OTOP1_DANRE
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 03-AUG-2022, entry version 78.
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";
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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 CTD; 133060; -.
DR ZFIN; ZDB-GENE-030131-1613; otop1.
DR InParanoid; Q7ZWK8; -.
DR OrthoDB; 524642at2759; -.
DR PhylomeDB; Q7ZWK8; -.
DR PRO; PR:Q7ZWK8; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IDA:ZFIN.
DR GO; GO:0005887; C:integral component of 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 interferon-gamma-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; PTHR21522; 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 otholith 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
