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Protein

Transient receptor potential cation channel subfamily V member 4

Gene

Trpv4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 Ca2+ 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 Ca2+ 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).By similarity9 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei192ATPBy similarity1
Binding sitei197ATPBy similarity1
Binding sitei201ATPBy similarity1
Binding sitei248ATPBy similarity1
Binding sitei344Phosphatidylinositol-1,4,5-trisphosphateBy similarity1
Metal bindingi682Calcium; shared with neighboring subunitsBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi236 – 239ATPBy similarity4

GO - Molecular functioni

GO - Biological processi

  • actin cytoskeleton reorganization Source: Ensembl
  • actin filament organization Source: GO_Central
  • blood vessel endothelial cell delamination Source: MGI
  • calcium ion import Source: BHF-UCL
  • calcium ion transmembrane transport Source: MGI
  • calcium ion transport Source: MGI
  • cartilage development involved in endochondral bone morphogenesis Source: MGI
  • cell-cell junction assembly Source: UniProtKB
  • cellular calcium ion homeostasis Source: UniProtKB
  • cellular hypotonic response Source: BHF-UCL
  • cellular hypotonic salinity response Source: UniProtKB
  • cellular response to heat Source: UniProtKB
  • cellular response to osmotic stress Source: UniProtKB
  • cortical microtubule organization Source: Ensembl
  • diet induced thermogenesis Source: UniProtKB
  • energy homeostasis Source: UniProtKB
  • glucose homeostasis Source: UniProtKB
  • hyperosmotic salinity response Source: MGI
  • microtubule polymerization Source: Ensembl
  • multicellular organismal water homeostasis Source: MGI
  • negative regulation of brown fat cell differentiation Source: UniProtKB
  • negative regulation of neuron projection development Source: Ensembl
  • negative regulation of transcription by RNA polymerase II Source: UniProtKB
  • osmosensory signaling pathway Source: BHF-UCL
  • positive regulation of chemokine (C-C motif) ligand 5 production Source: UniProtKB
  • positive regulation of chemokine (C-X-C motif) ligand 1 production Source: UniProtKB
  • positive regulation of cytosolic calcium ion concentration Source: MGI
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of inflammatory response Source: UniProtKB
  • positive regulation of interleukin-6 secretion Source: UniProtKB
  • positive regulation of JNK cascade Source: UniProtKB
  • positive regulation of macrophage chemotaxis Source: UniProtKB
  • positive regulation of macrophage inflammatory protein 1 alpha production Source: UniProtKB
  • positive regulation of microtubule depolymerization Source: Ensembl
  • positive regulation of monocyte chemotactic protein-1 production Source: UniProtKB
  • positive regulation of vascular permeability Source: UniProtKB
  • regulation of response to osmotic stress Source: MGI
  • response to insulin Source: UniProtKB
  • response to osmotic stress Source: MGI
  • signal transduction involved in regulation of aerobic respiration Source: UniProtKB
  • vasopressin secretion Source: MGI

Keywordsi

Molecular functionCalcium channel, Calmodulin-binding, Ion channel
Biological processCalcium transport, Ion transport, Transport
LigandATP-binding, Calcium, Lipid-binding, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-3295583 TRP channels

