Otop1
entrez
21906
canonical
uniprot
Q80VM9
canonical
ensembl
ENSMUSG00000051596
resolver
ensp
ENSMUSP00000109734
resolver
genesymbol
Otop1
resolver
uniprot
A0A0R4J1J4
resolver
uniprot
E9QMU2
resolver
uniprot
Q7M735
resolver
uniprot
Q8BRZ4
resolver
uniprot
Q8BS22
resolver
uniprot_entry
OTOP1_MOUSE
resolver
uniprot_sec
A0A0R4J1J4
resolver
uniprot_sec
E9QMU2
resolver
uniprot_sec
Q7M735
resolver
uniprot_sec
Q8BRZ4
resolver
uniprot_sec
Q8BS22
resolver
activity_regulation
ACTIVITY REGULATION: 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). {ECO:0000269|PubMed:29371428, ECO:0000269|PubMed:31543453, ECO:0000269|PubMed:36596786, ECO:0000269|PubMed:37053086, ECO:0000269|PubMed:37798269}.
uniprot
proteins
amino_acid_sequence
MPGGPGAPSSPAASSGSSRAAPSGIAACPLSPPPLARGSPQASGPRRGASVPQKLAETLSSQYGLNVFVAGLLFLLAWAVHATGVGKSDLLCVLTALMLLQLLWMLWYVGRSYMQRRLIRPKDTHAGARWLRGSITLFAFITVVLGCLKVAYFIGFSECLSATEGVFPVTHAVHTLLQVYFLWGHAKDIIMSFKTLERFGVIHSVFTNLLLWANSVLNESKHQLNEHKERLITLGFGNITIVLDDHTPQCNCTPPALCSALSHGIYYLYPFNIEYQILASTMLYVLWKNIGRRVDSSQHQKMQCRFDGVLVGSVLGLTVLAATIAVVVVYMIHIGRSKSKSESALIMFYLYAITVLLLMGAAGLVGSWIYRVDEKSLDESKNPARKLDVDLLVATGSGSWLLSWGSILAIACAETRPPYTWYNLPYSVLVIVEKYVQNIFIIESVHLEPEGVPEDVRTLRVVTVCSSEAAALAASTLGSQGMAQDGSPAVNGNLCLQQRCGKEDQESGWEGATGTTRCLDFLQGGMKRRLLRNITAFLFLCNISLWIPPAFGCRPEYDNGLEEIVFGFEPWIIVVNLAMPFSIFYRMHAAAALFEVYCKI
uniprot
proteins
function
FUNCTION: 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). {ECO:0000269|PubMed:12651873, ECO:0000269|PubMed:17606897, ECO:0000269|PubMed:20554841, ECO:0000269|PubMed:24379350, ECO:0000269|PubMed:29371428, ECO:0000269|PubMed:31160780, ECO:0000269|PubMed:31543264, ECO:0000269|PubMed:31543453, ECO:0000269|PubMed:36596786, ECO:0000269|PubMed:37053086, ECO:0000269|PubMed:37798269}.
