Q7RTM1 · OTOP1_HUMAN
- ProteinProton channel OTOP1
- GeneOTOP1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids612 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Proton-selective ion channel (PubMed:29371428, PubMed:36266567).
Biphasically modulated by acid and alkali, mediating proton influx and efflux in response to extracellular acid and base stimulation, respectively. Sour taste receptor, which carries inward currents in response to extracellular acidification (By similarity).
Sensor for ammonium chloride (NH4Cl) in taste receptor cells (PubMed:37798269).
NH4Cl 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. Plays a role in the regulation of Ca2+ flux in response to purigenic (ATP, ADP and UDP) stimuli, leading to increase in cytosolic Ca2+ due to influx of extracellular calcium. May play this role by inhibiting P2Y purinoceptor-mediated Ca2+ release in a Ca2+-dependent manner and promote an influx of Ca2+ in response to ATP. 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. 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. Following alkali activation, may also be permeable Na+, K+, Cs+ and Li+ (By similarity).
Biphasically modulated by acid and alkali, mediating proton influx and efflux in response to extracellular acid and base stimulation, respectively. Sour taste receptor, which carries inward currents in response to extracellular acidification (By similarity).
Sensor for ammonium chloride (NH4Cl) in taste receptor cells (PubMed:37798269).
NH4Cl 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. Plays a role in the regulation of Ca2+ flux in response to purigenic (ATP, ADP and UDP) stimuli, leading to increase in cytosolic Ca2+ due to influx of extracellular calcium. May play this role by inhibiting P2Y purinoceptor-mediated Ca2+ release in a Ca2+-dependent manner and promote an influx of Ca2+ in response to ATP. 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. 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. Following alkali activation, may also be permeable Na+, K+, Cs+ and Li+ (By similarity).
Catalytic activity
- H+(in) = H+(out)
Activity regulation
Activated by both acid and alkali, with proton influx in response to extracellular acid and proton efflux during alkali stimulation (By similarity).
Inhibited by Zn2+; this inhibition is thought to be pH-sensitive (PubMed:37798269).
Currents evoked in response to mild acid (pH 6.0) stimulus may also be mildly potentiated by exposure to Zn2+ (By similarity).
Activated by NH4Cl (By similarity).
Inhibited by Zn2+; this inhibition is thought to be pH-sensitive (PubMed:37798269).
Currents evoked in response to mild acid (pH 6.0) stimulus may also be mildly potentiated by exposure to Zn2+ (By similarity).
Activated by NH4Cl (By similarity).
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | membrane | |
Cellular Component | microvillus | |
Cellular Component | plasma membrane | |
Molecular Function | identical protein binding | |
Molecular Function | proton channel activity | |
Biological Process | biomineral tissue development | |
Biological Process | cellular response to insulin stimulus | |
Biological Process | detection of gravity | |
Biological Process | inner ear morphogenesis | |
Biological Process | negative regulation of type II interferon-mediated signaling pathway | |
Biological Process | proton transmembrane transport |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameProton channel OTOP1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ7RTM1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Note: Found in the gelatinous membrane overlying the inner ear macular epithelium. Also detected in the apical microvilli in inner ear supporting cells.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-58 | Cytoplasmic | ||||
Sequence: MLEGLGSPASPRAAASASVAGSSGPAACSPPSSSAPRSPESPAPRRGGVRASVPQKLA | ||||||
Transmembrane | 59-80 | Helical; Name=1 | ||||
Sequence: EMLSSQYGLIVFVAGLLLLLAW | ||||||
Topological domain | 81-88 | Extracellular | ||||
Sequence: AVHAAGVS | ||||||
Transmembrane | 89-112 | Helical; Name=2 | ||||
Sequence: KSDLLCFLTALMLLQLLWMLWYVG | ||||||
Topological domain | 113-130 | Cytoplasmic | ||||
Sequence: RSSAHRRLFRLKDTHAGA | ||||||
Transmembrane | 131-153 | Helical; Name=3 | ||||
Sequence: GWLRGSITLFAVITVILGCLKIG | ||||||
Topological domain | 154-163 | Extracellular | ||||
Sequence: YFIGFSECLS | ||||||
Transmembrane | 164-188 | Helical; Name=4 | ||||
Sequence: ATEGVFPVTHSVHTLLQVYFLWGHA | ||||||
Topological domain | 189-196 | Cytoplasmic | ||||
