General Information of Target

Target ID LDTP12168
Target Name Transient receptor potential cation channel subfamily V member 4 (TRPV4)
Gene Name TRPV4
Gene ID 59341
Synonyms
VRL2; VROAC; Transient receptor potential cation channel subfamily V member 4; TrpV4; Osm-9-like TRP channel 4; OTRPC4; Transient receptor potential protein 12; TRP12; Vanilloid receptor-like channel 2; Vanilloid receptor-like protein 2; VRL-2; Vanilloid receptor-related osmotically-activated channel; VR-OAC
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MATPDAGLPGAEGVEPAPWAQLEAPARLLLQALQAGPEGARRGLGVLRALGSRGWEPFDW
GRLLEALCREEPVVQGPDGRLELKPLLLRLPRICQRNLMSLLMAVRPSLPESGLLSVLQI
AQQDLAPDPDAWLRALGELLRRDLGVGTSMEGASPLSERCQRQLQSLCRGLGLGGRRLKS
PQAPDPEEEENRDSQQPGKRRKDSEEEAASPEGKRVPKRLRCWEEEEDHEKERPEHKSLE
SLADGGSASPIKDQPVMAVKTGEDGSNLDDAKGLAESLELPKAIQDQLPRLQQLLKTLEE
GLEGLEDAPPVELQLLHECSPSQMDLLCAQLQLPQLSDLGLLRLCTWLLALSPDLSLSNA
TVLTRSLFLGRILSLTSSASRLLTTALTSFCAKYTYPVCSALLDPVLQAPGTGPAQTELL
CCLVKMESLEPDAQVLMLGQILELPWKEETFLVLQSLLERQVEMTPEKFSVLMEKLCKKG
LAATTSMAYAKLMLTVMTKYQANITETQRLGLAMALEPNTTFLRKSLKAALKHLGP
Target Type
Clinical trial
Target Bioclass
Transporter and channel
Family
Transient receptor (TC 1.A.4) family, TrpV subfamily, TRPV4 sub-subfamily
Subcellular location
Endoplasmic reticulum; Cell membrane
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. Also activated by heat, low pH, citrate and phorbol esters . 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. Together with PKD2, forms mechano- and thermosensitive channels in cilium. Negatively regulates expression of PPARGC1A, UCP1, oxidative metabolism and respiration in adipocytes. Regulates expression of chemokines and cytokines related to pro-inflammatory pathway in adipocytes. Together with AQP5, controls regulatory volume decrease in salivary epithelial cells. Required for normal development and maintenance of bone and cartilage. 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. In neurons of the central nervous system, could play a role in triggering voluntary water intake in response to increased sodium concentration in body fluid.; [Isoform 1]: 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. Also activated by phorbol esters. Has the same channel activity as isoform 1, and is activated by the same stimuli.; [Isoform 5]: 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. Also activated by phorbol esters. Has the same channel activity as isoform 1, and is activated by the same stimuli.; [Isoform 2]: Lacks channel activity, due to impaired oligomerization and intracellular retention.; [Isoform 4]: Lacks channel activity, due to impaired oligomerization and intracellular retention.; [Isoform 6]: Lacks channel activity, due to impaired oligomerization and intracellular retention.; (Microbial infection) Facilitates hepatitis C virus (HCV) replication, possibly through its action on DDX3X.; (Microbial infection) Facilitates Dengue virus (DENV) replication, possibly through its action on DDX3X.; (Microbial infection) Facilitates Zika virus (ZIKV) replication, possibly through its action on DDX3X.
TTD ID
T64213
Uniprot ID
Q9HBA0
DrugMap ID
TTKP2SU
Ensemble ID
ENST00000261740.7
HGNC ID
HGNC:18083
ChEMBL ID
CHEMBL3119

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
22RV1 Insertion: p.Y281LfsTer53 .
CAL51 Insertion: p.I145HfsTer12 .
CHL1 SNV: p.S4F DBIA    Probe Info 
COLO320 SNV: p.S203N .
EGI1 SNV: p.R269L DBIA    Probe Info 
G361 SNV: p.D119N .
HCT15 SNV: p.Q267H .
HT115 SNV: p.D84N .
JURKAT SNV: p.M761T .
KYSE30 SNV: p.S630T .
L428 SNV: p.P844R .
LN18 SNV: p.A354V .
LNCaP clone FGC SNV: p.P99H .
MFE319 SNV: p.F108L .
MOLT4 SNV: p.R315L .
NCIH1666 SNV: p.P60Q .
OVK18 SNV: p.L752P .
RL952 Deletion: p.D21MfsTer49 .
WM793 SNV: p.E684K .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C853(1.16)  LDD3360  [1]
CY4
 Probe Info 
K344(0.00); D347(0.00); M345(0.00); Y346(0.00)  LDD0247  [2]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 A101D C853(3.23)  LDD2250  [1]
 LDCM0023  KB03 A101D C853(3.11)  LDD2667  [1]
 LDCM0024  KB05 NCI-H3122 C853(1.16)  LDD3360  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Transient receptor potential cation channel subfamily V member 4 (TRPV4) Transient receptor (TC 1.A.4) family Q9HBA0

The Drug(s) Related To This Target

Approved
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Cannabidiol Small molecular drug DB09061
Butamben . DB11148
Phase 2
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Phorbol 12-myristate 13-acetate Small molecular drug D09DHT
Gsk2798745 . D07HSR
Investigative
Click To Hide/Show 17 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
4-pyridin-2-yl-piperazine-1-carboxylic Acid Amide Small molecular drug D00ESG
4alpha-pdd Small molecular drug D09OHS
4alpha-pdh Small molecular drug D0J1SX
5'-iodoresiniferatoxin Small molecular drug D0N2QH
5,6-epoxyeicosatrienoic Acid Small molecular drug D0D5BI
Bisandrographolide Small molecular drug D02UVR
Capsazepine Small molecular drug D0G8BN
Citric Acid Small molecular drug D02RTS
Gsk1016790a Small molecular drug D03HJW
Gsk2193874 Small molecular drug D03LVL
Hc067047 Small molecular drug D0B1QM
Nabiximols Small molecular drug DB14011
Pyrrolidin-1-yl-thiourea Small molecular drug D03KQG
Rn1734 Small molecular drug D03OLU
Rn1747 Small molecular drug D0A5LY
Sc-0030 Small molecular drug D0X7AM
Medical Cannabis . DB14009

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.