jbc.M200062200. PMID 11827975. 
  11. ^ Vincent F, Acevedo A, Nguyen MT, et al. (November 2009). "Identification and characterization of novel TRPV4 modulators". Biochem. Biophys. Res. Commun. 389 (3): 490–4. doi:10.1016/j.bbrc.2009.09.007. PMID 19737537. 
  12. ^ Thorneloe KS, Sulpizio AC, Lin Z, et al. (August 2008). "N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I". J. Pharmacol. Exp. Ther. 326 (2): 432–42. doi:10.1124/jpet.108.139295. PMID 18499743. 
  13. ^ Everaerts W, Zhen X, Ghosh D, et al. (November 2010). "Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis". Proc. Natl. Acad. Sci. U.S.A. 107 (44): 19084–9. doi:10.1073/pnas.1005333107. PMC 2973867. PMID 20956320. 
  14. ^ Suzuki M, Hirao A, Mizuno A (December 2003). "Microtubule-associated [corrected] protein 7 increases the membrane expression of transient receptor potential vanilloid 4 (TRPV4)". J. Biol. Chem. 278 (51): 51448–53. doi:10.1074/jbc.M308212200. PMID 14517216. 
  15. ^ Xu, Hongshi; Zhao Hongyu, Tian Wei, Yoshida Kiyotsugu, Roullet Jean-Baptiste, Cohen David M (Mar 2003). "Regulation of a transient receptor potential (TRP) channel by tyrosine phosphorylation. SRC family kinase-dependent tyrosine phosphorylation of TRPV4 on TYR-253 mediates its response to hypotonic stress". J. Biol. Chem. (United States) 278 (13): 11520–7. doi:10.1074/jbc.M211061200. ISSN 0021-9258. PMID 12538589. 

External links[edit]

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