ID TRPV4_MOUSE Reviewed; 871 AA. AC Q9EPK8; A0JNY0; Q91XR5; Q9EQZ4; Q9ERZ7; Q9ES76; DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 27-MAR-2024, entry version 175. DE RecName: Full=Transient receptor potential cation channel subfamily V member 4; DE Short=TrpV4; DE AltName: Full=Osm-9-like TRP channel 4; DE Short=OTRPC4; DE AltName: Full=Transient receptor potential protein 12; DE Short=TRP12; DE AltName: Full=Vanilloid receptor-like channel 2; DE AltName: Full=Vanilloid receptor-like protein 2; DE AltName: Full=Vanilloid receptor-related osmotically-activated channel {ECO:0000303|PubMed:11081638}; DE Short=VR-OAC {ECO:0000303|PubMed:11081638}; GN Name=Trpv4; Synonyms=Trp12, Vrl2, Vroac; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Hypothalamus; RX PubMed=11081638; DOI=10.1016/s0092-8674(00)00143-4; RA Liedtke W.B., Choe Y., Marti-Renom M.A., Bell A.M., Denis C.S., Sali A., RA Hudspeth A.J., Friedman J.M., Heller S.; RT "Vanilloid receptor-related osmotically activated channel (VR-OAC), a RT candidate vertebrate osmoreceptor."; RL Cell 103:525-535(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR RP LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Kidney; RX PubMed=11094154; DOI=10.1016/s0014-5793(00)02212-2; RA Wissenbach U., Boedding M., Freichel M., Flockerzi V.; RT "Trp12, a novel Trp related protein from kidney."; RL FEBS Lett. 485:127-134(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC STRAIN=129/SvEv; RX PubMed=11025659; DOI=10.1038/35036318; RA Strotmann R., Harteneck C., Nunnenmacher K., Schultz G., Plant T.D.; RT "OTRPC4, a nonselective cation channel that confers sensitivity to RT extracellular osmolarity."; RL Nat. Cell Biol. 2:695-702(2000). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Kidney; RX PubMed=12692122; DOI=10.1074/jbc.m302561200; RA Suzuki M., Mizuno A., Kodaira K., Imai M.; RT "Impaired pressure sensation in mice lacking TRPV4."; RL J. Biol. Chem. 278:22664-22668(2003). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Kidney; RA Derst C., Schafer M.K.; RT "Cloning of mouse and human vanilloid receptor-like protein 2 (VRL-2)."; RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP ASP-672; LYS-675; MET-680 AND ASP-682. RX PubMed=12093812; DOI=10.1074/jbc.m204828200; RA Voets T., Prenen J., Vriens J., Watanabe H., Janssens A., Wissenbach U., RA Bodding M., Droogmans G., Nilius B.; RT "Molecular determinants of permeation through the cation channel TRPV4."; RL J. Biol. Chem. 277:33704-33710(2002). RN [8] RP INTERACTION WITH MAP7. RX PubMed=14517216; DOI=10.1074/jbc.m308212200; RA Suzuki M., Hirao A., Mizuno A.; RT "Microtubule-associated protein 7 increases the membrane expression of RT transient receptor potential vanilloid 4 (TRPV4)."; RL J. Biol. Chem. 278:51448-51453(2003). RN [9] RP FUNCTION, TRANSPORTER ACTIVITY, INTERACTION WITH LYN; SRC; FYN; HCK; LCK RP AND YES, PHOSPHORYLATION AT TYR-253, AND MUTAGENESIS OF TYR-253. RX PubMed=12538589; DOI=10.1074/jbc.m211061200; RA Xu H., Zhao H., Tian W., Yoshida K., Roullet J.B., Cohen D.M.; RT "Regulation of a transient receptor potential (TRP) channel by tyrosine RT phosphorylation. SRC family kinase-dependent tyrosine phosphorylation of RT TRPV4 on TYR-253 mediates its response to hypotonic stress."; RL J. Biol. Chem. 278:11520-11527(2003). RN [10] RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP TYR-253; TYR-556 AND SER-557. RX PubMed=14691263; DOI=10.1073/pnas.0303329101; RA Vriens J., Watanabe H., Janssens A., Droogmans G., Voets T., Nilius B.; RT "Cell swelling, heat, and chemical agonists use distinct pathways for the RT activation of the cation channel TRPV4."; RL Proc. Natl. Acad. Sci. U.S.A. 101:396-401(2004). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASN-651, AND GLYCOSYLATION RP AT ASN-651. RX PubMed=16368742; DOI=10.1152/ajprenal.00245.2005; RA Xu H., Fu Y., Tian W., Cohen D.M.; RT "Glycosylation of the osmoresponsive transient receptor potential channel RT TRPV4 on Asn-651 influences membrane trafficking."; RL Am. J. Physiol. 290:F1103-F1109(2006). RN [12] RP FUNCTION, INTERACTION WITH AQP5, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP AND DISRUPTION PHENOTYPE. RX PubMed=16571723; DOI=10.1074/jbc.m600549200; RA Liu X., Bandyopadhyay B.C., Bandyopadhyay B., Nakamoto T., Singh B., RA Liedtke W., Melvin J.E., Ambudkar I.; RT "A role for AQP5 in activation of TRPV4 by hypotonicity: concerted RT involvement of AQP5 and TRPV4 in regulation of cell volume recovery."; RL J. Biol. Chem. 281:15485-15495(2006). RN [13] RP SUBCELLULAR LOCATION, INTERACTION WITH PACSIN1; PACSIN2 AND PACSIN3, RP MUTAGENESIS OF 142-PRO-PRO-143, AND TISSUE SPECIFICITY. RX PubMed=16627472; DOI=10.1074/jbc.m602452200; RA Cuajungco M.P., Grimm C., Oshima K., D'hoedt D., Nilius B., RA Mensenkamp A.R., Bindels R.J., Plomann M., Heller S.; RT "PACSINs bind to the TRPV4 cation channel. PACSIN 3 modulates the RT subcellular localization of TRPV4."; RL J. Biol. Chem. 281:18753-18762(2006). RN [14] RP FUNCTION, AND INTERACTION WITH PACSIN3. RX PubMed=18174177; DOI=10.1074/jbc.m706386200; RA D'hoedt D., Owsianik G., Prenen J., Cuajungco M.P., Grimm C., Heller S., RA Voets T., Nilius B.; RT "Stimulus-specific modulation of the cation channel TRPV4 by PACSIN 3."; RL J. Biol. Chem. 283:6272-6280(2008). RN [15] RP FUNCTION, INTERACTION WITH PKD2, AND SUBCELLULAR LOCATION. RX PubMed=18695040; DOI=10.1083/jcb.200805124; RA Kottgen M., Buchholz B., Garcia-Gonzalez M.A., Kotsis F., Fu X., RA Doerken M., Boehlke C., Steffl D., Tauber R., Wegierski T., Nitschke R., RA Suzuki M., Kramer-Zucker A., Germino G.G., Watnick T., Prenen J., RA Nilius B., Kuehn E.W., Walz G.; RT "TRPP2 and TRPV4 form a polymodal sensory channel complex."; RL J. Cell Biol. 182:437-447(2008). RN [16] RP PHOSPHORYLATION AT TYR-110 AND TYR-805, AND MUTAGENESIS OF TYR-110 AND RP TYR-805. RX PubMed=19033444; DOI=10.1074/jbc.m805357200; RA Wegierski T., Lewandrowski U., Muller B., Sickmann A., Walz G.; RT "Tyrosine phosphorylation modulates the activity of TRPV4 in response to RT defined stimuli."; RL J. Biol. Chem. 284:2923-2933(2009). RN [17] RP TRANSPORTER ACTIVITY, PHOSPHORYLATION AT SER-824, AND MUTAGENESIS OF RP SER-824. RX PubMed=20043876; DOI=10.1016/j.bbrc.2009.12.140; RA Peng H., Lewandrowski U., Muller B., Sickmann A., Walz G., Wegierski T.; RT "Identification of a protein kinase C-dependent phosphorylation site RT involved in sensitization of TRPV4 channel."; RL Biochem. Biophys. Res. Commun. 391:1721-1725(2010). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Kidney; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [19] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=23021218; DOI=10.1016/j.cell.2012.08.034; RA Ye L., Kleiner S., Wu J., Sah R., Gupta R.K., Banks A.S., Cohen P., RA Khandekar M.J., Bostrom P., Mepani R.J., Laznik D., Kamenecka T.M., RA Song X., Liedtke W., Mootha V.K., Puigserver P., Griffin P.R., RA Clapham D.E., Spiegelman B.M.; RT "TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and RT energy homeostasis."; RL Cell 151:96-110(2012). RN [20] RP INTERACTION WITH ANO1, AND SUBCELLULAR LOCATION. RX PubMed=24509911; DOI=10.1096/fj.13-243436; RA Takayama Y., Shibasaki K., Suzuki Y., Yamanaka A., Tominaga M.; RT "Modulation of water efflux through functional interaction between TRPV4 RT and TMEM16A/anoctamin 1."; RL FASEB J. 28:2238-2248(2014). RN [21] RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND INTERACTION WITH RP