OTOP1_MOUSE
ID OTOP1_MOUSE Reviewed; 600 AA.
AC Q80VM9; A0A0R4J1J4; E9QMU2; Q7M735; Q8BRZ4; Q8BS22;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 3.
DT 03-AUG-2022, entry version 103.
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|MGI:MGI:2388363};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), FUNCTION, DISRUPTION
RP PHENOTYPE, TISSUE SPECIFICITY, AND MUTAGENESIS OF ALA-151 AND LEU-408.
RC STRAIN=C57BL/6J; TISSUE=Otocyst;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Aorta, and Vein;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP FUNCTION.
RX PubMed=17606897; DOI=10.1073/pnas.0705182104;
RA Hughes I., Saito M., Schlesinger P.H., Ornitz D.M.;
RT "Otopetrin 1 activation by purinergic nucleotides regulates intracellular
RT calcium.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:12023-12028(2007).
RN [5]
RP FUNCTION.
RX PubMed=20554841; DOI=10.1152/jn.00525.2010;
RA Kim E., Hyrc K.L., Speck J., Lundberg Y.W., Salles F.T., Kachar B.,
RA Goldberg M.P., Warchol M.E., Ornitz D.M.;
RT "Regulation of cellular calcium in vestibular supporting cells by otopetrin
RT 1.";
RL J. Neurophysiol. 104:3439-3450(2010).
RN [6]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF ALA-151 AND LEU-408.
RX PubMed=21236346; DOI=10.1016/j.mcn.2011.01.005;
RA Kim E., Hyrc K.L., Speck J., Salles F.T., Lundberg Y.W., Goldberg M.P.,
RA Kachar B., Warchol M.E., Ornitz D.M.;
RT "Missense mutations in Otopetrin 1 affect subcellular localization and
RT inhibition of purinergic signaling in vestibular supporting cells.";
RL Mol. Cell. Neurosci. 46:655-661(2011).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, INDUCTION, AND INTERACTION WITH STAT1.
RX PubMed=24379350; DOI=10.2337/db13-1139;
RA Wang G.X., Cho K.W., Uhm M., Hu C.R., Li S., Cozacov Z., Xu A.E.,
RA Cheng J.X., Saltiel A.R., Lumeng C.N., Lin J.D.;
RT "Otopetrin 1 protects mice from obesity-associated metabolic dysfunction
RT through attenuating adipose tissue inflammation.";
RL Diabetes 63:1340-1352(2014).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP ALA-151.
RX PubMed=29371428; DOI=10.1126/science.aao3264;
RA Tu Y.H., Cooper A.J., Teng B., Chang R.B., Artiga D.J., Turner H.N.,
RA Mulhall E.M., Ye W., Smith A.D., Liman E.R.;
RT "An evolutionarily conserved gene family encodes proton-selective ion
RT channels.";
RL Science 359:1047-1050(2018).
CC -!- FUNCTION: Proton-selective channel that specifically transports protons
CC into cells (PubMed:29371428). Proton channel activity is only weakly-
CC sensitive to voltage (PubMed:29371428). Proton-selective channel
CC activity is probably required in cell types that use changes in
CC intracellular pH for cell signaling or to regulate biochemical or
CC developmental processes (PubMed:29371428). In the vestibular system of
CC the inner ear, required for the formation and function of otoconia,
CC which are calcium carbonate crystals that sense gravity and
CC acceleration (PubMed:12651873). Probably acts by maintaining the pH
CC appropriate for formation of otoconia (PubMed:29371428). Regulates
CC purinergic control of intracellular calcium in vestibular supporting
CC cells (PubMed:17606897, PubMed:20554841). May be involved in sour taste
CC perception in sour taste cells by mediating entry of protons within the
CC cytosol (PubMed:29371428). Also involved in energy metabolism, by
CC reducing adipose tissue inflammation and protecting from obesity-
CC induced metabolic dysfunction (PubMed:24379350).
CC {ECO:0000269|PubMed:12651873, ECO:0000269|PubMed:17606897,
CC ECO:0000269|PubMed:20554841, ECO:0000269|PubMed:24379350,
CC ECO:0000269|PubMed:29371428}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:29371428};
CC Multi-pass membrane protein {ECO:0000255}. Note=Detected in the
CC gelatinous membrane overlying the inner ear macular epithelium.