Names & Taxonomyi

Protein namesi
Recommended name:
Transient receptor potential cation channel subfamily V member 4
Short name:
TrpV4
Alternative name(s):
Osm-9-like TRP channel 4
Short name:
OTRPC4
Transient receptor potential protein 12
Short name:
TRP12
Vanilloid receptor-like channel 2
Vanilloid receptor-like protein 2
Vanilloid receptor-related osmotically-activated channel1 Publication
Short name:
VR-OAC1 Publication
Gene namesi
Name:Trpv4
Synonyms:Trp12, Vrl2, Vroac
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1926945 Trpv4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 469CytoplasmicBy similarityAdd BLAST469
Transmembranei470 – 490HelicalBy similarityAdd BLAST21
Topological domaini491 – 507ExtracellularBy similarityAdd BLAST17
Transmembranei508 – 534HelicalBy similarityAdd BLAST27
Topological domaini535 – 547CytoplasmicBy similarityAdd BLAST13
Transmembranei548 – 568HelicalBy similarityAdd BLAST21
Topological domaini569 – 572ExtracellularBy similarity4
Transmembranei573 – 593HelicalBy similarityAdd BLAST21
Topological domaini594 – 608CytoplasmicBy similarityAdd BLAST15
Transmembranei609 – 636HelicalBy similarityAdd BLAST28
Topological domaini637 – 665ExtracellularBy similarityAdd BLAST29
Intramembranei666 – 685Pore-formingBy similarityAdd BLAST20
Topological domaini686 – 693ExtracellularBy similarity8
Transmembranei694 – 722HelicalBy similarityAdd BLAST29
Topological domaini723 – 871CytoplasmicBy similarityAdd BLAST149

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cilium, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice display impairment of the intercellular junction-dependent barrier function in the skin (PubMed:20413591). Increased energy expenditure and improved insulin sensitivity in white adipose tissues (PubMed:23021218). Reduced Ca2+ entry and loss of regulatory volume decrease in response to hypotonicity in acinar cells (PubMed:16571723).3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi110Y → F: Increases protein abundance at plasma membrane. Greatly reduces channel activity. 1 Publication1
Mutagenesisi142 – 143PP → AL: Strongly reduced interaction with PACSIN3. 1 Publication2
Mutagenesisi253Y → F: Results are conflicting as to whether hypotonicity-dependent channel activity is abolished. 2 Publications1
Mutagenesisi556Y → A: Reduces channel activation by 4-alpha-PDD and heat but not hypo-osmotic cell swelling. 1 Publication1
Mutagenesisi556Y → F: No changes in channel activation by 4-alpha-PDD or heat. 1 Publication1
Mutagenesisi557S → A: No changes in channel activity. 1 Publication1
Mutagenesisi651N → Q: Loss of a probable N-glycosylation site. Increased expression at the cell membrane, leading to increased ion currents. 1 Publication1
Mutagenesisi672D → A: Greatly reduces Ca(2+) permeation and channel rectification; when associated with A-682. 1 Publication1
Mutagenesisi675K → A: No effect on channel pore properties. 1 Publication1
Mutagenesisi680M → A: Impairs Ca(2+) permeation. 1 Publication1
Mutagenesisi682D → A: Greatly reduces Ca(2+) permeation and channel rectification; when associated with A-672. 1 Publication1
Mutagenesisi805Y → F: No changes in channel activity. 1 Publication1
Mutagenesisi824S → A: Loss of phosphorylation but no significant effect on channel activity. 1 Publication1
Mutagenesisi824S → D: Phosphomimetic mutant which enhances channel function. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL6126
GuidetoPHARMACOLOGYi510

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153481 – 871Transient receptor potential cation channel subfamily V member 4Add BLAST871

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei110Phosphotyrosine; by SRC-type Tyr-kinases1 Publication1
Modified residuei253Phosphotyrosine; by LYN1 Publication1
Glycosylationi651N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei805Phosphotyrosine; by SRC-type Tyr-kinases1 Publication1
Modified residuei824Phosphoserine; by PKC and PKA1 Publication1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ9EPK8
PaxDbiQ9EPK8
PRIDEiQ9EPK8

PTM databases

iPTMnetiQ9EPK8
PhosphoSitePlusiQ9EPK8

Expressioni

Tissue specificityi

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.6 Publications

Gene expression databases

BgeeiENSMUSG00000014158
ExpressionAtlasiQ9EPK8 baseline and differential
GenevisibleiQ9EPK8 MM

