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Q9HBA0 (TRPV4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·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
Short name=VRL-2
Vanilloid receptor-related osmotically-activated channel
Short name=VR-OAC
Gene names
Name:TRPV4
Synonyms:VRL2, VROAC
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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. Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers. 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. Ref.2 Ref.11 Ref.12

Subunit structure

Homotetramer Probable. Self-associates in a isoform-specific manner. Isoforms 1/A and 5/D but not isoform 2/B 4/C and 6/E can oligomerize. Interacts with calmodulin. 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. Interacts with PACSIN1, PACSIN2 and PACSIN3 (via SH3 domain) By similarity. Part of a complex containing MLC1, AQP4, HEPACAM and ATP1B1. Ref.11 Ref.15

Subcellular location

Cell membrane; Multi-pass membrane protein By similarity. Cell junctionadherens junction By similarity. Note: Assembly of the putative homotetramer occurs primarily in the endoplasmic reticulum. Ref.7 Ref.22 Ref.23

Isoform 1: Cell membrane Ref.7 Ref.22 Ref.23.

Isoform 5: Cell membrane Ref.7 Ref.22 Ref.23.

Tissue specificity

Found in the synoviocytes from patients with (RA) and without (CTR) rheumatoid arthritis (at protein level). Ref.12

Post-translational modification

Phosphorylation results in enhancement of its channel function.

Polymorphism

Genetic variations in TRPV4 determine the sodium serum level quantitative trait locus 1 (SSQTL1) [MIM:613508]. In some populations, variant Pro19Ser has been shown to be significantly associated with hyponatremia defined as serum sodium concentration below or equal to 135 mEq/L.

Involvement in disease

Brachyolmia 3 (BRAC3) [MIM:113500]: A form of brachyolmia, a clinically and genetically heterogeneous skeletal dysplasia primarily affecting the spine and characterized by a short trunk, short stature, and platyspondyly without significant epiphyseal or metaphyseal changes in the long bones. BRAC3 is an autosomal dominant form with severe scoliosis with or without kyphosis, and flattened irregular cervical vertebrae.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17

Spondylometaphyseal dysplasia Kozlowski type (SMDK) [MIM:184252]: A form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. It is characterized by postnatal dwarfism, significant scoliosis and mild metaphyseal abnormalities in the pelvis. The vertebrae exhibit platyspondyly and overfaced pedicles.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18 Ref.21

Metatropic dysplasia (MTD) [MIM:156530]: A severe spondyloepimetaphyseal dysplasia characterized by short limbs with limitation and enlargement of joints and usually severe kyphoscoliosis. Radiologic features include severe platyspondyly, severe metaphyseal enlargement and shortening of long bones.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.18 Ref.19 Ref.21

Distal spinal muscular atrophy, congenital non-progressive (DSMAC) [MIM:600175]: A clinically variable, neuromuscular disorder characterized by congenital lower motor neuron disorder restricted to the lower part of the body. Clinical manifestations include non-progressive muscular atrophy, thigh muscle atrophy, weak thigh adductors, weak knee and foot extensors, minimal jaw muscle and neck flexor weakness, flexion contractures of knees and pes equinovarus. Tendon reflexes are normal.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.22 Ref.28

Charcot-Marie-Tooth disease 2C (CMT2C) [MIM:606071]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.22 Ref.23 Ref.24 Ref.25 Ref.27

Scapuloperoneal spinal muscular atrophy (SPSMA) [MIM:181405]: A clinically variable neuromuscular disorder characterized by neurogenic scapuloperoneal amyotrophy, laryngeal palsy, congenital absence of muscles, progressive scapuloperoneal atrophy and progressive distal weakness and amyotrophy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23

Spondyloepiphyseal dysplasia Maroteaux type (SEDM) [MIM:184095]: A clinically variable spondyloepiphyseal dysplasia with manifestations limited to the musculoskeletal system. Clinical features include short stature, brachydactyly, platyspondyly, short and stubby hands and feet, epiphyseal hypoplasia of the large joints, and iliac hypoplasia. Intelligence is normal.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20

