TRPV4
entrez
59341
canonical
uniprot
Q9HBA0
canonical
ensembl
ENSG00000111199
resolver
ensp
ENSP00000261740
resolver
ensp
ENSP00000442167
resolver
ensp
ENSP00000442738
resolver
ensp
ENSP00000443611
resolver
ensp
ENSP00000444336
resolver
ensp
ENSP00000704327
resolver
genesymbol
TRPV4
resolver
genesymbol_syn
VRL2
resolver
genesymbol_syn
VROAC
resolver
hgnc
HGNC:18083
resolver
uniprot
B7ZKQ6
resolver
uniprot
Q17R79
resolver
uniprot
Q2Y122
resolver
uniprot
Q2Y123
resolver
uniprot
Q2Y124
resolver
uniprot
Q86YZ6
resolver
uniprot
Q8NDY7
resolver
uniprot
Q8NG64
resolver
uniprot
Q96Q92
resolver
uniprot
Q96RS7
resolver
uniprot
Q9HBC0
resolver
uniprot_entry
TRPV4_HUMAN
resolver
uniprot_sec
B7ZKQ6
resolver
uniprot_sec
Q17R79
resolver
uniprot_sec
Q2Y122
resolver
uniprot_sec
Q2Y123
resolver
uniprot_sec
Q2Y124
resolver
uniprot_sec
Q86YZ6
resolver
uniprot_sec
Q8NDY7
resolver
uniprot_sec
Q8NG64
resolver
uniprot_sec
Q96Q92
resolver
uniprot_sec
Q96RS7
resolver
uniprot_sec
Q9HBC0
resolver
activity_regulation
ACTIVITY REGULATION: Channel activation is inhibited by binding to phosphatidylinositol-4,5-bisphosphate, and to a much lesser degree by phosphatidylinositol-3,4,5-trisphosphate. Not inhibited by phosphatidylinositol-3,4-bisphosphate and phosphatidylinositol-3,5-bisphosphate. {ECO:0000269|PubMed:25256292}.
uniprot
proteins
amino_acid_sequence
MADSSEGPRAGPGEVAELPGDESGTPGGEAFPLSSLANLFEGEDGSLSPSPADASRPAGPGDGRPNLRMKFQGAFRKGVPNPIDLLESTLYESSVVPGPKKAPMDSLFDYGTYRHHSSDNKRWRKKIIEKQPQSPKAPAPQPPPILKVFNRPILFDIVSRGSTADLDGLLPFLLTHKKRLTDEEFREPSTGKTCLPKALLNLSNGRNDTIPVLLDIAERTGNMREFINSPFRDIYYRGQTALHIAIERRCKHYVELLVAQGADVHAQARGRFFQPKDEGGYFYFGELPLSLAACTNQPHIVNYLTENPHKKADMRRQDSRGNTVLHALVAIADNTRENTKFVTKMYDLLLLKCARLFPDSNLEAVLNNDGLSPLMMAAKTGKIGIFQHIIRREVTDEDTRHLSRKFKDWAYGPVYSSLYDLSSLDTCGEEASVLEILVYNSKIENRHEMLAVEPINELLRDKWRKFGAVSFYINVVSYLCAMVIFTLTAYYQPLEGTPPYPYRTTVDYLRLAGEVITLFTGVLFFFTNIKDLFMKKCPGVNSLFIDGSFQLLYFIYSVLVIVSAALYLAGIEAYLAVMVFALVLGWMNALYFTRGLKLTGTYSIMIQKILFKDLFRFLLVYLLFMIGYASALVSLLNPCANMKVCNEDQTNCTVPTYPSCRDSETFSTFLLDLFKLTIGMGDLEMLSSTKYPVVFIILLVTYIILTFVLLLNMLIALMGETVGQVSKESKHIWKLQWATTILDIERSFPVFLRKAFRSGEMVTVGKSSDGTPDRRWCFRVDEVNWSHWNQNLGIINEDPGKNETYQYYGFSHTVGRLRRDRWSSVVPRVVELNKNSNPDEVVVPLDSMGNPRCDGHQQGYPRKWRTDDAPL
uniprot
proteins
disease_involvement
DISEASE: Brachyolmia 3 (BCYM3) [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. BCYM3 is an autosomal dominant form with severe scoliosis with or without kyphosis, and flattened irregular cervical vertebrae. {ECO:0000269|PubMed:18587396}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:19232556, ECO:0000269|PubMed:20577006, ECO:0000269|PubMed:22702953}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:19232556, ECO:0000269|PubMed:20425821, ECO:0000269|PubMed:20577006, ECO:0000269|PubMed:22702953, ECO:0000269|PubMed:26249260, ECO:0000269|Ref.6}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neuronopathy, distal hereditary motor, autosomal dominant 8 (HMND8) [MIM:600175]: A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. {ECO:0000269|PubMed:20037588, ECO:0000269|PubMed:22526352, ECO:0000269|PubMed:22702953}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease, axonal, autosomal dominant, type 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. {ECO:0000269|PubMed:20037586, ECO:0000269|PubMed:20037587, ECO:0000269|PubMed:20037588, ECO:0000269|PubMed:21115951, ECO:0000269|PubMed:21288981, ECO:0000269|PubMed:22702953, ECO:0000269|PubMed:25256292}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:20037587, ECO:0000269|PubMed:22702953}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spondyloepiphyseal dysplasia, Maroteaux type (SEDM) [MIM:184095]: An autosomal dominant, 