ID   OTOP1_DANRE             Reviewed;         586 AA.
AC   Q7ZWK8; B2GQA4; Q5MKL8; Q5XJ61;
DT   15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT   15-JAN-2008, sequence version 2.
DT   27-MAR-2024, entry version 85.
DE   RecName: Full=Proton channel OTOP1 {ECO:0000305};
DE   AltName: Full=Otopetrin-1 {ECO:0000303|PubMed:12651873};
GN   Name=otop1 {ECO:0000303|PubMed:12651873};
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Embryo;
RX   PubMed=12651873; DOI=10.1093/hmg/ddg087;
RA   Hurle B., Ignatova E., Massironi S.M., Mashimo T., Rios X., Thalmann I.,
RA   Thalmann R., Ornitz D.M.;
RT   "Non-syndromic vestibular disorder with otoconial agenesis in
RT   tilted/mergulhador mice caused by mutations in otopetrin 1.";
RL   Hum. Mol. Genet. 12:777-789(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, SUBCELLULAR
RP   LOCATION, MUTAGENESIS OF GLU-429, AND DISRUPTION PHENOTYPE.
RX   PubMed=15480759; DOI=10.1007/s00427-004-0440-2;
RA   Soellner C., Schwarz H., Geisler R., Nicolson T.;
RT   "Mutated otopetrin 1 affects the genesis of otoliths and the localization
RT   of Starmaker in zebrafish.";
RL   Dev. Genes Evol. 214:582-590(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Larva;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=9007244; DOI=10.1242/dev.123.1.241;
RA   Whitfield T.T., Granato M., van Eeden F.J., Schach U., Brand M.,
RA   Furutani-Seiki M., Haffter P., Hammerschmidt M., Heisenberg C.P.,
RA   Jiang Y.J., Kane D.A., Kelsh R.N., Mullins M.C., Odenthal J.,
RA   Nuesslein-Volhard C.;
RT   "Mutations affecting development of the zebrafish inner ear and lateral
RT   line.";
RL   Development 123:241-254(1996).
RN   [5]
RP   FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX   PubMed=15581873; DOI=10.1016/j.ydbio.2004.09.001;
RA   Hughes I., Blasiole B., Huss D., Warchol M.E., Rath N.P., Hurle B.,
RA   Ignatova E., Dickman J.D., Thalmann R., Levenson R., Ornitz D.M.;
RT   "Otopetrin 1 is required for otolith formation in the zebrafish Danio
RT   rerio.";
RL   Dev. Biol. 276:391-402(2004).
CC   -!- FUNCTION: Proton-selective channel that specifically transports protons
CC       into cells (By similarity). Proton channel activity is only weakly-
CC       sensitive to voltage (By similarity). Proton-selective channel activity
CC       is probably required in cell types that use changes in intracellular pH
CC       for cell signaling or to regulate biochemical or developmental
CC       processes (By similarity). In the vestibular system of the inner ear,
CC       required for the formation and function of otoconia, which are calcium
CC       carbonate crystals that sense gravity and acceleration
CC       (PubMed:15480759, PubMed:15581873). Probably acts by maintaining the pH
CC       appropriate for formation of otoconia (By similarity). May be involved
CC       in sour taste perception in sour taste cells by mediating entry of
CC       protons within the cytosol (By similarity).
CC       {ECO:0000250|UniProtKB:Q80VM9, ECO:0000269|PubMed:15480759,
CC       ECO:0000269|PubMed:15581873}.
CC   -!- INTERACTION:
CC       Q7ZWK8; Q7ZWK8: otop1; NbExp=2; IntAct=EBI-22085919, EBI-22085919;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:15480759};
CC       Multi-pass membrane protein {ECO:0000255}. Note=Detected in the
CC       gelatinous membrane overlying the inner ear macular epithelium.
CC       {ECO:0000250|UniProtKB:Q80VM9}.
CC   -!- DEVELOPMENTAL STAGE: First detected in the otic placode at 16.5 hours
CC       post-fertilization (hpf). Detected in the developing inner ear sensory
CC       epithelium at 24 hpf. Detected in hair cells of the sensory epithelium
CC       at 4 days post-fertilization (dpf). At 5 dpf, levels are much reduced
CC       in the otolith organs, and not detectable at 7 dpf. Detected in
CC       neuromasts and in the lateral line system at 5 dpf and 7 dpf.
CC       {ECO:0000269|PubMed:15480759, ECO:0000269|PubMed:15581873}.
CC   -!- DISRUPTION PHENOTYPE: Fishes display the backstroke phenotype. Mutant
CC       fish exhibit otolith agenesis without additional effects on the sensory
CC       epithelium or other inner ear structures. Otoliths are essential for
CC       the perception of gravity and acceleration. Larvae without otoliths are
CC       unable to orient dorsal side up and rest mostly on their side in
CC       contact with the ground. {ECO:0000269|PubMed:15480759,
CC       ECO:0000269|PubMed:15581873, ECO:0000269|PubMed:9007244}.
CC   -!- SIMILARITY: Belongs to the otopetrin family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Ear of stone - Issue 89 of
CC       December 2007;
CC       URL="https://web.expasy.org/spotlight/back_issues/089";
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; AY170648; AAN62756.1; -; mRNA.
DR   EMBL; AY744157; AAV91780.1; -; mRNA.
DR   EMBL; BC083445; AAH83445.1; -; mRNA.
DR   EMBL; BC164660; AAI64660.1; -; mRNA.
DR   RefSeq; NP_942098.1; NM_198803.1.
DR   AlphaFoldDB; Q7ZWK8; -.
DR   SMR; Q7ZWK8; -.
DR   TCDB; 1.A.110.1.5; the channel-forming otopetrin (otop) family.
DR   GeneID; 322893; -.
DR   KEGG; dre:322893; -.
DR   AGR; ZFIN:ZDB-GENE-030131-1613; -.
DR   CTD; 133060; -.
DR   ZFIN; ZDB-GENE-030131-1613; otop1.
DR   InParanoid; Q7ZWK8; -.
DR   OrthoDB; 3682573at2759; -.
DR   PhylomeDB; Q7ZWK8; -.
DR   PRO; PR:Q7ZWK8; -.
DR   Proteomes; UP000000437; Chromosome 14.
DR   GO; GO:0016020; C:membrane; IDA:ZFIN.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0015485; F:cholesterol binding; IDA:ZFIN.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0015252; F:proton channel activity; IDA:ZFIN.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR   GO; GO:0042472; P:inner ear morphogenesis; IMP:ZFIN.
DR   GO; GO:0060336; P:negative regulation of type II interferon-mediated signaling pathway; ISS:UniProtKB.
DR   GO; GO:0032475; P:otolith formation; IMP:ZFIN.
DR   GO; GO:0045299; P:otolith mineralization; IMP:ZFIN.
DR   GO; GO:1902600; P:proton transmembrane transport; IDA:ZFIN.
DR   InterPro; IPR004878; Otopetrin.
DR   PANTHER; PTHR21522; PROTON CHANNEL OTOP; 1.
DR   PANTHER; PTHR21522:SF19; PROTON CHANNEL OTOP1; 1.
DR   Pfam; PF03189; Otopetrin; 3.
PE   1: Evidence at protein level;
KW   Biomineralization; Cell membrane; Hydrogen ion transport; Ion channel;
KW   Ion transport; Membrane; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..586
FT                   /note="Proton channel OTOP1"
FT                   /id="PRO_0000313819"
FT   TRANSMEM        54..74
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        86..106
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        124..144
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        146..166
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        167..180
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        195..215
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        260..280
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        303..323
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        342..362
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        385..405
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        519..539
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        551..571
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          484..505
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MUTAGEN         429
FT                   /note="E->V: In backstroke; causes otolith agenesis."
FT                   /evidence="ECO:0000269|PubMed:15480759"
FT   CONFLICT        171
FT                   /note="T -> A (in Ref. 3; AAH83445/AAI64660)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        251..252
FT                   /note="CS -> WL (in Ref. 1; AAN62756)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        300
FT                   /note="S -> T (in Ref. 3; AAH83445/AAI64660)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   586 AA;  65721 MW;  000ED7A4E690831E CRC64;
     MVEHGGTDSM WLNKYNPAAA SSASSSSSSD AENKLFSRLK VSLTKKYPQK NAELLSAQYG
     TNLLLLGVSV MLALAAQSGP VKEEHLLSFI TVLMLVQLVW MLCYMIRRER ERSPVPERDA
     HAGASWIRGG LTMLALLSLI MDAFRIGYFV GYHSCISAAL GVYPIVHALH TISQVHFLWF
     HIKDVIKKYE TFERFGVIHA VFTNLLLWCN GVMSETEHFM HNHRRRLIEM GYANLSTVDV
     QPHCNCTTSV CSMFSTSLYY LYPFNIEYHI FVSAMLFVMW KNIGRTLDRH SNRKRRSTGS
     TGLLLGPLGG LVALASSVSV LVVYLIHLEK TEEMHEAAVS MFYYYGVAMM ACMCVGSGTG
     LLVYRMENRP MDTGSNPART LDTELLLASS LGSWLMSWCS VVASVAEAGQ KSPSFSWTSL
     TYSLLLVLEK CIQNLFIVES LYRRHSEEEE DAAAPQVFSV AVPPYDGILN HGYEAHDKHR
     EAEPAAGSHA LSRKQPDAPL PAGQRLDVTP GRKRQILKNI CMFLFMCNIS LWILPAFGCR
     PQYDNPLENE TFGTSVWTTV LNVAIPLNLF YRMHSVASLF EVFRKV
//