TRPV4_HUMAN
ID TRPV4_HUMAN Reviewed; 871 AA.
AC Q9HBA0; B7ZKQ6; Q17R79; Q2Y122; Q2Y123; Q2Y124; Q86YZ6; Q8NDY7; Q8NG64;
AC Q96Q92; Q96RS7; Q9HBC0;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Transient receptor potential cation channel subfamily V member 4;
DE Short=TrpV4;
DE AltName: Full=Osm-9-like TRP channel 4;
DE Short=OTRPC4 {ECO:0000303|PubMed:11025659};
DE AltName: Full=Transient receptor potential protein 12;
DE Short=TRP12;
DE AltName: Full=Vanilloid receptor-like channel 2;
DE AltName: Full=Vanilloid receptor-like protein 2;
DE Short=VRL-2;
DE AltName: Full=Vanilloid receptor-related osmotically-activated channel {ECO:0000303|PubMed:11081638};
DE Short=VR-OAC {ECO:0000303|PubMed:11081638};
GN Name=TRPV4; Synonyms=VRL2, VROAC;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11081638; DOI=10.1016/s0092-8674(00)00143-4;
RA Liedtke W.B., Choe Y., Marti-Renom M.A., Bell A.M., Denis C.S., Sali A.,
RA Hudspeth A.J., Friedman J.M., Heller S.;
RT "Vanilloid receptor-related osmotically activated channel (VR-OAC), a
RT candidate vertebrate osmoreceptor.";
RL Cell 103:525-535(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC TISSUE=Kidney cortex;
RX PubMed=11025659; DOI=10.1038/35036318;
RA Strotmann R., Harteneck C., Nunnenmacher K., Schultz G., Plant T.D.;
RT "OTRPC4, a nonselective cation channel that confers sensitivity to
RT extracellular osmolarity.";
RL Nat. Cell Biol. 2:695-702(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=12692122; DOI=10.1074/jbc.m302561200;
RA Suzuki M., Mizuno A., Kodaira K., Imai M.;
RT "Impaired pressure sensation in mice lacking TRPV4.";
RL J. Biol. Chem. 278:22664-22668(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Ishibashi K.;
RT "Molecular cloning of a new member of vanilloid receptor channel-like
RT proteins.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Kelsell R.E.;
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT MTD PRO-618.
RC TISSUE=Aortic endothelium;
RA Xu F., Satoh E., Iijima T.;
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5 AND 6), FUNCTION (ISOFORMS 1; 2;
RP 4; 5 AND 6), SUBCELLULAR LOCATION (ISOFORMS 1; 2; 4; 5 AND 6),
RP SELF-ASSOCIATION, AND GLYCOSYLATION.
RX PubMed=16293632; DOI=10.1074/jbc.m511456200;
RA Arniges M., Fernandez-Fernandez J.M., Albrecht N., Schaefer M.,
RA Valverde M.A.;
RT "Human TRPV4 channel splice variants revealed a key role of ankyrin domains
RT in multimerization and trafficking.";
RL J. Biol. Chem. 281:1580-1586(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 69-871.
RA Derst C., Schafer M.K.;
RT "Cloning of mouse and human vanilloid receptor-like protein 2 (VRL-2).";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP FUNCTION, INTERACTION WITH CALMODULIN, AND MUTAGENESIS OF 186-ARG--SER-824
RP AND ARG-828.
RX PubMed=12724311; DOI=10.1074/jbc.m302590200;
RA Strotmann R., Schultz G., Plant T.D.;
RT "Ca2+-dependent potentiation of the nonselective cation channel TRPV4 is
RT mediated by a C-terminal calmodulin binding site.";
RL J. Biol. Chem. 278:26541-26549(2003).
RN [12]
RP FUNCTION, INTERACTION WITH ITPR3, AND SUBCELLULAR LOCATION.
RX PubMed=18826956; DOI=10.1074/jbc.c800184200;
RA Garcia-Elias A., Lorenzo I.M., Vicente R., Valverde M.A.;
RT "IP3 receptor binds to and sensitizes TRPV4 channel to osmotic stimuli via
RT a calmodulin-binding site.";
RL J. Biol. Chem. 283:31284-31288(2008).
RN [13]
RP FUNCTION, INTERACTION WITH PKD2, AND SUBCELLULAR LOCATION.
RX PubMed=18695040; DOI=10.1083/jcb.200805124;
RA Kottgen M., Buchholz B., Garcia-Gonzalez M.A., Kotsis F., Fu X.,
RA Doerken M., Boehlke C., Steffl D., Tauber R., Wegierski T., Nitschke R.,
RA Suzuki M., Kramer-Zucker A., Germino G.G., Watnick T., Prenen J.,
RA Nilius B., Kuehn E.W., Walz G.;
RT "TRPP2 and TRPV4 form a polymodal sensory channel complex.";
RL J. Cell Biol. 182:437-447(2008).
RN [14]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19759329; DOI=10.1152/ajpcell.00204.2009;
RA Itoh Y., Hatano N., Hayashi H., Onozaki K., Miyazawa K., Muraki K.;
RT "An environmental sensor, TRPV4 is a novel regulator of intracellular Ca2+
RT in human synoviocytes.";
RL Am. J. Physiol. 297:C1082-C1090(2009).
RN [15]
RP INVOLVEMENT IN SSQTL1, AND ASSOCIATION OF VARIANT SER-19 WITH HYPONATREMIA.
RX PubMed=19666518; DOI=10.1073/pnas.0904084106;
RA Tian W., Fu Y., Garcia-Elias A., Fernandez-Fernandez J.M., Vicente R.,
RA Kramer P.L., Klein R.F., Hitzemann R., Orwoll E.S., Wilmot B., McWeeney S.,
RA Valverde M.A., Cohen D.M.;
RT "A loss-of-function nonsynonymous polymorphism in the osmoregulatory TRPV4
RT gene is associated with human hyponatremia.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:14034-14039(2009).
RN [16]
RP SUBUNIT.
RX PubMed=22328087; DOI=10.1093/hmg/dds032;
RA Lanciotti A., Brignone M.S., Molinari P., Visentin S., De Nuccio C.,
RA Macchia G., Aiello C., Bertini E., Aloisi F., Petrucci T.C., Ambrosini E.;
RT "Megalencephalic leukoencephalopathy with subcortical cysts protein 1
RT functionally cooperates with the TRPV4 cation channel to activate the
RT response of astrocytes to osmotic stress: dysregulation by pathological
RT mutations.";
RL Hum. Mol. Genet. 21:2166-2180(2012).
RN [17]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, DOMAIN, MUTAGENESIS OF
RP LYS-251; ASN-296; HIS-299 AND LYS-344, AND CHARACTERIZATION OF VARIANTS
RP CMT2C CYS-232; HIS-269; TRP-315 AND HIS-316.
RX PubMed=25256292; DOI=10.1038/ncomms5994;
RA Takahashi N., Hamada-Nakahara S., Itoh Y., Takemura K., Shimada A.,
RA Ueda Y., Kitamata M., Matsuoka R., Hanawa-Suetsugu K., Senju Y., Mori M.X.,
RA Kiyonaka S., Kohda D., Kitao A., Mori Y., Suetsugu S.;
RT "TRPV4 channel activity is modulated by direct interaction of the ankyrin
RT domain to PI(4,5)P.";
RL Nat. Commun. 5:4994-4994(2014).
RN [18]
RP FUNCTION, VARIANT MTD LEU-799, AND CHARACTERIZATION OF VARIANT MTD LEU-799.
RX PubMed=26249260; DOI=10.1002/ajmg.a.37182;
RA Hurd L., Kirwin S.M., Boggs M., Mackenzie W.G., Bober M.B., Funanage V.L.,
RA Duncan R.L.;
RT "A mutation in TRPV4 results in altered chondrocyte calcium signaling in
RT severe metatropic dysplasia.";
RL Am. J. Med. Genet. A 167A:2286-2293(2015).
RN [19]
RP INVOLVEMENT IN ANFH2.
RX PubMed=27330106; DOI=10.1136/jmedgenet-2016-103829;
RA Mah W., Sonkusare S.K., Wang T., Azeddine B., Pupavac M., Carrot-Zhang J.,
RA Hong K., Majewski J., Harvey E.J., Russell L., Chalk C., Rosenblatt D.S.,
RA Nelson M.T., Seguin C.;
RT "Gain-of-function mutation in TRPV4 identified in patients with
RT osteonecrosis of the femoral head.";
RL J. Med. Genet. 53:705-709(2016).
RN [20]
RP FUNCTION, FUNCTION (MICROBIAL INFECTION), INTERACTION WITH DDX3X,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF MET-680.