CTNBB1 AND CDH1. RX PubMed=20413591; DOI=10.1074/jbc.m110.103606; RA Sokabe T., Fukumi-Tominaga T., Yonemura S., Mizuno A., Tominaga M.; RT "The TRPV4 channel contributes to intercellular junction formation in RT keratinocytes."; RL J. Biol. Chem. 285:18749-18758(2010). RN [22] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=27252474; DOI=10.1152/ajpregu.00352.2015; RA Sakuta H., Nishihara E., Hiyama T.Y., Lin C.H., Noda M.; RT "Nax signaling evoked by an increase in [Na+] in CSF induces water intake RT via EET-mediated TRPV4 activation."; RL Am. J. Physiol. 311:R299-R306(2016). CC -!- FUNCTION: Non-selective calcium permeant cation channel involved in CC osmotic sensitivity and mechanosensitivity (PubMed:11094154, CC PubMed:12093812, PubMed:12538589). Activation by exposure to CC hypotonicity within the physiological range exhibits an outward CC rectification (PubMed:12093812, PubMed:14691263, PubMed:16368742, CC PubMed:16571723). Also activated by heat, low pH, citrate and phorbol CC esters (PubMed:14691263). Increase of intracellular Ca(2+) potentiates CC currents. Channel activity seems to be regulated by a calmodulin- CC dependent mechanism with a negative feedback mechanism (By similarity). CC Acts as a regulator of intracellular Ca(2+) in synoviocytes (By CC similarity). Plays an obligatory role as a molecular component in the CC nonselective cation channel activation induced by 4-alpha-phorbol CC 12,13-didecanoate and hypotonic stimulation in synoviocytes and also CC regulates production of IL-8 (By similarity). Together with PKD2, forms CC mechano- and thermosensitive channels in cilium (PubMed:18695040). CC Promotes cell-cell junction formation in skin keratinocytes and plays CC an important role in the formation and/or maintenance of functional CC intercellular barriers (PubMed:20413591). Negatively regulates CC expression of PPARGC1A, UCP1, oxidative metabolism and respiration in CC adipocytes (PubMed:23021218). Regulates expression of chemokines and CC cytokines related to pro-inflammatory pathway in adipocytes CC (PubMed:23021218). Together with AQP5, controls regulatory volume CC decrease in salivary epithelial cells (PubMed:16571723). Required for CC normal development and maintenance of bone and cartilage (By CC similarity). In its inactive state, may sequester DDX3X at the plasma CC membrane. When activated, the interaction between both proteins is CC affected and DDX3X relocalizes to the nucleus (By similarity). In CC neurons of the central nervous system, could play a role in triggering CC voluntary water intake in response to increased sodium concentration in CC body fluid (PubMed:27252474). {ECO:0000250|UniProtKB:Q9HBA0, CC ECO:0000269|PubMed:11094154, ECO:0000269|PubMed:12093812, CC ECO:0000269|PubMed:12538589, ECO:0000269|PubMed:14691263, CC ECO:0000269|PubMed:16368742, ECO:0000269|PubMed:16571723, CC ECO:0000269|PubMed:18174177, ECO:0000269|PubMed:18695040, CC ECO:0000269|PubMed:20413591, ECO:0000269|PubMed:23021218, CC ECO:0000269|PubMed:27252474}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671, CC ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:11094154, CC ECO:0000269|PubMed:12093812, ECO:0000269|PubMed:12538589, CC ECO:0000269|PubMed:14691263}; CC -!- SUBUNIT: Homotetramer. Interacts with calmodulin (By similarity). CC Interacts with CTNNB1 (PubMed:20413591). The TRPV4 and CTNNB1 complex CC can interact with CDH1 (PubMed:20413591). Part of a complex containing CC MLC1, AQP4, HEPACAM and ATP1B1 (By similarity). Interacts with MAP7 and CC Src family Tyr protein kinases LYN, SRC, FYN, HCK, LCK and YES CC (PubMed:14517216, PubMed:12538589). Interacts with PACSIN1, PACSIN2 and CC PACSIN3 (via SH3 domain) (PubMed:16627472, PubMed:18174177). Interacts CC with ITPR3 (By similarity). Interacts with AQP5; the interaction is CC probably indirect and regulates TRPV4 activation by hypotonicity CC (PubMed:16571723). Interacts with ANO1 (PubMed:24509911). Interacts CC (via C-terminus) with PKD2 (via C-terminus) (PubMed:18695040). CC Interacts with DDX3X; this interaction is decreased when the channel is CC activated (By similarity). {ECO:0000250|UniProtKB:Q9HBA0, CC ECO:0000269|PubMed:12538589, ECO:0000269|PubMed:14517216, CC ECO:0000269|PubMed:16571723, ECO:0000269|PubMed:16627472, CC ECO:0000269|PubMed:18174177, ECO:0000269|PubMed:18695040, CC ECO:0000269|PubMed:20413591, ECO:0000269|PubMed:24509911}. CC -!- INTERACTION: CC Q9EPK8; P55088: Aqp4; NbExp=2; IntAct=EBI-7091763, EBI-6273066; CC Q9EPK8; Q13563: PKD2; Xeno; NbExp=11; IntAct=EBI-7091763, EBI-7813714; CC Q9EPK8; P48995: TRPC1; Xeno; NbExp=10; IntAct=EBI-7091763, EBI-929665; CC Q9EPK8; P0CG48: UBC; Xeno; NbExp=3; IntAct=EBI-7091763, EBI-3390054; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11094154, CC ECO:0000269|PubMed:14691263, ECO:0000269|PubMed:16571723, CC ECO:0000269|PubMed:16627472, ECO:0000269|PubMed:20413591, CC ECO:0000269|PubMed:24509911}. Apical cell membrane CC {ECO:0000269|PubMed:14691263, ECO:0000269|PubMed:16571723, CC ECO:0000269|PubMed:16627472, ECO:0000269|PubMed:24509911, CC ECO:0000305|PubMed:12093812, ECO:0000305|PubMed:16368742}; Multi-pass CC membrane protein {ECO:0000250|UniProtKB:Q9HBA0}. Cell junction, CC adherens junction {ECO:0000269|PubMed:20413591}. Cell projection, CC cilium {ECO:0000269|PubMed:18695040}. Note=Assembly of the putative CC homotetramer occurs primarily in the endoplasmic reticulum. CC Localization to the cell membrane is inhibited by WNK kinases (WNK1, CC WNK2, WNK3 or WNK4) in a kinase-independent mechanism. CC {ECO:0000250|UniProtKB:Q9HBA0}. CC -!- TISSUE SPECIFICITY: Detected in liver, kidney, heart, brain cortex, CC cerebellum and brainstem (at protein level). Expressed in salivary CC glands (at protein level) (PubMed:16571723). Expressed in heart, lung, CC spleen, liver, kidney, brain, skeletal muscle and testis. In the CC central nervous system, expressed in the lamina terminalis (arched CC vascular organ and neurons of the subfornical organ), median preoptic CC area, ventral hippocampal commissure, and ependymal cells of the CC choroid plexus. In the cochlea, expressed in both inner and outer hair CC cells, and in marginal cells of the cochlear stria vascularis. CC Expressed in large neurons of the trigeminal ganglion. In the kidney CC cortex, strongly expressed by epithelial cells of tubules and much CC weaker in glomeruli. {ECO:0000269|PubMed:11025659, CC ECO:0000269|PubMed:11081638, ECO:0000269|PubMed:11094154, CC ECO:0000269|PubMed:12692122, ECO:0000269|PubMed:16571723, CC ECO:0000269|PubMed:16627472}. CC -!- DOMAIN: The ANK repeat region mediates interaction with Ca(2+)- CC calmodulin and ATP binding. The ANK repeat region mediates interaction CC with phosphatidylinositol-4,5-bisphosphate and related CC phosphatidylinositides. {ECO:0000250|UniProtKB:A0A1D5PXA5}. CC -!- PTM: N-glycosylated. {ECO:0000305|PubMed:16368742}. CC -!- DISRUPTION PHENOTYPE: Knockout mice display impairment of the CC intercellular junction-dependent barrier function in the skin CC (PubMed:20413591). Increased energy expenditure and improved insulin CC sensitivity in white adipose tissues is also observed CC (PubMed:23021218). They also display reduced Ca2+ entry and loss of CC regulatory volume decrease in response to hypotonicity in acinar cells CC (PubMed:16571723). The voluntary water intake normally induced by CC sodium concentration increase in body fluid is impaired CC (PubMed:27252474). {ECO:0000269|PubMed:16571723, CC ECO:0000269|PubMed:20413591, ECO:0000269|PubMed:23021218, CC ECO:0000269|PubMed:27252474}. CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. TrpV CC subfamily. TRPV4 sub-subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAG28028.