Protein: Transient receptor potential cation channel subfamily V member 4 (TrpV4) (Osm-9-like TRP channel 4) (OTRPC4) (Transient receptor potential protein 12) (TRP12) (Vanilloid receptor-like channel 2) (Vanilloid receptor-like protein 2) (VRL-2) (Vanilloid receptor-related osmotically-activated channel) (VR-OAC) (Q9HBA0)
Organism: Homo sapiens (Human)
Function: 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 heat, low pH, citrate and phorbol esters. Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism. Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers (By similarity). Acts as a regulator of intracellular Ca(2+) in synoviocytes. Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8. Together with PKD2, forms mechano- and thermosensitive channels in cilium. Negatively regulates expression of PPARGC1A, UCP1, oxidative metabolism and respiration in adipocytes (By similarity). Regulates expression of chemokines and cytokines related to pro-inflammatory pathway in adipocytes (By similarity). Together with AQP5, controls regulatory volume decrease in salivary epithelial cells (By similarity). Required for normal development and maintenance of bone and cartilage. In its inactive state, may sequester DDX3X at the plasma membrane. When activated, the interaction between both proteins is affected and DDX3X relocalizes to the nucleus.
Subcellular location: Cell membrane {ECO:0000269|PubMed:16403833, ECO:0000269|PubMed:29899501}. Apical cell membrane {ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:18826956}; Multi-pass membrane protein {ECO:0000305}. Cell junction, adherens junction {ECO:0000250|UniProtKB:Q9EPK8}. Cell projection, cilium {ECO:0000269|PubMed:18695040}. Note=Assembly of the putative homotetramer occurs primarily in the endoplasmic reticulum (PubMed:16293632, PubMed:20037587, PubMed:20037588). Localization to the cell membrane is inhibited by WNK kinases (WNK1, WNK2, WNK3 or WNK4) in a kinase-independent mechanism (PubMed:16403833). {ECO:0000269|PubMed:16293632, ECO:0000269|PubMed:16403833, ECO:0000269|PubMed:20037587, ECO:0000269|PubMed:20037588}.; SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:16293632, ECO:0000269|PubMed:21964574, ECO:0000269|PubMed:25256292}.; SUBCELLULAR LOCATION: [Isoform 5]: Cell membrane {ECO:0000269|PubMed:16293632}.; SUBCELLULAR LOCATION: [Isoform 2]: Endoplasmic reticulum {ECO:0000269|PubMed:16293632}.; SUBCELLULAR LOCATION: [Isoform 4]: Endoplasmic reticulum {ECO:0000269|PubMed:16293632}.; SUBCELLULAR LOCATION: [Isoform 6]: Endoplasmic reticulum {ECO:0000269|PubMed:16293632}.
Sequence: MADSSEGPRAGPGEVAELPGDESGTPGGEAFPLSSLANLFEGEDGSLSPSPADASRPAGPGDGRPNLRMKFQGAFRKGVPNPIDLLESTLYESSVVPGPKKAPMDSLFDYGTYRHHSSDNKRWRKKIIEKQPQSPKAPAPQPPPILKVFNRPILFDIVSRGSTADLDGLLPFLLTHKKRLTDEEFREPSTGKTCLPKALLNLSNGRNDTIPVLLDIAERTGNMREFINSPFRDIYYRGQTALHIAIERRCKHYVELLVAQGADVHAQARGRFFQPKDEGGYFYFGELPLSLAACTNQPHIVNYLTENPHKKADMRRQDSRGNTVLHALVAIADNTRENTKFVTKMYDLLLLKCARLFPDSNLEAVLNNDGLSPLMMAAKTGKIGIFQHIIRREVTDEDTRHLSRKFKDWAYGPVYSSLYDLSSLDTCGEEASVLEILVYNSKIENRHEMLAVEPINELLRDKWRKFGAVSFYINVVSYLCAMVIFTLTAYYQPLEGTPPYPYRTTVDYLRLAGEVITLFTGVLFFFTNIKDLFMKKCPGVNSLFIDGSFQLLYFIYSVLVIVSAALYLAGIEAYLAVMVFALVLGWMNALYFTRGLKLTGTYSIMIQKILFKDLFRFLLVYLLFMIGYASALVSLLNPCANMKVCNEDQTNCTVPTYPSCRDSETFSTFLLDLFKLTIGMGDLEMLSSTKYPVVFIILLVTYIILTFVLLLNMLIALMGETVGQVSKESKHIWKLQWATTILDIERSFPVFLRKAFRSGEMVTVGKSSDGTPDRRWCFRVDEVNWSHWNQNLGIINEDPGKNETYQYYGFSHTVGRLRRDRWSSVVPRVVELNKNSNPDEVVVPLDSMGNPRCDGHQQGYPRKWRTDDAPL
InterPro domains: - IPR036770: Ankyrin repeat-containing domain superfamily (homologous_superfamily) [148-452]
- IPR024862: Transient receptor potential cation channel subfamily V (family) [124-835]
- IPR008348: Transient receptor potential cation channel subfamily V member 4 (family) [69-665]
- IPR002110: Ankyrin repeat (repeat) [237-398]
- IPR005821: Ion transport domain (domain) [475-729]
- IPR008347: Transient receptor potential cation channel subfamily V member 1-4 (family) [178-799]
Interaction partners: - Short transient receptor potential channel 1
- Polycystin-2
- Caveolin-1
- Short transient receptor potential channel 6
- Protein kinase C alpha type
- Protein kinase C gamma type
- Protein kinase C epsilon type
- Protein kinase C delta type
- Protein kinase C beta type
- Protein kinase C eta type
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005215 (transporter activity), GO:0022857 (transmembrane transporter activity), GO:0005515 (protein binding), GO:1901702 (salt transmembrane transporter activity), GO:0015075 (monoatomic ion transmembrane transporter activity), GO:0022803 (passive transmembrane transporter activity), GO:0015318 (inorganic molecular entity transmembrane transporter activity), GO:0005216 (monoatomic ion channel activity), GO:0022890 (inorganic cation transmembrane transporter activity), GO:0015085 (calcium ion transmembrane transporter activity), GO:0015267 (channel activity), GO:0008324 (monoatomic cation transmembrane transporter activity), GO:0005261 (monoatomic cation channel activity), GO:0005262 (calcium channel activity), GO:0046873 (metal ion transmembrane transporter activity)
Biological Process (BP): GO:0008150 (biological process), GO:0009987 (cellular process), GO:0051179 (localization), GO:0050896 (response to stimulus), GO:0032501 (multicellular organismal process), GO:0051234 (establishment of localization), GO:0009628 (response to abiotic stimulus), GO:0055085 (transmembrane transport), GO:0003008 (system process), GO:0009266 (response to temperature stimulus), GO:0050877 (nervous system process), GO:0034220 (monoatomic ion transmembrane transport), GO:0098660 (inorganic ion transmembrane transport), GO:0006810 (transport), GO:0098655 (monoatomic cation transmembrane transport), GO:0071702 (organic substance transport), GO:0098662 (inorganic cation transmembrane transport), GO:0006811 (monoatomic ion transport), GO:0007600 (sensory perception), GO:0070588 (calcium ion transmembrane transport), GO:0006816 (calcium ion transport), GO:0006812 (monoatomic cation transport), GO:0030001 (metal ion transport)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0071944 (cell periphery), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)