uniprot
proteins
mass_dalton
65755
uniprot
proteins
mutagenesis
MUTAGEN 149; /note="K->E: Does not affect proton channel activity."; /evidence="ECO:0000269|PubMed:31160780"; MUTAGEN 151; /note="A->E: In tlt (tilted 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. Impaired subcellular localization to the plasma membrane. Effects may be due to dysregulation of pH."; /evidence="ECO:0000269|PubMed:12651873, ECO:0000269|PubMed:21236346, ECO:0000269|PubMed:29371428"; MUTAGEN 185; /note="H->A: Does not affect alkali activation."; /evidence="ECO:0000269|PubMed:36596786"; MUTAGEN 187; /note="K->A: Does not affect the response to NH(4)Cl. Does affect alkali activation."; /evidence="ECO:0000269|PubMed:36596786, ECO:0000269|PubMed:37798269"; MUTAGEN 219; /note="E->K: Greatly reduced proton channel activity."; /evidence="ECO:0000269|PubMed:31160780"; MUTAGEN 221; /note="K->A: Affects alkali activation, but not acid activation."; /evidence="ECO:0000269|PubMed:36596786"; MUTAGEN 222; /note="H->A: Does affect alkali activation."; /evidence="ECO:0000269|PubMed:36596786"; MUTAGEN 292; /note="R->A: Greatly reduced the currents in response to NH(4)Cl. Does not affect response to acid stimulation."; /evidence="ECO:0000269|PubMed:37798269"; MUTAGEN 408; /note="L->Q: 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. Impaired subcellular localization to the plasma membrane."; /evidence="ECO:0000269|PubMed:12651873, ECO:0000269|PubMed:21236346"; MUTAGEN 433; /note="E->R: Greatly reduced proton channel activity."; /evidence="ECO:0000269|PubMed:31160780"; MUTAGEN 527; /note="K->A: Does not affect the response to NH(4)Cl."; /evidence="ECO:0000269|PubMed:37798269"; MUTAGEN 528; /note="R->A: Does not affect the response to NH(4)Cl."; /evidence="ECO:0000269|PubMed:37798269"; MUTAGEN 554; /note="R->A: Affects alkali activation, but not acid activation."; /evidence="ECO:0000269|PubMed:36596786"; MUTAGEN 554; /note="R->H: Increases sensitivity to potentiation by Zn(2+)."; /evidence="ECO:0000269|PubMed:37053086"; MUTAGEN 586; /note="R->E: Reduced proton channel activity."; /evidence="ECO:0000269|PubMed:31160780
uniprot
proteins
protein_family
Otopetrin family
uniprot
proteins
pubmed
12651873
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17606897
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20554841
uniprot
proteins
pubmed
21236346
uniprot
proteins
pubmed
24379350
uniprot
proteins
pubmed
29371428
uniprot
proteins
pubmed
31160780
uniprot
proteins
pubmed
31543264
uniprot
proteins
pubmed
31543453
uniprot
proteins
pubmed
36596786
uniprot
proteins
pubmed
37053086
uniprot
proteins
pubmed
37798269
uniprot
proteins
sequence_length
600
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:29371428}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q7ZWK8}. Cell projection, microvillus {ECO:0000269|PubMed:20554841}. Note=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). {ECO:0000269|PubMed:12651873, ECO:0000269|PubMed:20554841, ECO:0000269|PubMed:21236346}.
uniprot
proteins
transmembrane_region
TRANSMEM 57..78; /note="Helical; Name=1"; /evidence="ECO:0000250|UniProtKB:Q7ZWK8"; TRANSMEM 87..110; /note="Helical; Name=2"; /evidence="ECO:0000250|UniProtKB:Q7ZWK8"; TRANSMEM 129..151; /note="Helical; Name=3"; /evidence="ECO:0000250|UniProtKB:Q7ZWK8"; TRANSMEM 162..186; /note="Helical; Name=4"; /evidence="ECO:0000250|UniProtKB:Q7ZWK8"; TRANSMEM 195..217; /note="Helical; Name=5"; /evidence="ECO:0000250|UniProtKB:Q7ZWK8"; TRANSMEM 263..288; /note="Helical; Name=6"; /evidence="ECO:0000250|UniProtKB:Q7ZWK8"; TRANSMEM 310..332; /note="Helical; Name=7"; /evidence="ECO:0000250|UniProtKB:Q7ZWK8"; TRANSMEM 343..368; /note="Helical; Name=8"; /evidence="ECO:0000250|UniProtKB:Q7ZWK8"; TRANSMEM 387..411; /note="Helical; Name=9"; /evidence="ECO:0000250|UniProtKB:Q7ZWK8"; TRANSMEM 422..442; /note="Helical; Name=10"; /evidence="ECO:0000250|UniProtKB:Q7ZWK8"; TRANSMEM 533..551; /note="Helical; Name=11"; /evidence="ECO:0000250|UniProtKB:Q7ZWK8"; TRANSMEM 570..593; /note="Helical; Name=12"; /evidence="ECO:0000250|UniProtKB:Q7ZWK8
uniprot
proteins