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Protein

Transient receptor potential cation channel subfamily V member 4

Gene

TRPV4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (PubMed:18826956, PubMed:18695040). Also activated by heat, low pH, citrate and phorbol esters (PubMed:16293632, PubMed:18826956, PubMed:18695040, PubMed:25256292, PubMed:20037586, PubMed:21964574). Increase of intracellular Ca2+ 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 Ca2+ 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 proinflammatory 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).By similarity11 Publications
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.1 Publication
Isoform 2: Lacks channel activity, due to impaired oligomerization and intracellular retention.1 Publication
Isoform 4: Lacks channel activity, due to impaired oligomerization and intracellular retention.1 Publication
Isoform 6: Lacks channel activity, due to impaired oligomerization and intracellular retention.1 Publication

Enzyme regulationi

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei192ATPCombined sources1 Publication1
Binding sitei197ATPCombined sources1 Publication1
Binding sitei201ATPCombined sources1 Publication1
Binding sitei248ATPCombined sources1 Publication1
Binding sitei344Phosphatidylinositol-1,4,5-trisphosphateBy similarity1
Metal bindingi682Calcium; shared with neighboring subunitsBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi236 – 239ATPCombined sources1 Publication4

GO - Molecular functioni

  • actin binding Source: BHF-UCL
  • actin filament binding Source: BHF-UCL
  • alpha-tubulin binding Source: BHF-UCL
  • ATP binding Source: UniProtKB-KW
  • beta-tubulin binding Source: BHF-UCL
  • calcium channel activity Source: UniProtKB
  • calmodulin binding Source: UniProtKB
  • cation channel activity Source: UniProtKB
  • identical protein binding Source: IntAct
  • lipid binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • microtubule binding Source: BHF-UCL
  • osmosensor activity Source: Ensembl
  • protein kinase binding Source: BHF-UCL
  • protein kinase C binding Source: BHF-UCL
  • SH2 domain binding Source: BHF-UCL
  • stretch-activated, cation-selective, calcium channel activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionCalcium channel, Calmodulin-binding, Ion channel
Biological processCalcium transport, Ion transport, Transport
LigandATP-binding, Calcium, Lipid-binding, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-3295583 TRP channels
SignaLinkiQ9HBA0
SIGNORiQ9HBA0

Names & Taxonomyi

Protein namesi
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:
OTRPC41 Publication
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 channel1 Publication
Short name:
VR-OAC1 Publication
Gene namesi
Name:TRPV4
Synonyms:VRL2, VROAC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000111199.10
HGNCiHGNC:18083 TRPV4
MIMi605427 gene
neXtProtiNX_Q9HBA0

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 469CytoplasmicBy similarityAdd BLAST469
Transmembranei470 – 490HelicalBy similarityAdd BLAST21
Topological domaini491 – 507ExtracellularBy similarityAdd BLAST17
Transmembranei508 – 534HelicalBy similarityAdd BLAST27
Topological domaini535 – 547CytoplasmicBy similarityAdd BLAST13
Transmembranei548 – 568HelicalBy similarityAdd BLAST21
Topological domaini569 – 572ExtracellularBy similarity4
Transmembranei573 – 593HelicalBy similarityAdd BLAST21
Topological domaini594 – 608CytoplasmicBy similarityAdd BLAST15
Transmembranei609 – 636HelicalBy similarityAdd BLAST28
Topological domaini637 – 665ExtracellularBy similarityAdd BLAST29
Intramembranei666 – 685Pore-formingBy similarityAdd BLAST20
Topological domaini686 – 693ExtracellularBy similarity8
Transmembranei694 – 722HelicalBy similarityAdd BLAST29
Topological domaini723 – 871CytoplasmicBy similarityAdd BLAST149

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cilium, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Brachyolmia 3 (BCYM3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:113500
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054805616R → Q in BCYM3; results in a gain of function and a constitutive activation of the channel. 1 PublicationCorresponds to variant dbSNP:rs121912632EnsemblClinVar.1
Natural variantiVAR_054806620V → I in BCYM3; results in a gain of function and a constitutive activation of the channel. 1 PublicationCorresponds to variant dbSNP:rs121912633EnsemblClinVar.1
Spondylometaphyseal dysplasia Kozlowski type (SMDK)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:184252
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064521278E → K in SMDK; slightly increased ATP-binding; slightly decreased protein stability. 2 PublicationsCorresponds to variant dbSNP:rs267607148EnsemblClinVar.1
Natural variantiVAR_067992333 – 336Missing in SMDK. 4
Natural variantiVAR_062332333D → G in SMDK; decreased protein stability; no effect on ATP-binding. 2 PublicationsCorresponds to variant dbSNP:rs121912634EnsemblClinVar.1
Natural variantiVAR_064527596L → P in SMDK. 1 PublicationCorresponds to variant dbSNP:rs515726159EnsemblClinVar.1
Natural variantiVAR_064528600G → W in SMDK. 1 PublicationCorresponds to variant dbSNP:rs515726160EnsemblClinVar.1
Natural variantiVAR_064533625M → I in SMDK. 1 PublicationCorresponds to variant dbSNP:rs515726164EnsemblClinVar.1
Natural variantiVAR_064534709L → M in SMDK. 1 PublicationCorresponds to variant dbSNP:rs116571438EnsemblClinVar.1
Natural variantiVAR_062334716A → S in SMDK. 1 PublicationCorresponds to variant dbSNP:rs121912635EnsemblClinVar.1
Natural variantiVAR_064536777C → Y in SMDK. 1 PublicationCorresponds to variant dbSNP:rs515726165EnsemblClinVar.1
Metatropic dysplasia (MTD)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:156530
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06451789T → I in MTD; lethal form. 1 PublicationCorresponds to variant dbSNP:rs397514473EnsemblClinVar.1
Natural variantiVAR_064519197K → R in MTD; lethal form; decreased protein stability; reduced ATP-binding. 2 PublicationsCorresponds to variant dbSNP:rs387906903EnsemblClinVar.1
Natural variantiVAR_064520199L → F in MTD; decreased protein stability. 2 PublicationsCorresponds to variant dbSNP:rs515726167EnsemblClinVar.1
Natural variantiVAR_064522295T → A in MTD; impairs protein folding or stability. 2 PublicationsCorresponds to variant dbSNP:rs515726171EnsemblClinVar.1
Natural variantiVAR_062331331I → F in MTD; decreased protein stability; no effect on ATP-binding. 3 PublicationsCorresponds to variant dbSNP:rs121912636EnsemblClinVar.1
Natural variantiVAR_064523331I → T in MTD; no effect on protein stability; no effect on ATP-binding. 2 PublicationsCorresponds to variant dbSNP:rs515726172EnsemblClinVar.1
Natural variantiVAR_064524342V → F in MTD; decreased protein stability; decreased ATP-binding. 2 PublicationsCorresponds to variant dbSNP:rs515726152EnsemblClinVar.1
Natural variantiVAR_064525471Missing in MTD; lethal form. 2 Publications1
Natural variantiVAR_064526592F → L in MTD. 1 PublicationCorresponds to variant dbSNP:rs515726158EnsemblClinVar.1
Natural variantiVAR_064530604I → M in MTD; lethal form. 1 PublicationCorresponds to variant dbSNP:rs515726161EnsemblClinVar.1
Natural variantiVAR_064531617F → L in MTD. 1 PublicationCorresponds to variant dbSNP:rs515726162EnsemblClinVar.1
Natural variantiVAR_064532618L → P in MTD. 2 PublicationsCorresponds to variant dbSNP:rs515726163EnsemblClinVar.1