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. {ECO:0000269|PubMed:20503319, ECO:0000269|PubMed:22702953}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:20503319}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:21964574}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Avascular necrosis of the femoral head, primary 2 (ANFH2) [MIM:617383]: A disease characterized by mechanical failure of the subchondral bone, and degeneration of the hip joint. It usually leads to destruction of the hip joint in the third to fifth decade of life. The clinical manifestations, such as pain on exertion, a limping gait, and a discrepancy in leg length, cause considerable disability. {ECO:0000269|PubMed:27330106}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity (PubMed:16293632, PubMed:18695040, PubMed:18826956, PubMed:22526352, PubMed:23136043, PubMed:29899501). Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:18695040, PubMed:18826956, PubMed:29899501). Also activated by heat, low pH, citrate and phorbol esters (PubMed:16293632, PubMed:18695040, PubMed:18826956, PubMed:20037586, PubMed:21964574, PubMed:25256292). Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism (PubMed:12724311, PubMed:18826956). Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers (By similarity). Acts as a regulator of intracellular Ca(2+) in synoviocytes (PubMed:19759329). 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 (PubMed:19759329). Together with PKD2, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). Negatively regulates expression of PPARGC1A, UCP1, oxidative metabolism and respiration in adipocytes (By similarity). Regulates expression of chemokines and cytokines related to pro-inflammatory pathway in adipocytes (By similarity). Together with AQP5, controls regulatory volume decrease in salivary epithelial cells (By similarity). Required for normal development and maintenance of bone and cartilage (PubMed:26249260). In its inactive state, may sequester DDX3X at the plasma membrane. When activated, the interaction between both proteins is affected and DDX3X relocalizes to the nucleus (PubMed:29899501). In neurons of the central nervous system, could play a role in triggering voluntary water intake in response to increased sodium concentration in body fluid (By similarity). {ECO:0000250|UniProtKB:Q9EPK8, ECO:0000269|PubMed:11025659, ECO:0000269|PubMed:12724311, ECO:0000269|PubMed:16293632, ECO:0000269|PubMed:18587396, ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:18826956, ECO:0000269|PubMed:19759329, ECO:0000269|PubMed:20037586, ECO:0000269|PubMed:21964574, ECO:0000269|PubMed:23136043, ECO:0000269|PubMed:25256292, ECO:0000269|PubMed:26249260, ECO:0000269|PubMed:29899501}.; FUNCTION: [Isoform 1]: Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by phorbol esters. Has the same channel activity as isoform 1, and is activated by the same stimuli. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 5]: Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by phorbol esters. Has the same channel activity as isoform 1, and is activated by the same stimuli. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 2]: Lacks channel activity, due to impaired oligomerization and intracellular retention. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 4]: Lacks channel activity, due to impaired oligomerization and intracellular retention. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 6]: Lacks channel activity, due to impaired oligomerization and intracellular retention. {ECO:0000269|PubMed:16293632}.; FUNCTION: (Microbial infection) Facilitates hepatitis C virus (HCV) replication, possibly through its action on DDX3X. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Dengue virus (DENV) replication, possibly through its action on DDX3X. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Zika virus (ZIKV) replication, possibly through its action on DDX3X. {ECO:0000269|PubMed:29899501}.