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAK69486.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF263522; AAG28028.1; ALT_FRAME; mRNA. DR EMBL; AJ296078; CAC20703.1; -; mRNA. DR EMBL; AF208026; AAG17543.1; -; mRNA. DR EMBL; AB021875; BAA83731.2; -; mRNA. DR EMBL; AF279672; AAK69486.1; ALT_INIT; mRNA. DR EMBL; BC127052; AAI27053.1; -; mRNA. DR CCDS; CCDS19568.1; -. DR RefSeq; NP_071300.2; NM_022017.3. DR RefSeq; XP_006530495.2; XM_006530432.2. DR PDB; 8J1B; EM; 3.72 A; A/B/C/D=137-801. DR PDB; 8J1D; EM; 3.59 A; A/B/C/D=137-801. DR PDB; 8J1F; EM; 3.62 A; A/B/C/D=137-801. DR PDB; 8J1H; EM; 3.88 A; A/B/C/D=137-801. DR PDBsum; 8J1B; -. DR PDBsum; 8J1D; -. DR PDBsum; 8J1F; -. DR PDBsum; 8J1H; -. DR AlphaFoldDB; Q9EPK8; -. DR EMDB; EMD-35918; -. DR EMDB; EMD-35919; -. DR EMDB; EMD-35921; -. DR EMDB; EMD-35922; -. DR SMR; Q9EPK8; -. DR DIP; DIP-44011N; -. DR IntAct; Q9EPK8; 6. DR MINT; Q9EPK8; -. DR STRING; 10090.ENSMUSP00000071859; -. DR BindingDB; Q9EPK8; -. DR ChEMBL; CHEMBL6126; -. DR DrugCentral; Q9EPK8; -. DR GuidetoPHARMACOLOGY; 510; -. DR GlyCosmos; Q9EPK8; 1 site, No reported glycans. DR GlyGen; Q9EPK8; 1 site. DR iPTMnet; Q9EPK8; -. DR PhosphoSitePlus; Q9EPK8; -. DR jPOST; Q9EPK8; -. DR MaxQB; Q9EPK8; -. DR PaxDb; 10090-ENSMUSP00000071859; -. DR ProteomicsDB; 298140; -. DR Antibodypedia; 1477; 461 antibodies from 34 providers. DR DNASU; 63873; -. DR Ensembl; ENSMUST00000071968.9; ENSMUSP00000071859.3; ENSMUSG00000014158.13. DR Ensembl; ENSMUST00000112225.8; ENSMUSP00000107844.2; ENSMUSG00000014158.13. DR GeneID; 63873; -. DR KEGG; mmu:63873; -. DR UCSC; uc008yzu.1; mouse. DR AGR; MGI:1926945; -. DR CTD; 59341; -. DR MGI; MGI:1926945; Trpv4. DR VEuPathDB; HostDB:ENSMUSG00000014158; -. DR eggNOG; KOG3676; Eukaryota. DR GeneTree; ENSGT00940000158615; -. DR HOGENOM; CLU_012795_1_0_1; -. DR InParanoid; Q9EPK8; -. DR OMA; KVCNQDQ; -. DR OrthoDB; 1003028at2759; -. DR PhylomeDB; Q9EPK8; -. DR TreeFam; TF314711; -. DR Reactome; R-MMU-3295583; TRP channels. DR BioGRID-ORCS; 63873; 3 hits in 76 CRISPR screens. DR ChiTaRS; Trpv4; mouse. DR PRO; PR:Q9EPK8; -. DR Proteomes; UP000000589; Chromosome 5. DR RNAct; Q9EPK8; Protein. DR Bgee; ENSMUSG00000014158; Expressed in right kidney and 162 other cell types or tissues. DR ExpressionAtlas; Q9EPK8; baseline and differential. DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB. DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0009986; C:cell surface; ISO:MGI. DR GO; GO:0005929; C:cilium; IDA:MGI. DR GO; GO:0030864; C:cortical actin cytoskeleton; ISO:MGI. DR GO; GO:0005881; C:cytoplasmic microtubule; IEA:Ensembl. DR GO; GO:0030175; C:filopodium; ISO:MGI. DR GO; GO:0005925; C:focal adhesion; ISO:MGI. DR GO; GO:0030426; C:growth cone; ISO:MGI. DR GO; GO:0030027; C:lamellipodium; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0032587; C:ruffle membrane; ISO:MGI. DR GO; GO:0003779; F:actin binding; ISO:MGI. DR GO; GO:0051015; F:actin filament binding; ISO:MGI. DR GO; GO:0043014; F:alpha-tubulin binding; ISO:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0048487; F:beta-tubulin binding; ISO:MGI. DR GO; GO:0005262; F:calcium channel activity; IDA:BHF-UCL. DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0008017; F:microtubule binding; ISO:MGI. DR GO; GO:0005261; F:monoatomic cation channel activity; ISS:UniProtKB. DR GO; GO:0005034; F:osmosensor activity; IDA:MGI. DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL. DR GO; GO:0005080; F:protein