Interactioni

Subunit structurei

Homotetramer. Interacts with calmodulin (By similarity). Interacts with CTNNB1 (PubMed:20413591). The TRPV4 and CTNNB1 complex can interact with CDH1 (PubMed:20413591). Part of a complex containing MLC1, AQP4, HEPACAM and ATP1B1 (By similarity). Interacts with MAP7 and Src family Tyr protein kinases LYN, SRC, FYN, HCK, LCK and YES (PubMed:14517216, PubMed:12538589). Interacts with PACSIN1, PACSIN2 and PACSIN3 (via SH3 domain) (PubMed:16627472, PubMed:18174177). Interacts with ITPR3 (By similarity). Interacts with AQP5; the interaction is probably indirect and regulates TRPV4 activation by hypotonicity (PubMed:16571723). Interacts with ANO1 (PubMed:24509911). Interacts (via C-terminus) with PKD2 (via C-terminus) (PubMed:18695040).By similarity8 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-44011N
IntActiQ9EPK8, 3 interactors
MINTiQ9EPK8
STRINGi10090.ENSMUSP00000071859

Chemistry databases

BindingDBiQ9EPK8

Structurei

3D structure databases

ProteinModelPortaliQ9EPK8
SMRiQ9EPK8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati237 – 266ANK 1Add BLAST30
Repeati284 – 313ANK 2Add BLAST30
Repeati369 – 398ANK 3Add BLAST30

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni249 – 251Phosphatidylinositol-1,4,5-trisphosphate bindingBy similarity3
Regioni296 – 299Phosphatidylinositol-1,4,5-trisphosphate bindingBy similarity4
Regioni812 – 831Interaction with calmodulin and ITPR3By similarityAdd BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi679 – 682Selectivity filter1 Publication4

Domaini

The ANK repeat region mediates interaction with Ca2+-calmodulin and ATP binding. The ANK repeat region mediates interaction with phosphatidylinositol-4,5-bisphosphate and related phosphatidylinositides.By similarity

Sequence similaritiesi

Keywords - Domaini

ANK repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3676 Eukaryota
ENOG4110DG4 LUCA
GeneTreeiENSGT00550000074425
HOGENOMiHOG000234630
HOVERGENiHBG054085
InParanoidiQ9EPK8
KOiK04973
OMAiGDLEMIN
OrthoDBiEOG091G016O
PhylomeDBiQ9EPK8
TreeFamiTF314711

Family and domain databases

CDDicd00204 ANK, 1 hit
Gene3Di1.25.40.20, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR005821 Ion_trans_dom
IPR004729 TRP_channel
IPR024862 TRPV
IPR008347 TRPV1-4_channel
IPR008348 TRPV4_channel
PANTHERiPTHR10582 PTHR10582, 1 hit
PTHR10582:SF4 PTHR10582:SF4, 1 hit
PfamiView protein in Pfam
PF00023 Ank, 1 hit
PF00520 Ion_trans, 1 hit
PRINTSiPR01768 TRPVRECEPTOR
PR01769 VRL2RECEPTOR
SMARTiView protein in SMART
SM00248 ANK, 3 hits
SUPFAMiSSF48403 SSF48403, 1 hit
TIGRFAMsiTIGR00870 trp, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 1 hit

Sequencei

Sequence statusi: Complete.