Parastremmatic dwarfism (PSTD) [MIM:168400]: A bone dysplasia characterized by severe dwarfism, kyphoscoliosis, distortion and bowing of the extremities, and contractures of the large joints. Radiographically, the disease is characterized by a combination of decreased bone density, bowing of the long bones, platyspondyly and striking irregularities of endochondral ossification with areas of calcific stippling and streaking in radiolucent epiphyses, metaphyses and apophyses.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20

Digital arthropathy-brachydactyly, familial (FDAB) [MIM:606835]: A disorder characterized by irregularities in the proximal articular surfaces of the distal interphalangeal joints of the hand. Individuals appear normal at birth, with no clinical or radiographic evidence of a developmental skeletal dysplasia. The earliest changes appear during the first decade of life. By adulthood, all interphalangeal, metacarpophalangeal, and metatarsophalangeal joints are affected by a deforming, painful osteoarthritis. The remainder of the skeleton is clinically and radiographically unaffected.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26

Sequence similarities

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

Contains 3 ANK repeats.

Ontologies

Keywords
   Biological processCalcium transport
Ion transport
Transport
   Cellular componentCell junction
Cell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseCharcot-Marie-Tooth disease
Disease mutation
Dwarfism
Neurodegeneration
Neuropathy
   DomainANK repeat
Repeat
Transmembrane
Transmembrane helix
   LigandATP-binding
Calcium
Calmodulin-binding
Nucleotide-binding
   Molecular functionCalcium channel
Ion channel
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton reorganization

Inferred from sequence or structural similarity. Source: BHF-UCL

actin filament organization

Inferred from sequence or structural similarity. Source: BHF-UCL

calcium ion import

Inferred from sequence or structural similarity. Source: BHF-UCL

calcium ion transmembrane transport

Traceable author statement. Source: Reactome

calcium ion transport

Inferred from direct assay PubMed 18458941. Source: UniProtKB

cell death

Inferred from electronic annotation. Source: UniProtKB-KW

cell volume homeostasis

Traceable author statement Ref.11. Source: UniProtKB

cell-cell junction assembly

Inferred from sequence or structural similarity. Source: UniProtKB

cellular calcium ion homeostasis

Inferred from direct assay Ref.11. Source: UniProtKB

cellular hypotonic response

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular response to heat

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to osmotic stress

Inferred from sequence or structural similarity. Source: UniProtKB

cortical microtubule organization

Inferred from sequence or structural similarity. Source: BHF-UCL

hyperosmotic salinity response

Inferred from electronic annotation. Source: Ensembl

ion transmembrane transport

Traceable author statement. Source: Reactome

microtubule polymerization

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of neuron projection development

Inferred from sequence or structural similarity. Source: BHF-UCL

osmosensory signaling pathway

Traceable author statement Ref.11. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration

Inferred from direct assay PubMed 18458941. Source: UniProtKB

positive regulation of microtubule depolymerization

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of response to osmotic stress

