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Q9EPK8 (TRPV4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 channel
Short name=VR-OAC
Gene names
Name:Trpv4
Synonyms:Trp12, Vrl2, Vroac
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length871 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Non-selective calcium permeant cation channel probably involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by low pH, citrate and phorbol esters. Increase of intracellular Ca2+ potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism. Acts as a regulator of intracellular Ca2+ in synoviocytes. 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. Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers. Ref.2 Ref.11 Ref.12

Subunit structure

Interacts with calmodulin By similarity. Interacts with CTNNB1. The TRPV4 and CTNNB1 complex can interact with CDH1. 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. Interacts with PACSIN1, PACSIN2 and PACSIN3 (via SH3 domain). Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junctionadherens junction Ref.10 Ref.12.

Tissue specificity

Detected in liver, kidney, heart, brain cortex, cerebellum and brainstem (at protein level). 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. Ref.1 Ref.2 Ref.3 Ref.4 Ref.10

Post-translational modification

Phosphorylation results in enhancement of its channel function By similarity.

Disruption phenotype

Mice display impairment of the intercellular junction-dependent barrier function in the skin. Ref.12

Sequence similarities

Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV4 sub-subfamily. [View classification]

Contains 3 ANK repeats.

Sequence caution

The sequence AAG28028.1 differs from that shown. Reason: Frameshift at positions 47, 50, 53, 72 and 73.

The sequence AAK69486.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processCalcium transport
Ion transport
Transport
   Cellular componentCell junction
Cell membrane
Membrane
   DomainANK repeat
Repeat
Transmembrane
Transmembrane helix
   LigandATP-binding
Calcium
Calmodulin-binding
Nucleotide-binding
   Molecular functionCalcium channel
Ion channel
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton reorganization

Inferred from electronic annotation. Source: Ensembl

actin filament organization

Inferred from electronic annotation. Source: Ensembl

calcium ion import

Inferred from direct assay Ref.9. Source: BHF-UCL

cell-cell junction assembly

Inferred from mutant phenotype Ref.12. Source: UniProtKB

cellular calcium ion homeostasis

Inferred from mutant phenotype Ref.11. Source: UniProtKB

cellular hypotonic response

Inferred from direct assay Ref.9. Source: BHF-UCL

cellular response to heat

Inferred from mutant phenotype Ref.11. Source: UniProtKB

cellular response to osmotic stress

Inferred from mutant phenotype Ref.11. Source: UniProtKB

cortical microtubule organization

Inferred from electronic annotation. Source: Ensembl

hyperosmotic salinity response

Inferred from mutant phenotype PubMed 12777254. Source: MGI

microtubule polymerization

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron projection development

Inferred from electronic annotation. Source: Ensembl

osmosensory signaling pathway

Inferred from direct assay Ref.9. Source: BHF-UCL

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of microtubule depolymerization

Inferred from electronic annotation. Source: Ensembl

regulation of response to osmotic stress

Inferred from mutant phenotype PubMed 12777254. Source: MGI

response to osmotic stress

Inferred from direct assay Ref.3. Source: MGI

vasopressin secretion

Inferred from mutant phenotype PubMed 12777254. Source: MGI

   Cellular_componentadherens junction

Inferred from direct assay Ref.12. Source: UniProtKB

cell surface

Inferred from electronic annotation. Source: Ensembl

cilium

Inferred from direct assay PubMed 15858826. Source: MGI

cortical actin cytoskeleton

Inferred from electronic annotation. Source: Ensembl

cytoplasmic microtubule

Inferred from electronic annotation. Source: Ensembl

cytoplasmic vesicle

Inferred from electronic annotation. Source: Ensembl

filopodium

Inferred from electronic annotation. Source: Ensembl

focal adhesion

Inferred from electronic annotation. Source: Ensembl

growth cone

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

lamellipodium

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from direct assay Ref.12. Source: UniProtKB

ruffle membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

SH2 domain binding

Inferred from physical interaction Ref.9. Source: BHF-UCL

calcium channel activity

Inferred from mutant phenotype Ref.11. Source: UniProtKB

calmodulin binding

Inferred from sequence or structural similarity. Source: UniProtKB

cation channel activity

Inferred from sequence or structural similarity. Source: UniProtKB

osmosensor activity

Inferred from direct assay Ref.3. Source: MGI

protein binding

Inferred from physical interaction Ref.11Ref.12. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.9. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

UBCP0CG483EBI-7091763,EBI-3390054From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 871871Transient receptor potential cation channel subfamily V member 4
PRO_0000215348

Regions

Topological domain1 – 465465Cytoplasmic Potential
Transmembrane466 – 48621Helical; Potential
Topological domain487 – 50822Extracellular Potential
Transmembrane509 – 52921Helical; Potential
Topological domain530 – 55021Cytoplasmic Potential
Transmembrane551 – 57121Helical; Potential
Topological domain5721Extracellular Potential
Transmembrane573 – 59321Helical; Potential
Topological domain594 – 61623Cytoplasmic Potential
Transmembrane617 – 63721Helical; Potential
Intramembrane648 – 67831Pore-forming; Probable
Transmembrane691 – 71121Helical; Potential
Topological domain712 – 871160Cytoplasmic Potential
Repeat237 – 26630ANK 1
Repeat284 – 31330ANK 2
Repeat369 – 39830ANK 3
Region812 – 83120Interaction with calmodulin By similarity

Sites

Binding site1921ATP By similarity
Binding site2011ATP By similarity
Binding site2391ATP By similarity
Binding site2481ATP By similarity

Amino acid modifications

Modified residue2531Phosphotyrosine; by LYN Probable
Modified residue8241Phosphoserine; by PKC and PKA By similarity

Experimental info

Mutagenesis142 – 1432PP → AL: Strongly reduced interaction with PACSIN3. Ref.10
Mutagenesis2531Y → F: Abolishes hypotonicity-dependent channel activity. Ref.9 Ref.10
Mutagenesis6721D → A: Greatly reduces Ca(2+) permeation and channel rectification; when associated with A-682. Ref.7 Ref.10
Mutagenesis6751K → A: No effect on channel pore properties. Ref.7 Ref.10
Mutagenesis6801M → A: Impairs Ca(2+) permeation. Ref.7 Ref.10
Mutagenesis6821D → A: Greatly reduces Ca(2+) permeation and channel rectification; when associated with A-672. Ref.7 Ref.10
Sequence conflict451G → S in AAG28028. Ref.1
Sequence conflict901L → R in AAG17543. Ref.3
Sequence conflict901L → R in AAK69486. Ref.5
Sequence conflict1371A → T in BAA83731. Ref.4
Sequence conflict210 – 2112IP → LQ in BAA83731. Ref.4
Sequence conflict4771S → P in AAG28028. Ref.1
Sequence conflict7841N → S in BAA83731. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q9EPK8 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 5BAC6E33F89CEA05

FASTA87198,027
        10         20         30         40         50         60 
MADPGDGPRA APGEVAEPPG DESGTSGGEA FPLSSLANLF EGEEGSSSLS PVDASRPAGP 

        70         80         90        100        110        120 
GDGRPNLRMK FQGAFRKGVP NPIDLLESTL YESSVVPGPK KAPMDSLFDY GTYRHHPSDN 

       130        140        150        160        170        180 
KRWRRKVVEK QPQSPKAPAP QPPPILKVFN RPILFDIVSR GSTADLDGLL SFLLTHKKRL 

       190        200        210        220        230        240 
TDEEFREPST GKTCLPKALL NLSNGRNDTI PVLLDIAERT GNMREFINSP FRDIYYRGQT 

       250        260        270        280        290        300 
SLHIAIERRC KHYVELLVAQ GADVHAQARG RFFQPKDEGG YFYFGELPLS LAACTNQPHI 

       310        320        330        340        350        360 
VNYLTENPHK KADMRRQDSR GNTVLHALVA IADNTRENTK FVTKMYDLLL LKCSRLFPDS 

       370        380        390        400        410        420 
NLETVLNNDG LSPLMMAAKT GKIGVFQHII RREVTDEDTR HLSRKFKDWA YGPVYSSLYD 

       430        440        450        460        470        480 
LSSLDTCGEE VSVLEILVYN SKIENRHEML AVEPINELLR DKWRKFGAVS FYINVVSYLC 

       490        500        510        520        530        540 
AMVIFTLTAY YQPLEGTPPY PYRTTVDYLR LAGEVITLFT GVLFFFTSIK DLFTKKCPGV 

       550        560        570        580        590        600 
NSLFVDGSFQ LLYFIYSVLV VVSAALYLAG IEAYLAVMVF ALVLGWMNAL YFTRGLKLTG 

       610        620        630        640        650        660 
TYSIMIQKIL FKDLFRFLLV YLLFMIGYAS ALVTLLNPCT NMKVCDEDQS NCTVPTYPAC 

       670        680        690        700        710        720 
RDSETFSAFL LDLFKLTIGM GDLEMLSSAK YPVVFILLLV TYIILTFVLL LNMLIALMGE 

       730        740        750        760        770        780 
TVGQVSKESK HIWKLQWATT ILDIERSFPV FLRKAFRSGE MVTVGKSSDG TPDRRWCFRV 

       790        800        810        820        830        840 
DEVNWSHWNQ NLGIINEDPG KSEIYQYYGF SHTVGRLRRD RWSSVVPRVV ELNKNSSADE 

       850        860        870 
VVVPLDNLGN PNCDGHQQGY APKWRTDDAP L 

« Hide

References

« Hide 'large scale' references
[1]"Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor."
Liedtke W.B., Choe Y., Marti-Renom M.A., Bell A.M., Denis C.S., Sali A., Hudspeth A.J., Friedman J.M., Heller S.
Cell 103:525-535(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Hypothalamus.
[2]"Trp12, a novel Trp related protein from kidney."
Wissenbach U., Boedding M., Freichel M., Flockerzi V.
FEBS Lett. 485:127-134(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
Tissue: Kidney.
[3]"OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity."
Strotmann R., Harteneck C., Nunnenmacher K., Schultz G., Plant T.D.
Nat. Cell Biol. 2:695-702(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Strain: 129/SvEv.
[4]"Impaired pressure sensation in mice lacking TRPV4."
Suzuki M., Mizuno A., Kodaira K., Imai M.
J. Biol. Chem. 278:22664-22668(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Kidney.
[5]"Cloning of mouse and human vanilloid receptor-like protein 2 (VRL-2)."
Derst C., Schafer M.K.
Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Kidney.
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]"Molecular determinants of permeation through the cation channel TRPV4."
Voets T., Prenen J., Vriens J., Watanabe H., Janssens A., Wissenbach U., Bodding M., Droogmans G., Nilius B.
J. Biol. Chem. 277:33704-33710(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF CHANNEL PORE, MUTAGENESIS OF ASP-672; LYS-675; MET-680 AND ASP-682.
[8]"Microtubule-associated protein 7 increases the membrane expression of transient receptor potential vanilloid 4 (TRPV4)."
Suzuki M., Hirao A., Mizuno A.
J. Biol. Chem. 278:51448-51453(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAP7.
[9]"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."
Xu H., Zhao H., Tian W., Yoshida K., Roullet J.B., Cohen D.M.
J. Biol. Chem. 278:11520-11527(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LYN; SRC; FYN; HCK; LCK AND YES, PHOSPHORYLATION AT TYR-253, MUTAGENESIS OF TYR-253.
[10]"PACSINs bind to the TRPV4 cation channel. PACSIN 3 modulates the subcellular localization of TRPV4."
Cuajungco M.P., Grimm C., Oshima K., D'hoedt D., Nilius B., Mensenkamp A.R., Bindels R.J., Plomann M., Heller S.
J. Biol. Chem. 281:18753-18762(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PACSIN1; PACSIN2 AND PACSIN3, MUTAGENESIS OF 142-PRO-PRO-143, TISSUE SPECIFICITY.
[11]"Stimulus-specific modulation of the cation channel TRPV4 by PACSIN 3."
D'hoedt D., Owsianik G., Prenen J., Cuajungco M.P., Grimm C., Heller S., Voets T., Nilius B.
J. Biol. Chem. 283:6272-6280(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PACSIN3.
[12]"The TRPV4 channel contributes to intercellular junction formation in keratinocytes."
Sokabe T., Fukumi-Tominaga T., Yonemura S., Mizuno A., Tominaga M.
J. Biol. Chem. 285:18749-18758(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, INTERACTION WITH CTNBB1 AND CDH1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS19568.1.
RefSeqNP_071300.2. NM_022017.3.
UniGeneMm.266450.

3D structure databases

ProteinModelPortalQ9EPK8.
SMRQ9EPK8. Positions 148-755.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-44011N.
IntActQ9EPK8. 2 interactions.
MINTMINT-4050076.

Chemistry

BindingDBQ9EPK8.
ChEMBLCHEMBL6126.
GuidetoPHARMACOLOGY510.

PTM databases

PhosphoSiteQ9EPK8.

Proteomic databases

PaxDbQ9EPK8.
PRIDEQ9EPK8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000071968; ENSMUSP00000071859; ENSMUSG00000014158.
ENSMUST00000112225; ENSMUSP00000107844; ENSMUSG00000014158.
GeneID63873.
KEGGmmu:63873.
UCSCuc008yzu.1. mouse.

Organism-specific databases

CTD59341.
MGIMGI:1926945. Trpv4.

Phylogenomic databases

eggNOGNOG278734.
GeneTreeENSGT00550000074425.
HOGENOMHOG000234630.
HOVERGENHBG054085.
InParanoidA0JNY0.
KOK04973.
OMAEDQTNCT.
OrthoDBEOG70S74P.
PhylomeDBQ9EPK8.
TreeFamTF314711.

Gene expression databases

ArrayExpressQ9EPK8.
BgeeQ9EPK8.
GenevestigatorQ9EPK8.

Family and domain databases

Gene3D1.25.40.20. 1 hit.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR005821. Ion_trans_dom.
IPR004729. TRP_channel.
IPR008347. TRPV1-4_channel.
IPR008348. TRPV4_channel.
[Graphical view]
PANTHERPTHR10582:SF4. PTHR10582:SF4. 1 hit.
PfamPF12796. Ank_2. 1 hit.
PF00520. Ion_trans. 1 hit.
[Graphical view]
PRINTSPR01768. TRPVRECEPTOR.
PR01769. VRL2RECEPTOR.
SMARTSM00248. ANK. 3 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
TIGRFAMsTIGR00870. trp. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio319803.
PROQ9EPK8.
SOURCESearch...

Entry information

Entry nameTRPV4_MOUSE
AccessionPrimary (citable) accession number: Q9EPK8
Secondary accession number(s): A0JNY0 expand/collapse secondary AC list , Q91XR5, Q9EQZ4, Q9ERZ7, Q9ES76
Entry history
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot