General Information of the Protein
Protein ID
PT03081
Protein Name
Transient receptor potential cation channel subfamily V member 4
Secondarily
Protein Name
Osm-9-like TRP channel 4
Transient receptor potential protein 12
Vanilloid receptor-like channel 2
Vanilloid receptor-like protein 2
Vanilloid receptor-related osmotically-activated channel
Gene Name
TRPV4
Secondarily
Gene Name
VRL2
VROAC
Sequence
MADSSEGPRAGPGEVAELPGDESGTPGGEAFPLSSLANLFEGEDGSLSPSPADASRPAGPGDGRPNLRMKFQGAFRKGVPNPIDLLESTLYESSVVPGPKKAPMDSLFDYGTYRHHSSDNKRWRKKIIEKQPQSPKAPAPQPPPILKVFNRPILFDIVSRGSTADLDGLLPFLLTHKKRLTDEEFREPSTGKTCLPKALLNLSNGRNDTIPVLLDIAERTGNMREFINSPFRDIYYRGQTALHIAIERRCKHYVELLVAQGADVHAQARGRFFQPKDEGGYFYFGELPLSLAACTNQPHIVNYLTENPHKKADMRRQDSRGNTVLHALVAIADNTRENTKFVTKMYDLLLLKCARLFPDSNLEAVLNNDGLSPLMMAAKTGKIGIFQHIIRREVTDEDTRHLSRKFKDWAYGPVYSSLYDLSSLDTCGEEASVLEILVYNSKIENRHEMLAVEPINELLRDKWRKFGAVSFYINVVSYLCAMVIFTLTAYYQPLEGTPPYPYRTTVDYLRLAGEVITLFTGVLFFFTNIKDLFMKKCPGVNSLFIDGSFQLLYFIYSVLVIVSAALYLAGIEAYLAVMVFALVLGWMNALYFTRGLKLTGTYSIMIQKILFKDLFRFLLVYLLFMIGYASALVSLLNPCANMKVCNEDQTNCTVPTYPSCRDSETFSTFLLDLFKLTIGMGDLEMLSSTKYPVVFIILLVTYIILTFVLLLNMLIALMGETVGQVSKESKHIWKLQWATTILDIERSFPVFLRKAFRSGEMVTVGKSSDGTPDRRWCFRVDEVNWSHWNQNLGIINEDPGKNETYQYYGFSHTVGRLRRDRWSSVVPRVVELNKNSNPDEVVVPLDSMGNPRCDGHQQGYPRKWRTDDAPL
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Organism
Homo sapiens, Human
Protein Classification
Ion channel
>
Voltage-gated ion channel
>
Transient receptor potential channel
Function
Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:18826956, PubMed:18695040, PubMed:29899501). Also activated by heat, low pH, citrate and phorbol esters (PubMed:16293632, PubMed:18826956, PubMed:18695040, PubMed:25256292, PubMed:20037586, PubMed:21964574). Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism (PubMed:12724311, PubMed:18826956). Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers (By similarity). Acts as a regulator of intracellular Ca(2+) in synoviocytes (PubMed:19759329). 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 (PubMed:19759329). Together with PKD2, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). Negatively regulates expression of PPARGC1A, UCP1, oxidative metabolism and respiration in adipocytes (By similarity). Regulates expression of chemokines and cytokines related to pro-inflammatory pathway in adipocytes (By similarity). Together with AQP5, controls regulatory volume decrease in salivary epithelial cells (By similarity). Required for normal development and maintenance of bone and cartilage (PubMed:26249260). In its inactive state, may sequester DDX3X at the plasma membrane. When activated, the interaction between both proteins is affected and DDX3X relocalizes to the nucleus (PubMed:29899501).
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Uniprot ID
Primary ID:
Q9HBA0

Secondarily ID:
B7ZKQ6
Q17R79
Q2Y122
Q2Y123
Q2Y124
Q86YZ6
Q8NDY7
Q8NG64
Q96Q92
Q96RS7
Q9HBC0
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Ensembl ID
ENSG00000111199
HGNC ID
HGNC:18083
Subcellular Location
Cell membrane
Apical cell membrane
Cell junction
Adherens junction
Cell projection
Cilium
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000932 , BHK/AC9
Compound ID Compound Name Compound Formula
CP0340177
4-[(3S,4S)-3-(aminomethyl)-4-(4-chlorophenyl)sulfonyl-3-hydroxypyrrolidin-1-yl]sulfonyl-3-chlorobenzonitrile
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C18H17Cl2N3O5S2
 1
1
IC50 = 0.3 nM
   TI
   LI
   LO
   TS
CP0323255
4-[(3S,4S)-3-(aminomethyl)-4-(5-chloropyridin-2-yl)sulfonyl-3-hydroxypyrrolidin-1-yl]sulfonyl-3-chlorobenzonitrile
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C17H16Cl2N4O5S2
 1
1
IC50 = 0.5 nM
   TI
   LI
   LO
   TS
CP0340178
4-[(3R,4S)-3-(aminomethyl)-4-(5-chloropyridin-2-yl)sulfonyl-3-hydroxypyrrolidin-1-yl]sulfonyl-3-chlorobenzonitrile
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C17H16Cl2N4O5S2
 1
1
IC50 = 0.5 nM
   TI
   LI
   LO
   TS
CP0535240
4-[(3S,4R)-1-(2,4-dichlorophenyl)sulfonyl-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl]sulfonyl-2-fluorobenzonitrile
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C18H15Cl2FN2O6S2
 1
1
IC50 = 2 nM
   TI
   LI
   LO
   TS
CP0560780
5-chloro-2-[(3R,4S)-4-(4-cyanophenyl)sulfonyl-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile
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C19H16ClN3O6S2
 1
1
IC50 = 2 nM
   TI
   LI
   LO
   TS
CP0032823