Inferred from electronic annotation. Source: Ensembl

response to mechanical stimulus

Traceable author statement PubMed 15753126. Source: UniProtKB

transmembrane transport

Traceable author statement. Source: Reactome

vasopressin secretion

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentadherens junction

Inferred from sequence or structural similarity. Source: UniProtKB

cell surface

Inferred from electronic annotation. Source: Ensembl

cilium

Inferred from electronic annotation. Source: Ensembl

cortical actin cytoskeleton

Inferred from sequence or structural similarity. Source: BHF-UCL

cytoplasmic microtubule

Inferred from electronic annotation. Source: Ensembl

cytoplasmic vesicle

Inferred from electronic annotation. Source: Ensembl

filopodium

Inferred from sequence or structural similarity. Source: BHF-UCL

focal adhesion

Inferred from sequence or structural similarity. Source: BHF-UCL

growth cone

Inferred from sequence or structural similarity. Source: BHF-UCL

integral component of membrane

Non-traceable author statement Ref.2. Source: UniProtKB

lamellipodium

Inferred from sequence or structural similarity. Source: BHF-UCL

plasma membrane

Inferred from direct assay PubMed 15753126. Source: UniProtKB

ruffle membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

SH2 domain binding

Inferred from sequence or structural similarity. Source: BHF-UCL

actin binding

Inferred from sequence or structural similarity. Source: BHF-UCL

actin filament binding

Inferred from sequence or structural similarity. Source: BHF-UCL

alpha-tubulin binding

Inferred from sequence or structural similarity. Source: BHF-UCL

beta-tubulin binding

Inferred from sequence or structural similarity. Source: BHF-UCL

calcium channel activity

Inferred from direct assay PubMed 18458941. Source: UniProtKB

calmodulin binding

Inferred from mutant phenotype Ref.11. Source: UniProtKB

cation channel activity

Inferred from direct assay Ref.11. Source: UniProtKB

microtubule binding

Inferred from sequence or structural similarity. Source: BHF-UCL

osmosensor activity

Inferred from electronic annotation. Source: Ensembl

protein kinase C binding

Inferred from sequence or structural similarity. Source: BHF-UCL

protein kinase binding

Inferred from physical interaction PubMed 12538589. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9HBA0-1)

Also known as: A;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9HBA0-2)

Also known as: B; OTRPC4beta;

The sequence of this isoform differs from the canonical sequence as follows:
     385-444: Missing.
Isoform 3 (identifier: Q9HBA0-3)

Also known as: TRPV-SV;

The sequence of this isoform differs from the canonical sequence as follows:
     844-871: PLDSMGNPRCDGHQQGYPRKWRTDDAPL → RHLCRVRRKR
Isoform 4 (identifier: Q9HBA0-4)

Also known as: C;

The sequence of this isoform differs from the canonical sequence as follows:
     239-285: Missing.
Isoform 5 (identifier: Q9HBA0-5)

Also known as: D;

The sequence of this isoform differs from the canonical sequence as follows:
     28-61: Missing.
Isoform 6 (identifier: Q9HBA0-6)

Also known as: E;

The sequence of this isoform differs from the canonical sequence as follows:
     239-285: Missing.
     385-444: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 871871Transient receptor potential cation channel subfamily V member 4
PRO_0000215347

