{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q80VM9","secondaryAccessions":["A0A0R4J1J4","E9QMU2","Q7M735","Q8BRZ4","Q8BS22"],"uniProtkbId":"OTOP1_MOUSE","entryAudit":{"firstPublicDate":"2008-01-15","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2018-03-28","entryVersion":120,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Mus musculus","commonName":"Mouse","taxonId":10090,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Glires","Rodentia","Myomorpha","Muroidea","Muridae","Murinae","Mus","Mus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Proton channel OTOP1"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"12651873"}],"value":"Otopetrin-1"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"12651873"},{"evidenceCode":"ECO:0000312","source":"MGI","id":"MGI:2388363"}],"value":"Otop1"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12651873"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17606897"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20554841"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24379350"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29371428"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31160780"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31543264"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31543453"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36596786"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37053086"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37798269"}],"value":"Proton-selective ion channel (PubMed:29371428, PubMed:31160780, PubMed:31543453, PubMed:36596786, PubMed:37798269). Biphasically modulated by acid and alkali, mediating proton influx and efflux in response to extracellular acid and base stimulation, respectively (PubMed:36596786, PubMed:37798269). Sour taste receptor, which carries inward currents in response to extracellular acidification (PubMed:29371428, PubMed:31543264, PubMed:31543453, PubMed:37053086). Sensor for ammonium chloride (NH(4)Cl) in taste receptor cells. NH(4)Cl acts by increasing the intracellular pH, thereby generating a driving force for proton entry through OTOP1 channel (PubMed:37798269). Might also participate in alkaline sensation (PubMed:37798269). Plays a role in the regulation of Ca(2+) flux in response to purigenic (ATP, ADP and UDP) stimuli, leading to increase in cytosolic Ca(2+) due to influx of extracellular calcium (PubMed:17606897, PubMed:20554841). May play this role by inhibiting P2Y purinoceptor-mediated Ca(2+) release in a Ca(2+)-dependent manner and promote an influx of Ca(2+) in response to ATP (PubMed:20554841). Through this mechanism and possibly others, plays a role in the formation and function of calcium carbonate-based structures in the vestibular system of the inner ear, called otoconia, that sense gravity and linear acceleration (PubMed:12651873, PubMed:20554841). In obesity, may attenuate adipose tissue inflammation, through the negative regulation of IFNG signaling, hence may play an adaptive role in the maintainance of metabolic homeostasis (PubMed:24379350). Following alkali activation, may also be permeable Na(+), K(+), Cs(+) and Li(+) (PubMed:37798269)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"H(+)(in) = H(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:34979"},{"database":"ChEBI","id":"CHEBI:15378"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29371428"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31160780"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31543453"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36596786"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37798269"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29371428"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31543453"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36596786"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37053086"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37798269"}],"value":"Activated by both acid and alkali, with proton influx in response to extracellular acid and proton efflux during alkali stimulation (PubMed:29371428, PubMed:36596786). Inhibited by Zn(2+); this inhibition is thought to be pH-sensitive (PubMed:29371428, PubMed:31543453, PubMed:36596786, PubMed:37798269). Currents evoked in response to mild acid (pH 6.0) stimulus may also be mildly potentiated by exposure to Zn(2+) (PubMed:37053086, PubMed:37798269). Activated by NH(4)Cl (PubMed:37798269)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q7ZWK8"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24379350"}],"value":"Homodimer (By similarity). Interacts with STAT1, independently of STAT1 phosphorylation status (PubMed:24379350)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12651873"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20554841"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21236346"}],"value":"Found in the gelatinous membrane overlying the inner ear macular epithelium (PubMed:12651873, PubMed:21236346). Also detected in the apical microvilli in inner ear supporting cells (PubMed:20554841)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29371428"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q7ZWK8"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20554841"}],"value":"Cell projection, microvillus","id":"SL-0293"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"synonyms":[{"value":"A"},{"value":"Otopetrin-1a"},{"value":"Otop1-a"}],"isoformIds":["Q80VM9-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"synonyms":[{"value":"C"},{"value":"Otopetrin-1c"},{"value":"Otop1-c"}],"isoformIds":["Q80VM9-2"],"sequenceIds":["VSP_030160"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"synonyms":[{"value":"B"},{"value":"Otopetrin-1b"},{"value":"Otop1-b"}],"isoformIds":["Q80VM9-3"],"sequenceIds":["VSP_030161"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12651873"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20554841"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24379350"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29371428"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31543264"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31543453"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36596786"}],"value":"Expressed in thymus, heart, kidney, skin, vestibular system of the inner ear, sour taste cells, heart, uterus, dorsal root ganglion, adrenal gland, lactating mammary gland and stimulated mast cells (PubMed:12651873, PubMed:29371428). In the inner ear, expressed in the supporting cells in extrastriolar regions of the saccule and in the utricle, but not in the cochlea (PubMed:20554841). Expressed in brown