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Showing Protein Transient receptor potential cation channel subfamily V member 4 (HMDBP14024)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 0 metabolites
Identification
HMDB Protein ID HMDBP14024
Secondary Accession Numbers None
Name Transient receptor potential cation channel subfamily V member 4
Synonyms
  1. TrpV4
  2. Osm-9-like TRP channel 4
  3. Transient receptor potential protein 12
  4. Vanilloid receptor-like channel 2
  5. Vanilloid receptor-like protein 2
  6. Vanilloid receptor-related osmotically-activated channel
  7. OTRPC4
  8. TRP12
  9. VR-OAC
Gene Name TRPV4
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity (PubMed:11094154). 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 proinflammatory 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).
Pathways
  • Cellular senescence
  • Fluid shear stress and atherosclerosis
  • Inflammatory mediator regulation of TRP channels
Reactions Not Available
GO Classification
Biological Process
calcium ion import across plasma membrane
negative regulation of neuron projection development
cellular response to heat
positive regulation of JNK cascade
response to osmotic stress
positive regulation of vascular permeability
positive regulation of interleukin-6 production
cellular hypotonic response
positive regulation of monocyte chemotactic protein-1 production
energy homeostasis
regulation of aerobic respiration
vasopressin secretion
osmosensory signaling pathway
positive regulation of macrophage inflammatory protein 1 alpha production
blood vessel endothelial cell delamination
positive regulation of inflammatory response
calcium ion import into cytosol
cell-cell junction assembly
cellular hypotonic salinity response
cortical microtubule organization
diet induced thermogenesis
hyperosmotic salinity response
hypotonic response
microtubule polymerization
multicellular organismal water homeostasis
negative regulation of brown fat cell differentiation
positive regulation of chemokine (C-X-C motif) ligand 1 production
positive regulation of macrophage chemotaxis
positive regulation of microtubule depolymerization
regulation of response to osmotic stress
positive regulation of gene expression
response to insulin stimulus
cartilage development involved in endochondral bone morphogenesis
actin cytoskeleton reorganization
cellular calcium ion homeostasis
calcium ion import
positive regulation of striated muscle contraction
elevation of cytosolic calcium ion concentration
calcium ion transmembrane transport
negative regulation of transcription from RNA polymerase II promoter
actin filament organization
positive regulation of ERK1 and ERK2 cascade
glucose homeostasis
calcium ion transport
cellular response to osmotic stress
positive regulation of chemokine (C-C motif) ligand 5 production
Cellular Component
plasma membrane
growth cone
cilium
apical plasma membrane
cell surface
integral to plasma membrane
ruffle membrane
cytoplasmic microtubule
focal adhesion
cytoplasmic vesicle
cortical actin cytoskeleton
lamellipodium
filopodium
adherens junction
Molecular Function
actin binding
ATP binding
identical protein binding
microtubule binding
calmodulin binding
metal ion binding
protein kinase binding
lipid binding
alpha-tubulin binding
cation channel activity
stretch-activated, cation-selective, calcium channel activity
osmosensor activity
beta-tubulin binding
calcium channel activity
SH2 domain binding
actin filament binding
ion channel activity
protein kinase C binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 871
Molecular Weight 98025.76
Theoretical pI 7.33
Pfam Domain Function
Signals Not Available
Transmembrane Regions
  • 470-490;508-534;548-568;573-593;609-636;694-722;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q9EPK8
UniProtKB/Swiss-Prot Entry Name TRPV4_MOUSE
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Liedtke W, Choe Y, Marti-Renom MA, Bell AM, Denis CS, Sali A, Hudspeth AJ, Friedman JM, Heller S: Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell. 2000 Oct 27;103(3):525-35. [PubMed:11081638 ]
  3. Strotmann R, Harteneck C, Nunnenmacher K, Schultz G, Plant TD: OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat Cell Biol. 2000 Oct;2(10):695-702. [PubMed:11025659 ]
