TRPV4_MOUSE
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 03-AUG-2022, entry version 166.
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, 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 CHARACTERIZATION OF CHANNEL PORE, FUNCTION, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF 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 INTERACTION WITH LYN; SRC; FYN; HCK; LCK AND YES, PHOSPHORYLATION AT
RP 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, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-253; TYR-556 AND
RP 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.
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 PHOSPHORYLATION AT SER-824, AND MUTAGENESIS OF 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).
CC -!- FUNCTION: Non-selective calcium permeant cation channel involved in
CC osmotic sensitivity and mechanosensitivity (PubMed:11094154).
CC Activation by exposure to hypotonicity within the physiological range
CC exhibits an outward rectification (PubMed:12093812, PubMed:14691263,
CC PubMed:16368742, PubMed:16571723). Also activated by heat, low pH,
CC citrate and phorbol esters (PubMed:14691263). Increase of intracellular
CC Ca(2+) potentiates currents. Channel activity seems to be regulated by
CC a calmodulin-dependent mechanism with a negative feedback mechanism (By
CC similarity). Acts as a regulator of intracellular Ca(2+) in
CC synoviocytes (By similarity). Plays an obligatory role as a molecular
CC component in the nonselective cation channel activation induced by 4-
CC alpha-phorbol 12,13-didecanoate and hypotonic stimulation in
CC synoviocytes and also regulates production of IL-8 (By similarity).
CC Together with PKD2, forms mechano- and thermosensitive channels in
CC cilium (PubMed:18695040). Promotes cell-cell junction formation in skin
CC keratinocytes and plays an important role in the formation and/or
CC maintenance of functional intercellular barriers (PubMed:20413591).
CC Negatively regulates expression of PPARGC1A, UCP1, oxidative metabolism
CC and respiration in adipocytes (PubMed:23021218). Regulates expression
CC of chemokines and cytokines related to pro-inflammatory pathway in
CC adipocytes (PubMed:23021218). Together with AQP5, controls regulatory
CC volume decrease in salivary epithelial cells (PubMed:16571723).
CC Required for normal development and maintenance of bone and cartilage
CC (By similarity). In its inactive state, may sequester DDX3X at the
CC plasma membrane. When activated, the interaction between both proteins
CC is affected and DDX3X relocalizes to the nucleus (By similarity).
CC {ECO:0000250|UniProtKB:Q9HBA0, ECO:0000269|PubMed:11094154,
CC ECO:0000269|PubMed:12093812, 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 -!- 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:0000250|UniProtKB:Q9HBA0}.
CC Apical cell membrane {ECO:0000269|PubMed:14691263,
CC ECO:0000269|PubMed:16571723, ECO:0000269|PubMed:16627472,
CC ECO:0000269|PubMed:24509911, ECO:0000305|PubMed:12093812,
CC ECO:0000305|PubMed:16368742}; Multi-pass membrane protein
CC {ECO:0000305}. Cell junction, adherens junction
CC {ECO:0000269|PubMed:20413591}. Cell projection, cilium
CC {ECO:0000269|PubMed:18695040}. Note=Assembly of the putative
CC homotetramer occurs primarily in the endoplasmic reticulum.
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: Mice display impairment of the intercellular
CC junction-dependent barrier function in the skin (PubMed:20413591).
CC Increased energy expenditure and improved insulin sensitivity in white
CC adipose tissues (PubMed:23021218). Reduced Ca2+ entry and loss of
CC regulatory volume decrease in response to hypotonicity in acinar cells
CC (PubMed:16571723). {ECO:0000269|PubMed:16571723,
CC ECO:0000269|PubMed:20413591, ECO:0000269|PubMed:23021218}.
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};
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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 AlphaFoldDB; Q9EPK8; -.
DR SMR; Q9EPK8; -.
DR DIP; DIP-44011N; -.
DR IntAct; Q9EPK8; 5.
DR MINT; Q9EPK8; -.
DR STRING; 10090.ENSMUSP00000071859; -.
DR BindingDB; Q9EPK8; -.
DR ChEMBL; CHEMBL6126; -.
DR DrugCentral; Q9EPK8; -.
DR GuidetoPHARMACOLOGY; 510; -.
DR GlyGen; Q9EPK8; 1 site.
DR iPTMnet; Q9EPK8; -.
DR PhosphoSitePlus; Q9EPK8; -.
DR jPOST; Q9EPK8; -.
DR MaxQB; Q9EPK8; -.
DR PaxDb; Q9EPK8; -.
DR PRIDE; Q9EPK8; -.
DR ProteomicsDB; 298140; -.
DR Antibodypedia; 1477; 390 antibodies from 34 providers.
DR DNASU; 63873; -.
DR Ensembl; ENSMUST00000071968; ENSMUSP00000071859; ENSMUSG00000014158.
DR Ensembl; ENSMUST00000112225; ENSMUSP00000107844; ENSMUSG00000014158.
DR GeneID; 63873; -.
DR KEGG; mmu:63873; -.
DR UCSC; uc008yzu.1; mouse.
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; YPECNLE; -.
DR OrthoDB; 693004at2759; -.
DR PhylomeDB; Q9EPK8; -.
DR TreeFam; TF314711; -.
DR Reactome; R-MMU-3295583; TRP channels.
DR BioGRID-ORCS; 63873; 2 hits in 71 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 160 other tissues.
DR ExpressionAtlas; Q9EPK8; baseline and differential.
DR Genevisible; Q9EPK8; MM.
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; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
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:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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:0005261; F:cation channel activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005216; F:ion channel activity; IBA:GO_Central.
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: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, cation-selective, calcium channel activity; ISO:MGI.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; 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:0098703; P:calcium ion import across plasma membrane; IBA:GO_Central.
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:0006874; P:cellular calcium ion homeostasis; 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:0046785; P:microtubule polymerization; ISO:MGI.
DR GO; GO:0050891; P:multicellular organismal 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: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 Gene3D; 1.25.40.20; -; 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 PANTHER; PTHR10582; PTHR10582; 1.
DR PANTHER; PTHR10582:SF4; PTHR10582:SF4; 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; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
PE 1: Evidence at protein level;
KW ANK repeat; ATP-binding; Calcium; Calcium channel; Calcium transport;
KW Calmodulin-binding; Cell junction; Cell membrane; Cell projection; Cilium;
KW Glycoprotein; Ion channel; Ion transport; Lipid-binding; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW 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 4-alpha-
FT 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
