TRPV4

TRPV4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4DX1, 4DX2
Identifiers
Aliases	TRPV4, BCYM3, CMT2C, HMSN2C, OTRPC4, SMAL, SPSMA, SSQTL1, TRP12, VRL2, VROAC, transient receptor potential cation channel subfamily V member 4
External IDs	OMIM: 605427; MGI: 1926945; HomoloGene: 11003; GeneCards: TRPV4; OMA:TRPV4 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q24.11 Start 109,783,087 bp[1] End 109,833,406 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 F Start 114,760,213 bp[2] End 114,796,482 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cartilage tissue olfactory zone of nasal mucosa minor salivary glands stromal cell of endometrium oocyte testicle human kidney tibia bronchial epithelial cell skin of abdomen Top expressed in right kidney intervertebral disk of lumbar vertebra proximal tubule intervertebral disk of cervical vertebra intervertebral disk of thoracic vertebra Epithelium of choroid plexus human kidney stroma of bone marrow Dermatocranium facial skeleton More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding stretch-activated, cation-selective, calcium channel activity osmosensor activity microtubule binding alpha-tubulin binding SH2 domain binding calmodulin binding actin filament binding ion channel activity protein binding beta-tubulin binding cation channel activity actin binding ATP binding protein kinase binding protein kinase C binding calcium channel activity lipid binding identical protein binding metal ion binding Cellular component integral component of membrane cell projection membrane focal adhesion filopodium growth cone adherens junction plasma membrane ruffle membrane cell surface cell junction apical plasma membrane cortical actin cytoskeleton cytoplasmic microtubule cytoplasmic vesicle lamellipodium integral component of plasma membrane cilium endoplasmic reticulum Biological process actin cytoskeleton reorganization cell volume homeostasis cellular response to heat positive regulation of inflammatory response negative regulation of neuron projection development glucose homeostasis cellular hypotonic salinity response positive regulation of chemokine (C-X-C motif) ligand 1 production positive regulation of cytosolic calcium ion concentration calcium ion import positive regulation of monocyte chemotactic protein-1 production response to mechanical stimulus negative regulation of brown fat cell differentiation osmosensory signaling pathway cellular calcium ion homeostasis hyperosmotic salinity response microtubule polymerization negative regulation of transcription by RNA polymerase II positive regulation of JNK cascade cellular hypotonic response ion transport vasopressin secretion cellular response to osmotic stress regulation of response to osmotic stress diet induced thermogenesis response to osmotic stress response to insulin positive regulation of gene expression positive regulation of vascular permeability calcium ion transmembrane transport cortical microtubule organization positive regulation of chemokine (C-C motif) ligand 5 production cell-cell junction assembly positive regulation of ERK1 and ERK2 cascade hypotonic response positive regulation of macrophage inflammatory protein 1 alpha production blood vessel endothelial cell delamination multicellular organismal water homeostasis positive regulation of macrophage chemotaxis calcium ion transport positive regulation of microtubule depolymerization actin filament organization transmembrane transport cartilage development involved in endochondral bone morphogenesis energy homeostasis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 59341 63873 Ensembl ENSG00000111199 ENSMUSG00000014158 UniProt Q9HBA0 Q9EPK8 RefSeq (mRNA) NM_001177428 NM_001177431 NM_001177433 NM_021625 NM_147204 NM_022017 RefSeq (protein) NP_001170899 NP_001170902 NP_001170904 NP_067638 NP_671737 NP_071300 Location (UCSC) Chr 12: 109.78 – 109.83 Mb Chr 5: 114.76 – 114.8 Mb PubMed search [3] [4]
Wikidata
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Transient receptor potential cation channel subfamily V member 4 is an ion channel protein that in humans is encoded by the TRPV4 gene.

The TRPV4 gene encodes TRPV4, initially named "vanilloid-receptor related osmotically activated channel" (VR-OAC) and "OSM9-like transient receptor potential channel, member 4 (OTRPC4)",^[5][6] a member of the vanilloid subfamily in the transient receptor potential (TRP) superfamily of ion channels.^[7][8][9] The encoded protein is a Ca²⁺-permeable, nonselective cation channel that has been found involved in multiple physiologic functions, dysfunctions and also disease. It functions in the regulation of systemic osmotic pressure by the brain, in vascular function, in liver, intestinal, renal and bladder function, in skin barrier function and response of the skin to ultraviolet-B radiation, in growth and structural integrity of the skeleton, in function of joints, in airway- and lung function, in retinal and inner ear function, and in pain. The channel is activated by osmotic, mechanical and chemical cues. It also responds to thermal changes (warmth). Channel activation can be sensitized by inflammation and injury.

The TRPV4 gene has been co-discovered by W. Liedtke et al.^[5] and R. Strotmann et al.^[6]

Channelopathy mutations in the TRPV4 gene lead to skeletal dysplasias, premature osteoarthritis, and neurological motor function disorders and are associated with a range of disorders, including brachyolmia type 3, congenital distal spinal muscular atrophy, Familial digital arthropathy-brachydactyly (FDAB),^[10] scapuloperoneal spinal muscular atrophy, and subtype 2C of Charcot–Marie–Tooth disease.^[11]

A number of TRPV4 agonists and antagonists have been identified since its discovery.^[12] The discovery of unselective modulators (e.g. antagonist ruthenium red) was followed by the apparition of more potent (agonist 4aPDD)^[13] or selective (antagonist RN-1734)^[14] compounds, including some with bioavailability suitable for in vivo pharmacology studies such as agonist GSK1016790A^[15] (with ~10 fold selectivity vs TRPV1), and antagonists HC-067047^[16] (with ~5 fold selectivity vs hERG and ~10 fold selectivity vs TRPM8) and RN-9893^[17] (with ~50 fold selectivity vs TRPM8 and ~10 fold selectivity vs M1).

Resolvin D1 (RvD1), a metabolite of the omega 3 fatty acid, docosahexaenoic acid, is a member of the specialized proresolving mediators (SPMs) class of metabolites that function to resolve diverse inflammatory reactions and diseases in animal models and, it is proposed, humans. This SPM also dampens pain perception arising from various inflammation-based causes in animal models. The mechanism behind this pain-dampening effect involves the inhibition of TRPV4, probably (in at least certain cases) by an indirect effect wherein it activates another receptor located on neurons or nearby microglia or astrocytes. CMKLR1, GPR32, FPR2, and NMDA receptors have been proposed to be the receptors through which a SPM may operate to down-regulate TRPs and thereby pain perception.^{[18][19][20][21][22]}

TRPV4 has been shown to interact with MAP7^[23] and LYN.^[24]

TRPV4 has been proposed to be the thermal sensor in gonads of Alligator mississipiensis, a species with temperature-dependent sex determination.^[25] However the data were over interpreted and TRPV4 is probably not involved in temperature-dependent sex determination due to large overlap of expression at male producing temperature and female producing temperature for example.

• TRPV

• GeneReviews/NCBI/NIH/UW entry on Charcot-Marie-Tooth Neuropathy Type 2
• TRPV4+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.