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

Sites

Binding site1921ATP
Binding site2011ATP
Binding site2391ATP
Binding site2481ATP

Amino acid modifications

Modified residue8241Phosphoserine; by PKC and PKA Ref.14

Natural variations

Alternative sequence28 – 6134Missing in isoform 5.
VSP_026614
Alternative sequence239 – 28547Missing in isoform 4 and isoform 6.
VSP_026615
Alternative sequence385 – 44460Missing in isoform 2 and isoform 6.
VSP_013436
Alternative sequence844 – 87128PLDSM…DDAPL → RHLCRVRRKR in isoform 3.
VSP_013437
Natural variant191P → S Associated with lower sodium concentraions in serum; shows diminished response to hypotonic stress relative to wild-type. Ref.13
Corresponds to variant rs3742030 [ dbSNP | Ensembl ].
VAR_052391
Natural variant891T → I in MTD; lethal form. Ref.19
VAR_064517
Natural variant971P → R in DSMAC; loss of function mutation. Ref.28
VAR_067989
Natural variant1831E → K Found in a patient with spondyloepiphyseal dysplasia Maroteaux type. Ref.20
VAR_064518
Natural variant1971K → R in MTD; lethal form. Ref.19
VAR_064519
Natural variant1991L → F in MTD. Ref.21
VAR_064520
Natural variant2321R → C in DSMAC and CMT2C; does not affect channel localization to plasma membrane; results in increased agonist-induced channel activity and increased basal intracellular calcium concentration; causes increased cell death. Ref.27 Ref.28
VAR_067990
Natural variant2691R → C in CMT2C. Ref.24 Ref.27
VAR_063528
Natural variant2691R → H in DSMAC and CMT2C; increased agonist-induced channel activity and increased basal intracellular calcium concentration; causes increased cell death. Ref.22 Ref.23 Ref.24 Ref.27
VAR_063529
Natural variant2701G → V in FDAB; poorly expressed on the cell surface; mutant channels show a significantly reduced response to agonists. Ref.26
VAR_068498
Natural variant2711R → P in FDAB; poorly expressed on the cell surface; mutant channels show a significantly reduced response to agonists. Ref.26
VAR_068499
Natural variant2731F → L in FDAB; poorly expressed on the cell surface; mutant channels show a significantly reduced response to agonists. Ref.26
VAR_068500
Natural variant2781E → K in SMDK. Ref.21
VAR_064521
Natural variant2951T → A in MTD. Ref.21
VAR_064522
Natural variant3151R → W in CMT2C. Ref.22 Ref.25
VAR_063541
Natural variant3161R → C in CMT2C and SPSMA. Ref.22 Ref.23
VAR_063530
Natural variant3161R → H in CMT2C; does not affect channel localization to plasma membrane; results in increased agonist-induced channel activity and increased basal intracellular calcium concentration; causes increased cell death. Ref.27
VAR_067991
Natural variant3311I → F in MTD. Ref.18 Ref.19
VAR_062331
Natural variant3311I → T in MTD. Ref.21
VAR_064523
Natural variant333 – 3364Missing in SMDK.
VAR_067992
Natural variant3331D → G in SMDK. Ref.18
VAR_062332
Natural variant3421V → F in MTD. Ref.21
VAR_064524
Natural variant4711Missing in MTD; lethal form. Ref.19 Ref.21
VAR_064525
Natural variant5421S → Y in CMT2C. Ref.25
VAR_067993
Natural variant5921F → L in MTD. Ref.21
VAR_064526
Natural variant5941R → H in SMDK and PSTD. Ref.18 Ref.20 Ref.21
VAR_062333
Natural variant5961L → P in SMDK. Ref.21
VAR_064527
Natural variant6001G → W in SMDK. Ref.21
VAR_064528
Natural variant6021Y → C Found in a patient with spondyloepiphyseal dysplasia Maroteaux type. Ref.20
VAR_064529
Natural variant6041I → M in MTD; lethal form. Ref.19
VAR_064530
Natural variant6161R → Q in BRAC3; this mutation results in a gain of function and a constitutive activation of the channel. Ref.17
VAR_054805
Natural variant6171F → L in MTD. Ref.19
VAR_064531
Natural variant6181L → P in MTD. Ref.6 Ref.19
VAR_064532
Natural variant6201V → I in BRAC3; this mutation results in a gain of function and a constitutive activation of the channel. Ref.17
VAR_054806
Natural variant6251M → I in SMDK. Ref.21
VAR_064533
Natural variant7091L → M in SMDK. Ref.21
VAR_064534
Natural variant7161A → S in SMDK. Ref.18
VAR_062334
Natural variant7751R → K in MTD. Ref.21
VAR_064535
Natural variant7771C → Y in SMDK. Ref.21
VAR_064536
Natural variant7971E → K in MTD and SMDK; also found in a patient with spondyloepiphyseal dysplasia Maroteaux type. Ref.19 Ref.20 Ref.21
VAR_064537
Natural variant7991P → A in MTD. Ref.21
VAR_064538
Natural variant7991P → L in MTD; also found in a patient with spondyloepiphyseal dysplasia Maroteaux type. Ref.18 Ref.19 Ref.20 Ref.21
VAR_062335
Natural variant7991P → R in MTD. Ref.21
VAR_064539
Natural variant7991P → S in MTD. Ref.21
VAR_064540

Experimental info

Mutagenesis816 – 8216RLRRDR → ELEEDE: Loss of calmodulin binding; when associated with A-828.
Mutagenesis821 – 8244RWSS → AASA: Loss of calmodulin binding. Ref.14
Mutagenesis8221W → A: Loss of Ca(2+) dependent current potentiation.
Mutagenesis8241S → A: Loss of phosphorylation. Ref.14
Mutagenesis8241S → D: Up-regulation of its function. Ref.14
Mutagenesis8281R → A: Loss of calmodulin binding; when associated with 816-ELEEDE-821. Ref.11
Sequence conflict3851I → V in AAG28029. Ref.1
Sequence conflict4521V → A in BAC06573. Ref.6
Sequence conflict7811D → N in AAG28029. Ref.1
Sequence conflict8201D → T in BAB69040. Ref.4
Sequence conflict8611P → T in BAC06573. Ref.6
Sequence conflict8671D → E in AAG16127. Ref.2

Secondary structure

.......................................... 871
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (A) [UniParc].