Natural variantiVAR_064535775R → K in MTD. 1 Publication1
Natural variantiVAR_064538799P → A in MTD. 1 PublicationCorresponds to variant dbSNP:rs267607147EnsemblClinVar.1
Natural variantiVAR_062335799P → L in MTD; also found in a patient with spondyloepiphyseal dysplasia Maroteaux type. 5 PublicationsCorresponds to variant dbSNP:rs121912637EnsemblClinVar.1
Natural variantiVAR_064539799P → R in MTD. 1 PublicationCorresponds to variant dbSNP:rs121912637EnsemblClinVar.1
Natural variantiVAR_064540799P → S in MTD. 1 PublicationCorresponds to variant dbSNP:rs267607147EnsemblClinVar.1
Neuronopathy, distal hereditary motor, 8 (HMN8)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:600175
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06798997P → R in HMN8; loss of function mutation. 1 PublicationCorresponds to variant dbSNP:rs876661124EnsemblClinVar.1
Charcot-Marie-Tooth disease 2C (CMT2C)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:606071
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063528269R → C in CMT2C; increased agonist-induced channel activity; causes increased cell death; no effect on protein stability and ATP-binding. 3 PublicationsCorresponds to variant dbSNP:rs267607146EnsemblClinVar.1
Natural variantiVAR_063541315R → W in CMT2C; increased basal and agonist-induced channel activity, decreased protein stability; decreased ATP-binding; decreases binding to membranes enriched in phosphatidylinositol-2,4-bisphosphate; causes increased cell death. 4 PublicationsCorresponds to variant dbSNP:rs267607143EnsemblClinVar.1
Natural variantiVAR_067991316R → H in CMT2C; does not affect channel localization to plasma membrane; results in increased agonist-induced channel activity and increased basal intracellular calcium concentration; decreases protein stability; causes increased cell death. 2 PublicationsCorresponds to variant dbSNP:rs387906905EnsemblClinVar.1
Natural variantiVAR_067993542S → Y in CMT2C. 1 PublicationCorresponds to variant dbSNP:rs387906902EnsemblClinVar.1
Scapuloperoneal spinal muscular atrophy (SPSMA)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA clinically variable neuromuscular disorder characterized by neurogenic scapuloperoneal amyotrophy, laryngeal palsy, congenital absence of muscles, progressive scapuloperoneal atrophy and progressive distal weakness and amyotrophy.
See also OMIM:181405
Spondyloepiphyseal dysplasia Maroteaux type (SEDM)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:184095
Parastremmatic dwarfism (PSTD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:168400
Digital arthropathy-brachydactyly, familial (FDAB)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:606835
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068498270G → V in FDAB; poorly expressed on the cell surface; mutant channels show a significantly reduced response to agonists. 1 PublicationCorresponds to variant dbSNP:rs387907220EnsemblClinVar.1
Natural variantiVAR_068499271R → P in FDAB; poorly expressed on the cell surface; mutant channels show a significantly reduced response to agonists. 1 PublicationCorresponds to variant dbSNP:rs387907219EnsemblClinVar.1
Natural variantiVAR_068500273F → L in FDAB; poorly expressed on the cell surface; mutant channels show a significantly reduced response to agonists. 1 PublicationCorresponds to variant dbSNP:rs515726170EnsemblClinVar.1
Avascular necrosis of the femoral head, primary 2 (ANFH2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:617383