  4. Suzuki M, Mizuno A, Kodaira K, Imai M: Impaired pressure sensation in mice lacking TRPV4. J Biol Chem. 2003 Jun 20;278(25):22664-8. Epub 2003 Apr 13. [PubMed:12692122 ]
  5. Peng H, Lewandrowski U, Muller B, Sickmann A, Walz G, Wegierski T: Identification of a Protein Kinase C-dependent phosphorylation site involved in sensitization of TRPV4 channel. Biochem Biophys Res Commun. 2010 Jan 22;391(4):1721-5. doi: 10.1016/j.bbrc.2009.12.140. Epub 2009 Dec 30. [PubMed:20043876 ]
  6. Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP: A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010 Dec 23;143(7):1174-89. doi: 10.1016/j.cell.2010.12.001. [PubMed:21183079 ]
  7. Wissenbach U, Bodding M, Freichel M, Flockerzi V: Trp12, a novel Trp related protein from kidney. FEBS Lett. 2000 Nov 24;485(2-3):127-34. doi: 10.1016/s0014-5793(00)02212-2. [PubMed:11094154 ]
  8. Voets T, Prenen J, Vriens J, Watanabe H, Janssens A, Wissenbach U, Bodding M, Droogmans G, Nilius B: Molecular determinants of permeation through the cation channel TRPV4. J Biol Chem. 2002 Sep 13;277(37):33704-10. doi: 10.1074/jbc.M204828200. Epub 2002 Jul 1. [PubMed:12093812 ]
  9. Suzuki M, Hirao A, Mizuno A: Microtubule-associated [corrected] protein 7 increases the membrane expression of transient receptor potential vanilloid 4 (TRPV4). J Biol Chem. 2003 Dec 19;278(51):51448-53. doi: 10.1074/jbc.M308212200. Epub 2003 Sep 28. [PubMed:14517216 ]
  10. Xu H, Zhao H, Tian W, Yoshida K, Roullet JB, Cohen DM: Regulation of a transient receptor potential (TRP) channel by tyrosine phosphorylation. SRC family kinase-dependent tyrosine phosphorylation of TRPV4 on TYR-253 mediates its response to hypotonic stress. J Biol Chem. 2003 Mar 28;278(13):11520-7. doi: 10.1074/jbc.M211061200. Epub 2003 Jan 21. [PubMed:12538589 ]
  11. Xu H, Fu Y, Tian W, Cohen DM: Glycosylation of the osmoresponsive transient receptor potential channel TRPV4 on Asn-651 influences membrane trafficking. Am J Physiol Renal Physiol. 2006 May;290(5):F1103-9. doi: 10.1152/ajprenal.00245.2005. Epub 2005 Dec 20. [PubMed:16368742 ]
  12. Liu X, Bandyopadhyay BC, Nakamoto T, Singh B, Liedtke W, Melvin JE, Ambudkar I: A role for AQP5 in activation of TRPV4 by hypotonicity: concerted involvement of AQP5 and TRPV4 in regulation of cell volume recovery. J Biol Chem. 2006 Jun 2;281(22):15485-95. doi: 10.1074/jbc.M600549200. Epub 2006 Mar 29. [PubMed:16571723 ]
  13. Cuajungco MP, Grimm C, Oshima K, D'hoedt D, Nilius B, Mensenkamp AR, Bindels RJ, Plomann M, Heller S: PACSINs bind to the TRPV4 cation channel. PACSIN 3 modulates the subcellular localization of TRPV4. J Biol Chem. 2006 Jul 7;281(27):18753-62. doi: 10.1074/jbc.M602452200. Epub 2006 Apr 20. [PubMed:16627472 ]
  14. Kottgen M, Buchholz B, Garcia-Gonzalez MA, Kotsis F, Fu X, Doerken M, Boehlke C, Steffl D, Tauber R, Wegierski T, Nitschke R, Suzuki M, Kramer-Zucker A, Germino GG, Watnick T, Prenen J, Nilius B, Kuehn EW, Walz G: TRPP2 and TRPV4 form a polymodal sensory channel complex. J Cell Biol. 2008 Aug 11;182(3):437-47. doi: 10.1083/jcb.200805124. [PubMed:18695040 ]
  15. Wegierski T, Lewandrowski U, Muller B, Sickmann A, Walz G: Tyrosine phosphorylation modulates the activity of TRPV4 in response to defined stimuli. J Biol Chem. 2009 Jan 30;284(5):2923-2933. doi: 10.1074/jbc.M805357200. Epub 2008 Nov 25. [PubMed:19033444 ]
  16. Ye L, Kleiner S, Wu J, Sah R, Gupta RK, Banks AS, Cohen P, Khandekar MJ, Bostrom P, Mepani RJ, Laznik D, Kamenecka TM, Song X, Liedtke W, Mootha VK, Puigserver P, Griffin PR, Clapham DE, Spiegelman BM: TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis. Cell. 2012 Sep 28;151(1):96-110. doi: 10.1016/j.cell.2012.08.034. [PubMed:23021218 ]
  17. Takayama Y, Shibasaki K, Suzuki Y, Yamanaka A, Tominaga M: Modulation of water efflux through functional interaction between TRPV4 and TMEM16A/anoctamin 1. FASEB J. 2014 May;28(5):2238-48. doi: 10.1096/fj.13-243436. Epub 2014 Feb 7. [PubMed:24509911 ]
  18. Sokabe T, Fukumi-Tominaga T, Yonemura S, Mizuno A, Tominaga M: The TRPV4 channel contributes to intercellular junction formation in keratinocytes. J Biol Chem. 2010 Jun 11;285(24):18749-58. doi: 10.1074/jbc.M110.103606. Epub 2010 Apr 22. [PubMed:20413591 ]