Last modified April 26, 2005. Version 2.
Checksum: C62056B86C5A6FB6

FASTA87198,281
        10         20         30         40         50         60 
MADSSEGPRA GPGEVAELPG DESGTPGGEA FPLSSLANLF EGEDGSLSPS PADASRPAGP 

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

       130        140        150        160        170        180 
KRWRKKIIEK QPQSPKAPAP QPPPILKVFN RPILFDIVSR GSTADLDGLL PFLLTHKKRL 

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

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

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

       370        380        390        400        410        420 
NLEAVLNNDG LSPLMMAAKT GKIGIFQHII RREVTDEDTR HLSRKFKDWA YGPVYSSLYD 

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

       490        500        510        520        530        540 
AMVIFTLTAY YQPLEGTPPY PYRTTVDYLR LAGEVITLFT GVLFFFTNIK DLFMKKCPGV 

       550        560        570        580        590        600 
NSLFIDGSFQ LLYFIYSVLV IVSAALYLAG IEAYLAVMVF ALVLGWMNAL YFTRGLKLTG 

       610        620        630        640        650        660 
TYSIMIQKIL FKDLFRFLLV YLLFMIGYAS ALVSLLNPCA NMKVCNEDQT NCTVPTYPSC 

       670        680        690        700        710        720 
RDSETFSTFL LDLFKLTIGM GDLEMLSSTK YPVVFIILLV TYIILTFVLL LNMLIALMGE 

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

       790        800        810        820        830        840 
DEVNWSHWNQ NLGIINEDPG KNETYQYYGF SHTVGRLRRD RWSSVVPRVV ELNKNSNPDE 

       850        860        870 
VVVPLDSMGN PRCDGHQQGY PRKWRTDDAP L 

« Hide

Isoform 2 (B) (OTRPC4beta) [UniParc].

Checksum: A498FF4BBA1CD7A5
Show »

FASTA81191,261
Isoform 3 (TRPV-SV) [UniParc].

Checksum: EAA07196606AED20
Show »

FASTA85396,449
Isoform 4 (C) [UniParc].

Checksum: EA7AFC7497D14495
Show »

FASTA82492,904
Isoform 5 (D) [UniParc].

Checksum: 1538A7B2E76C8CDF
Show »

FASTA83794,998
Isoform 6 (E) [UniParc].

Checksum: B1307888F82B0E31
Show »