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi231F → C: Decreased ATP-binding. 1 Publication1
Mutagenesisi251K → E: No effect on channel activity. No effect on interaction with membranes enriched in phosphatidylinositol-2,4-bisphosphate. 1 Publication1
Mutagenesisi296N → D: Loss of interaction with membranes enriched in phosphatidylinositol-2,4-bisphosphate; when associated with P-299. 1 Publication1
Mutagenesisi299H → 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. 1 Publication1
Mutagenesisi344K → E: No effect on channel activity. No effect on interaction with membranes enriched in phosphatidylinositol-2,4-bisphosphate. 1 Publication1
Mutagenesisi816 – 821RLRRDR → ELEEDE: Loss of calmodulin binding; when associated with A-828. 6
Mutagenesisi821 – 824RWSS → AASA: Loss of calmodulin binding. 4
Mutagenesisi822W → A: Loss of Ca(2+) dependent current potentiation. 1
Mutagenesisi828R → A: Loss of calmodulin binding; when associated with 816-ELEEDE-821. 1 Publication1

Keywords - Diseasei

Charcot-Marie-Tooth disease, Disease mutation, Dwarfism, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi59341
GeneReviewsiTRPV4
MalaCardsiTRPV4
MIMi113500 phenotype
156530 phenotype
168400 phenotype
181405 phenotype
184095 phenotype
184252 phenotype
600175 phenotype
606071 phenotype
606835 phenotype
613508 phenotype
617383 phenotype
OpenTargetsiENSG00000111199
Orphaneti93304 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
263482 Spondyloepiphyseal dysplasia, Maroteaux type
93314 Spondylometaphyseal dysplasia, Kozlowski type
PharmGKBiPA38293

Chemistry databases

ChEMBLiCHEMBL3119
GuidetoPHARMACOLOGYi510

Polymorphism and mutation databases

BioMutaiTRPV4
DMDMi62901470

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153471 – 871Transient receptor potential cation channel subfamily V member 4Add BLAST871

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei110PhosphotyrosineBy similarity1
Modified residuei253PhosphotyrosineBy similarity1
Modified residuei805PhosphotyrosineBy similarity1
Modified residuei824PhosphoserineBy similarity1

Post-translational modificationi

N-glycosylated.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9HBA0
MaxQBiQ9HBA0
PaxDbiQ9HBA0
PeptideAtlasiQ9HBA0
PRIDEiQ9HBA0
ProteomicsDBi81511
81512 [Q9HBA0-2]
81513 [Q9HBA0-3]
81514 [Q9HBA0-4]
81515 [Q9HBA0-5]
81516 [Q9HBA0-6]

PTM databases

iPTMnetiQ9HBA0
PhosphoSitePlusiQ9HBA0

Expressioni

Tissue specificityi

Found in the synoviocytes from patients with (RA) and without (CTR) rheumatoid arthritis (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000111199
ExpressionAtlasiQ9HBA0 baseline and differential
GenevisibleiQ9HBA0 HS

Organism-specific databases

HPAiHPA007150

Interactioni

Subunit structurei

Homotetramer (Probable). Self-associates in a isoform-specific manner (PubMed:16293632). Isoform 1 and isoform 5 can oligomerize, but isoform 2, isoform 4 and isoform 6 cannnot oligomerize (PubMed:16293632). Interacts with calmodulin (PubMed:12724311). Interacts with Map7 and Src family Tyr protein kinases LYN, SRC, FYN, HCK, LCK and YES (By similarity). Interacts with CTNNB1 (By similarity). The TRPV4 and CTNNB1 complex can interact with CDH1 (By similarity). Interacts with PACSIN1, PACSIN2 and PACSIN3 (via SH3 domain) (By similarity). Part of a complex containing MLC1, AQP4, HEPACAM and ATP1B1 (PubMed:22328087). Interacts with ITPR3 (PubMed:18826956). Interacts with AQP5; the interaction is probably indirect and regulates TRPV4 activation by hypotonicity (By similarity). Interacts with ANO1 (By similarity). Interacts (via C-terminus) with PKD2 (via C-terminus) (PubMed:18695040).By similarityCurated6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • actin binding Source: BHF-UCL
  • actin filament binding Source: BHF-UCL
  • alpha-tubulin binding Source: BHF-UCL
  • beta-tubulin binding Source: BHF-UCL
  • calmodulin binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • microtubule binding Source: BHF-UCL
  • protein kinase binding Source: BHF-UCL
  • protein kinase C binding Source: BHF-UCL
  • SH2 domain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi121883, 12 interactors
CORUMiQ9HBA0
DIPiDIP-35702N
IntActiQ9HBA0, 8 interactors
MINTiQ9HBA0
STRINGi9606.ENSP00000261740

Chemistry databases

BindingDBiQ9HBA0

Structurei

Secondary structure

1871
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi151 – 159Combined sources9
Helixi164 – 166Combined sources3
Helixi169 – 175Combined sources7
Helixi183 – 185Combined sources3
Beta strandi188 – 190Combined sources3
Helixi194 – 200Combined sources7
Helixi209 – 220Combined sources12
Helixi223 – 228Combined sources6
Beta strandi234 – 239Combined sources6
Helixi241 – 247Combined sources7
Helixi251 – 260Combined sources10
Helixi271 – 273Combined sources3
Turni276 – 279Combined sources4
Helixi288 – 294Combined sources7
Helixi298 – 306Combined sources9
Helixi324 – 331Combined sources8
Helixi336 – 356Combined sources21
Beta strandi357 – 360Combined sources4
Helixi362 – 364Combined sources3
Helixi373 – 379Combined sources7
Helixi383 – 395Combined sources13

3D structure databases

ProteinModelPortaliQ9HBA0
SMRiQ9HBA0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati237 – 266ANK 1Add BLAST30
Repeati284 – 313ANK 2Add BLAST30
Repeati369 – 398ANK 3Add BLAST30

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni249 – 251Phosphatidylinositol-1,4,5-trisphosphate bindingBy similarity3
Regioni296 – 299Phosphatidylinositol-1,4,5-trisphosphate bindingBy similarity4
Regioni812 – 831Interaction with calmodulin and ITPR32 PublicationsAdd BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi679 – 682Selectivity filterBy similarity4

Domaini

The ANK repeat region mediates interaction with Ca2+-calmodulin and ATP binding (By similarity). The ANK repeat region mediates interaction with phosphatidylinositol-4,5-bisphosphate and related phosphatidylinositides (PubMed:25256292).By similarity1 Publication

Sequence similaritiesi

Keywords - Domaini

ANK repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3676 Eukaryota
ENOG4110DG4 LUCA
GeneTreeiENSGT00550000074425
HOVERGENiHBG054085
InParanoidiQ9HBA0
KOiK04973
OMAiKVCNEDQ
OrthoDBiEOG091G016O
PhylomeDBiQ9HBA0
TreeFamiTF314711

Family and domain databases

CDDicd00204 ANK, 1 hit
Gene3Di1.25.40.20, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR005821 Ion_trans_dom
IPR004729 TRP_channel
IPR024862 TRPV
IPR008347 TRPV1-4_channel
IPR008348 TRPV4_channel
PANTHERiPTHR10582 PTHR10582, 1 hit
PTHR10582:SF4 PTHR10582:SF4, 1 hit
PfamiView protein in Pfam
PF00023 Ank, 1 hit
PF00520 Ion_trans, 1 hit
PRINTSiPR01768 TRPVRECEPTOR
PR01769 VRL2RECEPTOR
SMARTiView protein in SMART
SM00248 ANK, 3 hits
SUPFAMiSSF48403 SSF48403, 1 hit
TIGRFAMsiTIGR00870 trp, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 1 hit

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9HBA0-1) [UniParc]FASTAAdd to basket
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.

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        10         20         30         40         50
MADSSEGPRA GPGEVAELPG DESGTPGGEA FPLSSLANLF EGEDGSLSPS
60 70 80 90 100
PADASRPAGP GDGRPNLRMK FQGAFRKGVP NPIDLLESTL YESSVVPGPK
110 120 130 140 150
KAPMDSLFDY GTYRHHSSDN KRWRKKIIEK QPQSPKAPAP QPPPILKVFN
160 170 180 190 200
RPILFDIVSR GSTADLDGLL PFLLTHKKRL TDEEFREPST GKTCLPKALL
210 220 230 240 250
NLSNGRNDTI PVLLDIAERT GNMREFINSP FRDIYYRGQT ALHIAIERRC
260 270 280 290 300
KHYVELLVAQ GADVHAQARG RFFQPKDEGG YFYFGELPLS LAACTNQPHI
310 320 330 340 350
VNYLTENPHK KADMRRQDSR GNTVLHALVA IADNTRENTK FVTKMYDLLL
360 370 380 390 400
LKCARLFPDS NLEAVLNNDG LSPLMMAAKT GKIGIFQHII RREVTDEDTR
410 420 430 440 450
HLSRKFKDWA YGPVYSSLYD LSSLDTCGEE ASVLEILVYN SKIENRHEML
460 470 480 490 500
AVEPINELLR DKWRKFGAVS FYINVVSYLC AMVIFTLTAY YQPLEGTPPY
510 520 530 540 550
PYRTTVDYLR LAGEVITLFT GVLFFFTNIK DLFMKKCPGV NSLFIDGSFQ
560 570 580 590 600
LLYFIYSVLV IVSAALYLAG IEAYLAVMVF ALVLGWMNAL YFTRGLKLTG
610 620 630 640 650
TYSIMIQKIL FKDLFRFLLV YLLFMIGYAS ALVSLLNPCA NMKVCNEDQT
660 670 680 690 700
NCTVPTYPSC RDSETFSTFL LDLFKLTIGM GDLEMLSSTK YPVVFIILLV
710 720 730 740 750
TYIILTFVLL LNMLIALMGE TVGQVSKESK HIWKLQWATT ILDIERSFPV
760 770 780 790 800
FLRKAFRSGE MVTVGKSSDG TPDRRWCFRV DEVNWSHWNQ NLGIINEDPG
810 820 830 840 850
KNETYQYYGF SHTVGRLRRD RWSSVVPRVV ELNKNSNPDE VVVPLDSMGN
860 870
PRCDGHQQGY PRKWRTDDAP L
Length:871
Mass (Da):98,281
Last modified:April 26, 2005 - v2
Checksum:iC62056B86C5A6FB6
GO
Isoform 2 (identifier: Q9HBA0-2) [UniParc]FASTAAdd to basket
Also known as: B, OTRPC4beta

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

Note: Lacks channel activity, due to impaired oligomerization and intracellular retention.1 Publication
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Length:811
Mass (Da):91,261
Checksum:iA498FF4BBA1CD7A5
GO
Isoform 3 (identifier: Q9HBA0-3) [UniParc]FASTAAdd to basket
Also known as: TRPV-SV

The sequence of this isoform differs from the canonical sequence as follows:
     844-871: PLDSMGNPRCDGHQQGYPRKWRTDDAPL → RHLCRVRRKR

Show »
Length:853
Mass (Da):96,449
Checksum:iEAA07196606AED20
GO
Isoform 4 (identifier: Q9HBA0-4) [UniParc]FASTAAdd to basket
Also known as: C

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

Note: Lacks channel activity, due to impaired oligomerization and intracellular retention.1 Publication
Show »
Length:824
Mass (Da):92,904
Checksum:iEA7AFC7497D14495
GO
Isoform 5 (identifier: Q9HBA0-5) [UniParc]FASTAAdd to basket
Also known as: D

The sequence of this isoform differs from the canonical sequence as follows:
     28-61: Missing.

Note: Forms active ion channels.1 Publication
Show »
Length:837
Mass (Da):94,998
Checksum:i1538A7B2E76C8CDF
GO
Isoform 6 (identifier: Q9HBA0-6) [UniParc]FASTAAdd to basket
Also known as: E

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

Note: Lacks channel activity, due to impaired oligomerization and intracellular retention.1 Publication
Show »
Length:764
Mass (Da):85,884
Checksum:iB1307888F82B0E31
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti385I → V in AAG28029 (PubMed:11081638).Curated1
Sequence conflicti452V → A in BAC06573 (Ref. 6) Curated1
Sequence conflicti781D → N in AAG28029 (PubMed:11081638).Curated1
Sequence conflicti820D → T in BAB69040 (Ref. 4) Curated1
Sequence conflicti861P → T in BAC06573 (Ref. 6) Curated1
Sequence conflicti867D → E in AAG16127 (PubMed:11025659).Curated1

Polymorphismi

Genetic variations in TRPV4 determine the sodium serum level quantitative trait locus 1 (SSQTL1) [MIMi: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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05239119P → S Associated with lower sodium concentrations in serum; shows diminished response to hypotonic stress relative to wild-type. Corresponds to variant dbSNP:rs3742030EnsemblClinVar.1
Natural variantiVAR_06451789T → I in MTD; lethal form. 1 PublicationCorresponds to variant dbSNP:rs397514473EnsemblClinVar.1
Natural variantiVAR_06798997P → R in HMN8; loss of function mutation. 1 PublicationCorresponds to variant dbSNP:rs876661124EnsemblClinVar.1
Natural variantiVAR_064518183E → K Found in a patient with spondyloepiphyseal dysplasia Maroteaux type; decreased protein stability; increased ATP-binding. 2 PublicationsCorresponds to variant dbSNP:rs387906324EnsemblClinVar.1
Natural variantiVAR_064519197K → R in MTD; lethal form; decreased protein stability; reduced ATP-binding. 2 PublicationsCorresponds to variant dbSNP:rs387906903EnsemblClinVar.1
Natural variantiVAR_064520199L → F in MTD; decreased protein stability. 2 PublicationsCorresponds to variant dbSNP:rs515726167EnsemblClinVar.1
Natural variantiVAR_067990232R → C in HMN8 and CMT2C; does not affect channel localization to plasma membrane; results in increased agonist-induced channel activity and increased basal intracellular calcium concentration; decreases ATP-binding; no effect on protein stability; decreases binding to membranes enriched in phosphatidylinositol-2,4-bisphosphate; causes increased cell death. 4 PublicationsCorresponds to variant dbSNP:rs387906904EnsemblClinVar.1
Natural variantiVAR_063528269R → C in CMT2C; increased agonist-induced channel activity; causes increased cell death; no effect on protein stability and ATP-binding. 3 PublicationsCorresponds to variant dbSNP:rs267607146EnsemblClinVar.1
Natural variantiVAR_063529269R → H in HMN8 and CMT2C; increased agonist-induced channel activity and increased basal intracellular calcium concentration; slightly decreased protein stability and ATP-binding; decreases binding to membranes enriched in phosphatidylinositol-2,4-bisphosphate; causes increased cell death. 6 PublicationsCorresponds to variant dbSNP:rs267607144EnsemblClinVar.1
Natural variantiVAR_068498270G → V in FDAB; poorly expressed on the cell surface; mutant channels show a significantly reduced response to agonists. 1 PublicationCorresponds to variant dbSNP:rs387907220EnsemblClinVar.1
Natural variantiVAR_068499271R → P in FDAB; poorly expressed on the cell surface; mutant channels show a significantly reduced response to agonists. 1 PublicationCorresponds to variant dbSNP:rs387907219EnsemblClinVar.1
Natural variantiVAR_068500273F → L in FDAB; poorly expressed on the cell surface; mutant channels show a significantly reduced response to agonists. 1 PublicationCorresponds to variant dbSNP:rs515726170EnsemblClinVar.1
Natural variantiVAR_064521278E → K in SMDK; slightly increased ATP-binding; slightly decreased protein stability. 2 PublicationsCorresponds to variant dbSNP:rs267607148EnsemblClinVar.1
Natural variantiVAR_064522295T → A in MTD; impairs protein folding or stability. 2 PublicationsCorresponds to variant dbSNP:rs515726171EnsemblClinVar.1
Natural variantiVAR_063541315R → W in CMT2C; increased basal and agonist-induced channel activity, decreased protein stability; decreased ATP-binding; decreases binding to membranes enriched in phosphatidylinositol-2,4-bisphosphate; causes increased cell death. 4 PublicationsCorresponds to variant dbSNP:rs267607143EnsemblClinVar.1
Natural variantiVAR_063530316R → C in CMT2C and SPSMA; decreased protein stability; decreased ATP-binding. 2 PublicationsCorresponds to variant dbSNP:rs267607145EnsemblClinVar.1
Natural variantiVAR_067991316R → H in CMT2C; does not affect channel localization to plasma membrane; results in increased agonist-induced channel activity and increased basal intracellular calcium concentration; decreases protein stability; causes increased cell death. 2 PublicationsCorresponds to variant dbSNP:rs387906905EnsemblClinVar.1
Natural variantiVAR_062331331I → F in MTD; decreased protein stability; no effect on ATP-binding. 3 PublicationsCorresponds to variant dbSNP:rs121912636EnsemblClinVar.1
Natural variantiVAR_064523331I → T in MTD; no effect on protein stability; no effect on ATP-binding. 2 PublicationsCorresponds to variant dbSNP:rs515726172EnsemblClinVar.1
Natural variantiVAR_067992333 – 336Missing in SMDK. 4
Natural variantiVAR_062332333D → G in SMDK; decreased protein stability; no effect on ATP-binding. 2 PublicationsCorresponds to variant dbSNP:rs121912634EnsemblClinVar.1
Natural variantiVAR_064524342V → F in MTD; decreased protein stability; decreased ATP-binding. 2 PublicationsCorresponds to variant dbSNP:rs515726152EnsemblClinVar.1
Natural variantiVAR_064525471Missing in MTD; lethal form. 2 Publications1
Natural variantiVAR_067993542S → Y in CMT2C. 1 PublicationCorresponds to variant dbSNP:rs387906902EnsemblClinVar.1
Natural variantiVAR_064526592F → L in MTD. 1 PublicationCorresponds to variant dbSNP:rs515726158EnsemblClinVar.1
Natural variantiVAR_062333594R → H in SMDK and PSTD. 3 PublicationsCorresponds to variant dbSNP:rs77975504EnsemblClinVar.1
Natural variantiVAR_064527596L → P in SMDK. 1 PublicationCorresponds to variant dbSNP:rs515726159EnsemblClinVar.1
Natural variantiVAR_064528600G → W in SMDK. 1 PublicationCorresponds to variant dbSNP:rs515726160EnsemblClinVar.1
Natural variantiVAR_064529602Y → C Found in a patient with spondyloepiphyseal dysplasia Maroteaux type. 1 PublicationCorresponds to variant dbSNP:rs267607150EnsemblClinVar.1
Natural variantiVAR_064530604I → M in MTD; lethal form. 1 PublicationCorresponds to variant dbSNP:rs515726161EnsemblClinVar.1
Natural variantiVAR_054805616R → Q in BCYM3; results in a gain of function and a constitutive activation of the channel. 1 PublicationCorresponds to variant dbSNP:rs121912632EnsemblClinVar.1
Natural variantiVAR_064531617F → L in MTD. 1 PublicationCorresponds to variant dbSNP:rs515726162EnsemblClinVar.1
Natural variantiVAR_064532618L → P in MTD. 2 PublicationsCorresponds to variant dbSNP:rs515726163EnsemblClinVar.1
Natural variantiVAR_054806620V → I in BCYM3; results in a gain of function and a constitutive activation of the channel. 1 PublicationCorresponds to variant dbSNP:rs121912633EnsemblClinVar.1
Natural variantiVAR_064533625M → I in SMDK. 1 PublicationCorresponds to variant dbSNP:rs515726164EnsemblClinVar.1
Natural variantiVAR_064534709L → M in SMDK. 1 PublicationCorresponds to variant dbSNP:rs116571438EnsemblClinVar.1
Natural variantiVAR_062334716A → S in SMDK. 1 PublicationCorresponds to variant dbSNP:rs121912635EnsemblClinVar.1
Natural variantiVAR_064535775R → K in MTD. 1 Publication1
Natural variantiVAR_064536777C → Y in SMDK. 1 PublicationCorresponds to variant dbSNP:rs515726165EnsemblClinVar.1
Natural variantiVAR_064537797E → K in MTD and SMDK; also found in a patient with spondyloepiphyseal dysplasia Maroteaux type. 3 PublicationsCorresponds to variant dbSNP:rs267607149EnsemblClinVar.1
Natural variantiVAR_064538799P → A in MTD. 1 PublicationCorresponds to variant dbSNP:rs267607147EnsemblClinVar.1
Natural variantiVAR_062335799P → L in MTD; also found in a patient with spondyloepiphyseal dysplasia Maroteaux type. 5 Publications