image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

TRPV4

Family: Transient Receptor Potential channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Ion Selectivity and Conductance
Voltage Dependence
Activators
Pore Blockers
Tissue Distribution
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
References
Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 871 12q24.1 TRPV4 transient receptor potential cation channel, subfamily V, member 4 5
Mouse 6 1 871 5 F Trpv4 transient receptor potential cation channel, subfamily V, member 4 5
Rat 6 1 871 12q16 Trpv4 transient receptor potential cation channel, subfamily V, member 4 5
Previous and Unofficial Names
OTRPC4
VRL-2
VR-OAC
TRP12
VROAC
CMT2C
osmosensitive transient receptor potential channel 4
Otrpc4-pending
osm-9-like TRP channel 4
transient receptor potential cation channel subfamily 5 member 4
transient receptor potential cation channel subfamily V member 4
transient receptor potential cation channel, subfamily 5, member 4
transient receptor potential cation channel, subfamily V, member 4
vanilloid receptor-related osmotically activated channel (Vroac)
vanilloid receptor-related osmotically-activated channel
0610033B08Rik
Database Links
Ensembl ENSG00000111199 (Hs), ENSMUSG00000014158 (Mm), ENSRNOG00000001195 (Rn)
Entrez Gene 59341 (Hs), 63873 (Mm), 66026 (Rn)
GeneCards TRPV4 (Hs)
GenitoUrinary Development Molecular Anatomy Project Trpv4 (Mm)
HomoloGene 11003 (Hs)
Human Protein Reference Database 05667 (Hs)
InterPro Q9HBA0 (Hs), Q9EPK8 (Mm), Q9ERZ8 (Rn)
KEGG Gene hsa:59341 (Hs), mmu:63873 (Mm), rno:66026 (Rn)
OMIM 605427 (Hs)
Orphanet Gene ORPHA171081 (Hs)
PharmGKB Gene PA38293 (Hs)
PhosphoSitePlus Q9HBA0 (Hs), Q9EPK8 (Mm), Q9ERZ8 (Rn)
Protein Ontology (PRO) PRO:000001068 (Hs)
RefSeq Nucleotide NM_021625 (Hs), NM_022017 (Mm), NM_023970 (Rn)
RefSeq Protein NP_067638 (Hs), NP_071300 (Mm), NP_076460 (Rn)
TreeFam ENSG00000111199 (Hs), ENSMUSG00000014158 (Mm), ENSRNOG00000001195 (Rn)
UniGene Hs. 506713 (Hs)
UniProt Q9HBA0 (Hs), Q9EPK8 (Mm), Q9ERZ8 (Rn)
Wikipedia TRPV4
Transient Receptor Potential channels
Search for 3D structures on the PDB
Search by keyword: Transient Receptor Potential channels TRPV4 Search by accession number: Q9HBA0, Q9ERZ8, Q9EPK8
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
pacsin 3 2
aquaporin 5 6,8
calmodulin 11
Ion Selectivity and Conductance
Species:  Mouse
Rank order:  Ca2+ > Mg2+ > K+ > Cs+ > Rb+ > Na+ > Li+
References:  10,15,18
Ion Selectivity and Conductance Comments
Conductance is ~30-60 pS at -60 mV, and ~88-100 pS at +60 mV.
Voltage Dependence Comments
Activation of TRPV4 is not voltage dependent.
Other chemical activators (Human)
epoxyeicosatrieonic acids and NO-mediated cysteine S-nitrosylation
Physical activators (Human)
constitutively active, heat (> 24°C - 32°C), mechanical stimuli
Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
4α-PDD Hs - - 3x10-7 Physiological 19
phorbol 12-myristate 13-acetate Hs 7.9 pEC50 - Physiological 19
5,6-epoxyeicosatrienoic acid Mm 6.9 pEC50 - -60.0 17
4α-PDD Mm 6.7 pEC50 - -80.0 16
bisandrographolide Mm 6.0 pEC50 - -60.0 9
citric acid Mm 5.6 pEC50 - 90.0 12
phorbol 12-myristate 13-acetate Mm 5.5 pEC50 - -80.0 16
View species-specific activator tables
Pore Blockers
Key to terms and symbols Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
ruthenium red Mm - - 1x10-6 -80.0 – 80.0 16