adipose tissue. Expressed in epididymal white adipose tissue (eWAT), as well as in inguinal fat, in obese animals, but hardly detectable in eWAT from lean mice (PubMed:24379350). Expressed in acid-sensing taste receptor cells (PKD2L1-positive cells), but not in other types of taste cells (at protein level) (PubMed:29371428, PubMed:31543264, PubMed:31543453, PubMed:36596786)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12651873"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20554841"}],"value":"In the developing ear, first detected at 13.5 dpc in the utricule. Expression in the saccule begins at 14.5 dpc (PubMed:20554841). At 16.5 dpc, present throughout the whole epithelium in the utricle and saccule. At this stage, expressed in macula nonstriolar, but not striolar regions (PubMed:12651873, PubMed:20554841). At 16.5 dpc, also found in the gelatinous membrane overlying macular epithelia (at protein level) (PubMed:12651873). At 18.5 dpc, expressed in otocyst (PubMed:12651873)"}],"commentType":"DEVELOPMENTAL STAGE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24379350"}],"value":"Up-regulated in adipocytes in response to TNF, but not IFNG (PubMed:24379350). Up-regulated in epididymal white adipose tissue in animals on high-fat diet (PubMed:24379350)"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36596786"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37053086"}],"value":"Residues involved in the gating by extracellular Zn (2+) and pH are located in the extracellular loops between transmembrane domain 5-6 and transmembrane domain 11-12"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20554841"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31543264"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31543453"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37798269"}],"value":"Knockout mice are phenotypically normal. They show vestibular dysfunction (inability to swim) and otoconial agenesis (PubMed:20554841, PubMed:31543453). They also exhibit severely diminished cellular and gustatory nerve response to acids (PubMed:31543264, PubMed:31543453). However, they do not exhibit any difference compared to wild-type mice in behavioral aversion to solutions containing high concentrations of mineral or organic acids, possibly because of the activation of nociceptive neurons through an OTOP1-independent mechanism (PubMed:31543264, PubMed:31543453). Knockout mice show a significantly diminished aversion to NH(4)Cl compared to wild-type animals (PubMed:37798269)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the otopetrin family"}],"commentType":"SIMILARITY"},{"commentType":"WEB RESOURCE","resourceName":"Protein Spotlight","resourceUrl":"https://www.proteinspotlight.org/back_issues/089","ftp":false,"note":"Ear of stone - Issue 89 of December 2007"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":600,"modifier":"EXACT"}},"description":"Proton channel OTOP1","featureId":"PRO_0000313817"},{"type":"Topological domain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":56,"modifier":"EXACT"}},"description":"Cytoplasmic","evidences":[{"evidenceCode":"ECO:0000305"}]},{"type":"Transmembrane","location":{"start":{"value":57,"modifier":"EXACT"},"end":{"value":78,"modifier":"EXACT"}},"description":"Helical; Name=1","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q7ZWK8"}]},{"type":"Topological domain","location":{"start":{"value":79,"modifier":"EXACT"},"end":{"value":86,"modifier":"EXACT"}},"description":"Extracellular","evidences":[{"evidenceCode":"ECO:0000305"}]},{"type":"Transmembrane","location":{"start":{"value":87,"modifier":"EXACT"},"end":{"value":110,"modifier":"EXACT"}},"description":"Helical; 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affected mice have defects in the formation of otoconia in the inner ear, but do not suffer from deafness or other inner ear defects. They cannot perceive gravity and have problems with spatial orientation and with keeping their equilibrium. They show typical head-tilting behavior and are unable to swim. Impaired subcellular localization to the plasma membrane. Effects may be due to dysregulation of pH.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12651873"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21236346"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29371428"}],"alternativeSequence":{"originalSequence":"A","alternativeSequences":["E"]}},{"type":"Mutagenesis","location":{"start":{"value":185,"modifier":"EXACT"},"end":{"value":185,"modifier":"EXACT"}},"description":"Does not affect alkali activation.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36596786"}],"alternativeSequence":{"originalSequence":"H","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":187,"modifier":"EXACT"},"end":{"value":187,"modifier":"EXACT"}},"description":"Does not affect the response to NH(4)Cl. Does affect alkali activation.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36596786"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37798269"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":219,"modifier":"EXACT"},"end":{"value":219,"modifier":"EXACT"}},"description":"Greatly reduced proton channel activity.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31160780"}],"alternativeSequence":{"originalSequence":"E","alternativeSequences":["K"]}},{"type":"Mutagenesis","location":{"start":{"value":221,"modifier":"EXACT"},"end":{"value":221,"modifier":"EXACT"}},"description":"Affects alkali activation, but not acid activation.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36596786"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":222,"modifier":"EXACT"},"end":{"value":222,"modifier":"EXACT"}},"description":"Does affect alkali activation.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36596786"}],"alternativeSequence":{"originalSequence":"H","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":292,"modifier":"EXACT"},"end":{"value":292,"modifier":"EXACT"}},"description":"Greatly reduced the currents in response to NH(4)Cl. Does not affect response to acid stimulation.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37798269"}],"alternativeSequence":{"originalSequence":"R","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":408,"modifier":"EXACT"},"end":{"value":408,"modifier":"EXACT"}},"description":"In mlh (mergulhador phenotype); affected mice have defects in the formation of otoconia in the inner ear, but do not suffer from deafness or other inner ear defects. They cannot perceive gravity and have problems with spatial orientation and with keeping their equilibrium. They show typical head-tilting behavior and are unable to swim. 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