Q9EPK8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADPGDGPRA APGEVAEPPG DESGTSGGEA FPLSSLANLF EGEEGSSSLS
60 70 80 90 100
PVDASRPAGP GDGRPNLRMK FQGAFRKGVP NPIDLLESTL YESSVVPGPK
110 120 130 140 150
KAPMDSLFDY GTYRHHPSDN KRWRRKVVEK QPQSPKAPAP QPPPILKVFN
160 170 180 190 200
RPILFDIVSR GSTADLDGLL SFLLTHKKRL TDEEFREPST GKTCLPKALL
210 220 230 240 250
NLSNGRNDTI PVLLDIAERT GNMREFINSP FRDIYYRGQT SLHIAIERRC
260 270 280 290 300
KHYVELLVAQ GADVHAQARG RFFQPKDEGG YFYFGELPLS LAACTNQPHI
310 320 330 340 350
VNYLTENPHK KADMRRQDSR GNTVLHALVA IADNTRENTK FVTKMYDLLL
360 370 380 390 400
LKCSRLFPDS NLETVLNNDG LSPLMMAAKT GKIGVFQHII RREVTDEDTR
410 420 430 440 450
HLSRKFKDWA YGPVYSSLYD LSSLDTCGEE VSVLEILVYN SKIENRHEML
460 470 480 490 500
AVEPINELLR DKWRKFGAVS FYINVVSYLC AMVIFTLTAY YQPLEGTPPY
510 520 530 540 550
PYRTTVDYLR LAGEVITLFT GVLFFFTSIK DLFTKKCPGV NSLFVDGSFQ
560 570 580 590 600
LLYFIYSVLV VVSAALYLAG IEAYLAVMVF ALVLGWMNAL YFTRGLKLTG
610 620 630 640 650
TYSIMIQKIL FKDLFRFLLV YLLFMIGYAS ALVTLLNPCT NMKVCDEDQS
660 670 680 690 700
NCTVPTYPAC RDSETFSAFL LDLFKLTIGM GDLEMLSSAK YPVVFILLLV
710 720 730 740 750
TYIILTFVLL LNMLIALMGE TVGQVSKESK HIWKLQWATT ILDIERSFPV
760 770 780 790 800
FLRKAFRSGE MVTVGKSSDG TPDRRWCFRV DEVNWSHWNQ NLGIINEDPG
810 820 830 840 850
KSEIYQYYGF SHTVGRLRRD RWSSVVPRVV ELNKNSSADE VVVPLDNLGN
860 870
PNCDGHQQGY APKWRTDDAP L
Length:871
Mass (Da):98,027
Last modified:March 1, 2001 - v1
Checksum:i5BAC6E33F89CEA05
GO

Sequence cautioni

The sequence AAG28028 differs from that shown. Reason: Frameshift at positions 47, 50, 53, 72 and 73.Curated
The sequence AAK69486 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti45G → S in AAG28028 (PubMed:11081638).Curated1
Sequence conflicti90L → R in AAG17543 (PubMed:11025659).Curated1
Sequence conflicti90L → R in AAK69486 (Ref. 5) Curated1
Sequence conflicti137A → T in BAA83731 (PubMed:12692122).Curated1
Sequence conflicti210 – 211IP → LQ in BAA83731 (PubMed:12692122).Curated2
Sequence conflicti477S → P in AAG28028 (PubMed:11081638).Curated1
Sequence conflicti784N → S in BAA83731 (PubMed:12692122).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF263522 mRNA Translation: AAG28028.1 Frameshift.
AJ296078 mRNA Translation: CAC20703.1
AF208026 mRNA Translation: AAG17543.1
AB021875 mRNA Translation: BAA83731.2
AF279672 mRNA Translation: AAK69486.1 Different initiation.
BC127052 mRNA Translation: AAI27053.1
CCDSiCCDS19568.1
RefSeqiNP_071300.2, NM_022017.3
XP_006530495.2, XM_006530432.2
UniGeneiMm.266450

Genome annotation databases

EnsembliENSMUST00000071968; ENSMUSP00000071859; ENSMUSG00000014158
ENSMUST00000112225; ENSMUSP00000107844; ENSMUSG00000014158
GeneIDi63873
KEGGimmu:63873
UCSCiuc008yzu.1 mouse

Similar proteinsi

Entry informationi

Entry nameiTRPV4_MOUSE
AccessioniPrimary (citable) accession number: Q9EPK8
Secondary accession number(s): A0JNY0
, Q91XR5, Q9EQZ4, Q9ERZ7, Q9ES76
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: March 1, 2001
Last modified: May 23, 2018
This is version 142 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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