Explore drug-target interactions for this set of compounds using iPHACE

Tissue Distribution
Trachea, kidney, liver, lung, spleen, skin.
Species:  Human
Technique:  Northern Blot
References:  3
Brain, trigeminal ganglia, cochlea, lung, spleen, kidney, testes, fat.
Species:  Mouse
Technique:  In situ hybridisation, Northern Blot.
References:  5
Heart, kidney, liver, testes.
Species:  Mouse
Technique:  Northern Blot
References:  10
Functional Assays
Patch clamp (whole-cell and single-channel recordings).
Species:  Mouse
Tissue:  HEK 293 cells transfected with the TRPV4 vector.
Response measured:  Activation by osmotic changes.
References:  10
Patch clamp (whole-cell recordings).
Species:  Mouse
Tissue:  HEK 293, EA and mouse aortic endothelial cells.
Response measured:  Activation by 4α-phorbol 12,13-didecanoate and phorbol 12-myristate 13-acetate
References:  16
Intracellular Ca2+ imaging.
Species:  Mouse
Tissue:  CHO cells transfected with the TRPV4 vector.
Response measured:  Activation by osmotic changes.
References:  10
Patch clamp (whole-cell and single-channel recordings), intracellular Ca2+ imaging.
Species:  Mouse
Tissue:  HEK 293 cells transfected with the TRPV4 vector.
Response measured:  Activation by 5,6-epoxyeicosatrienoic acids.
References:  17
Patch clamp (whole-cell recordings), intracellular Ca2+ imaging, two-electrode voltage clamp.
Species:  Rat
Tissue:  Xenopus laevis oocytes injected with TRPV4 cDNA, HEK 293 cells transfected with the TRPV4 vector.
Response measured:  Activation by heat.
References:  4
Physiological Functions
Thermosensation (moderate heat).
Species:  Rat
Tissue:  Thermosensory regions of the hypothalamus.
References:  4
Osmotic stimulus-induced nociception, detection and integration of osmotic/mechanical stimuli.
Species:  Rat
Tissue:  Sensory neurones.
References:  1
Osmosensation.
Species:  Human
Tissue:  Dorsal root ganglia neurones, CHO cells.
References:  5
Physiological Consequences of Altering Gene Expression
Sensorineural hearing impairment
Species:  Mouse
Tissue:  Cochlea.
Technique:  TRPV4 knockdown
References:  13
Thermal hyperalgesia.
Species:  Mouse
Tissue:  Sensory neurons.
Technique:  TRPV4 knockdown
References:  14
Suppressed unloading-induced trabecular bone loss.
Species:  Mouse
Tissue:  Bone
Technique:  TRPV4 knockdown
References:  7
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpv4tm1Rck Trpv4tm1Rck/Trpv4tm1Rck
Not Specified		 MGI:1926945  MP:0001422 abnormal drinking behavior PMID: 14581612 
Trpv4tm1Rck Trpv4tm1Rck/Trpv4tm1Rck
Not Specified		 MGI:1926945  MP:0001784 abnormal fluid regulation PMID: 14581612 
Trpv4tm1Msz Trpv4tm1Msz/Trpv4tm1Msz
involves: 129X1/SvJ * C57BL/6		 MGI:1926945  MP:0005316 abnormal response to tactile stimuli PMID: 12692122 
Trpv4tm1Msz Trpv4tm1Msz/Trpv4tm1Msz
involves: 129X1/SvJ * C57BL/6		 MGI:1926945  MP:0002067 abnormal sensory capabilities/reflexes/nociception PMID: 12692122 
Trpv4tm1Rck Trpv4tm1Rck/Trpv4tm1Rck
Not Specified		 MGI:1926945  MP:0008998 decreased blood osmolality PMID: 14581612 
Trpv4tm1Msz Trpv4tm1Msz/Trpv4tm1Msz
involves: 129X1/SvJ * C57BL/6		 MGI:1926945  MP:0004765 decreased brainstem auditory evoked potential PMID: 15925108 
Trpv4tm1Rck Trpv4tm1Rck/Trpv4tm1Rck
Not Specified		 MGI:1926945  MP:0005611 decreased circulating antidiuretic hormone level PMID: 14581612 
Trpv4tm1Rck Trpv4tm1Rck/Trpv4tm1Rck
Not Specified		 MGI:1926945  MP:0003912 decreased drinking behavior PMID: 14581612 
Trpv4tm1Rck Trpv4tm1Rck/Trpv4tm1Rck
Not Specified		 MGI:1926945  MP:0005498 hyporesponsive to tactile stimuli PMID: 14581612 
Trpv4tm1Msz Trpv4tm1Msz/Trpv4tm1Msz
involves: 129X1/SvJ * C57BL/6		 MGI:1926945  MP:0006325 impaired hearing PMID: 15925108 
Trpv4tm1Rck Trpv4tm1Rck/Trpv4tm1Rck
Not Specified		 MGI:1926945  MP:0008997 increased blood osmolality PMID: 14581612 
Trpv4tm1Msz Trpv4tm1Msz/Trpv4tm1Msz
involves: 129X1/SvJ * C57BL/6		 MGI:1926945  MP:0008531 increased chemical nociceptive threshold PMID: 12692122 
Trpv4tm1Msz Trpv4tm1Msz/Trpv4tm1Msz
involves: 129X1/SvJ * C57BL/6		 MGI:1926945  MP:0004597 increased susceptibility to noise-induced hearing loss PMID: 15925108 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Spondyloepiphyseal dysplasia, Maroteaux type
OMIM:  184095
Orphanet:  263482
References: 
Mutations not determined
Disease:  Brachyolmia type 3
OMIM:  113500
Orphanet:  93304
References: 
Mutations not determined
Disease:  Parastremmatic dwarfism
OMIM:  168400
Orphanet:  2646
References: 
Mutations not determined
Disease:  Metatropic dysplasia
OMIM:  156530
Orphanet:  2635
References: 
Mutations not determined
Disease:  Congenital nonprogressive spinal muscular atrophy of lower limbs
OMIM:  600175
Orphanet:  1216
References: 
Mutations not determined
Disease:  Scapuloperoneal spinal muscular atrophy; SPSMA
OMIM:  181405
Orphanet:  85146
References: 
Mutations not determined
Disease:  Spondylometaphyseal dysplasia, Kozlowski type; SMDK
OMIM:  184252
Orphanet:  93314
References: 
Mutations not determined
Disease:  Hereditary motor and sensory neuropathy, type IIc
OMIM:  606071
Orphanet:  99937
References: 
Mutations not determined

