Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

TRPV4 (Q9HBA0) - Overview - Molecular Target Synopsis

Protein


TRPV4, Transient receptor potential cation channel subfamily V member 4
UniProt Q9HBA0

Also Known as TRPV4_HUMAN, TRPV4, VRL2, VROAC

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). 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 proinflammatory 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)., 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. Homotetramer (Probable). Self-associates in an isoform-specific manner (PubMed:16293632). Isoform 1 and isoform 5 can oligomerize, but isoform 2, isoform 4 and isoform 6 cannnot oligomerize (PubMed:16293632). Interacts with calmodulin (PubMed:12724311). Interacts with Map7 and Src family Tyr protein kinases LYN, SRC, FYN, HCK, LCK and YES (By similarity). Interacts with CTNNB1 (By similarity). The TRPV4 and CTNNB1 complex can interact with CDH1 (By similarity). Interacts with PACSIN1, PACSIN2 and PACSIN3 (via SH3 domain) (By similarity). Part of a complex containing MLC1, AQP4, HEPACAM and ATP1B1 (PubMed:22328087). Interacts with ITPR3 (PubMed:18826956). Interacts with AQP5; the interaction is probably indirect and regulates TRPV4 activation by hypotonicity (By similarity). Interacts with ANO1 (By similarity). Interacts (via C-terminus) with PKD2 (via C-terminus) (PubMed:18695040).

4DX1
CRYSTAL STRUCTURE OF THE HUMAN TRPV4 ANKYRIN REPEAT DOMAIN
RCSB/PDB
Inspect Structure
See all 3D Structures for TRPV4

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: TRPV4 is active in the following subcellular-locations: adherens junction, apical cell membrane, cell junction, cell membrane, cell projection, cilium, endoplasmic reticulum.
GO terms: TRPV4 is active in the following subcellular-locations: adherens junction, apical plasma membrane, cell surface, cilium, cortical actin cytoskeleton, cytoplasmic microtubule, cytoplasmic vesicle, endoplasmic reticulum, filopodium, focal adhesion, growth cone, integral component of membrane, integral component of plasma membrane, lamellipodium, plasma membrane, ruffle membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project TRPV4 has gain in 1 cell-lines, loss in 0 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MALME_3M, MCF7, M14

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SK-MEL-24, COLO-818, MeWo

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HUVEC, HMEC, SK-N-SH

(see details)

3D Structures


For TRPV4 there are:
2 structures (4 chains) solved
1 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

TRPV4 is solved in complex with the approved drug(s):

BGC/DEXTROSE (4DX2_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


TRPV4 has been screened with 428 compounds (526 bioactivities), 162 compounds have bioactivities that show binding affinity of <= 500nM (190 bioactivities). (see details)