RX PubMed=29899501; DOI=10.1038/s41467-018-04776-7;
RA Donate-Macian P., Jungfleisch J., Perez-Vilaro G., Rubio-Moscardo F.,
RA Peralvarez-Marin A., Diez J., Valverde M.A.;
RT "The TRPV4 channel links calcium influx to DDX3X activity and viral
RT infectivity.";
RL Nat. Commun. 9:2307-2307(2018).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 149-397 ALONE AND IN COMPLEX WITH
RP ATP, MUTAGENESIS OF PHE-231, CHARACTERIZATION OF VARIANTS MTD ARG-197;
RP PHE-199; ALA-295; PHE-331; THR-331 AND PHE-342, CHARACTERIZATION OF
RP VARIANTS SMDK LYS-278 AND GLY-333, CHARACTERIZATION OF VARIANTS CMT2C
RP CYS-232; HIS-269; TRP-315 AND CYS-316, CHARACTERIZATION OF VARIANT SPSMA
RP CYS-316, CHARACTERIZATION OF VARIANT LYS-183, AND CHARACTERIZATION OF
RP VARIANTS HMN8 CYS-232 AND HIS-269.
RX PubMed=22702953; DOI=10.1021/bi300279b;
RA Inada H., Procko E., Sotomayor M., Gaudet R.;
RT "Structural and biochemical consequences of disease-causing mutations in
RT the ankyrin repeat domain of the human TRPV4 channel.";
RL Biochemistry 51:6195-6206(2012).
RN [22]
RP VARIANTS BCYM3 GLN-616 AND ILE-620, AND CHARACTERIZATION OF VARIANTS BCYM3
RP GLN-616 AND ILE-620.
RX PubMed=18587396; DOI=10.1038/ng.166;
RA Rock M.J., Prenen J., Funari V.A., Funari T.L., Merriman B., Nelson S.F.,
RA Lachman R.S., Wilcox W.R., Reyno S., Quadrelli R., Vaglio A., Owsianik G.,
RA Janssens A., Voets T., Ikegawa S., Nagai T., Rimoin D.L., Nilius B.,
RA Cohn D.H.;
RT "Gain-of-function mutations in TRPV4 cause autosomal dominant
RT brachyolmia.";
RL Nat. Genet. 40:999-1003(2008).
RN [23]
RP VARIANTS SMDK GLY-333; HIS-594 AND SER-716, AND VARIANTS MTD PHE-331 AND
RP LEU-799.
RX PubMed=19232556; DOI=10.1016/j.ajhg.2009.01.021;
RA Krakow D., Vriens J., Camacho N., Luong P., Deixler H., Funari T.L.,
RA Bacino C.A., Irons M.B., Holm I.A., Sadler L., Okenfuss E.B., Janssens A.,
RA Voets T., Rimoin D.L., Lachman R.S., Nilius B., Cohn D.H.;
RT "Mutations in the gene encoding the calcium-permeable ion channel TRPV4
RT produce spondylometaphyseal dysplasia, Kozlowski type and metatropic
RT dysplasia.";
RL Am. J. Hum. Genet. 84:307-315(2009).
RN [24]
RP VARIANTS MTD ILE-89; ARG-197; PHE-331; PHE-471 DEL; MET-604; LEU-617;
RP PRO-618; LYS-797 AND LEU-799.
RX PubMed=20425821; DOI=10.1002/ajmg.a.33392;
RA Camacho N., Krakow D., Johnykutty S., Katzman P.J., Pepkowitz S.,
RA Vriens J., Nilius B., Boyce B.F., Cohn D.H.;
RT "Dominant TRPV4 mutations in nonlethal and lethal metatropic dysplasia.";
RL Am. J. Med. Genet. A 152:1169-1177(2010).
RN [25]
RP INVOLVEMENT IN SEDM, VARIANT PSTD HIS-594, AND VARIANTS LYS-183; CYS-602;
RP LYS-797 AND LEU-799.
RX PubMed=20503319; DOI=10.1002/ajmg.a.33414;
RA Nishimura G., Dai J., Lausch E., Unger S., Megarbane A., Kitoh H.,
RA Kim O.H., Cho T.J., Bedeschi F., Benedicenti F., Mendoza-Londono R.,
RA Silengo M., Schmidt-Rimpler M., Spranger J., Zabel B., Ikegawa S.,
RA Superti-Furga A.;
RT "Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome
RT type 2), and parastremmatic dysplasia are caused by TRPV4 mutations.";
RL Am. J. Med. Genet. A 152:1443-1449(2010).
RN [26]
RP VARIANTS MTD PHE-199; ALA-295; THR-331; PHE-342; PHE-471 DEL; LEU-592;
RP LYS-775; ALA-799; SER-799; LEU-799 AND ARG-799, AND VARIANTS SMDK LYS-278;
RP HIS-594; PRO-596; TRP-600; ILE-625; MET-709; TYR-777 AND LYS-797.
RX PubMed=20577006; DOI=10.1136/jmg.2009.075358;
RA Dai J., Kim O.H., Cho T.J., Schmidt-Rimpler M., Tonoki H., Takikawa K.,
RA Haga N., Miyoshi K., Kitoh H., Yoo W.J., Choi I.H., Song H.R., Jin D.K.,
RA Kim H.T., Kamasaki H., Bianchi P., Grigelioniene G., Nampoothiri S.,
RA Minagawa M., Miyagawa S.I., Fukao T., Marcelis C., Jansweijer M.C.,
RA Hennekam R.C., Bedeschi F., Mustonen A., Jiang Q., Ohashi H., Furuichi T.,
RA Unger S., Zabel B., Lausch E., Superti-Furga A., Nishimura G., Ikegawa S.;
RT "Novel and recurrent TRPV4 mutations and their association with distinct
RT phenotypes within the TRPV4 dysplasia family.";
RL J. Med. Genet. 47:704-709(2010).
RN [27]
RP VARIANTS CMT2C TRP-315 AND CYS-316, VARIANT HMN8 HIS-269, AND SUBCELLULAR
RP LOCATION.
RX PubMed=20037588; DOI=10.1038/ng.508;
RA Auer-Grumbach M., Olschewski A., Papic L., Kremer H., McEntagart M.E.,
RA Uhrig S., Fischer C., Frohlich E., Balint Z., Tang B., Strohmaier H.,
RA Lochmuller H., Schlotter-Weigel B., Senderek J., Krebs A., Dick K.J.,
RA Petty R., Longman C., Anderson N.E., Padberg G.W., Schelhaas H.J.,
RA van Ravenswaaij-Arts C.M., Pieber T.R., Crosby A.H., Guelly C.;
RT "Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA,
RT scapuloperoneal SMA and HMSN2C.";
RL Nat. Genet. 42:160-164(2010).
RN [28]
RP VARIANT CMT2C HIS-269, VARIANT SPSMA CYS-316, AND SUBCELLULAR LOCATION.
RX PubMed=20037587; DOI=10.1038/ng.509;
RA Deng H.X., Klein C.J., Yan J., Shi Y., Wu Y., Fecto F., Yau H.J., Yang Y.,
RA Zhai H., Siddique N., Hedley-Whyte E.T., Delong R., Martina M., Dyck P.J.,
RA Siddique T.;
RT "Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders
RT caused by alterations in TRPV4.";
RL Nat. Genet. 42:165-169(2010).
RN [29]
RP VARIANTS CMT2C CYS-269 AND HIS-269, CHARACTERIZATION OF VARIANTS CMT2C
RP CYS-269 AND HIS-269, AND FUNCTION.
RX PubMed=20037586; DOI=10.1038/ng.512;
RA Landoure G., Zdebik A.A., Martinez T.L., Burnett B.G., Stanescu H.C.,
RA Inada H., Shi Y., Taye A.A., Kong L., Munns C.H., Choo S.S., Phelps C.B.,
RA Paudel R., Houlden H., Ludlow C.L., Caterina M.J., Gaudet R., Kleta R.,
RA Fischbeck K.H., Sumner C.J.;
RT "Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.";
RL Nat. Genet. 42:170-174(2010).
RN [30]
RP VARIANTS CMT2C TRP-315 AND TYR-542.
RX PubMed=21115951; DOI=10.1212/wnl.0b013e3181ffe4bb;
RA Chen D.H., Sul Y., Weiss M., Hillel A., Lipe H., Wolff J., Matsushita M.,
RA Raskind W., Bird T.;
RT "CMT2C with vocal cord paresis associated with short stature and mutations
RT in the TRPV4 gene.";
RL Neurology 75:1968-1975(2010).
RN [31]
RP VARIANTS FDAB VAL-270; PRO-271 AND LEU-273, CHARACTERIZATION OF VARIANTS
RP FDAB VAL-270; PRO-271 AND LEU-273, FUNCTION, SUBCELLULAR LOCATION, AND
RP GLYCOSYLATION.
RX PubMed=21964574; DOI=10.1038/ng.945;
RA Lamande S.R., Yuan Y., Gresshoff I.L., Rowley L., Belluoccio D.,
RA Kaluarachchi K., Little C.B., Botzenhart E., Zerres K., Amor D.J.,
RA Cole W.G., Savarirayan R., McIntyre P., Bateman J.F.;
RT "Mutations in TRPV4 cause an inherited arthropathy of hands and feet.";
RL Nat. Genet. 43:1142-1146(2011).
RN [32]
RP VARIANTS CMT2C CYS-232 AND HIS-316, AND CHARACTERIZATION OF VARIANTS CMT2C
RP CYS-232; CYS-269; HIS-269 AND HIS-316.
RX PubMed=21288981; DOI=10.1212/wnl.0b013e31820f2de3;
RA Klein C.J., Shi Y., Fecto F., Donaghy M., Nicholson G., McEntagart M.E.,
RA Crosby A.H., Wu Y., Lou H., McEvoy K.M., Siddique T., Deng H.X., Dyck P.J.;
RT "TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth
RT neuropathies.";
RL Neurology 76:887-894(2011).
RN [33]
RP VARIANTS HMN8 ARG-97 AND CYS-232, AND CHARACTERIZATION OF VARIANT HMN8
RP ARG-97.
RX PubMed=22526352; DOI=10.1007/s10048-012-0328-7;
RA Fiorillo C., Moro F., Brisca G., Astrea G., Nesti C., Balint Z.,
RA Olschewski A., Meschini M.C., Guelly C., Auer-Grumbach M., Battini R.,
RA Pedemonte M., Romano A., Menchise V., Biancheri R., Santorelli F.M.,
RA Bruno C.;
RT "TRPV4 mutations in children with congenital distal spinal muscular
RT atrophy.";
RL Neurogenetics 13:195-203(2012).
CC -!- FUNCTION: Non-selective calcium permeant cation channel involved in
CC osmotic sensitivity and mechanosensitivity. Activation by exposure to
CC hypotonicity within the physiological range exhibits an outward
CC rectification (PubMed:18826956, PubMed:18695040, PubMed:29899501). Also
CC activated by heat, low pH, citrate and phorbol esters (PubMed:16293632,
CC PubMed:18826956, PubMed:18695040, PubMed:25256292, PubMed:20037586,
CC PubMed:21964574). Increase of intracellular Ca(2+) potentiates
CC currents. Channel activity seems to be regulated by a calmodulin-
CC dependent mechanism with a negative feedback mechanism
CC (PubMed:12724311, PubMed:18826956). Promotes cell-cell junction
CC formation in skin keratinocytes and plays an important role in the
CC formation and/or maintenance of functional intercellular barriers (By
CC similarity). Acts as a regulator of intracellular Ca(2+) in
CC synoviocytes (PubMed:19759329). Plays an obligatory role as a molecular
CC component in the nonselective cation channel activation induced by 4-
CC alpha-phorbol 12,13-didecanoate and hypotonic stimulation in
CC synoviocytes and also regulates production of IL-8 (PubMed:19759329).
CC Together with PKD2, forms mechano- and thermosensitive channels in
CC cilium (PubMed:18695040). Negatively regulates expression of PPARGC1A,
CC UCP1, oxidative metabolism and respiration in adipocytes (By
CC similarity). Regulates expression of chemokines and cytokines related
CC to pro-inflammatory pathway in adipocytes (By similarity). Together
CC with AQP5, controls regulatory volume decrease in salivary epithelial
CC cells (By similarity). Required for normal development and maintenance
CC of bone and cartilage (PubMed:26249260). In its inactive state, may
CC sequester DDX3X at the plasma membrane. When activated, the interaction
CC between both proteins is affected and DDX3X relocalizes to the nucleus
CC (PubMed:29899501). {ECO:0000250|UniProtKB:Q9EPK8,
CC ECO:0000269|PubMed:11025659, ECO:0000269|PubMed:12724311,
CC ECO:0000269|PubMed:16293632, ECO:0000269|PubMed:18587396,
CC ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:18826956,
CC ECO:0000269|PubMed:19759329, ECO:0000269|PubMed:20037586,
CC ECO:0000269|PubMed:21964574, ECO:0000269|PubMed:25256292,
CC ECO:0000269|PubMed:26249260, ECO:0000269|PubMed:29899501}.
CC -!- FUNCTION: [Isoform 5]: Non-selective calcium permeant cation channel
CC involved in osmotic sensitivity and mechanosensitivity. Activation by
CC exposure to hypotonicity within the physiological range exhibits an
CC outward rectification. Also activated by phorbol esters. Has the same
CC channel activity as isoform 1, and is activated by the same stimuli.
CC {ECO:0000269|PubMed:16293632}.
CC -!- FUNCTION: [Isoform 2]: Lacks channel activity, due to impaired
CC oligomerization and intracellular retention.
CC {ECO:0000269|PubMed:16293632}.
CC -!- FUNCTION: [Isoform 4]: Lacks channel activity, due to impaired
CC oligomerization and intracellular retention.
CC {ECO:0000269|PubMed:16293632}.
CC -!- FUNCTION: [Isoform 6]: Lacks channel activity, due to impaired
CC oligomerization and intracellular retention.
CC {ECO:0000269|PubMed:16293632}.
CC -!- FUNCTION: (Microbial infection) Facilitates hepatitis C virus (HCV)
CC replication, possibly through its action on DDX3X.
CC {ECO:0000269|PubMed:29899501}.
CC -!- FUNCTION: (Microbial infection) Facilitates Dengue virus (DENV)
CC replication, possibly through its action on DDX3X.
CC {ECO:0000269|PubMed:29899501}.
CC -!- FUNCTION: (Microbial infection) Facilitates Zika virus (ZIKV)
CC replication, possibly through its action on DDX3X.
CC {ECO:0000269|PubMed:29899501}.
CC -!- ACTIVITY REGULATION: Channel activation is inhibited by binding to
CC phosphatidylinositol-4,5-bisphosphate, and to a much lesser degree by
CC phosphatidylinositol-3,4,5-trisphosphate. Not inhibited by
CC phosphatidylinositol-3,4-bisphosphate and phosphatidylinositol-3,5-
CC bisphosphate. {ECO:0000269|PubMed:25256292}.
CC -!- SUBUNIT: Homotetramer (Probable). Self-associates in an isoform-
CC specific manner (PubMed:16293632). Isoform 1 and isoform 5 can
CC oligomerize, but isoform 2, isoform 4 and isoform 6 cannot oligomerize
CC (PubMed:16293632). Interacts with calmodulin (PubMed:12724311).
CC Interacts with Map7 and Src family Tyr protein kinases LYN, SRC, FYN,
CC HCK, LCK and YES (By similarity). Interacts with CTNNB1 (By
CC similarity). The TRPV4 and CTNNB1 complex can interact with CDH1 (By
CC similarity). Interacts with PACSIN1, PACSIN2 and PACSIN3 (via SH3
CC domain) (By similarity). Part of a complex containing MLC1, AQP4,
CC HEPACAM and ATP1B1 (PubMed:22328087). Interacts with ITPR3
CC (PubMed:18826956). Interacts with AQP5; the interaction is probably
CC indirect and regulates TRPV4 activation by hypotonicity (By
CC similarity). Interacts with ANO1 (By similarity). Interacts (via C-
CC terminus) with PKD2 (via C-terminus) (PubMed:18695040). Interacts with
CC DDX3X; this interaction is decreased when the channel is activated
CC (PubMed:29899501). {ECO:0000250|UniProtKB:Q9EPK8,
CC ECO:0000269|PubMed:12724311, ECO:0000269|PubMed:16293632,
CC ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:18826956,
CC ECO:0000269|PubMed:22328087, ECO:0000269|PubMed:22702953,
CC ECO:0000269|PubMed:29899501, ECO:0000305}.
CC -!- INTERACTION:
CC Q9HBA0; Q9HBA0: TRPV4; NbExp=3; IntAct=EBI-962786, EBI-962786;
CC Q9HBA0; P47863: Aqp4; Xeno; NbExp=2; IntAct=EBI-962786, EBI-15907593;
CC Q9HBA0; P47863-1: Aqp4; Xeno; NbExp=2; IntAct=EBI-962786, EBI-15907676;
CC Q9HBA0-1; Q9HBA0-5: TRPV4; NbExp=3; IntAct=EBI-961969, EBI-10048039;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:29899501}.
CC Apical cell membrane {ECO:0000269|PubMed:18695040,
CC ECO:0000269|PubMed:18826956}; Multi-pass membrane protein
CC {ECO:0000305}. Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:Q9EPK8}. Cell projection, cilium
CC {ECO:0000269|PubMed:18695040}. Note=Assembly of the putative
CC homotetramer occurs primarily in the endoplasmic reticulum.
CC {ECO:0000269|PubMed:16293632, ECO:0000269|PubMed:20037587,
CC ECO:0000269|PubMed:20037588}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:16293632, ECO:0000269|PubMed:21964574,
CC ECO:0000269|PubMed:25256292}.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Cell membrane
CC {ECO:0000269|PubMed:16293632}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Endoplasmic reticulum
CC {ECO:0000269|PubMed:16293632}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Endoplasmic reticulum
CC {ECO:0000269|PubMed:16293632}.
CC -!- SUBCELLULAR LOCATION: [Isoform 6]: Endoplasmic reticulum
CC {ECO:0000269|PubMed:16293632}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=A;
CC IsoId=Q9HBA0-1; Sequence=Displayed;
CC Name=2; Synonyms=B, OTRPC4beta;
CC IsoId=Q9HBA0-2; Sequence=VSP_013436;
CC Name=3; Synonyms=TRPV-SV;
CC IsoId=Q9HBA0-3; Sequence=VSP_013437;
CC Name=4; Synonyms=C;
CC IsoId=Q9HBA0-4; Sequence=VSP_026615;
CC Name=5; Synonyms=D;
CC IsoId=Q9HBA0-5; Sequence=VSP_026614;
CC Name=6; Synonyms=E;
CC IsoId=Q9HBA0-6; Sequence=VSP_026615, VSP_013436;
CC -!- TISSUE SPECIFICITY: Found in the synoviocytes from patients with (RA)
CC and without (CTR) rheumatoid arthritis (at protein level).
CC {ECO:0000269|PubMed:19759329}.
CC -!- DOMAIN: The ANK repeat region mediates interaction with Ca(2+)-
CC calmodulin and ATP binding (By similarity). The ANK repeat region
CC mediates interaction with phosphatidylinositol-4,5-bisphosphate and
CC related phosphatidylinositides (PubMed:25256292).
CC {ECO:0000250|UniProtKB:A0A1D5PXA5, ECO:0000269|PubMed:25256292}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16293632,
CC ECO:0000269|PubMed:21964574}.
CC -!- POLYMORPHISM: Genetic variations in TRPV4 determine the sodium serum
CC level quantitative trait locus 1 (SSQTL1) [MIM:613508]. In some
CC populations, variant Pro19Ser has been shown to be significantly
CC associated with hyponatremia defined as serum sodium concentration
CC below or equal to 135 mEq/L.
CC -!- DISEASE: Brachyolmia 3 (BCYM3) [MIM:113500]: A form of brachyolmia, a
CC clinically and genetically heterogeneous skeletal dysplasia primarily
CC affecting the spine and characterized by a short trunk, short stature,
CC and platyspondyly. BCYM3 is an autosomal dominant form with severe
CC scoliosis with or without kyphosis, and flattened irregular cervical
CC vertebrae. {ECO:0000269|PubMed:18587396}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Spondylometaphyseal dysplasia Kozlowski type (SMDK)
CC [MIM:184252]: A form of spondylometaphyseal dysplasia, a group of short
CC stature disorders distinguished by abnormalities in the vertebrae and
CC the metaphyses of the tubular bones. It is characterized by postnatal
CC dwarfism, significant scoliosis and mild metaphyseal abnormalities in
CC the pelvis. The vertebrae exhibit platyspondyly and overfaced pedicles.
CC {ECO:0000269|PubMed:19232556, ECO:0000269|PubMed:20577006,
CC ECO:0000269|PubMed:22702953}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Metatropic dysplasia (MTD) [MIM:156530]: A severe
CC spondyloepimetaphyseal dysplasia characterized by short limbs with
CC limitation and enlargement of joints and usually severe kyphoscoliosis.
CC Radiologic features include severe platyspondyly, severe metaphyseal
CC enlargement and shortening of long bones. {ECO:0000269|PubMed:19232556,
CC ECO:0000269|PubMed:20425821, ECO:0000269|PubMed:20577006,
CC ECO:0000269|PubMed:22702953, ECO:0000269|PubMed:26249260,
CC ECO:0000269|Ref.6}. Note=The disease is caused by variants affecting
CC the gene represented in this entry.
CC -!- DISEASE: Neuronopathy, distal hereditary motor, 8 (HMN8) [MIM:600175]:
CC A clinically variable, neuromuscular disorder characterized by
CC congenital lower motor neuron disorder restricted to the lower part of
CC the body. Clinical manifestations include non-progressive muscular
CC atrophy, thigh muscle atrophy, weak thigh adductors, weak knee and foot
CC extensors, minimal jaw muscle and neck flexor weakness, flexion
CC contractures of knees and pes equinovarus. Tendon reflexes are normal.
CC {ECO:0000269|PubMed:20037588, ECO:0000269|PubMed:22526352,
CC ECO:0000269|PubMed:22702953}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Charcot-Marie-Tooth disease 2C (CMT2C) [MIM:606071]: An axonal
CC form of Charcot-Marie-Tooth disease, a disorder of the peripheral
CC nervous system, characterized by progressive weakness and atrophy,
CC initially of the peroneal muscles and later of the distal muscles of
CC the arms. Charcot-Marie-Tooth disease is classified in two main groups
CC on the basis of electrophysiologic properties and histopathology:
CC primary peripheral demyelinating neuropathies (designated CMT1 when
CC they are dominantly inherited) and primary peripheral axonal
CC neuropathies (CMT2). Neuropathies of the CMT2 group are characterized
CC by signs of axonal degeneration in the absence of obvious myelin
CC alterations, normal or slightly reduced nerve conduction velocities,
CC and progressive distal muscle weakness and atrophy.
CC {ECO:0000269|PubMed:20037586, ECO:0000269|PubMed:20037587,
CC ECO:0000269|PubMed:20037588, ECO:0000269|PubMed:21115951,
CC ECO:0000269|PubMed:21288981, ECO:0000269|PubMed:22702953,
CC ECO:0000269|PubMed:25256292}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Scapuloperoneal spinal muscular atrophy (SPSMA) [MIM:181405]:
CC A clinically variable neuromuscular disorder characterized by
CC neurogenic scapuloperoneal amyotrophy, laryngeal palsy, congenital
CC absence of muscles, progressive scapuloperoneal atrophy and progressive
CC distal weakness and amyotrophy. {ECO:0000269|PubMed:20037587,
CC ECO:0000269|PubMed:22702953}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Spondyloepiphyseal dysplasia Maroteaux type (SEDM)
CC [MIM:184095]: A clinically variable spondyloepiphyseal dysplasia with
CC manifestations limited to the musculoskeletal system. Clinical features
CC include short stature, brachydactyly, platyspondyly, short and stubby
CC hands and feet, epiphyseal hypoplasia of the large joints, and iliac
CC hypoplasia. Intelligence is normal. {ECO:0000269|PubMed:20503319,
CC ECO:0000269|PubMed:22702953}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Parastremmatic dwarfism (PSTD) [MIM:168400]: A bone dysplasia
CC characterized by severe dwarfism, kyphoscoliosis, distortion and bowing
CC of the extremities, and contractures of the large joints.
CC Radiographically, the disease is characterized by a combination of
CC decreased bone density, bowing of the long bones, platyspondyly and
CC striking irregularities of endochondral ossification with areas of
CC calcific stippling and streaking in radiolucent epiphyses, metaphyses
CC and apophyses. {ECO:0000269|PubMed:20503319}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Digital arthropathy-brachydactyly, familial (FDAB)
CC [MIM:606835]: A disorder characterized by irregularities in the
CC proximal articular surfaces of the distal interphalangeal joints of the
CC hand. Individuals appear normal at birth, with no clinical or
CC radiographic evidence of a developmental skeletal dysplasia. The
CC earliest changes appear during the first decade of life. By adulthood,
CC all interphalangeal, metacarpophalangeal, and metatarsophalangeal
CC joints are affected by a deforming, painful osteoarthritis. The
CC remainder of the skeleton is clinically and radiographically
CC unaffected. {ECO:0000269|PubMed:21964574}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- DISEASE: Avascular necrosis of the femoral head, primary 2 (ANFH2)
CC [MIM:617383]: A disease characterized by mechanical failure of the
CC subchondral bone, and degeneration of the hip joint. It usually leads
CC to destruction of the hip joint in the third to fifth decade of life.
CC The clinical manifestations, such as pain on exertion, a limping gait,
CC and a discrepancy in leg length, cause considerable disability.
CC {ECO:0000269|PubMed:27330106}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Lacks channel activity, due to impaired
CC oligomerization and intracellular retention.
CC {ECO:0000269|PubMed:16293632}.
CC -!- MISCELLANEOUS: [Isoform 4]: Lacks channel activity, due to impaired
CC oligomerization and intracellular retention.
CC {ECO:0000269|PubMed:16293632}.
CC -!- MISCELLANEOUS: [Isoform 5]: Forms active ion channels.
CC {ECO:0000269|PubMed:16293632}.
CC -!- MISCELLANEOUS: [Isoform 6]: Lacks channel activity, due to impaired
CC oligomerization and intracellular retention.
CC {ECO:0000269|PubMed:16293632}.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. TrpV
CC subfamily. TRPV4 sub-subfamily. {ECO:0000305}.
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DR EMBL; AF263523; AAG28029.1; -; mRNA.
DR EMBL; AF258465; AAG16127.1; -; mRNA.
DR EMBL; AB100308; BAC55864.1; -; mRNA.
DR EMBL; AB032427; BAB69040.1; -; mRNA.
DR EMBL; AB073669; BAC06573.1; -; mRNA.
DR EMBL; AJ296305; CAC82937.1; -; mRNA.
DR EMBL; DQ059644; AAZ04918.1; -; mRNA.
DR EMBL; DQ059645; AAZ04919.1; -; mRNA.
DR EMBL; DQ059646; AAZ04920.1; -; mRNA.
DR EMBL; CH471054; EAW97879.1; -; Genomic_DNA.
DR EMBL; BC117426; AAI17427.1; -; mRNA.
DR EMBL; BC143315; AAI43316.1; -; mRNA.
DR EMBL; AF279673; AAK69487.1; -; mRNA.
DR CCDS; CCDS53827.1; -. [Q9HBA0-6]
DR CCDS; CCDS53828.1; -. [Q9HBA0-4]
DR CCDS; CCDS53829.1; -. [Q9HBA0-5]
DR CCDS; CCDS9134.1; -. [Q9HBA0-1]
DR CCDS; CCDS9135.1; -. [Q9HBA0-2]
DR RefSeq; NP_001170899.1; NM_001177428.1. [Q9HBA0-4]
DR RefSeq; NP_001170902.1; NM_001177431.1. [Q9HBA0-5]
DR RefSeq; NP_001170904.1; NM_001177433.1. [Q9HBA0-6]
DR RefSeq; NP_067638.3; NM_021625.4. [Q9HBA0-1]
DR RefSeq; NP_671737.1; NM_147204.2. [Q9HBA0-2]
DR RefSeq; XP_005253975.1; XM_005253918.1. [Q9HBA0-1]
DR RefSeq; XP_016875263.1; XM_017019774.1. [Q9HBA0-1]
DR PDB; 4DX1; X-ray; 2.85 A; A/B=149-397.
DR PDB; 4DX2; X-ray; 2.95 A; A/B=149-397.
DR PDB; 7AA5; EM; 4.18 A; A/B/C/D=148-787.
DR PDBsum; 4DX1; -.
DR PDBsum; 4DX2; -.
DR PDBsum; 7AA5; -.
DR AlphaFoldDB; Q9HBA0; -.
DR SMR; Q9HBA0; -.
DR BioGRID; 121883; 13.
DR CORUM; Q9HBA0; -.
DR DIP; DIP-35702N; -.
DR IntAct; Q9HBA0; 7.
DR MINT; Q9HBA0; -.
DR STRING; 9606.ENSP00000406191; -.
DR BindingDB; Q9HBA0; -.
DR ChEMBL; CHEMBL3119; -.
DR DrugBank; DB11148; Butamben.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB14011; Nabiximols.
DR GuidetoPHARMACOLOGY; 510; -.
DR iPTMnet; Q9HBA0; -.
DR PhosphoSitePlus; Q9HBA0; -.
DR BioMuta; TRPV4; -.
DR DMDM; 62901470; -.
DR EPD; Q9HBA0; -.
DR jPOST; Q9HBA0; -.
DR MassIVE; Q9HBA0; -.
DR MaxQB; Q9HBA0; -.
DR PaxDb; Q9HBA0; -.
DR PeptideAtlas; Q9HBA0; -.
DR PRIDE; Q9HBA0; -.
DR ProteomicsDB; 81511; -. [Q9HBA0-1]
DR ProteomicsDB; 81512; -. [Q9HBA0-2]
DR ProteomicsDB; 81513; -. [Q9HBA0-3]
DR ProteomicsDB; 81514; -. [Q9HBA0-4]
DR ProteomicsDB; 81515; -. [Q9HBA0-5]
DR ProteomicsDB; 81516; -. [Q9HBA0-6]
DR Antibodypedia; 1477; 390 antibodies from 34 providers.
DR DNASU; 59341; -.
DR Ensembl; ENST00000261740.7; ENSP00000261740.2; ENSG00000111199.12. [Q9HBA0-1]
DR Ensembl; ENST00000418703.7; ENSP00000406191.2; ENSG00000111199.12. [Q9HBA0-1]
DR Ensembl; ENST00000536838.1; ENSP00000444336.1; ENSG00000111199.12. [Q9HBA0-5]
DR Ensembl; ENST00000537083.5; ENSP00000442738.1; ENSG00000111199.12. [Q9HBA0-2]
DR Ensembl; ENST00000541794.5; ENSP00000442167.1; ENSG00000111199.12. [Q9HBA0-4]
DR Ensembl; ENST00000544971.5; ENSP00000443611.1; ENSG00000111199.12. [Q9HBA0-6]
DR Ensembl; ENST00000675670.1; ENSP00000502135.1; ENSG00000111199.12. [Q9HBA0-1]
DR GeneID; 59341; -.
DR KEGG; hsa:59341; -.
DR MANE-Select; ENST00000261740.7; ENSP00000261740.2; NM_021625.5; NP_067638.3.
DR UCSC; uc001tpg.3; human. [Q9HBA0-1]
DR CTD; 59341; -.
DR DisGeNET; 59341; -.
DR GeneCards; TRPV4; -.
DR GeneReviews; TRPV4; -.
DR HGNC; HGNC:18083; TRPV4.
DR HPA; ENSG00000111199; Tissue enhanced (choroid plexus, salivary gland).
DR MalaCards; TRPV4; -.
DR MIM; 113500; phenotype.
DR MIM; 156530; phenotype.
DR MIM; 168400; phenotype.
DR MIM; 181405; phenotype.
DR MIM; 184095; phenotype.
DR MIM; 184252; phenotype.
DR MIM; 600175; phenotype.
DR MIM; 605427; gene.
DR MIM; 606071; phenotype.
DR MIM; 606835; phenotype.
DR MIM; 613508; phenotype.
DR MIM; 617383; phenotype.
DR neXtProt; NX_Q9HBA0; -.
DR OpenTargets; ENSG00000111199; -.
DR Orphanet; 93304; Autosomal dominant brachyolmia.
DR Orphanet; 99937; Autosomal dominant Charcot-Marie-Tooth disease type 2C.
DR Orphanet; 1216; Autosomal dominant congenital benign spinal muscular atrophy.
DR Orphanet; 86820; Familial avascular necrosis of femoral head.
DR Orphanet; 85169; Familial digital arthropathy-brachydactyly.
DR Orphanet; 2635; Metatropic dysplasia.
DR Orphanet; 2646; Parastremmatic dwarfism.
DR Orphanet; 431255; Scapuloperoneal spinal muscular atrophy.
DR Orphanet; 263482; Spondyloepiphyseal dysplasia, Maroteaux type.
DR Orphanet; 93314; Spondylometaphyseal dysplasia, Kozlowski type.
DR PharmGKB; PA38293; -.
DR VEuPathDB; HostDB:ENSG00000111199; -.
DR eggNOG; KOG3676; Eukaryota.
DR GeneTree; ENSGT00940000158615; -.
DR HOGENOM; CLU_012795_1_0_1; -.
DR InParanoid; Q9HBA0; -.
DR OMA; YPECNLE; -.
DR OrthoDB; 693004at2759; -.
DR PhylomeDB; Q9HBA0; -.
DR TreeFam; TF314711; -.
DR PathwayCommons; Q9HBA0; -.
DR Reactome; R-HSA-3295583; TRP channels.
DR SignaLink; Q9HBA0; -.
DR SIGNOR; Q9HBA0; -.
DR BioGRID-ORCS; 59341; 10 hits in 1071 CRISPR screens.
DR ChiTaRS; TRPV4; human.
DR GeneWiki; TRPV4; -.
DR GenomeRNAi; 59341; -.
DR Pharos; Q9HBA0; Tchem.
DR PRO; PR:Q9HBA0; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9HBA0; protein.
DR Bgee; ENSG00000111199; Expressed in cartilage tissue and 122 other tissues.
DR ExpressionAtlas; Q9HBA0; baseline and differential.
DR Genevisible; Q9HBA0; HS.
DR GO; GO:0005912; C:adherens junction; ISS:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
DR GO; GO:0030864; C:cortical actin cytoskeleton; ISS:BHF-UCL.
DR GO; GO:0005881; C:cytoplasmic microtubule; IEA:Ensembl.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0030175; C:filopodium; ISS:BHF-UCL.
DR GO; GO:0005925; C:focal adhesion; ISS:BHF-UCL.
DR GO; GO:0030426; C:growth cone; ISS:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0030027; C:lamellipodium; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; ISS:BHF-UCL.
DR GO; GO:0003779; F:actin binding; ISS:BHF-UCL.
DR GO; GO:0051015; F:actin filament binding; ISS:BHF-UCL.
DR GO; GO:0043014; F:alpha-tubulin binding; ISS:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0048487; F:beta-tubulin binding; ISS:BHF-UCL.
DR GO; GO:0005262; F:calcium channel activity; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IMP:UniProtKB.
DR GO; GO:0005261; F:cation channel activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005216; F:ion channel activity; IBA:GO_Central.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; ISS:BHF-UCL.
DR GO; GO:0005034; F:osmosensor activity; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0005080; F:protein kinase C binding; ISS:BHF-UCL.
DR GO; GO:0042169; F:SH2 domain binding; ISS:BHF-UCL.
DR GO; GO:0015275; F:stretch-activated, cation-selective, calcium channel activity; IMP:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:BHF-UCL.
DR GO; GO:0007015; P:actin filament organization; ISS:BHF-UCL.
DR GO; GO:0097497; P:blood vessel endothelial cell delamination; IMP:UniProtKB.
DR GO; GO:0070509; P:calcium ion import; ISS:BHF-UCL.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; IBA:GO_Central.
DR GO; GO:1902656; P:calcium ion import into cytosol; IDA:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB.
DR GO; GO:0060351; P:cartilage development involved in endochondral bone morphogenesis; IMP:UniProtKB.
DR GO; GO:0006884; P:cell volume homeostasis; TAS:UniProtKB.
DR GO; GO:0007043; P:cell-cell junction assembly; ISS:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IDA:UniProtKB.
DR GO; GO:0071476; P:cellular hypotonic response; IMP:UniProtKB.
DR GO; GO:0071477; P:cellular hypotonic salinity response; IEA:Ensembl.
DR GO; GO:0034605; P:cellular response to heat; ISS:UniProtKB.
DR GO; GO:0071470; P:cellular response to osmotic stress; ISS:UniProtKB.
DR GO; GO:0043622; P:cortical microtubule organization; ISS:BHF-UCL.
DR GO; GO:0002024; P:diet induced thermogenesis; IEA:Ensembl.
DR GO; GO:0097009; P:energy homeostasis; IEA:Ensembl.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0042538; P:hyperosmotic salinity response; IEA:Ensembl.
DR GO; GO:0046785; P:microtubule polymerization; ISS:BHF-UCL.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; IMP:UniProtKB.
DR GO; GO:1903444; P:negative regulation of brown fat cell differentiation; IEA:Ensembl.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISS:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0007231; P:osmosensory signaling pathway; ISS:BHF-UCL.
DR GO; GO:0071651; P:positive regulation of chemokine (C-C motif) ligand 5 production; IEA:Ensembl.
DR GO; GO:2000340; P:positive regulation of chemokine (C-X-C motif) ligand 1 production; IEA:Ensembl.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IEA:Ensembl.
DR GO; GO:0071642; P:positive regulation of macrophage inflammatory protein 1 alpha production; IEA:Ensembl.
DR GO; GO:0031117; P:positive regulation of microtubule depolymerization; ISS:BHF-UCL.
DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; IEA:Ensembl.
DR GO; GO:0045989; P:positive regulation of striated muscle contraction; IEA:Ensembl.
DR GO; GO:0043117; P:positive regulation of vascular permeability; IMP:UniProtKB.
DR GO; GO:1903715; P:regulation of aerobic respiration; IEA:Ensembl.
DR GO; GO:0047484; P:regulation of response to osmotic stress; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0009612; P:response to mechanical stimulus; TAS:UniProtKB.
DR GO; GO:0030103; P:vasopressin secretion; IEA:Ensembl.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR024862; TRPV.
DR InterPro; IPR008347; TrpV1-4.
DR InterPro; IPR008348; TrpV4.
DR PANTHER; PTHR10582; PTHR10582; 1.
DR PANTHER; PTHR10582:SF4; PTHR10582:SF4; 1.
DR Pfam; PF00023; Ank; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR PRINTS; PR01768; TRPVRECEPTOR.
DR PRINTS; PR01769; VRL2RECEPTOR.
DR SMART; SM00248; ANK; 3.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ANK repeat; ATP-binding; Calcium;
KW Calcium channel; Calcium transport; Calmodulin-binding; Cell junction;
KW Cell membrane; Cell projection; Charcot-Marie-Tooth disease; Cilium;
KW Disease variant; Dwarfism; Endoplasmic reticulum; Ion channel;
KW Ion transport; Lipid-binding; Membrane; Metal-binding; Neurodegeneration;
KW Neuropathy; Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..871
FT /note="Transient receptor potential cation channel
FT subfamily V member 4"
FT /id="PRO_0000215347"
FT TOPO_DOM 1..469
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 470..490
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 491..507
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 508..534
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 535..547
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 548..568
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 569..572
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 573..593
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 594..608
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 609..636
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 637..665
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT INTRAMEM 666..685
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 686..693
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 694..722
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 723..871
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT REPEAT 237..266
FT /note="ANK 1"
FT REPEAT 284..313
FT /note="ANK 2"
FT REPEAT 369..398
FT /note="ANK 3"
FT REGION 1..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 812..831
FT /note="Interaction with calmodulin and ITPR3"
FT /evidence="ECO:0000269|PubMed:12724311,
FT ECO:0000269|PubMed:18826956"
FT REGION 849..871
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 679..682
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 192
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22702953,
FT ECO:0007744|PDB:4DX2"
FT BINDING 197
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22702953,
FT ECO:0007744|PDB:4DX2"
FT BINDING 201
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22702953,
FT ECO:0007744|PDB:4DX2"
FT BINDING 236..239
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22702953,
FT ECO:0007744|PDB:4DX2"
FT BINDING 248
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22702953,
FT ECO:0007744|PDB:4DX2"
FT BINDING 249..251
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250|UniProtKB:A0A1D5PXA5"
FT BINDING 296..299
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250|UniProtKB:A0A1D5PXA5"
FT BINDING 344
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250|UniProtKB:A0A1D5PXA5"
FT BINDING 682
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:Q9R186"
FT MOD_RES 110
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9EPK8"
FT MOD_RES 253
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9EPK8"
FT MOD_RES 805
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9EPK8"
FT MOD_RES 824
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9EPK8"
FT VAR_SEQ 28..61
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16293632"
FT /id="VSP_026614"
FT VAR_SEQ 239..285
FT /note="Missing (in isoform 4 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:16293632"
FT /id="VSP_026615"
FT VAR_SEQ 385..444
FT /note="Missing (in isoform 2 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:16293632, ECO:0000303|Ref.6"
FT /id="VSP_013436"
FT VAR_SEQ 844..871
FT /note="PLDSMGNPRCDGHQQGYPRKWRTDDAPL -> RHLCRVRRKR (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:12692122"
FT /id="VSP_013437"
FT VARIANT 19
FT /note="P -> S (associated with lower sodium concentrations
FT in serum; shows diminished response to hypotonic stress
FT relative to wild-type; dbSNP:rs3742030)"
FT /id="VAR_052391"
FT VARIANT 89
FT /note="T -> I (in MTD; lethal form; dbSNP:rs397514473)"
FT /evidence="ECO:0000269|PubMed:20425821"
FT /id="VAR_064517"
FT VARIANT 97
FT /note="P -> R (in HMN8; loss of function mutation;
FT dbSNP:rs876661124)"
FT /evidence="ECO:0000269|PubMed:22526352"
FT /id="VAR_067989"
FT VARIANT 183
FT /note="E -> K (found in a patient with spondyloepiphyseal
FT dysplasia Maroteaux type; decreased protein stability;
FT increased ATP-binding; dbSNP:rs387906324)"
FT /evidence="ECO:0000269|PubMed:20503319,
FT ECO:0000269|PubMed:22702953"
FT /id="VAR_064518"
FT VARIANT 197
FT /note="K -> R (in MTD; lethal form; decreased protein
FT stability; reduced ATP-binding; dbSNP:rs387906903)"
FT /evidence="ECO:0000269|PubMed:20425821,
FT ECO:0000269|PubMed:22702953"
FT /id="VAR_064519"
FT VARIANT 199
FT /note="L -> F (in MTD; decreased protein stability;
FT dbSNP:rs515726167)"
FT /evidence="ECO:0000269|PubMed:20577006,
FT ECO:0000269|PubMed:22702953"
FT /id="VAR_064520"
FT VARIANT 232
FT /note="R -> C (in HMN8 and CMT2C; does not affect channel
FT localization to plasma membrane; results in increased
FT agonist-induced channel activity and increased basal
FT intracellular calcium concentration; decreases ATP-binding;
FT no effect on protein stability; decreases binding to
FT membranes enriched in phosphatidylinositol-2,4-
FT bisphosphate; causes increased cell death;
FT dbSNP:rs387906904)"
FT /evidence="ECO:0000269|PubMed:21288981,
FT ECO:0000269|PubMed:22526352, ECO:0000269|PubMed:22702953,
FT ECO:0000269|PubMed:25256292"
FT /id="VAR_067990"
FT VARIANT 269
FT /note="R -> C (in CMT2C; increased agonist-induced channel
FT activity; causes increased cell death; no effect on protein
FT stability and ATP-binding; dbSNP:rs267607146)"
FT /evidence="ECO:0000269|PubMed:20037586,
FT ECO:0000269|PubMed:21288981, ECO:0000269|PubMed:22702953"
FT /id="VAR_063528"
FT VARIANT 269
FT /note="R -> H (in HMN8 and CMT2C; increased agonist-induced
FT channel activity and increased basal intracellular calcium
FT concentration; slightly decreased protein stability and
FT ATP-binding; decreases binding to membranes enriched in
FT phosphatidylinositol-2,4-bisphosphate; causes increased
FT cell death; dbSNP:rs267607144)"
FT /evidence="ECO:0000269|PubMed:20037586,
FT ECO:0000269|PubMed:20037587, ECO:0000269|PubMed:20037588,
FT ECO:0000269|PubMed:21288981, ECO:0000269|PubMed:22702953,
FT ECO:0000269|PubMed:25256292"
FT /id="VAR_063529"
FT VARIANT 270
FT /note="G -> V (in FDAB; poorly expressed on the cell
FT surface; mutant channels show a significantly reduced
FT response to agonists; dbSNP:rs387907220)"
FT /evidence="ECO:0000269|PubMed:21964574"
FT /id="VAR_068498"
FT VARIANT 271
FT /note="R -> P (in FDAB; poorly expressed on the cell
FT surface; mutant channels show a significantly reduced
FT response to agonists; dbSNP:rs387907219)"
FT /evidence="ECO:0000269|PubMed:21964574"
FT /id="VAR_068499"
FT VARIANT 273
FT /note="F -> L (in FDAB; poorly expressed on the cell
FT surface; mutant channels show a significantly reduced
FT response to agonists; dbSNP:rs515726170)"
FT /evidence="ECO:0000269|PubMed:21964574"
FT /id="VAR_068500"
FT VARIANT 278
FT /note="E -> K (in SMDK; slightly increased ATP-binding;
FT slightly decreased protein stability; dbSNP:rs267607148)"
FT /evidence="ECO:0000269|PubMed:20577006,
FT ECO:0000269|PubMed:22702953"
FT /id="VAR_064521"
FT VARIANT 295
FT /note="T -> A (in MTD; impairs protein folding or
FT stability; dbSNP:rs515726171)"
FT /evidence="ECO:0000269|PubMed:20577006,
FT ECO:0000269|PubMed:22702953"
FT /id="VAR_064522"
FT VARIANT 315
FT /note="R -> W (in CMT2C; increased basal and agonist-
FT induced channel activity, decreased protein stability;
FT decreased ATP-binding; decreases binding to membranes
FT enriched in phosphatidylinositol-2,4-bisphosphate; causes
FT increased cell death; dbSNP:rs267607143)"
FT /evidence="ECO:0000269|PubMed:20037588,
FT ECO:0000269|PubMed:21115951, ECO:0000269|PubMed:22702953,
FT ECO:0000269|PubMed:25256292"
FT /id="VAR_063541"
FT VARIANT 316
FT /note="R -> C (in CMT2C and SPSMA; decreased protein
FT stability; decreased ATP-binding; dbSNP:rs267607145)"
FT /evidence="ECO:0000269|PubMed:20037587,
FT ECO:0000269|PubMed:20037588"
FT /id="VAR_063530"
FT VARIANT 316
FT /note="R -> H (in CMT2C; does not affect channel
FT localization to plasma membrane; results in increased
FT agonist-induced channel activity and increased basal
FT intracellular calcium concentration; decreases protein
FT stability; causes increased cell death; dbSNP:rs387906905)"
FT /evidence="ECO:0000269|PubMed:21288981,
FT ECO:0000269|PubMed:25256292"
FT /id="VAR_067991"
FT VARIANT 331
FT /note="I -> F (in MTD; decreased protein stability; no
FT effect on ATP-binding; dbSNP:rs121912636)"
FT /evidence="ECO:0000269|PubMed:19232556,
FT ECO:0000269|PubMed:20425821, ECO:0000269|PubMed:22702953"
FT /id="VAR_062331"
FT VARIANT 331
FT /note="I -> T (in MTD; no effect on protein stability; no
FT effect on ATP-binding; dbSNP:rs515726172)"
FT /evidence="ECO:0000269|PubMed:20577006,
FT ECO:0000269|PubMed:22702953"
FT /id="VAR_064523"
FT VARIANT 333..336
FT /note="Missing (in SMDK)"
FT /id="VAR_067992"
FT VARIANT 333
FT /note="D -> G (in SMDK; decreased protein stability; no
FT effect on ATP-binding; dbSNP:rs121912634)"
FT /evidence="ECO:0000269|PubMed:19232556,
FT ECO:0000269|PubMed:22702953"
FT /id="VAR_062332"
FT VARIANT 342
FT /note="V -> F (in MTD; decreased protein stability;
FT decreased ATP-binding; dbSNP:rs515726152)"
FT /evidence="ECO:0000269|PubMed:20577006,
FT ECO:0000269|PubMed:22702953"
FT /id="VAR_064524"
FT VARIANT 471
FT /note="Missing (in MTD; lethal form)"
FT /evidence="ECO:0000269|PubMed:20425821,
FT ECO:0000269|PubMed:20577006"
FT /id="VAR_064525"
FT VARIANT 542
FT /note="S -> Y (in CMT2C; dbSNP:rs387906902)"
FT /evidence="ECO:0000269|PubMed:21115951"
FT /id="VAR_067993"
FT VARIANT 592
FT /note="F -> L (in MTD; dbSNP:rs515726158)"
FT /evidence="ECO:0000269|PubMed:20577006"
FT /id="VAR_064526"
FT VARIANT 594
FT /note="R -> H (in SMDK and PSTD; dbSNP:rs77975504)"
FT /evidence="ECO:0000269|PubMed:19232556,
FT ECO:0000269|PubMed:20503319, ECO:0000269|PubMed:20577006"
FT /id="VAR_062333"
FT VARIANT 596
FT /note="L -> P (in SMDK; dbSNP:rs515726159)"
FT /evidence="ECO:0000269|PubMed:20577006"
FT /id="VAR_064527"
FT VARIANT 600
FT /note="G -> W (in SMDK; dbSNP:rs515726160)"
FT /evidence="ECO:0000269|PubMed:20577006"
FT /id="VAR_064528"
FT VARIANT 602
FT /note="Y -> C (found in a patient with spondyloepiphyseal
FT dysplasia Maroteaux type; dbSNP:rs267607150)"
FT /evidence="ECO:0000269|PubMed:20503319"
FT /id="VAR_064529"
FT VARIANT 604
FT /note="I -> M (in MTD; lethal form; dbSNP:rs515726161)"
FT /evidence="ECO:0000269|PubMed:20425821"
FT /id="VAR_064530"
FT VARIANT 616
FT /note="R -> Q (in BCYM3; results in a gain of function and
FT a constitutive activation of the channel;
FT dbSNP:rs121912632)"
FT /evidence="ECO:0000269|PubMed:18587396"
FT /id="VAR_054805"
FT VARIANT 617
FT /note="F -> L (in MTD; dbSNP:rs515726162)"
FT /evidence="ECO:0000269|PubMed:20425821"
FT /id="VAR_064531"
FT VARIANT 618
FT /note="L -> P (in MTD; dbSNP:rs515726163)"
FT /evidence="ECO:0000269|PubMed:20425821, ECO:0000269|Ref.6"
FT /id="VAR_064532"
FT VARIANT 620
FT /note="V -> I (in BCYM3; results in a gain of function and
FT a constitutive activation of the channel;
FT dbSNP:rs121912633)"
FT /evidence="ECO:0000269|PubMed:18587396"
FT /id="VAR_054806"
FT VARIANT 625
FT /note="M -> I (in SMDK; dbSNP:rs515726164)"
FT /evidence="ECO:0000269|PubMed:20577006"
FT /id="VAR_064533"
FT VARIANT 709
FT /note="L -> M (in SMDK; dbSNP:rs116571438)"
FT /evidence="ECO:0000269|PubMed:20577006"
FT /id="VAR_064534"
FT VARIANT 716
FT /note="A -> S (in SMDK; dbSNP:rs121912635)"
FT /evidence="ECO:0000269|PubMed:19232556"
FT /id="VAR_062334"
FT VARIANT 775
FT /note="R -> K (in MTD)"
FT /evidence="ECO:0000269|PubMed:20577006"
FT /id="VAR_064535"
FT VARIANT 777
FT /note="C -> Y (in SMDK; dbSNP:rs515726165)"
FT /evidence="ECO:0000269|PubMed:20577006"
FT /id="VAR_064536"
FT VARIANT 797
FT /note="E -> K (in MTD and SMDK; also found in a patient
FT with spondyloepiphyseal dysplasia Maroteaux type;
FT dbSNP:rs267607149)"
FT /evidence="ECO:0000269|PubMed:20425821,
FT ECO:0000269|PubMed:20503319, ECO:0000269|PubMed:20577006"
FT /id="VAR_064537"
FT VARIANT 799
FT /note="P -> A (in MTD; dbSNP:rs267607147)"
FT /evidence="ECO:0000269|PubMed:20577006"
FT /id="VAR_064538"
FT VARIANT 799
FT /note="P -> L (in MTD; also found in a patient with
FT spondyloepiphyseal dysplasia Maroteaux type;
FT dbSNP:rs121912637)"
FT /evidence="ECO:0000269|PubMed:19232556,
FT ECO:0000269|PubMed:20425821, ECO:0000269|PubMed:20503319,
FT ECO:0000269|PubMed:20577006, ECO:0000269|PubMed:26249260"
FT /id="VAR_062335"
FT VARIANT 799
FT /note="P -> R (in MTD; dbSNP:rs121912637)"
FT /evidence="ECO:0000269|PubMed:20577006"
FT /id="VAR_064539"
FT VARIANT 799
FT /note="P -> S (in MTD; dbSNP:rs267607147)"
FT /evidence="ECO:0000269|PubMed:20577006"
FT /id="VAR_064540"
FT MUTAGEN 231
FT /note="F->C: Decreased ATP-binding."
FT /evidence="ECO:0000269|PubMed:22702953"
FT MUTAGEN 251
FT /note="K->E: No effect on channel activity. No effect on
FT interaction with membranes enriched in
FT phosphatidylinositol-2,4-bisphosphate."
FT /evidence="ECO:0000269|PubMed:25256292"
FT MUTAGEN 296
FT /note="N->D: Loss of interaction with membranes enriched in
FT phosphatidylinositol-2,4-bisphosphate; when associated with
FT P-299."
FT /evidence="ECO:0000269|PubMed:25256292"
FT MUTAGEN 299
FT /note="H->P: Strongly decreased interaction with membranes
FT enriched in phosphatidylinositol-2,4-bisphosphate. Loss of
FT interaction with membranes enriched in
FT phosphatidylinositol-2,4-bisphosphate; when associated with
FT D-296."
FT /evidence="ECO:0000269|PubMed:25256292"
FT MUTAGEN 344
FT /note="K->E: No effect on channel activity. No effect on
FT interaction with membranes enriched in
FT phosphatidylinositol-2,4-bisphosphate."
FT /evidence="ECO:0000269|PubMed:25256292"
FT MUTAGEN 680
FT /note="M->D: Loss of Ca(2+) influx. Loss of DDX3X
FT translocation to the nucleus."
FT /evidence="ECO:0000269|PubMed:29899501"
FT MUTAGEN 816..821
FT /note="RLRRDR->ELEEDE: Loss of calmodulin binding; when
FT associated with A-828."
FT MUTAGEN 821..824
FT /note="RWSS->AASA: Loss of calmodulin binding."
FT MUTAGEN 822
FT /note="W->A: Loss of Ca(2+) dependent current
FT potentiation."
FT MUTAGEN 828
FT /note="R->A: Loss of calmodulin binding; when associated
FT with 816-ELEEDE-821."
FT /evidence="ECO:0000269|PubMed:12724311"
FT CONFLICT 385
FT /note="I -> V (in Ref. 1; AAG28029)"
FT /evidence="ECO:0000305"
FT CONFLICT 452
FT /note="V -> A (in Ref. 6; BAC06573)"
FT /evidence="ECO:0000305"
FT CONFLICT 781
FT /note="D -> N (in Ref. 1; AAG28029)"
FT /evidence="ECO:0000305"
FT CONFLICT 820
FT /note="D -> T (in Ref. 4; BAB69040)"
FT /evidence="ECO:0000305"
FT CONFLICT 861
FT /note="P -> T (in Ref. 6; BAC06573)"
FT /evidence="ECO:0000305"
FT CONFLICT 867
FT /note="D -> E (in Ref. 2; AAG16127)"
FT /evidence="ECO:0000305"
FT HELIX 151..159
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 169..175
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:4DX1"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 194..200
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 209..220
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 223..228
FT /evidence="ECO:0007829|PDB:4DX1"
FT STRAND 234..239
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 241..247
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 251..260
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:4DX2"
FT TURN 276..279
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 288..294
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 298..306
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 324..331
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 336..356
FT /evidence="ECO:0007829|PDB:4DX1"
FT STRAND 357..360
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 362..364
FT /evidence="ECO:0007829|PDB:4DX2"
FT HELIX 373..379
FT /evidence="ECO:0007829|PDB:4DX1"
FT HELIX 383..395
FT /evidence="ECO:0007829|PDB:4DX1"
SQ SEQUENCE 871 AA; 98281 MW; C62056B86C5A6FB6 CRC64;
MADSSEGPRA GPGEVAELPG DESGTPGGEA FPLSSLANLF EGEDGSLSPS PADASRPAGP
GDGRPNLRMK FQGAFRKGVP NPIDLLESTL YESSVVPGPK KAPMDSLFDY GTYRHHSSDN
KRWRKKIIEK QPQSPKAPAP QPPPILKVFN RPILFDIVSR GSTADLDGLL PFLLTHKKRL
TDEEFREPST GKTCLPKALL NLSNGRNDTI PVLLDIAERT GNMREFINSP FRDIYYRGQT
ALHIAIERRC KHYVELLVAQ GADVHAQARG RFFQPKDEGG YFYFGELPLS LAACTNQPHI
VNYLTENPHK KADMRRQDSR GNTVLHALVA IADNTRENTK FVTKMYDLLL LKCARLFPDS
NLEAVLNNDG LSPLMMAAKT GKIGIFQHII RREVTDEDTR HLSRKFKDWA YGPVYSSLYD
LSSLDTCGEE ASVLEILVYN SKIENRHEML AVEPINELLR DKWRKFGAVS FYINVVSYLC
AMVIFTLTAY YQPLEGTPPY PYRTTVDYLR LAGEVITLFT GVLFFFTNIK DLFMKKCPGV
NSLFIDGSFQ LLYFIYSVLV IVSAALYLAG IEAYLAVMVF ALVLGWMNAL YFTRGLKLTG
TYSIMIQKIL FKDLFRFLLV YLLFMIGYAS ALVSLLNPCA NMKVCNEDQT NCTVPTYPSC
RDSETFSTFL LDLFKLTIGM GDLEMLSSTK YPVVFIILLV TYIILTFVLL LNMLIALMGE
TVGQVSKESK HIWKLQWATT ILDIERSFPV FLRKAFRSGE MVTVGKSSDG TPDRRWCFRV
DEVNWSHWNQ NLGIINEDPG KNETYQYYGF SHTVGRLRRD RWSSVVPRVV ELNKNSNPDE
VVVPLDSMGN PRCDGHQQGY PRKWRTDDAP L