uniprot
proteins
mass_dalton
98281
uniprot
proteins
mutagenesis
MUTAGEN 231; /note="F->C: Decreased ATP-binding."; /evidence="ECO:0000269|PubMed:22702953"; MUTAGEN 251; /note="K->E: No effect on channel activity. No effect on interaction with membranes enriched in phosphatidylinositol-2,4-bisphosphate."; /evidence="ECO:0000269|PubMed:25256292"; MUTAGEN 296; /note="N->D: Loss of interaction with membranes enriched in phosphatidylinositol-2,4-bisphosphate; when associated with P-299."; /evidence="ECO:0000269|PubMed:25256292"; MUTAGEN 299; /note="H->P: Strongly decreased interaction with membranes enriched in phosphatidylinositol-2,4-bisphosphate. Loss of interaction with membranes enriched in phosphatidylinositol-2,4-bisphosphate; when associated with D-296."; /evidence="ECO:0000269|PubMed:25256292"; MUTAGEN 344; /note="K->E: No effect on channel activity. No effect on interaction with membranes enriched in phosphatidylinositol-2,4-bisphosphate."; /evidence="ECO:0000269|PubMed:25256292"; MUTAGEN 680; /note="M->D: Loss of Ca(2+) influx. Loss of DDX3X translocation to the nucleus."; /evidence="ECO:0000269|PubMed:29899501"; MUTAGEN 816..821; /note="RLRRDR->ELEEDE: Loss of calmodulin binding; when associated with A-828."; MUTAGEN 821..824; /note="RWSS->AASA: Loss of calmodulin binding."; MUTAGEN 822; /note="W->A: Loss of Ca(2+) dependent current potentiation."; MUTAGEN 828; /note="R->A: Loss of calmodulin binding; when associated with 816-ELEEDE-821."; /evidence="ECO:0000269|PubMed:12724311
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:16293632, ECO:0000269|PubMed:21964574}.
uniprot
proteins
protein_family
TRPV4 sub-subfamily
uniprot
proteins
protein_family
Transient receptor (TC 1.A.4) family
uniprot
proteins
protein_family
TrpV subfamily
uniprot
proteins
pubmed
11025659
uniprot
proteins
pubmed
11081638
uniprot
proteins
pubmed
12692122
uniprot
proteins
pubmed
12724311
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16293632
uniprot
proteins
pubmed
16403833
uniprot
proteins
pubmed
18587396
uniprot
proteins
pubmed
18695040
uniprot
proteins
pubmed
18826956
uniprot
proteins
pubmed
19232556
uniprot
proteins
pubmed
19666518
uniprot
proteins
pubmed
19759329
uniprot
proteins
pubmed
20037586
uniprot
proteins
pubmed
20037587
uniprot
proteins
pubmed
20037588
uniprot
proteins
pubmed
20425821
uniprot
proteins
pubmed
20503319
uniprot
proteins
pubmed
20577006
uniprot
proteins
pubmed
21115951
uniprot
proteins
pubmed
21288981
uniprot
proteins
pubmed
21964574
uniprot
proteins
pubmed
22328087
uniprot
proteins
pubmed
22526352
uniprot
proteins
pubmed
22702953
uniprot
proteins
pubmed
23136043
uniprot
proteins
pubmed
25256292
uniprot
proteins
pubmed
26249260
uniprot
proteins
pubmed
27330106
uniprot
proteins
pubmed
29899501
uniprot
proteins
sequence_length
871
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16403833, ECO:0000269|PubMed:29899501}. Apical cell membrane {ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:18826956}; Multi-pass membrane protein {ECO:0000305}. Cell junction, adherens junction {ECO:0000250|UniProtKB:Q9EPK8}. Cell projection, cilium {ECO:0000269|PubMed:18695040}. Note=Assembly of the putative homotetramer occurs primarily in the endoplasmic reticulum (PubMed:16293632, PubMed:20037587, PubMed:20037588). Localization to the cell membrane is inhibited by WNK kinases (WNK1, WNK2, WNK3 or WNK4) in a kinase-independent mechanism (PubMed:16403833). {ECO:0000269|PubMed:16293632, ECO:0000269|PubMed:16403833, ECO:0000269|PubMed:20037587, ECO:0000269|PubMed:20037588}.; SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:16293632, ECO:0000269|PubMed:21964574, ECO:0000269|PubMed:25256292}.; SUBCELLULAR LOCATION: [Isoform 5]: Cell membrane {ECO:0000269|PubMed:16293632}.; SUBCELLULAR LOCATION: [Isoform 2]: Endoplasmic reticulum {ECO:0000269|PubMed:16293632}.; SUBCELLULAR LOCATION: [Isoform 4]: Endoplasmic reticulum {ECO:0000269|PubMed:16293632}.; SUBCELLULAR LOCATION: [Isoform 6]: Endoplasmic reticulum {ECO:0000269|PubMed:16293632}.
uniprot
proteins
transmembrane_region
TRANSMEM 470..490; /note="Helical"; /evidence="ECO:0000250|UniProtKB:O35433"; TRANSMEM 508..534; /note="Helical"; /evidence="ECO:0000250|UniProtKB:O35433"; TRANSMEM 548..568; /note="Helical"; /evidence="ECO:0000250|UniProtKB:O35433"; TRANSMEM 573..593; /note="Helical"; /evidence="ECO:0000250|UniProtKB:O35433"; TRANSMEM 609..636; /note="Helical"; /evidence="ECO:0000250|UniProtKB:O35433"; TRANSMEM 694..722; /note="Helical"; /evidence="ECO:0000250|UniProtKB:O35433
uniprot
proteins