kinase C binding; ISO:MGI. DR GO; GO:0042169; F:SH2 domain binding; IPI:BHF-UCL. DR GO; GO:0015275; F:stretch-activated, monoatomic cation-selective, calcium channel activity; ISO:MGI. DR GO; GO:0030036; P:actin cytoskeleton organization; ISO:MGI. DR GO; GO:0007015; P:actin filament organization; ISO:MGI. DR GO; GO:0097497; P:blood vessel endothelial cell delamination; ISO:MGI. DR GO; GO:0070509; P:calcium ion import; IDA:BHF-UCL. DR GO; GO:1902656; P:calcium ion import into cytosol; ISS:UniProtKB. DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:MGI. DR GO; GO:0006816; P:calcium ion transport; ISO:MGI. DR GO; GO:0060351; P:cartilage development involved in endochondral bone morphogenesis; ISO:MGI. DR GO; GO:0007043; P:cell-cell junction assembly; IMP:UniProtKB. DR GO; GO:0071476; P:cellular hypotonic response; IDA:BHF-UCL. DR GO; GO:0071477; P:cellular hypotonic salinity response; IMP:UniProtKB. DR GO; GO:0034605; P:cellular response to heat; IMP:UniProtKB. DR GO; GO:0071470; P:cellular response to osmotic stress; IMP:UniProtKB. DR GO; GO:0043622; P:cortical microtubule organization; ISO:MGI. DR GO; GO:0002024; P:diet induced thermogenesis; IMP:UniProtKB. DR GO; GO:0097009; P:energy homeostasis; IMP:UniProtKB. DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB. DR GO; GO:0042538; P:hyperosmotic salinity response; IMP:MGI. DR GO; GO:0006971; P:hypotonic response; ISO:MGI. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IMP:UniProtKB. DR GO; GO:0046785; P:microtubule polymerization; ISO:MGI. DR GO; GO:0050891; P:multicellular organismal-level water homeostasis; ISO:MGI. DR GO; GO:1903444; P:negative regulation of brown fat cell differentiation; IMP:UniProtKB. DR GO; GO:0010977; P:negative regulation of neuron projection development; ISO:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0007231; P:osmosensory signaling pathway; IDA:BHF-UCL. DR GO; GO:0071651; P:positive regulation of chemokine (C-C motif) ligand 5 production; IMP:UniProtKB. DR GO; GO:2000340; P:positive regulation of chemokine (C-X-C motif) ligand 1 production; IMP:UniProtKB. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:UniProtKB. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:UniProtKB. DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB. DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IMP:UniProtKB. DR GO; GO:0071642; P:positive regulation of macrophage inflammatory protein 1 alpha production; IMP:UniProtKB. DR GO; GO:0031117; P:positive regulation of microtubule depolymerization; ISO:MGI. DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; IMP:UniProtKB. DR GO; GO:0045989; P:positive regulation of striated muscle contraction; ISO:MGI. DR GO; GO:0043117; P:positive regulation of vascular permeability; IMP:UniProtKB. DR GO; GO:1903715; P:regulation of aerobic respiration; IMP:UniProtKB. DR GO; GO:0047484; P:regulation of response to osmotic stress; IMP:MGI. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0032868; P:response to insulin; IMP:UniProtKB. DR GO; GO:0006970; P:response to osmotic stress; IDA:MGI. DR GO; GO:0030103; P:vasopressin secretion; IMP:MGI. DR CDD; cd22195; TRPV4; 1. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR036770; Ankyrin_rpt-contain_sf. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR024862; TRPV. DR InterPro; IPR008347; TrpV1-4. DR InterPro; IPR008348; TrpV4. DR NCBIfam; TIGR00870; trp; 1. DR PANTHER; PTHR10582:SF4; TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL SUBFAMILY V MEMBER 4; 1. DR PANTHER; PTHR10582; TRANSIENT RECEPTOR POTENTIAL ION CHANNEL PROTEIN; 1. DR Pfam; PF00023; Ank; 1. DR Pfam; PF00520; Ion_trans; 1. DR PRINTS; PR01768; TRPVRECEPTOR. DR PRINTS; PR01769; VRL2RECEPTOR. DR SMART; SM00248; ANK; 3. DR SUPFAM; SSF48403; Ankyrin repeat; 1. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 1. DR Genevisible; Q9EPK8; MM. PE 1: Evidence at protein level; KW 3D-structure; ANK repeat; ATP-binding; Calcium; Calcium channel; KW Calcium transport; Calmodulin-binding; Cell junction; Cell membrane; KW Cell projection; Cilium; Glycoprotein; Ion channel; Ion transport; KW Lipid-binding; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..871 FT /note="Transient receptor potential cation channel FT subfamily V member 4" FT /id="PRO_0000215348" FT TOPO_DOM 1..469 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:O35433" FT TRANSMEM 470..490 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:O35433" FT TOPO_DOM 491..507 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:O35433" FT TRANSMEM 508..534 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:O35433" FT TOPO_DOM 535..547 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:O35433" FT TRANSMEM 548..568 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:O35433" FT TOPO_DOM 569..572 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:O35433" FT TRANSMEM 573..593 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:O35433" FT TOPO_DOM 594..608 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:O35433" FT TRANSMEM 609..636 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:O35433" FT TOPO_DOM 637..665 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:O35433" FT INTRAMEM 666..685 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:O35433" FT TOPO_DOM 686..693 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:O35433" FT TRANSMEM 694..722 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:O35433" FT TOPO_DOM 723..871 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:O35433" FT REPEAT 237..266 FT /note="ANK 1" FT REPEAT 284..313 FT /note="ANK 2" FT REPEAT 369..398 FT /note="ANK 3" FT REGION 1..68 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 110..143 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 812..831 FT /note="Interaction with calmodulin and ITPR3" FT /evidence="ECO:0000250|UniProtKB:Q9HBA0" FT REGION 850..871 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 679..682 FT /note="Selectivity filter" FT /evidence="ECO:0000305|PubMed:12093812" FT COMPBIAS 112..131 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 192 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9HBA0" FT BINDING 197 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9HBA0" FT BINDING 201 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9HBA0" FT BINDING 236..239 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9HBA0" FT BINDING 248 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9HBA0" FT BINDING 249..251 FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- FT inositol-4,5-bisphosphate)" FT /ligand_id="ChEBI:CHEBI:58456" FT /evidence="ECO:0000250|UniProtKB:A0A1D5PXA5" FT BINDING 296..299 FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- FT inositol-4,5-bisphosphate)" FT /ligand_id="ChEBI:CHEBI:58456" FT /evidence="ECO:0000250|UniProtKB:A0A1D5PXA5" FT BINDING 344 FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- FT inositol-4,5-bisphosphate)" FT /ligand_id="ChEBI:CHEBI:58456" FT /evidence="ECO:0000250|UniProtKB:A0A1D5PXA5" FT BINDING 682 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /evidence="ECO:0000250|UniProtKB:Q9R186" FT MOD_RES 110 FT /note="Phosphotyrosine; by SRC-type Tyr-kinases" FT /evidence="ECO:0000269|PubMed:19033444" FT MOD_RES 253 FT /note="Phosphotyrosine; by LYN" FT /evidence="ECO:0000305|PubMed:12538589" FT MOD_RES 805 FT /note="Phosphotyrosine; by SRC-type Tyr-kinases" FT /evidence="ECO:0000269|PubMed:19033444" FT MOD_RES 824 FT /note="Phosphoserine; by PKC and PKA" FT /evidence="ECO:0000269|PubMed:20043876" FT CARBOHYD 651 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305|PubMed:16368742" FT MUTAGEN 110 FT /note="Y->F: Increases protein abundance at plasma FT membrane. Greatly reduces channel activity." FT /evidence="ECO:0000269|PubMed:19033444" FT MUTAGEN 142..143 FT /note="PP->AL: Strongly reduced interaction with PACSIN3." FT /evidence="ECO:0000269|PubMed:16627472" FT MUTAGEN 253 FT /note="Y->F: Results are conflicting as to whether FT hypotonicity-dependent channel activity is abolished." FT /evidence="ECO:0000269|PubMed:12538589, FT ECO:0000269|PubMed:14691263" FT MUTAGEN 556 FT /note="Y->A: Reduces channel activation by 4-alpha-PDD and FT heat but not hypo-osmotic cell swelling." FT /evidence="ECO:0000269|PubMed:14691263" FT MUTAGEN 556 FT /note="Y->F: No changes in channel activation by FT 4-alpha-PDD or heat." FT /evidence="ECO:0000269|PubMed:14691263" FT MUTAGEN 557 FT /note="S->A: No changes in channel activity." FT /evidence="ECO:0000269|PubMed:14691263" FT MUTAGEN 651 FT /note="N->Q: Loss of a probable N-glycosylation site. FT Increased expression at the cell membrane, leading to FT increased ion currents." FT /evidence="ECO:0000269|PubMed:16368742" FT MUTAGEN 672 FT /note="D->A: Greatly reduces Ca(2+) permeation and channel FT rectification; when associated with A-682." FT /evidence="ECO:0000269|PubMed:12093812" FT MUTAGEN 675 FT /note="K->A: No effect on channel pore properties." FT /evidence="ECO:0000269|PubMed:12093812" FT MUTAGEN 680 FT /note="M->A: Impairs Ca(2+) permeation." FT /evidence="ECO:0000269|PubMed:12093812" FT MUTAGEN 682 FT /note="D->A: Greatly reduces Ca(2+) permeation and channel FT rectification; when associated with A-672." FT /evidence="ECO:0000269|PubMed:12093812" FT MUTAGEN 805 FT /note="Y->F: No changes in channel activity." FT /evidence="ECO:0000269|PubMed:19033444" FT MUTAGEN 824 FT /note="S->A: Loss of phosphorylation but no significant FT effect on channel activity." FT /evidence="ECO:0000269|PubMed:20043876" FT MUTAGEN 824 FT /note="S->D: Phosphomimetic mutant which enhances channel FT function." FT /evidence="ECO:0000269|PubMed:20043876" FT CONFLICT 45 FT /note="G -> S (in Ref. 1; AAG28028)" FT /evidence="ECO:0000305" FT CONFLICT 90 FT /note="L -> R (in Ref. 3; AAG17543 and 5; AAK69486)" FT /evidence="ECO:0000305" FT CONFLICT 137 FT /note="A -> T (in Ref. 4; BAA83731)" FT /evidence="ECO:0000305" FT CONFLICT 210..211 FT /note="IP -> LQ (in Ref. 4; BAA83731)" FT /evidence="ECO:0000305" FT CONFLICT 477 FT /note="S -> P (in Ref. 1; AAG28028)" FT /evidence="ECO:0000305" FT CONFLICT 784 FT /note="N -> S (in Ref. 4; BAA83731)" FT /evidence="ECO:0000305" SQ SEQUENCE 871 AA; 98027 MW; 5BAC6E33F89CEA05 CRC64; MADPGDGPRA APGEVAEPPG DESGTSGGEA FPLSSLANLF EGEEGSSSLS PVDASRPAGP GDGRPNLRMK FQGAFRKGVP NPIDLLESTL YESSVVPGPK KAPMDSLFDY GTYRHHPSDN KRWRRKVVEK QPQSPKAPAP QPPPILKVFN RPILFDIVSR GSTADLDGLL SFLLTHKKRL TDEEFREPST GKTCLPKALL NLSNGRNDTI PVLLDIAERT GNMREFINSP FRDIYYRGQT SLHIAIERRC KHYVELLVAQ GADVHAQARG RFFQPKDEGG YFYFGELPLS LAACTNQPHI VNYLTENPHK KADMRRQDSR GNTVLHALVA IADNTRENTK FVTKMYDLLL LKCSRLFPDS NLETVLNNDG LSPLMMAAKT GKIGVFQHII RREVTDEDTR HLSRKFKDWA YGPVYSSLYD LSSLDTCGEE VSVLEILVYN SKIENRHEML AVEPINELLR DKWRKFGAVS FYINVVSYLC AMVIFTLTAY YQPLEGTPPY PYRTTVDYLR LAGEVITLFT GVLFFFTSIK DLFTKKCPGV NSLFVDGSFQ LLYFIYSVLV VVSAALYLAG IEAYLAVMVF ALVLGWMNAL YFTRGLKLTG TYSIMIQKIL FKDLFRFLLV YLLFMIGYAS ALVTLLNPCT NMKVCDEDQS NCTVPTYPAC RDSETFSAFL LDLFKLTIGM GDLEMLSSAK YPVVFILLLV TYIILTFVLL LNMLIALMGE TVGQVSKESK HIWKLQWATT ILDIERSFPV FLRKAFRSGE MVTVGKSSDG TPDRRWCFRV DEVNWSHWNQ NLGIINEDPG KSEIYQYYGF SHTVGRLRRD RWSSVVPRVV ELNKNSSADE VVVPLDNLGN PNCDGHQQGY APKWRTDDAP L //