REFERENCES

Show »

1. Alessandri-Haber, N; Yeh, JJ; Boyd, AE; Parada, CA; Chen, X; Reichling, DB; Levine, JD. (2003) Hypotonicity induces TRPV4-mediated nociception in rat. Neuron, 39 (3): 497-511. [PMID:12895423]

2. Cuajungco, MP; Grimm, C; Oshima, K; D'hoedt, D; Nilius, B; Mensenkamp, AR; Bindels, RJ; Plomann, M; Heller, S. (2006) PACSINs bind to the TRPV4 cation channel. PACSIN 3 modulates the subcellular localization of TRPV4. J. Biol. Chem., 281 (27): 18753-62. [PMID:16627472]

3. Delany, NS; Hurle, M; Facer, P; Alnadaf, T; Plumpton, C; Kinghorn, I; See, CG; Costigan, M; Anand, P; Woolf, CJ; Crowther, D; Sanseau, P; Tate, SN. (2001) Identification and characterization of a novel human vanilloid receptor-like protein, VRL-2. Physiol. Genomics, 4 (3): 165-74. [PMID:11160995]

4. Guler, AD; Lee, H; Iida, T; Shimizu, I; Tominaga, M; Caterina, M. (2002) Heat-evoked activation of the ion channel, TRPV4. J. Neurosci., 22 (15): 6408-14. [PMID:12151520]

5. Liedtke, W; Choe, Y; Martí-Renom, MA; Bell, AM; Denis, CS; Sali, A; Hudspeth, AJ; Friedman, JM; Heller, S. (2000) Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell, 103 (3): 525-35. [PMID:11081638]

6. Liu, X; Bandyopadhyay, BC; Bandyopadhyay, B; Nakamoto, T; Singh, B; Liedtke, W; Melvin, JE; Ambudkar, I. (2006) A role for AQP5 in activation of TRPV4 by hypotonicity: concerted involvement of AQP5 and TRPV4 in regulation of cell volume recovery. J. Biol. Chem., 281 (22): 15485-95. [PMID:16571723]

7. Mizoguchi, F; Mizuno, A; Hayata, T; Nakashima, K; Heller, S; Ushida, T; Sokabe, M; Miyasaka, N; Suzuki, M; Ezura, Y; Noda, M. (2008) Transient receptor potential vanilloid 4 deficiency suppresses unloading-induced bone loss. J. Cell. Physiol., 216 (1): 47-53. [PMID:18264976]

8. Sidhaye, VK; Guler, AD; Schweitzer, KS; D'Alessio, F; Caterina, MJ; King, LS. (2006) Transient receptor potential vanilloid 4 regulates aquaporin-5 abundance under hypotonic conditions. Proc. Natl. Acad. Sci. U.S.A., 103 (12): 4747-52. [PMID:16537379]

9. Smith, PL; Maloney, KN; Pothen, RG; Clardy, J; Clapham, DE. (2006) Bisandrographolide from Andrographis paniculata activates TRPV4 channels. J. Biol. Chem., 281 (40): 29897-904. [PMID:16899456]

10. Strotmann, R; Harteneck, C; Nunnenmacher, K; Schultz, G; Plant, TD. (2000) OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat. Cell Biol., 2 (10): 695-702. [PMID:11025659]

11. Strotmann, R; Schultz, G; Plant, TD. (2003) Ca2+-dependent potentiation of the nonselective cation channel TRPV4 is mediated by a C-terminal calmodulin binding site. J. Biol. Chem., 278 (29): 26541-9. [PMID:12724311]

12. Suzuki, M; Mizuno, A; Kodaira, K; Imai, M. (2003) Impaired pressure sensation in mice lacking TRPV4. J. Biol. Chem., 278 (25): 22664-8. [PMID:12692122]

13. Tabuchi, K; Suzuki, M; Mizuno, A; Hara, A. (2005) Hearing impairment in TRPV4 knockout mice. Neurosci. Lett., 382 (3): 304-8. [PMID:15925108]

14. Todaka, H; Taniguchi, J; Satoh, J; Mizuno, A; Suzuki, M. (2004) Warm temperature-sensitive transient receptor potential vanilloid 4 (TRPV4) plays an essential role in thermal hyperalgesia. J. Biol. Chem., 279 (34): 35133-8. [PMID:15187078]

15. Voets, T; Prenen, J; Vriens, J; Watanabe, H; Janssens, A; Wissenbach, U; Bödding, M; Droogmans, G; Nilius, B. (2002) Molecular determinants of permeation through the cation channel TRPV4. J. Biol. Chem., 277 (37): 33704-10. [PMID:12093812]

16. Watanabe, H; Davis, JB; Smart, D; Jerman, JC; Smith, GD; Hayes, P; Vriens, J; Cairns, W; Wissenbach, U; Prenen, J; Flockerzi, V; Droogmans, G; Benham, CD; Nilius, B. (2002) Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives. J. Biol. Chem., 277 (16): 13569-77. [PMID:11827975]

17. Watanabe, H; Vriens, J; Prenen, J; Droogmans, G; Voets, T; Nilius, B. (2003) Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature, 424 (6947): 434-8. [PMID:12879072]

18. Watanabe, H; Vriens, J; Suh, SH; Benham, CD; Droogmans, G; Nilius, B. (2002) Heat-evoked activation of TRPV4 channels in a HEK293 cell expression system and in native mouse aorta endothelial cells. J. Biol. Chem., 277 (49): 47044-51. [PMID:12354759]

19. Xu, F; Satoh, E; Iijima, T. (2003) Protein kinase C-mediated Ca2+ entry in HEK 293 cells transiently expressing human TRPV4. Br. J. Pharmacol., 140 (2): 413-21. [PMID:12970074]

To cite this database page, please use the following:

David E. Clapham, Bernd Nilius, Grzegorz Owsianik.
Transient Receptor Potential channels: TRPV4. Last modified on 11/10/2012. Accessed on 20/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=510.


Contact us | Print | Back to top | Help