FASTA76485,884

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] (ISOFORM 1).
[2]"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] (ISOFORM 1), FUNCTION.
Tissue: Kidney cortex.
[3]"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] (ISOFORM 3).
[4]"Molecular cloning of a new member of vanilloid receptor channel-like proteins."
Ishibashi K.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]Kelsell R.E.
Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]Xu F., Satoh E., Iijima T.
Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT MTD PRO-618.
Tissue: Aortic endothelium.
[7]"Human TRPV4 channel splice variants revealed a key role of ankyrin domains in multimerization and trafficking."
Arniges M., Fernandez-Fernandez J.M., Albrecht N., Schaefer M., Valverde M.A.
J. Biol. Chem. 281:1580-1586(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5 AND 6), SUBCELLULAR LOCATION, SELF-ASSOCIATION.
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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] (ISOFORM 1).
Tissue: Colon.
[10]"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] OF 69-871.
[11]"Ca2+-dependent potentiation of the nonselective cation channel TRPV4 is mediated by a C-terminal calmodulin binding site."
Strotmann R., Schultz G., Plant T.D.
J. Biol. Chem. 278:26541-26549(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CALMODULIN, MUTAGENESIS OF 186-ARG--SER-824 AND ARG-828.
[12]"An environmental sensor, TRPV4 is a novel regulator of intracellular Ca2+ in human synoviocytes."
Itoh Y., Hatano N., Hayashi H., Onozaki K., Miyazawa K., Muraki K.
Am. J. Physiol. 297:C1082-C1090(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[13]"A loss-of-function nonsynonymous polymorphism in the osmoregulatory TRPV4 gene is associated with human hyponatremia."
Tian W., Fu Y., Garcia-Elias A., Fernandez-Fernandez J.M., Vicente R., Kramer P.L., Klein R.F., Hitzemann R., Orwoll E.S., Wilmot B., McWeeney S., Valverde M.A., Cohen D.M.
Proc. Natl. Acad. Sci. U.S.A. 106:14034-14039(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SSQTL1, ASSOCIATION OF VARIANT SER-19 WITH HYPONATREMIA.
[14]"Identification of a Protein Kinase C-dependent phosphorylation site involved in sensitization of TRPV4 channel."
Peng H., Lewandrowski U., Muller B., Sickmann A., Walz G., Wegierski T.
Biochem. Biophys. Res. Commun. 391:1721-1725(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-824, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF SER-824.
[15]"Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations."
Lanciotti A., Brignone M.S., Molinari P., Visentin S., De Nuccio C., Macchia G., Aiello C., Bertini E., Aloisi F., Petrucci T.C., Ambrosini E.
Hum. Mol. Genet. 21:2166-2180(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[16]"Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel."
Inada H., Procko E., Sotomayor M., Gaudet R.
Biochemistry 51:6195-6206(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 149-397 ALONE AND IN COMPLEX WITH ATP.
[17]"Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia."
Rock M.J., Prenen J., Funari V.A., Funari T.L., Merriman B., Nelson S.F., Lachman R.S., Wilcox W.R., Reyno S., Quadrelli R., Vaglio A., Owsianik G., Janssens A., Voets T., Ikegawa S., Nagai T., Rimoin D.L., Nilius B., Cohn D.H.
Nat. Genet. 40:999-1003(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BRAC3 GLN-616 AND ILE-620, CHARACTERIZATION OF VARIANTS BRAC3 GLN-616 AND ILE-620.
[18]"Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia."
Krakow D., Vriens J., Camacho N., Luong P., Deixler H., Funari T.L., Bacino C.A., Irons M.B., Holm I.A., Sadler L., Okenfuss E.B., Janssens A., Voets T., Rimoin D.L., Lachman R.S., Nilius B., Cohn D.H.
Am. J. Hum. Genet. 84:307-315(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SMDK GLY-333; HIS-594 AND SER-716, VARIANTS MTD PHE-331 AND LEU-799.
[19]"Dominant TRPV4 mutations in nonlethal and lethal metatropic dysplasia."
Camacho N., Krakow D., Johnykutty S., Katzman P.J., Pepkowitz S., Vriens J., Nilius B., Boyce B.F., Cohn D.H.
Am. J. Med. Genet. A 152:1169-1177(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTD ILE-89; ARG-197; PHE-331; PHE-471 DEL; MET-604; LEU-617; PRO-618; LYS-797 AND LEU-799.
[20]"Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations."
Nishimura G., Dai J., Lausch E., Unger S., Megarbane A., Kitoh H., Kim O.H., Cho T.J., Bedeschi F., Benedicenti F., Mendoza-Londono R., Silengo M., Schmidt-Rimpler M., Spranger J., Zabel B., Ikegawa S., Superti-Furga A.
Am. J. Med. Genet. A 152:1443-1449(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SEDM, VARIANT PSTD HIS-594, VARIANTS LYS-183; CYS-602; LYS-797 AND LEU-799.
[21]"Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family."
Dai J., Kim O.H., Cho T.J., Schmidt-Rimpler M., Tonoki H., Takikawa K., Haga N., Miyoshi K., Kitoh H., Yoo W.J., Choi I.H., Song H.R., Jin D.K., Kim H.T., Kamasaki H., Bianchi P., Grigelioniene G., Nampoothiri S. expand/collapse author list , Minagawa M., Miyagawa S.I., Fukao T., Marcelis C., Jansweijer M.C., Hennekam R.C., Bedeschi F., Mustonen A., Jiang Q., Ohashi H., Furuichi T., Unger S., Zabel B., Lausch E., Superti-Furga A., Nishimura G., Ikegawa S.
J. Med. Genet. 47:704-709(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTD PHE-199; ALA-295; THR-331; PHE-342; PHE-471 DEL; LEU-592; LYS-775; ALA-799; SER-799; LEU-799 AND ARG-799, VARIANTS SMDK LYS-278; HIS-594; PRO-596; TRP-600; ILE-625; MET-709; TYR-777 AND LYS-797.
[22]"Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C."
Auer-Grumbach M., Olschewski A., Papic L., Kremer H., McEntagart M.E., Uhrig S., Fischer C., Frohlich E., Balint Z., Tang B., Strohmaier H., Lochmuller H., Schlotter-Weigel B., Senderek J., Krebs A., Dick K.J., Petty R., Longman C. expand/collapse author list , Anderson N.E., Padberg G.W., Schelhaas H.J., van Ravenswaaij-Arts C.M., Pieber T.R., Crosby A.H., Guelly C.
Nat. Genet. 42:160-164(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMT2C TRP-315 AND CYS-316, VARIANT DSMAC HIS-269, SUBCELLULAR LOCATION.
[23]"Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4."
Deng H.X., Klein C.J., Yan J., Shi Y., Wu Y., Fecto F., Yau H.J., Yang Y., Zhai H., Siddique N., Hedley-Whyte E.T., Delong R., Martina M., Dyck P.J., Siddique T.
Nat. Genet. 42:165-169(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMT2C HIS-269, VARIANT SPSMA CYS-316, SUBCELLULAR LOCATION.
[24]"Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C."
Landoure G., Zdebik A.A., Martinez T.L., Burnett B.G., Stanescu H.C., Inada H., Shi Y., Taye A.A., Kong L., Munns C.H., Choo S.S., Phelps C.B., Paudel R., Houlden H., Ludlow C.L., Caterina M.J., Gaudet R., Kleta R., Fischbeck K.H., Sumner C.J.
Nat. Genet. 42:170-174(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMT2C CYS-269 AND HIS-269.
[25]"CMT2C with vocal cord paresis associated with short stature and mutations in the TRPV4 gene."
Chen D.H., Sul Y., Weiss M., Hillel A., Lipe H., Wolff J., Matsushita M., Raskind W., Bird T.
Neurology 75:1968-1975(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMT2C TRP-315 AND TYR-542.
[26]"Mutations in TRPV4 cause an inherited arthropathy of hands and feet."
Lamande S.R., Yuan Y., Gresshoff I.L., Rowley L., Belluoccio D., Kaluarachchi K., Little C.B., Botzenhart E., Zerres K., Amor D.J., Cole W.G., Savarirayan R., McIntyre P., Bateman J.F.
Nat. Genet. 43:1142-1146(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS FDAB VAL-270; PRO-271 AND LEU-273, CHARACTERIZATION OF VARIANTS FDAB VAL-270; PRO-271 AND LEU-273.
[27]"TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies."
Klein C.J., Shi Y., Fecto F., Donaghy M., Nicholson G., McEntagart M.E., Crosby A.H., Wu Y., Lou H., McEvoy K.M., Siddique T., Deng H.X., Dyck P.J.
Neurology 76:887-894(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMT2C CYS-232 AND HIS-316, CHARACTERIZATION OF VARIANTS CMT2C CYS-232; CYS-269; HIS-269 AND HIS-316.
[28]"TRPV4 mutations in children with congenital distal spinal muscular atrophy."
Fiorillo C., Moro F., Brisca G., Astrea G., Nesti C., Balint Z., Olschewski A., Meschini M.C., Guelly C., Auer-Grumbach M., Battini R., Pedemonte M., Romano A., Menchise V., Biancheri R., Santorelli F.M., Bruno C.
Neurogenetics 13:195-203(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS DSMAC ARG-97 AND CYS-232, CHARACTERIZATION OF VARIANT DSMAC ARG-97.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF263523 mRNA. Translation: AAG28029.1.
AF258465 mRNA. Translation: AAG16127.1.
AB100308 mRNA. Translation: BAC55864.1.
AB032427 mRNA. Translation: BAB69040.1.
AB073669 mRNA. Translation: BAC06573.1.
AJ296305 mRNA. Translation: CAC82937.1.
DQ059644 mRNA. Translation: AAZ04918.1.
DQ059645 mRNA. Translation: AAZ04919.1.
DQ059646 mRNA. Translation: AAZ04920.1.
CH471054 Genomic DNA. Translation: EAW97879.1.
BC117426 mRNA. Translation: AAI17427.1.
BC143315 mRNA. Translation: AAI43316.1.
AF279673 mRNA. Translation: AAK69487.1.
RefSeqNP_001170899.1. NM_001177428.1.
NP_001170902.1. NM_001177431.1.
NP_001170904.1. NM_001177433.1.
NP_067638.3. NM_021625.4.
NP_671737.1. NM_147204.2.
XP_005253975.1. XM_005253918.1.
XP_005253976.1. XM_005253919.1.
UniGeneHs.506713.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4DX1X-ray2.85A/B149-397[»]
4DX2X-ray2.95A/B149-397[»]
ProteinModelPortalQ9HBA0.
SMRQ9HBA0. Positions 148-397.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121883. 12 interactions.
DIPDIP-35702N.
IntActQ9HBA0. 3 interactions.
MINTMINT-4535111.

Chemistry

BindingDBQ9HBA0.
ChEMBLCHEMBL3119.
GuidetoPHARMACOLOGY510.

PTM databases

PhosphoSiteQ9HBA0.

Polymorphism databases

DMDM62901470.

Proteomic databases

PaxDbQ9HBA0.
PRIDEQ9HBA0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261740; ENSP00000261740; ENSG00000111199. [Q9HBA0-1]
ENST00000346520; ENSP00000319003; ENSG00000111199. [Q9HBA0-2]
ENST00000392719; ENSP00000376480; ENSG00000111199. [Q9HBA0-4]
ENST00000418703; ENSP00000406191; ENSG00000111199. [Q9HBA0-1]
ENST00000536838; ENSP00000444336; ENSG00000111199. [Q9HBA0-5]
ENST00000537083; ENSP00000442738; ENSG00000111199. [Q9HBA0-2]
ENST00000541794; ENSP00000442167; ENSG00000111199. [Q9HBA0-4]
ENST00000544971; ENSP00000443611; ENSG00000111199. [Q9HBA0-6]
GeneID59341.
KEGGhsa:59341.
UCSCuc001tpg.2. human. [Q9HBA0-5]
uc001tph.2. human. [Q9HBA0-4]
uc001tpi.2. human. [Q9HBA0-6]
uc001tpj.2. human. [Q9HBA0-1]
uc021rdp.1. human. [Q9HBA0-2]

Organism-specific databases

CTD59341.
GeneCardsGC12M110220.
HGNCHGNC:18083. TRPV4.
HPAHPA007150.
MIM113500. phenotype.
156530. phenotype.
168400. phenotype.
181405. phenotype.
184095. phenotype.
184252. phenotype.
600175. phenotype.
605427. gene.
606071. phenotype.
606835. phenotype.
613508. phenotype.
neXtProtNX_Q9HBA0.
Orphanet93304. Autosomal dominant brachyolmia.
99937. Autosomal dominant Charcot-Marie-Tooth disease type 2C.
1216. Autosomal dominant congenital benign spinal muscular atrophy.
85169. Familial digital arthropathy-brachydactyly.
2635. Metatropic dysplasia.
2646. Parastremmatic dwarfism.
85146. Scapuloperoneal amyotrophy.
263482. Spondyloepiphyseal dysplasia, Maroteaux type.
93314. Spondylometaphyseal dysplasia, Kozlowski type.
PharmGKBPA38293.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG278734.
HOVERGENHBG054085.
InParanoidQ9HBA0.
KOK04973.
OMAEDQTNCT.
OrthoDBEOG70S74P.
PhylomeDBQ9HBA0.
TreeFamTF314711.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.
SignaLinkQ9HBA0.

Gene expression databases

ArrayExpressQ9HBA0.
BgeeQ9HBA0.
GenevestigatorQ9HBA0.

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.
IPR024862. TRPV.
IPR008347. TRPV1-4_channel.
IPR008348. TRPV4_channel.
[Graphical view]
PANTHERPTHR10582. PTHR10582. 1 hit.
PTHR10582:SF4. PTHR10582:SF4. 1 hit.
PfamPF00023. Ank. 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

GeneWikiTRPV4.
GenomeRNAi59341.
NextBio65228.
PROQ9HBA0.
SOURCESearch...

Entry information

Entry nameTRPV4_HUMAN
AccessionPrimary (citable) accession number: Q9HBA0
Secondary accession number(s): B7ZKQ6 expand/collapse secondary AC list , Q17R79, Q2Y122, Q2Y123, Q2Y124, Q86YZ6, Q8NDY7, Q8NG64, Q96Q92, Q96RS7, Q9HBC0
Entry history
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: April 26, 2005
Last modified: April 16, 2014
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM