TRPV4_CHICK
ID TRPV4_CHICK Reviewed; 852 AA.
AC A0A1D5PXA5; Q9DFS3;
DT 28-MAR-2018, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2016, sequence version 1.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=Transient receptor potential cation channel subfamily V member 4;
DE Short=TrpV4;
DE AltName: Full=Vanilloid receptor-related osmotically activated channel {ECO:0000303|PubMed:11081638};
DE Short=VR-OAC {ECO:0000303|PubMed:11081638};
GN Name=TRPV4;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031 {ECO:0000312|Proteomes:UP000000539};
RN [1] {ECO:0000312|EMBL:AAG28026.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Cochlea {ECO:0000312|EMBL:AAG28026.1};
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=Red jungle fowl;
RX PubMed=15592404; DOI=10.1038/nature03154;
RA Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P.,
RA Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B.,
RA Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C.,
RA Fulton R.S., Graves T.A., Kremitzki C., Layman D., Magrini V.,
RA McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O.,
RA Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W.,
RA Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D.,
RA Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K.,
RA Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L.,
RA Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B.,
RA Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M.,
RA Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K.,
RA Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E.,
RA Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M.,
RA Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M.,
RA Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S.,
RA Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M.,
RA Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M.,
RA Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A.,
RA Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S.,
RA Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J.,
RA Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J.,
RA Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E.,
RA Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M.,
RA Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A.,
RA Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M.,
RA Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O.,
RA Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E.,
RA Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S.,
RA Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E.,
RA Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R.,
RA Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R.,
RA Wilson R.K.;
RT "Sequence and comparative analysis of the chicken genome provide unique
RT perspectives on vertebrate evolution.";
RL Nature 432:695-716(2004).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CALMODULIN, ATP-BINDING,
RP DOMAIN, ACTIVITY REGULATION, AND MUTAGENESIS OF LYS-178; LYS-183 AND
RP LYS-205.
RX PubMed=19864432; DOI=10.1074/jbc.m109.052548;
RA Phelps C.B., Wang R.R., Choo S.S., Gaudet R.;
RT "Differential regulation of TRPV1, TRPV3, and TRPV4 sensitivity through a
RT conserved binding site on the ankyrin repeat domain.";
RL J. Biol. Chem. 285:731-740(2010).
RN [4] {ECO:0007744|PDB:3JXI, ECO:0007744|PDB:3JXJ}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 133-382.
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 [5] {ECO:0007744|PDB:3W9F, ECO:0007744|PDB:3W9G}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 133-382 IN COMPLEX WITH
RP MYO-INOSITOL-1,4,5-TRISPHOSPHATE, LIPID-BINDING, AND DOMAIN.
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).
CC -!- FUNCTION: Non-selective calcium permeant cation channel involved in
CC osmotic sensitivity and mechanosensitivity (PubMed:11081638).
CC Activation by exposure to hypotonicity within the physiological range
CC exhibits an outward rectification (PubMed:11081638). Also activated by
CC phorbol esters (PubMed:19864432). Channel activity seems to be
CC regulated by a calmodulin-dependent mechanism (By similarity).
CC {ECO:0000250|UniProtKB:Q9HBA0, ECO:0000269|PubMed:11081638,
CC ECO:0000269|PubMed:19864432}.
CC -!- ACTIVITY REGULATION: ATP binding enhances channel sensitivity to
CC agonists. Ca(2+)-calmodulin prevents the ATP-mediated increased
CC sensitivity to agonists. {ECO:0000269|PubMed:19864432}.
CC -!- SUBUNIT: Homotetramer (By similarity). Interacts with Ca(2+)-calmodulin
CC (PubMed:19864432). {ECO:0000250|UniProtKB:Q9HBA0,
CC ECO:0000269|PubMed:19864432}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000305|PubMed:11081638, ECO:0000305|PubMed:19864432}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:Q9EPK8}. Cell junction,
CC adherens junction {ECO:0000250|UniProtKB:Q9EPK8}.
