Transient receptor potential cation channel subfamily V member 4

Contribute

Send feedback

Read comments (?) or add your own

Q9EPK8 (TRPV4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 100. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

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 channel
Short name=VR-OAC

Gene names

Name:	Trpv4
Synonyms:	Trp12, Vrl2, Vroac

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	871 AA.
Sequence status	Complete.
Protein existence	Evidence 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.10
Subunit structure	Interacts with calmodulin By similarity. Interacts with Map7 and Src family Tyr protein kinases LYN, SRC, FYN, HCK, LCK and YES. Interacts with CTNNB1. The TRPV4 and CTNNB1 complex can interact with CDH1. Part of a complex containing MLC1, AQP4, HEPACAM and ATP1B1 By similarity. Ref.8 Ref.9 Ref.10
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › adherens junction Ref.10.
Tissue specificity	Expressed heart, liver, kidney 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
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.10
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.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane
Domain	ANK repeat Repeat Transmembrane Transmembrane helix
Ligand	ATP-binding Calcium Calmodulin-binding Nucleotide-binding
Molecular function	Calcium channel Ion channel
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton reorganization Inferred from electronic annotation. Source: Compara actin filament organization Inferred from electronic annotation. Source: Compara calcium ion import Inferred from direct assay Ref.9. Source: BHF-UCL cell-cell junction assembly Inferred from mutant phenotype Ref.10. Source: UniProtKB cellular calcium ion homeostasis Inferred from sequence or structural similarity. Source: UniProtKB cellular hypotonic response Inferred from direct assay Ref.9. Source: BHF-UCL cortical microtubule organization Inferred from electronic annotation. Source: Compara elevation of cytosolic calcium ion concentration Inferred from electronic annotation. Source: Compara hyperosmotic salinity response Inferred from mutant phenotype PubMed 12777254. Source: MGI microtubule polymerization Inferred from electronic annotation. Source: Compara negative regulation of neuron projection development Inferred from electronic annotation. Source: Compara osmosensory signaling pathway Inferred from direct assay Ref.9. Source: BHF-UCL positive regulation of microtubule depolymerization Inferred from electronic annotation. Source: Compara regulation of response to osmotic stress Inferred from mutant phenotype PubMed 12777254. Source: MGI vasopressin secretion Inferred from mutant phenotype PubMed 12777254. Source: MGI
Cellular_component	adherens junction Inferred from direct assay Ref.10. Source: UniProtKB cilium Inferred from direct assay PubMed 15858826. Source: MGI cortical actin cytoskeleton Inferred from electronic annotation. Source: Compara cytoplasmic microtubule Inferred from electronic annotation. Source: Compara filopodium Inferred from electronic annotation. Source: Compara focal adhesion Inferred from electronic annotation. Source: Compara growth cone Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lamellipodium Inferred from electronic annotation. Source: Compara plasma membrane Inferred from direct assay Ref.10. Source: UniProtKB ruffle membrane Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium channel activity Inferred from direct assay Ref.9. Source: BHF-UCL calmodulin binding Inferred from sequence or structural similarity. Source: UniProtKB osmosensor activity Inferred from direct assay Ref.3. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 871

871

Transient receptor potential cation channel subfamily V member 4

PRO_0000215348

Regions

Topological domain

1 – 465

465

Cytoplasmic Potential

Transmembrane

466 – 486

Helical; Potential

Topological domain

487 – 508

Extracellular Potential

Transmembrane

509 – 529

Helical; Potential

Topological domain

530 – 550

Cytoplasmic Potential

Transmembrane

551 – 571

Helical; Potential

Topological domain

572

Extracellular Potential

Transmembrane

573 – 593

Helical; Potential

Topological domain

594 – 616

Cytoplasmic Potential

Transmembrane

617 – 637

Helical; Potential

Intramembrane

648 – 678

Pore-forming; Probable

Transmembrane

691 – 711

Helical; Potential

Topological domain

712 – 871

160

Cytoplasmic Potential

Repeat

237 – 266

ANK 1

Repeat

284 – 313

ANK 2

Repeat

369 – 398

ANK 3

Region

812 – 831

Interaction with calmodulin By similarity

Sites

Binding site

192

ATP By similarity

Binding site

201

ATP By similarity

Binding site

239

ATP By similarity

Binding site

248

ATP By similarity

Amino acid modifications

Modified residue

253

Phosphotyrosine; by LYN Probable

Modified residue

824

Phosphoserine; by PKC and PKA By similarity

Experimental info

Mutagenesis

253

Y → F: Abolishes hypotonicity-dependent channel activity. Ref.9

Mutagenesis

672

D → A: Greatly reduces Ca(2+) permeation and channel rectification; when associated with A-682. Ref.7

Mutagenesis

675

K → A: No effect on channel pore properties. Ref.7

Mutagenesis

680

M → A: Impairs Ca(2+) permeation. Ref.7

Mutagenesis

682

D → A: Greatly reduces Ca(2+) permeation and channel rectification; when associated with A-672. Ref.7

Sequence conflict

G → S in AAG28028. Ref.1

Sequence conflict

L → R Ref.3

Sequence conflict

L → R Ref.5

Sequence conflict

137

A → T in BAA83731. Ref.4

Sequence conflict

210 – 211

IP → LQ in BAA83731. Ref.4

Sequence conflict

477

S → P in AAG28028. Ref.1

Sequence conflict

784

N → S in BAA83731. Ref.4

Sequences

Sequence

Length

Mass (Da)

Tools

Q9EPK8 [UniParc].

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

FASTA

871

98,027

        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' referencesShow '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]	"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.
IPI	IPI00112949.
RefSeq	NP_071300.2. NM_022017.3.
UniGene	Mm.266450.
3D structure databases
ProteinModelPortal	Q9EPK8.
SMR	Q9EPK8. Positions 148-397.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4050076.
PTM databases
PhosphoSite	Q9EPK8.
Proteomic databases
PaxDb	Q9EPK8.
PRIDE	Q9EPK8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000071968; ENSMUSP00000071859; ENSMUSG00000014158. ENSMUST00000112225; ENSMUSP00000107844; ENSMUSG00000014158.
GeneID	63873.
KEGG	mmu:63873.
UCSC	uc008yzv.2. mouse.
Organism-specific databases
CTD	59341.
MGI	MGI:1926945. Trpv4.
Phylogenomic databases
eggNOG	NOG278734.
GeneTree	ENSGT00550000074425.
HOGENOM	HOG000234630.
HOVERGEN	HBG054085.
InParanoid	A0JNY0.
KO	K04973.
OMA	EDPGKSE.
OrthoDB	EOG4JQ3WW.
Gene expression databases
ArrayExpress	Q9EPK8.
Bgee	Q9EPK8.
Genevestigator	Q9EPK8.
GermOnline	ENSMUSG00000014158. Mus musculus.
Family and domain databases
Gene3D	1.25.40.20. 1 hit.
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR005821. Ion_trans_dom. IPR004729. TRP_channel. IPR008347. TRPV1-4_channel. IPR008348. TRPV4_channel. IPR024862. TRPV_channel. [Graphical view]
PANTHER	PTHR10582. PTHR10582. 1 hit. PTHR10582:SF4. PTHR10582:SF4. 1 hit.
Pfam	PF12796. Ank_2. 1 hit. PF00520. Ion_trans. 1 hit. [Graphical view]
PRINTS	PR01768. TRPVRECEPTOR. PR01769. VRL2RECEPTOR.
SMART	SM00248. ANK. 3 hits. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit.
TIGRFAMs	TIGR00870. trp. 1 hit.
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9EPK8.
ChEMBL	CHEMBL6126.
NextBio	319803.
SOURCE	Search...

Entry information

Entry name

TRPV4_MOUSE

Accession

Primary (citable) accession number: Q9EPK8
Secondary accession number(s): A0JNY0

Q9ES76

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2005
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents