ID   OTOP1_RAT               Reviewed;         600 AA.
AC   Q7M734;
DT   15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-2003, sequence version 1.
DT   03-AUG-2022, 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, ECO:0000312|RGD:631389};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2]
RP   IDENTIFICATION.
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).
CC   -!- FUNCTION: Proton-selective channel that specifically transports protons
CC       into cells. Proton channel activity is only weakly-sensitive to
CC       voltage. Proton-selective channel activity is probably required in cell
CC       types that use changes in intracellular pH for cell signaling or to
CC       regulate biochemical or developmental processes. In the vestibular
CC       system of the inner ear, required for the formation and function of
CC       otoconia, which are calcium carbonate crystals that sense gravity and
CC       acceleration. Probably acts by maintaining the pH appropriate for
CC       formation of otoconia. Regulates purinergic control of intracellular
CC       calcium in vestibular supporting cells. May be involved in sour taste
CC       perception in sour taste cells by mediating entry of protons within the
CC       cytosol. Also involved in energy metabolism, by reducing adipose tissue
CC       inflammation and protecting from obesity-induced metabolic dysfunction.
CC       {ECO:0000250|UniProtKB:Q80VM9}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q80VM9};
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   -!- SIMILARITY: Belongs to the otopetrin family. {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; AC099417; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BK000651; DAA00899.1; -; mRNA.
DR   RefSeq; NP_852098.1; NM_181433.1.
DR   AlphaFoldDB; Q7M734; -.
DR   SMR; Q7M734; -.
DR   STRING; 10116.ENSRNOP00000047534; -.
DR   PaxDb; Q7M734; -.
DR   PRIDE; Q7M734; -.
DR   Ensembl; ENSRNOT00000050367; ENSRNOP00000047534; ENSRNOG00000028423.
DR   GeneID; 305427; -.
DR   KEGG; rno:305427; -.
DR   CTD; 133060; -.
DR   RGD; 631389; Otop1.
DR   eggNOG; KOG4740; Eukaryota.
DR   GeneTree; ENSGT00940000159350; -.
DR   HOGENOM; CLU_032913_1_0_1; -.
DR   InParanoid; Q7M734; -.
DR   OMA; HPRYTWY; -.
DR   OrthoDB; 524642at2759; -.
DR   PhylomeDB; Q7M734; -.
DR   TreeFam; TF313428; -.
DR   PRO; PR:Q7M734; -.
DR   Proteomes; UP000002494; Chromosome 14.
DR   Bgee; ENSRNOG00000028423; Expressed in thymus and 4 other tissues.
DR   GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR   GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; ISO:RGD.
DR   GO; GO:0015252; F:proton channel activity; ISS:UniProtKB.
DR   GO; GO:0031214; P:biomineral tissue development; IEA:UniProtKB-KW.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR   GO; GO:0009590; P:detection of gravity; ISO:RGD.
DR   GO; GO:0042472; P:inner ear morphogenesis; ISO:RGD.
DR   GO; GO:0060336; P:negative regulation of interferon-gamma-mediated signaling pathway; ISS:UniProtKB.
DR   GO; GO:1902600; P:proton transmembrane transport; ISS:UniProtKB.
DR   InterPro; IPR004878; Otopetrin.
DR   PANTHER; PTHR21522; PTHR21522; 1.
DR   Pfam; PF03189; Otopetrin; 3.
PE   2: Evidence at transcript level;
KW   Biomineralization; Cell membrane; Hydrogen ion transport; Ion channel;
KW   Ion transport; Membrane; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..600
FT                   /note="Proton channel OTOP1"
FT                   /id="PRO_0000313818"
FT   TRANSMEM        65..85
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        90..110
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        135..155
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        166..186
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        199..219
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        267..287
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        309..329
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        345..365
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        391..411
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        422..442
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        533..553
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        564..584
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          1..50
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        24..38
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   600 AA;  65929 MW;  A993A8D845F46532 CRC64;
     MPGDRGALSS PAASSGSPSA APSGIAACPP PPSPLARASP QASGPRRGAS VPQKLAETLS
     SQYGLNVFVA GLLFLLAWAV HATGVGKSDL LCVLTALMLL QLLWMLWYVG RSYMQRRLIR
     PKDTHAGARW LRGSITLFAF ITIVLGCLKV AYFIGFSECL SATEGVFPVT HAVHTLLQVY
     FLWGHAKDII MSFKTLERFG VIHSVFTNLL LWANSVLNES KHQLNEHKER LITLGFGNIT
     IVLDDHTPQC NCTPPALCSA LSHGIYYLYP FNIEYQILAS TMLYVLWKNI GRRVDSSRHQ
     KMQCRFDGVL VGSVLGLTVL AATIAVVVVY MIHIGRSKSK SESALIMFYL YAITVLLLMG
     AAGLVGSWIY RVDEKSLDES KNPARKLDAD LLVATASGSW LLSWGSILAI ACAETRPPYT
     WYNLPYSVLV IVEKYVQNIF IIESVHLEPE GVPEDVRTLR VVTVCSGEAA ALAASSLGSQ
     GTAQDGSPAV NGNLHLQQRC EKEDQEADWE GATGTTRCLD FLQGGMKRRL LRNITAFLFL
     CNISLWIPPA FGCRPEYDNG LEEIVFGFEP WIIVVNLAMP FSIFYRMHAA AALFEVYCKI