CC -!- DOMAIN: The ANK repeat region mediates interaction with Ca(2+)-
CC calmodulin and ATP binding (PubMed:19864432). The ANK repeat region
CC mediates interaction with phosphatidylinositol-4,5-bisphosphate and
CC related phosphatidylinositides (PubMed:25256292).
CC {ECO:0000269|PubMed:19864432, ECO:0000269|PubMed:25256292}.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. TrpV
CC subfamily. TRPV4 sub-subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF261883; AAG28026.1; -; mRNA.
DR EMBL; AADN04000193; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_990023.1; NM_204692.1.
DR PDB; 3JXI; X-ray; 2.30 A; A/B/C/D=133-382.
DR PDB; 3JXJ; X-ray; 2.80 A; A/B=133-382.
DR PDB; 3W9F; X-ray; 1.90 A; A/B/C/D=133-382.
DR PDB; 3W9G; X-ray; 2.00 A; A/B/C/D=133-382.
DR PDB; 6F55; NMR; -; B=121-135.
DR PDBsum; 3JXI; -.
DR PDBsum; 3JXJ; -.
DR PDBsum; 3W9F; -.
DR PDBsum; 3W9G; -.
DR PDBsum; 6F55; -.
DR AlphaFoldDB; A0A1D5PXA5; -.
DR SMR; A0A1D5PXA5; -.
DR STRING; 9031.ENSGALP00000008256; -.
DR GeneID; 395427; -.
DR KEGG; gga:395427; -.
DR CTD; 59341; -.
DR VEuPathDB; HostDB:geneid_395427; -.
DR eggNOG; KOG3676; Eukaryota.
DR OrthoDB; 693004at2759; -.
DR PRO; PR:A0A1D5PXA5; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005262; F:calcium channel activity; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
DR GO; GO:0005261; F:cation channel activity; ISS:UniProtKB.
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:0007015; P:actin filament organization; IBA:GO_Central.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; IBA:GO_Central.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0007231; P:osmosensory signaling pathway; IBA:GO_Central.
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; ANK repeat; ATP-binding; Calcium; Calcium channel;
KW Calcium transport; Calmodulin-binding; Cell junction; Cell membrane;
KW Ion channel; Ion transport; Lipid-binding; Membrane; Metal-binding;
KW Nucleotide-binding; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..852
FT /note="Transient receptor potential cation channel
FT subfamily V member 4"
FT /id="PRO_0000443481"
FT TOPO_DOM 1..455
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 456..476
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 477..493
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 494..520
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 521..533
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 534..554
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 555..558
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 559..579
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 580..594
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 595..622
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 623..651
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT INTRAMEM 652..671
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 672..679
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 680..708
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 709..852
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT REPEAT 223..252
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 270..299
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 355..387
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REGION 30..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 665..668
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 178
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9HBA0"
FT BINDING 183
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9HBA0"
FT BINDING 187
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9HBA0"
FT BINDING 222..225
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9HBA0"
FT BINDING 234
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9HBA0"
FT BINDING 235..237
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:0000305|PubMed:25256292,
FT ECO:0007744|PDB:3W9F"
FT BINDING 282..285
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:0000305|PubMed:25256292,
FT ECO:0007744|PDB:3W9F"
FT BINDING 330
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:0000305|PubMed:25256292,
FT ECO:0007744|PDB:3W9F"
FT BINDING 668
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 MUTAGEN 178
FT /note="K->A: Strongly decreased affinity for ATP and
FT Ca(2+)-calmodulin. Abolishes ATP-mediated increase in
FT channel sensitivity to agonists."
FT /evidence="ECO:0000269|PubMed:19864432"
FT MUTAGEN 183
FT /note="K->A: Strongly decreased affinity for ATP and
FT slightly decreased affinity for Ca(2+)-calmodulin."
FT /evidence="ECO:0000269|PubMed:19864432"
FT MUTAGEN 205
FT /note="K->A: No significant effect on affinity for ATP and
FT Ca(2+)-calmodulin."
FT /evidence="ECO:0000269|PubMed:19864432"
FT CONFLICT 47
FT /note="V -> G (in Ref. 1; AAG28026)"
FT /evidence="ECO:0000305"
FT CONFLICT 131
FT /note="I -> V (in Ref. 1; AAG28026)"
FT /evidence="ECO:0000305"
FT CONFLICT 741
FT /note="V -> A (in Ref. 1; AAG28026)"
FT /evidence="ECO:0000305"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:6F55"
FT HELIX 137..146
FT /evidence="ECO:0007829|PDB:3W9F"
FT HELIX 149..152
FT /evidence="ECO:0007829|PDB:3W9F"
FT HELIX 155..161
FT /evidence="ECO:0007829|PDB:3W9F"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:3W9F"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:3W9F"
FT HELIX 180..185
FT /evidence="ECO:0007829|PDB:3W9F"
FT STRAND 189..191
FT /evidence="ECO:0007829|PDB:3JXJ"
FT HELIX 195..205
FT /evidence="ECO:0007829|PDB:3W9F"
FT HELIX 209..214
FT /evidence="ECO:0007829|PDB:3W9F"
FT STRAND 220..225
FT /evidence="ECO:0007829|PDB:3W9F"
FT HELIX 227..233
FT /evidence="ECO:0007829|PDB:3W9F"
FT HELIX 237..245
FT /evidence="ECO:0007829|PDB:3W9F"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:3W9F"
FT HELIX 274..280
FT /evidence="ECO:0007829|PDB:3W9F"
FT HELIX 284..292
FT /evidence="ECO:0007829|PDB:3W9F"
FT HELIX 310..317
FT /evidence="ECO:0007829|PDB:3W9F"
FT HELIX 322..342
FT /evidence="ECO:0007829|PDB:3W9F"
FT HELIX 348..350
FT /evidence="ECO:0007829|PDB:3W9F"
FT HELIX 359..365
FT /evidence="ECO:0007829|PDB:3W9F"
FT HELIX 369..382
FT /evidence="ECO:0007829|PDB:3W9F"
SQ SEQUENCE 852 AA; 96282 MW; 0A799C76C6598845 CRC64;
MADPEDPRDA GDVLGDDSFP LSSLANLFEV EDTPSPAEPS RGPPGAVDGK QNLRMKFHGA
FRKGPPKPME LLESTIYESS VVPAPKKAPM DSLFDYGTYR QHPSENKRWR RRVVEKPVAG
TKGPAPNPPP ILKVFNRPIL FDIVSRGSPD GLEGLLSFLL THKKRLTDEE FREPSTGKTC
LPKALLNLSA GRNDTIPILL DIAEKTGNMR EFINSPFRDV YYRGQTALHI AIERRCKHYV
ELLVEKGADV HAQARGRFFQ PKDEGGYFYF GELPLSLAAC TNQPHIVHYL TENGHKQADL
RRQDSRGNTV LHALVAIADN TRENTKFVTK MYDLLLIKCA KLFPDTNLEA LLNNDGLSPL
MMAAKTGKIG IFQHIIRREI ADEDVRHLSR KFKDWAYGPV YSSLYDLSSL DTCGEEVSVL
EILVYNSKIE NRHEMLAVEP INELLRDKWR KFGAVSFYIS VVSYLCAMII FTLIAYYRPM
EGPPPYPYTT TIDYLRLAGE IITLLTGILF FFSNIKDLFM KKCPGVNSFF IDGSFQLLYF
IYSVLVIVTA GLYLGGVEAY LAVMVFALVL GWMNALYFTR GLKLTGTYSI MIQKILFKDL
FRFLLVYLLF MIGYASALVS LLNPCPSSES CSEDHSNCTL PTYPSCRDSQ TFSTFLLDLF
KLTIGMGDLE MLESAKYPGV FIILLVTYII LTFVLLLNML IALMGETVGQ VSKESKHIWK
LQWATTILDI ERSFPLFLRR VFRSGEMVTV GKGTDGTPDR RWCFRVDEVN WSHWNQNLGI
ISEDPGKSDT YQYYGFSHTV GRLRRDRWST VVPRVVELNK SCPTEDVVVP LGTMGTAEAR
ERRHGQTPSS PL
