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Protein

Transient receptor potential cation channel subfamily V member 4

Gene

TRPV4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity 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
<p>This subsection of the ‘Function’ section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei192ATPCombined sources1 Publication1
Binding sitei197ATPCombined sources1 Publication1
Binding sitei201ATPCombined sources1 Publication1
Binding sitei248ATPCombined sources1 Publication1
Binding sitei344Phosphatidylinositol-1,4,5-trisphosphateBy similarity1
<p>This subsection of the ‘Function’ section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi682Calcium; shared with neighboring subunitsBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi236 – 239ATPCombined sources1 Publication4

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>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
  • ion channel activity Source: GO_Central
  • 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

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>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

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-3295583 TRP channels

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
Q9HBA0

SIGNOR Signaling Network Open Resource

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SIGNORi
Q9HBA0

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>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
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:TRPV4
Synonyms:VRL2, VROAC
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 12

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000111199.10

Human Gene Nomenclature Database

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HGNCi
HGNC:18083 TRPV4

Online Mendelian Inheritance in Man (OMIM)

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MIMi
605427 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_Q9HBA0

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini1 – 469CytoplasmicBy similarityAdd BLAST469
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>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
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a region that is buried within a membrane, but does not cross it.<p><a href='/help/intramem' target='_top'>More...</a></p>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

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>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
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>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.
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
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>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

DisGeNET

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DisGeNETi
59341

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
TRPV4

MalaCards human disease database

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MalaCardsi
TRPV4
MIMi113500 phenotype
156530 phenotype
168400 phenotype
181405 phenotype
184095 phenotype
184252 phenotype
600175 phenotype
606071 phenotype
606835 phenotype
613508 phenotype
617383 phenotype

Open Targets

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OpenTargetsi
ENSG00000111199

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
93304 Autosomal dominant brachyolmia
99937 Autosomal dominant Charcot-Marie-Tooth disease type 2C
1216 Autosomal dominant congenital benign spinal muscular atrophy
86820 Familial avascular necrosis of femoral head
85169 Familial digital arthropathy-brachydactyly
2635 Metatropic dysplasia
2646 Parastremmatic dwarfism
431255 Scapuloperoneal spinal muscular atrophy
263482 Spondyloepiphyseal dysplasia, Maroteaux type
93314 Spondylometaphyseal dysplasia, Kozlowski type

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA38293

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL3119

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
510

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
TRPV4

Domain mapping of disease mutations (DMDM)

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DMDMi
62901470

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00002153471 – 871Transient receptor potential cation channel subfamily V member 4Add BLAST871

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei110PhosphotyrosineBy similarity1
Modified residuei253PhosphotyrosineBy similarity1
Modified residuei805PhosphotyrosineBy similarity1
Modified residuei824PhosphoserineBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

N-glycosylated.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q9HBA0

MaxQB - The MaxQuant DataBase

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MaxQBi
Q9HBA0

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q9HBA0

PeptideAtlas

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PeptideAtlasi
Q9HBA0

PRoteomics IDEntifications database

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PRIDEi
Q9HBA0

ProteomicsDB human proteome resource

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ProteomicsDBi
81511
81512 [Q9HBA0-2]
81513 [Q9HBA0-3]
81514 [Q9HBA0-4]
81515 [Q9HBA0-5]
81516 [Q9HBA0-6]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q9HBA0

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
Q9HBA0

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000111199 Expressed in 125 organ(s), highest expression level in cartilage tissue

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q9HBA0 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q9HBA0 HS

Organism-specific databases

Human Protein Atlas

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HPAi
HPA007150

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
121883, 12 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
Q9HBA0

Database of interacting proteins

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DIPi
DIP-35702N

Protein interaction database and analysis system

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IntActi
Q9HBA0, 8 interactors

Molecular INTeraction database

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MINTi
Q9HBA0

STRING: functional protein association networks

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STRINGi
9606.ENSP00000261740

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q9HBA0

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1871
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
Q9HBA0

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q9HBA0

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati237 – 266ANK 1Add BLAST30
Repeati284 – 313ANK 2Add BLAST30
Repeati369 – 398ANK 3Add BLAST30

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>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
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi679 – 682Selectivity filterBy similarity4

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>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

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

ANK repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG3676 Eukaryota
ENOG4110DG4 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000158615

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG054085

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q9HBA0

KEGG Orthology (KO)

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KOi
K04973

Identification of Orthologs from Complete Genome Data

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OMAi
LNPCANL

Database of Orthologous Groups

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OrthoDBi
EOG091G016O

Database for complete collections of gene phylogenies

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PhylomeDBi
Q9HBA0

TreeFam database of animal gene trees

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TreeFami
TF314711

Family and domain databases

Conserved Domains Database

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CDDi
cd00204 ANK, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
1.25.40.20, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR005821 Ion_trans_dom
IPR024862 TRPV
IPR008347 TRPV1-4_channel
IPR008348 TRPV4_channel

The PANTHER Classification System

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PANTHERi
PTHR10582 PTHR10582, 1 hit
PTHR10582:SF4 PTHR10582:SF4, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF00023 Ank, 1 hit
PF00520 Ion_trans, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR01768 TRPVRECEPTOR
PR01769 VRL2RECEPTOR

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00248 ANK, 3 hits

Superfamily database of structural and functional annotation

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SUPFAMi
SSF48403 SSF48403, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (6+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 6 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 6 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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.

« Hide
        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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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
Show »
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

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H6Q4F5H6Q4_HUMAN
Transient receptor potential cation...
TRPV4
552Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>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

<p>This subsection of the ‘Sequence’ section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement_in_disease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>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 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

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_02661428 – 61Missing in isoform 5. 1 PublicationAdd BLAST34
Alternative sequenceiVSP_026615239 – 285Missing in isoform 4 and isoform 6. 1 PublicationAdd BLAST47
Alternative sequenceiVSP_013436385 – 444Missing in isoform 2 and isoform 6. 2 PublicationsAdd BLAST60
Alternative sequenceiVSP_013437844 – 871PLDSM…DDAPL → RHLCRVRRKR in isoform 3. 1 PublicationAdd BLAST28

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
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

The Consensus CDS (CCDS) project

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CCDSi
CCDS53827.1 [Q9HBA0-6]
CCDS53828.1 [Q9HBA0-4]
CCDS53829.1 [Q9HBA0-5]
CCDS9134.1 [Q9HBA0-1]
CCDS9135.1 [Q9HBA0-2]

NCBI Reference Sequences

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RefSeqi
NP_001170899.1, NM_001177428.1 [Q9HBA0-4]
NP_001170902.1, NM_001177431.1 [Q9HBA0-5]
NP_001170904.1, NM_001177433.1 [Q9HBA0-6]
NP_067638.3, NM_021625.4 [Q9HBA0-1]
NP_671737.1, NM_147204.2 [Q9HBA0-2]
XP_005253975.1, XM_005253918.1 [Q9HBA0-1]
XP_016875263.1, XM_017019774.1 [Q9HBA0-1]

UniGene gene-oriented nucleotide sequence clusters

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UniGenei
Hs.506713

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENST00000261740; ENSP00000261740; ENSG00000111199 [Q9HBA0-1]
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]

Database of genes from NCBI RefSeq genomes

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GeneIDi
59341

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:59341

UCSC genome browser

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UCSCi
uc001tpg.3 human [Q9HBA0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS53827.1 [Q9HBA0-6]
CCDS53828.1 [Q9HBA0-4]
CCDS53829.1 [Q9HBA0-5]
CCDS9134.1 [Q9HBA0-1]
CCDS9135.1 [Q9HBA0-2]
RefSeqiNP_001170899.1, NM_001177428.1 [Q9HBA0-4]
NP_001170902.1, NM_001177431.1 [Q9HBA0-5]
NP_001170904.1, NM_001177433.1 [Q9HBA0-6]
NP_067638.3, NM_021625.4 [Q9HBA0-1]
NP_671737.1, NM_147204.2 [Q9HBA0-2]
XP_005253975.1, XM_005253918.1 [Q9HBA0-1]
XP_016875263.1, XM_017019774.1 [Q9HBA0-1]
UniGeneiHs.506713

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4DX1X-ray2.85A/B149-397[»]
4DX2X-ray2.95A/B149-397[»]
ProteinModelPortaliQ9HBA0
SMRiQ9HBA0
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

BindingDBiQ9HBA0
ChEMBLiCHEMBL3119
GuidetoPHARMACOLOGYi510

PTM databases

iPTMnetiQ9HBA0
PhosphoSitePlusiQ9HBA0

Polymorphism and mutation databases

BioMutaiTRPV4
DMDMi62901470

Proteomic databases

EPDiQ9HBA0
MaxQBiQ9HBA0
PaxDbiQ9HBA0
PeptideAtlasiQ9HBA0
PRIDEiQ9HBA0
ProteomicsDBi81511
81512 [Q9HBA0-2]
81513