Target Information

Target General Infomation
Target ID
T64213
Former ID
TTDR01160
Target Name
Transient receptor potential cation channel subfamily V member 4
Gene Name
TRPV4
Synonyms
OTRPC4; Osm-9-like TRP channel 4; TRP12; Transient receptor potential protein 12; TrpV4; VR-OAC; VRL-2; VRL2; VROAC; Vanilloid receptor-like channel 2; Vanilloid receptor-like protein 2; Vanilloid receptor-related osmotically-activated channel; TRPV4
Target Type
Research
Function
Non-selective calcium permeant cation channel probably involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by low pH, citrate and phorbolesters. Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism. Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers. Acts as a regulator of intracellular Ca(2+) in synoviocytes. Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8. {ECO:0000269|PubMed:11025659, ECO:0000269|PubMed:12724311, ECO:0000269|PubMed:19759329}.
BioChemical Class
Transient receptor family
Target Validation
T64213
UniProt ID
Q9HBA0
Sequence
MADSSEGPRAGPGEVAELPGDESGTPGGEAFPLSSLANLFEGEDGSLSPSPADASRPAGP
GDGRPNLRMKFQGAFRKGVPNPIDLLESTLYESSVVPGPKKAPMDSLFDYGTYRHHSSDN
KRWRKKIIEKQPQSPKAPAPQPPPILKVFNRPILFDIVSRGSTADLDGLLPFLLTHKKRL
TDEEFREPSTGKTCLPKALLNLSNGRNDTIPVLLDIAERTGNMREFINSPFRDIYYRGQT
ALHIAIERRCKHYVELLVAQGADVHAQARGRFFQPKDEGGYFYFGELPLSLAACTNQPHI
VNYLTENPHKKADMRRQDSRGNTVLHALVAIADNTRENTKFVTKMYDLLLLKCARLFPDS
NLEAVLNNDGLSPLMMAAKTGKIGIFQHIIRREVTDEDTRHLSRKFKDWAYGPVYSSLYD
LSSLDTCGEEASVLEILVYNSKIENRHEMLAVEPINELLRDKWRKFGAVSFYINVVSYLC
AMVIFTLTAYYQPLEGTPPYPYRTTVDYLRLAGEVITLFTGVLFFFTNIKDLFMKKCPGV
NSLFIDGSFQLLYFIYSVLVIVSAALYLAGIEAYLAVMVFALVLGWMNALYFTRGLKLTG
TYSIMIQKILFKDLFRFLLVYLLFMIGYASALVSLLNPCANMKVCNEDQTNCTVPTYPSC
RDSETFSTFLLDLFKLTIGMGDLEMLSSTKYPVVFIILLVTYIILTFVLLLNMLIALMGE
TVGQVSKESKHIWKLQWATTILDIERSFPVFLRKAFRSGEMVTVGKSSDGTPDRRWCFRV
DEVNWSHWNQNLGIINEDPGKNETYQYYGFSHTVGRLRRDRWSSVVPRVVELNKNSNPDE
VVVPLDSMGNPRCDGHQQGYPRKWRTDDAPL
Structure
4DX1; 4DX2
Inhibitor 4-Pyridin-2-yl-piperazine-1-carboxylic acid amide Drug Info [1]
CAPSAZEPINE Drug Info [2]
IODORESINIFERATOXIN Drug Info [1]
MK-056 Drug Info [3]
Pyrrolidin-1-yl-thiourea Drug Info [1]
SC-0030 Drug Info [3]
Activator 4alpha-PDD Drug Info [4]
4alpha-PDH Drug Info [5]
5,6-epoxyeicosatrienoic acid Drug Info [6]
bisandrographolide Drug Info [7]
citric acid Drug Info [8]
GSK1016790A Drug Info [9]
phorbol 12-myristate 13-acetate Drug Info [4]
RN1747 Drug Info [10]
Blocker (channel blocker) GSK2193874 Drug Info [11]
HC067047 Drug Info [12]
RN1734 Drug Info [10]
Pathways
KEGG Pathway Inflammatory mediator regulation of TRP channels
Reactome TRP channels
References
REF 1Bioorg Med Chem Lett. 2004 Apr 5;14(7):1693-6.N-4-methansulfonamidobenzyl-N'-2-substituted-4-tert-butyl-benzyl thioureas as potent vanilloid receptor antagonistic ligands.
REF 2Bioorg Med Chem Lett. 2003 May 5;13(9):1549-52.Chain-branched acyclic phenethylthiocarbamates as vanilloid receptor antagonists.
REF 3Bioorg Med Chem Lett. 2003 Dec 15;13(24):4389-93.Novel non-vanilloid VR1 antagonist of high analgesic effects and its structural requirement for VR1 antagonistic effects.
REF 4Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives. J Biol Chem. 2002 Apr 19;277(16):13569-77. Epub 2002 Feb 4.
REF 5Modulation of the transient receptor potential vanilloid channel TRPV4 by 4alpha-phorbol esters: a structure-activity study. J Med Chem. 2009 May 14;52(9):2933-9.
REF 6Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature. 2003 Jul 24;424(6947):434-8.
REF 7Bisandrographolide from Andrographis paniculata activates TRPV4 channels. J Biol Chem. 2006 Oct 6;281(40):29897-904. Epub 2006 Aug 9.
REF 8Impaired pressure sensation in mice lacking TRPV4. J Biol Chem. 2003 Jun 20;278(25):22664-8. Epub 2003 Apr 13.
REF 9N-((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. 2008 Aug;326(2):432-42.
REF 10Identification and characterization of novel TRPV4 modulators. Biochem Biophys Res Commun. 2009 Nov 20;389(3):490-4.
REF 11An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci Transl Med. 2012 Nov 7;4(159):159ra148.
REF 12Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis. Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):19084-9.

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