CC {ECO:0000269|PubMed:12651873, ECO:0000269|PubMed:21236346}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=A, Otopetrin-1a, Otop1-a;
CC IsoId=Q80VM9-1; Sequence=Displayed;
CC Name=2; Synonyms=C, Otopetrin-1c, Otop1-c;
CC IsoId=Q80VM9-2; Sequence=VSP_030160;
CC Name=3; Synonyms=B, Otopetrin-1b, Otop1-b;
CC IsoId=Q80VM9-3; Sequence=VSP_030161;
CC -!- TISSUE SPECIFICITY: Detected in embryonic inner ear macular epithelia
CC (PubMed:12651873). Expressed in thymus, heart, kidney, skin, vestibular
CC system of the inner ear, sour taste cells, brown adipose tissue, heart,
CC uterus, dorsal root ganglion, adrenal gland, lactating mammary gland
CC and stimulated mast cells (PubMed:12651873, PubMed:29371428).
CC Specifically expressed in sour taste cells and not other types of taste
CC cells (PubMed:29371428). {ECO:0000269|PubMed:12651873,
CC ECO:0000269|PubMed:29371428}.
CC -!- INDUCTION: Up-regulated in white adipose tissue in response to pro-
CC inflammatory signaling. {ECO:0000269|PubMed:24379350}.
CC -!- DISRUPTION PHENOTYPE: Mice display defects in the formation of otoconia
CC in the inner ear, but do not suffer from deafness or other inner ear
CC defects (PubMed:12651873). They cannot perceive gravity and have
CC problems with spatial orientation and with keeping their equilibrium
CC (PubMed:12651873). They show typical head-tilting behavior and are
CC unable to swim (PubMed:12651873). Mice develop more severe diet-induced
CC metabolic disorders: they respond to high-fat diet with pronounced
CC insulin resistance and hepatic steatosis, accompanied by augmented
CC adipose tissue inflammation (PubMed:24379350).
CC {ECO:0000269|PubMed:12651873, ECO:0000269|PubMed:24379350}.
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; AF548337; AAO33824.1; -; mRNA.
DR EMBL; BK000650; DAA00897.1; -; Genomic_DNA.
DR EMBL; BK000650; DAA00898.1; -; Genomic_DNA.
DR EMBL; AK040792; BAC30704.1; -; mRNA.
DR EMBL; AK041023; BAC30785.1; -; mRNA.
DR EMBL; AC084071; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_766297.2; NM_172709.3. [Q80VM9-1]
DR AlphaFoldDB; Q80VM9; -.
DR SMR; Q80VM9; -.
DR STRING; 10090.ENSMUSP00000109734; -.
DR TCDB; 1.A.110.1.1; the channel-forming otopetrin (otop) family.
DR iPTMnet; Q80VM9; -.
DR PhosphoSitePlus; Q80VM9; -.
DR PaxDb; Q80VM9; -.
DR PRIDE; Q80VM9; -.
DR ProteomicsDB; 295486; -. [Q80VM9-1]
DR ProteomicsDB; 372053; -.
DR Antibodypedia; 22553; 83 antibodies from 20 providers.
DR DNASU; 21906; -.
DR Ensembl; ENSMUST00000114099; ENSMUSP00000109734; ENSMUSG00000051596. [Q80VM9-1]
DR GeneID; 21906; -.
DR KEGG; mmu:21906; -.
DR UCSC; uc008xgm.1; mouse. [Q80VM9-1]
DR UCSC; uc012dvn.1; mouse.
DR CTD; 133060; -.
DR MGI; MGI:2388363; Otop1.
DR VEuPathDB; HostDB:ENSMUSG00000051596; -.
DR eggNOG; KOG4740; Eukaryota.
DR GeneTree; ENSGT00940000159350; -.
DR InParanoid; Q80VM9; -.
DR OMA; HPRYTWY; -.
DR OrthoDB; 524642at2759; -.
DR PhylomeDB; Q80VM9; -.
DR TreeFam; TF313428; -.
DR BioGRID-ORCS; 21906; 1 hit in 33 CRISPR screens.
DR PRO; PR:Q80VM9; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q80VM9; protein.
DR Bgee; ENSMUSG00000051596; Expressed in otolith organ and 46 other tissues.
DR ExpressionAtlas; Q80VM9; baseline and differential.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015252; F:proton channel activity; IDA:UniProtKB.
DR GO; GO:0031214; P:biomineral tissue development; IEA:UniProtKB-KW.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IMP:UniProtKB.
DR GO; GO:0009590; P:detection of gravity; IMP:MGI.
DR GO; GO:0042472; P:inner ear morphogenesis; IMP:MGI.
DR GO; GO:0060336; P:negative regulation of interferon-gamma-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:1902600; P:proton transmembrane transport; IDA:UniProtKB.
DR InterPro; IPR004878; Otopetrin.
DR PANTHER; PTHR21522; PTHR21522; 1.
DR Pfam; PF03189; Otopetrin; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Biomineralization; Cell membrane;
KW Hydrogen ion transport; Ion channel; Ion transport; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..600
FT /note="Proton channel OTOP1"
FT /id="PRO_0000313817"
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 VAR_SEQ 1..190
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030160"
FT VAR_SEQ 1..35
FT /note="MPGGPGAPSSPAASSGSSRAAPSGIAACPLSPPPL -> MLTPPETLSAFLA
FT GGFLGCLCLLEGLGCLRIA (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12651873"
FT /id="VSP_030161"
FT MUTAGEN 151
FT /note="A->E: In tlt (tilted phenotype); affected mice have
FT defects in the formation of otoconia in the inner ear, but
FT do not suffer from deafness or other inner ear defects.
FT They cannot perceive gravity and have problems with spatial
FT orientation and with keeping their equilibrium. They show
FT typical head-tilting behavior and are unable to swim.
FT Impaired subcellular localization to the plasma membrane.
FT Effects may be due to dysregulation of pH."
FT /evidence="ECO:0000269|PubMed:12651873,
FT ECO:0000269|PubMed:21236346, ECO:0000269|PubMed:29371428"
FT MUTAGEN 408
FT /note="L->Q: In mlh (mergulhador phenotype); affected mice
FT have defects in the formation of otoconia in the inner ear,
FT but do not suffer from deafness or other inner ear defects.
FT They cannot perceive gravity and have problems with spatial
FT orientation and with keeping their equilibrium. They show
FT typical head-tilting behavior and are unable to swim.
FT Impaired subcellular localization to the plasma membrane."
FT /evidence="ECO:0000269|PubMed:12651873,
FT ECO:0000269|PubMed:21236346"
FT CONFLICT 396
FT /note="G -> A (in Ref. 2; BAC30704/BAC30785)"
FT CONFLICT 401
FT /note="L -> P (in Ref. 2; BAC30704)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 600 AA; 65755 MW; CC10FA749803064B CRC64;
MPGGPGAPSS PAASSGSSRA APSGIAACPL SPPPLARGSP QASGPRRGAS VPQKLAETLS
SQYGLNVFVA GLLFLLAWAV HATGVGKSDL LCVLTALMLL QLLWMLWYVG RSYMQRRLIR
PKDTHAGARW LRGSITLFAF ITVVLGCLKV AYFIGFSECL SATEGVFPVT HAVHTLLQVY
FLWGHAKDII MSFKTLERFG VIHSVFTNLL LWANSVLNES KHQLNEHKER LITLGFGNIT
IVLDDHTPQC NCTPPALCSA LSHGIYYLYP FNIEYQILAS TMLYVLWKNI GRRVDSSQHQ
KMQCRFDGVL VGSVLGLTVL AATIAVVVVY MIHIGRSKSK SESALIMFYL YAITVLLLMG
AAGLVGSWIY RVDEKSLDES KNPARKLDVD LLVATGSGSW LLSWGSILAI ACAETRPPYT
WYNLPYSVLV IVEKYVQNIF IIESVHLEPE GVPEDVRTLR VVTVCSSEAA ALAASTLGSQ
GMAQDGSPAV NGNLCLQQRC GKEDQESGWE GATGTTRCLD FLQGGMKRRL LRNITAFLFL
CNISLWIPPA FGCRPEYDNG LEEIVFGFEP WIIVVNLAMP FSIFYRMHAA AALFEVYCKI
