Trpv4
Domain
The ANK repeat region mediates interaction with Ca(2+)-calmodulin and ATP binding. The ANK repeat region mediates interaction with phosphatidylinositol-4,5-bisphosphate and related phosphatidylinositides.
Function
Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity (PubMed:11094154, PubMed:12093812, PubMed:12538589). Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:12093812, PubMed:14691263, PubMed:16368742, PubMed:16571723). Also activated by heat, low pH, citrate and phorbol esters (PubMed:14691263). Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism (By similarity). Acts as a regulator of intracellular Ca(2+) in synoviocytes (By similarity). 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 (By similarity). Together with PKD2, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers (PubMed:20413591). Negatively regulates expression of PPARGC1A, UCP1, oxidative metabolism and respiration in adipocytes (PubMed:23021218). Regulates expression of chemokines and cytokines related to pro-inflammatory pathway in adipocytes (PubMed:23021218). Together with AQP5, controls regulatory volume decrease in salivary epithelial cells (PubMed:16571723). Required for normal development and maintenance of bone and cartilage (By similarity). 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 (By similarity). 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 (PubMed:27252474).
Post-translational modifications
N-glycosylated.
Sequence Similarities
Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV4 sub-subfamily.
Tissue Specificity
Detected in liver, kidney, heart, brain cortex, cerebellum and brainstem (at protein level). Expressed in salivary glands (at protein level) (PubMed:16571723). Expressed in heart, lung, spleen, liver, kidney, brain, skeletal muscle and testis. In the central nervous system, expressed in the lamina terminalis (arched vascular organ and neurons of the subfornical organ), median preoptic area, ventral hippocampal commissure, and ependymal cells of the choroid plexus. In the cochlea, expressed in both inner and outer hair cells, and in marginal cells of the cochlear stria vascularis. Expressed in large neurons of the trigeminal ganglion. In the kidney cortex, strongly expressed by epithelial cells of tubules and much weaker in glomeruli.
Cellular localization
- Cell membrane
- Apical cell membrane
- Multi-pass membrane protein
- Cell junction
- Adherens junction
- Cell projection
- Cilium
- Assembly of the putative homotetramer occurs primarily in the endoplasmic reticulum. Localization to the cell membrane is inhibited by WNK kinases (WNK1, WNK2, WNK3 or WNK4) in a kinase-independent mechanism.
Alternative names
Trp12, Vrl2, Vroac, Trpv4, Transient receptor potential cation channel subfamily V member 4, TrpV4, 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, OTRPC4, TRP12, VR-OAC