3-chloro-4-[(3R,4S)-4-(4-chlorophenyl)sulfonyl-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile
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C18H16Cl2N2O6S2
 1
1
IC50 = 3.2 nM
   TI
   LI
   LO
   TS
CP0565341
3-chloro-4-[(3R,4S)-4-(4-cyanophenyl)sulfonyl-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile
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C19H16ClN3O6S2
 1
1
IC50 = 3.2 nM
   TI
   LI
   LO
   TS
CP0416896
3-chloro-4-[(3R,4S)-4-(5-chloropyridin-2-yl)sulfonyl-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile
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C17H15Cl2N3O6S2
 1
1
IC50 = 5 nM
   TI
   LI
   LO
   TS
CP0560111
3-chloro-4-[(3R,4S)-4-[(4-chlorophenyl)sulfonimidoyl]-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile
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C18H17Cl2N3O5S2
 1
1
IC50 = 20 nM
   TI
   LI
   LO
   TS
CP0573114
5-[(3R,4S)-4-(4-chlorophenyl)sulfonyl-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonyl-6-(trifluoromethyl)pyridine-2-carbonitrile
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C18H15ClF3N3O6S2
 1
1
IC50 = 20 nM
   TI
   LI
   LO
   TS
CP0517621
3-chloro-4-[[(3R,4S)-4-(4-chlorophenyl)sulfonyl-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonimidoyl]benzonitrile
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C18H17Cl2N3O5S2
 1
1
IC50 = 40 nM
   TI
   LI
   LO
   TS
CP0536343
5-[(3R,4S)-4-(4-chlorophenyl)sulfonyl-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylpyridine-2-carbonitrile
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C17H16ClN3O6S2
 1
1
IC50 = 631 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0140132
[6-[[4-(2,4-dimethyl-1,3-thiazol-5-yl)-1,3-thiazol-2-yl]amino]pyridin-3-yl]-[3-[5-(trifluoromethyl)pyrimidin-2-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]methanone
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C25H23F3N8OS2
 2
1 IC50 = 0.22 nM
2 IC50 = 0.4 nM
CP0307946
[3-(5-chloropyrimidin-2-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]-[6-[[4-(2,4-dimethyl-1,3-thiazol-5-yl)-1,3-thiazol-2-yl]amino]pyridin-3-yl]methanone
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C24H23ClN8OS2
 1
1 IC50 = 0.3 nM
CP0032823
3-chloro-4-[(3R,4S)-4-(4-chlorophenyl)sulfonyl-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl]sulfonylbenzonitrile
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C18H16Cl2N2O6S2
 1
1 IC50 = 3.2 nM
CP0180295
4-[[1-(2,4-dichlorophenyl)sulfonyl-3-hydroxyazetidin-3-yl]methoxy]-2-fluorobenzonitrile
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C17H13Cl2FN2O4S
 1
1 IC50 = 4 nM
CP0350860
2-methyl-1-(3-morpholin-4-ylpropyl)-5-phenyl-N-[3-(trifluoromethyl)phenyl]pyrrole-3-carboxamide
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C26H28F3N3O2
 3
1 IC50 = 18 nM
2 IC50 = 48 nM
3 IC50 = 57 nM
CP0180290
9-[6-[[4-(2,4-dimethyl-1,3-thiazol-5-yl)-1,3-thiazol-2-yl]amino]pyridine-3-carbonyl]-3-oxa-9-azabicyclo[3.3.1]nonan-7-one
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C21H21N5O3S2
 1
1 IC50 = 19 nM
CP0191222
8-[6-[[4-(2,4-dimethyl-1,3-thiazol-5-yl)-1,3-thiazol-2-yl]amino]pyridine-3-carbonyl]-8-azabicyclo[3.2.1]octan-3-one
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C21H21N5O2S2
 1
1 IC50 = 24 nM
CP0232506
5,6-dichloro-1-[1-[4-(2-cyanopropan-2-yl)phenyl]piperidin-4-yl]-N,N-dimethyl-2-(propan-2-ylamino)benzimidazole-4-carboxamide
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C28H34Cl2N6O
 1
1 IC50 = 32 nM
CP0113739
7-bromo-N-(1-phenylcyclopropyl)-3-[(4-piperidin-1-ylpiperidin-1-yl)methyl]-2-[3-(trifluoromethyl)phenyl]quinoline-4-carboxamide
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C37H38BrF3N4O
 1
1 IC50 = 40 nM
CP0315551
2,4-dichloro-N-propan-2-yl-N-[2-(propan-2-ylamino)ethyl]benzenesulfonamide
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C14H22Cl2N2O2S
 1
1 IC50 = 2300 nM
CP0243136
(1R,3R,4aR,7S,8R,8aR)-7-[(E)-but-2-en-2-yl]-3,6,8-trimethyl-8-(pyridine-3-carbonyl)-2,3,4,4a,7,8a-hexahydro-1H-naphthalene-1-carboxylic acid
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C24H31NO3
 1
1 IC50 = 81800 nM
Clinical Information about the Protein
Target 1 ( Transient receptor potential cation channel V4 (TRPV4) )
Target Type Clinical trial Target
Disease 1 Target-related Disease  1
1 Acute myeloid leukaemia [ICD-11: 2A60]
Clinical Trial Drug(s) 1 Clinical Trial Drug  1
1 phorbol 12-myristate 13-acetate Phase 2
Acute myeloid leukaemia