Sequence: KDIIQSFK | ||||||
Transmembrane | 197-223 | Helical; Name=5 | ||||
Sequence: TLERFGVIHSVFTNLLLWANGVLNESK | ||||||
Topological domain | 224-264 | Extracellular | ||||
Sequence: HQLNEHKERLITLGFGNITTVLDDHTPQCNCTPPTLCTAIS | ||||||
Transmembrane | 265-290 | Helical; Name=6 | ||||
Sequence: HGIYYLYPFNIEYQILASTMLYVLWK | ||||||
Topological domain | 291-311 | Cytoplasmic | ||||
Sequence: NIGRKVDSHQHQKMQFKSDGV | ||||||
Transmembrane | 312-334 | Helical; Name=7 | ||||
Sequence: MVGAVLGLTVLAATIAVVVVYLI | ||||||
Topological domain | 335-344 | Extracellular | ||||
Sequence: HIGRSKTKSE | ||||||
Transmembrane | 345-370 | Helical; Name=8 | ||||
Sequence: SALIMFYLYAITLLMLMGAAGLAGIR | ||||||
Topological domain | 371-388 | Cytoplasmic | ||||
Sequence: IYRIDEKSLDESKNPARK | ||||||
Transmembrane | 389-413 | Helical; Name=9 | ||||
Sequence: LDSDLLVGTASGSWLISWGSILAIL | ||||||
Topological domain | 414-423 | Extracellular | ||||
Sequence: CAEGHPRYTW | ||||||
Transmembrane | 424-444 | Helical; Name=10 | ||||
Sequence: YNLPYSILAIVEKYIQNLFIF | ||||||
Topological domain | 445-544 | Cytoplasmic | ||||
Sequence: ESIHREPEKLSEDIQTLRVVTVCNGNTMPLASSCPKSGGVARDVAPQGKDMPPAANGNVCMRESHDKEEEKQEESSWGGSPSPVRLPRFLQGNAKRKVLR | ||||||
Transmembrane | 545-563 | Helical; Name=11 | ||||
Sequence: NIAAFLFLCNISLWIPPAF | ||||||
Topological domain | 564-581 | Extracellular | ||||
Sequence: GCRPEYDNGLEEIVFGFE | ||||||
Transmembrane | 582-605 | Helical; Name=12 | ||||
Sequence: PWIIVVNLAMPFSIFYRMHAAASL | ||||||
Topological domain | 606-612 | Cytoplasmic | ||||
Sequence: FEVYCKI |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 229 | Complete loss of H+ current at pH 5 and 4.5. | ||||
Sequence: H → Q, C, or E | ||||||
Mutagenesis | 229 | Abolishes proton channel activity at pH 5 and 4.5. | ||||
Sequence: H → R, K, or D | ||||||
Natural variant | VAR_037755 | 241 | in dbSNP:rs28394859 | |||
Sequence: I → V | ||||||
Natural variant | VAR_037756 | 309 | in dbSNP:rs2916414 | |||
Sequence: D → E | ||||||
Natural variant | VAR_037757 | 434 | in dbSNP:rs11736799 | |||
Sequence: V → M | ||||||
Natural variant | VAR_037758 | 493 | in dbSNP:rs34666677 | |||
Sequence: K → T | ||||||
Natural variant | VAR_037759 | 516 | in dbSNP:rs35106142 | |||
Sequence: Q → H | ||||||
Mutagenesis | 570 | Does not affect cell membrane localization. Reduction of proton channel activity. | ||||
Sequence: D → E | ||||||
Mutagenesis | 570 | Does not affect proton channel activity. | ||||
Sequence: D → H | ||||||
Mutagenesis | 570 | Does not affect cell membrane localization. Strong reduction of proton channel activity. | ||||
Sequence: D → N |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 887 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000313816 | 1-612 | Proton channel OTOP1 | |||
Sequence: MLEGLGSPASPRAAASASVAGSSGPAACSPPSSSAPRSPESPAPRRGGVRASVPQKLAEMLSSQYGLIVFVAGLLLLLAWAVHAAGVSKSDLLCFLTALMLLQLLWMLWYVGRSSAHRRLFRLKDTHAGAGWLRGSITLFAVITVILGCLKIGYFIGFSECLSATEGVFPVTHSVHTLLQVYFLWGHAKDIIQSFKTLERFGVIHSVFTNLLLWANGVLNESKHQLNEHKERLITLGFGNITTVLDDHTPQCNCTPPTLCTAISHGIYYLYPFNIEYQILASTMLYVLWKNIGRKVDSHQHQKMQFKSDGVMVGAVLGLTVLAATIAVVVVYLIHIGRSKTKSESALIMFYLYAITLLMLMGAAGLAGIRIYRIDEKSLDESKNPARKLDSDLLVGTASGSWLISWGSILAILCAEGHPRYTWYNLPYSILAIVEKYIQNLFIFESIHREPEKLSEDIQTLRVVTVCNGNTMPLASSCPKSGGVARDVAPQGKDMPPAANGNVCMRESHDKEEEKQEESSWGGSPSPVRLPRFLQGNAKRKVLRNIAAFLFLCNISLWIPPAFGCRPEYDNGLEEIVFGFEPWIIVVNLAMPFSIFYRMHAAASLFEVYCKI |
Proteomic databases
PTM databases
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-50 | Disordered | ||||
Sequence: MLEGLGSPASPRAAASASVAGSSGPAACSPPSSSAPRSPESPAPRRGGVR | ||||||
Region | 499-525 | Disordered | ||||
Sequence: ANGNVCMRESHDKEEEKQEESSWGGSP | ||||||
Compositional bias | 505-519 | Basic and acidic residues | ||||
Sequence: MRESHDKEEEKQEES |
Domain
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.
Sequence similarities
Belongs to the otopetrin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length612
- Mass (Da)67,353
- Last updated2003-12-15 v1
- Checksum7EF5C9F676D20D0F
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 40 | in Ref. 1; AAI30431/AAI30433 | ||||
Sequence: E → K | ||||||
Compositional bias | 505-519 | Basic and acidic residues | ||||
Sequence: MRESHDKEEEKQEES |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
BC130430 EMBL· GenBank· DDBJ | AAI30431.1 EMBL· GenBank· DDBJ | mRNA | ||
BC130432 EMBL· GenBank· DDBJ | AAI30433.1 EMBL· GenBank· DDBJ | mRNA | ||
BK000653 EMBL· GenBank· DDBJ | DAA00901.1 EMBL· GenBank· DDBJ | mRNA | ||
BK000654 EMBL· GenBank· DDBJ | DAA00902.1 EMBL· GenBank· DDBJ | Genomic DNA |