Transient receptor potential cation channel subfamily V member 4

UniProt Q9HBA0 Organism Homo sapiens Gene TRPV4, VRL2, VROAC

Also known as: TRPV4, VRL2, VROAC

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 (By similarity). 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 (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. 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 (By similarity).

Classification

Family (Pfam): PF00023 Ank, PF00520 Ion_trans
InterPro: Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ion_trans_dom, TRPV, TrpV1-4, TrpV4
Functional cluster: Translational GTPases (EF-Tu/EF-G)

Experimental structures · PDB · 19

4DX1 X-ray 2.85A
4DX2 X-ray 2.95A
7AA5 EM 4.18A
8FC7 EM 3.30A
8FC8 EM 3.47A
8FC9 EM 3.75A
8FCA EM 3.41A
8FCB EM 3.52A
8JU5 EM 3.74A
8JU6 EM 3.45A
8JVI EM 3.21A
8JVJ EM 3.44A
… and 7 more

A predicted model is available from AlphaFold.

Gene Ontology · 73

Disease associations

autosomal dominant brachyolmia MONDO:0007232
metatropic dysplasia MONDO:0007986
parastremmatic dwarfism MONDO:0008196
scapuloperoneal spinal muscular atrophy, autosomal dominant MONDO:0008408
spondyloepimetaphyseal dysplasia, Maroteaux type MONDO:0008473
spondylometaphyseal dysplasia, Kozlowski type MONDO:0008477
neuronopathy, distal hereditary motor, autosomal dominant 8 MONDO:0010839
Charcot-Marie-Tooth disease axonal type 2C MONDO:0011633
familial digital arthropathy-brachydactyly MONDO:0011732
OMIM:613508 RAW:OMIM_613508
avascular necrosis of femoral head, primary, 2 MONDO:0054551

Drugs targeting this protein · 3

BUTAMBEN inhibitor
BUTAMBEN PICRATE inhibitor
GSK2798745 antagonist

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Transient receptor potential cation channel subfamily V member 4 3 shared papers
Transient receptor potential cation channel subfamily V member 4 4 shared papers
Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 1 shared papers
Membrane protein MLC1 1 shared papers
Transient receptor potential cation channel subfamily V member 4 1 shared papers
ATP-dependent RNA helicase DDX3X 1 shared papers
Hepatic and glial cell adhesion molecule 1 shared papers
Aquaporin-4 1 shared papers
Serine/threonine-protein kinase WNK4 1 shared papers
Serine/threonine-protein kinase WNK1 1 shared papers
Sodium/potassium-transporting ATPase subunit beta-1 1 shared papers
Polycystin-2 1 shared papers

Literature · 30 cited papers

The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity. Nat. Commun. · 2018
Gain-of-function mutation in TRPV4 identified in patients with osteonecrosis of the femoral head. J. Med. Genet. · 2016
A mutation in TRPV4 results in altered chondrocyte calcium signaling in severe metatropic dysplasia. Am. J. Med. Genet. A · 2015
TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P. Nat. Commun. · 2014
An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci. Transl. Med. · 2012
Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel. Biochemistry · 2012
TRPV4 mutations in children with congenital distal spinal muscular atrophy. Neurogenetics · 2012
Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations. Hum. Mol. Genet. · 2012
Mutations in TRPV4 cause an inherited arthropathy of hands and feet. Nat. Genet. · 2011
TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies. Neurology · 2011
CMT2C with vocal cord paresis associated with short stature and mutations in the TRPV4 gene. Neurology · 2010
Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family. J. Med. Genet. · 2010
… and 18 more in the literature graph

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