ID   OTOP1_HUMAN             Reviewed;         612 AA.
AC   Q7RTM1; A1L476;
DT   15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-2003, sequence version 1.
DT   24-JAN-2024, entry version 122.
DE   RecName: Full=Proton channel OTOP1 {ECO:0000305};
DE   AltName: Full=Otopetrin-1 {ECO:0000303|PubMed:12651873};
DE            Short=hOtop1 {ECO:0000303|PubMed:29371428};
GN   Name=OTOP1 {ECO:0000303|PubMed:12651873, ECO:0000312|HGNC:HGNC:19656};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(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).
RN   [3]
RP   FUNCTION.
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 (By similarity). Proton-selective channel activity
CC       is probably required in cell types that use changes in intracellular pH
CC       for cell signaling or to regulate biochemical or developmental
CC       processes (PubMed:29371428). In the vestibular system of the inner ear,
CC       required for the formation and function of otoconia, which are calcium
CC       carbonate crystals that sense gravity and acceleration (By similarity).
CC       Probably acts by maintaining the pH appropriate for formation of
CC       otoconia (By similarity). Regulates purinergic control of intracellular
CC       calcium in vestibular supporting cells (By similarity). May be involved
CC       in sour taste perception in sour taste cells by mediating entry of
CC       protons within the cytosol (By similarity). Also involved in energy
CC       metabolism, by reducing adipose tissue inflammation and protecting from
CC       obesity-induced metabolic dysfunction (By similarity).
CC       {ECO:0000250|UniProtKB:Q80VM9, ECO:0000269|PubMed:29371428}.
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   -!- 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";
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; BC130430; AAI30431.1; -; mRNA.
DR   EMBL; BC130432; AAI30433.1; -; mRNA.
DR   EMBL; BK000653; DAA00901.1; -; mRNA.
DR   EMBL; BK000654; DAA00902.1; -; Genomic_DNA.
DR   CCDS; CCDS3372.1; -.
DR   RefSeq; NP_819056.1; NM_177998.1.
DR   AlphaFoldDB; Q7RTM1; -.
DR   SMR; Q7RTM1; -.
DR   BioGRID; 126348; 20.
DR   STRING; 9606.ENSP00000296358; -.
DR   TCDB; 1.A.110.1.2; the channel-forming otopetrin (otop) family.
DR   iPTMnet; Q7RTM1; -.
DR   PhosphoSitePlus; Q7RTM1; -.
DR   BioMuta; OTOP1; -.
DR   DMDM; 74713136; -.
DR   MassIVE; Q7RTM1; -.
DR   PaxDb; 9606-ENSP00000296358; -.
DR   PeptideAtlas; Q7RTM1; -.
DR   ProteomicsDB; 68872; -.
DR   Antibodypedia; 22553; 105 antibodies from 21 providers.
DR   DNASU; 133060; -.
DR   Ensembl; ENST00000296358.5; ENSP00000296358.4; ENSG00000163982.6.
DR   GeneID; 133060; -.
DR   KEGG; hsa:133060; -.
DR   MANE-Select; ENST00000296358.5; ENSP00000296358.4; NM_177998.3; NP_819056.1.
DR   UCSC; uc003ghp.2; human.
DR   AGR; HGNC:19656; -.
DR   CTD; 133060; -.
DR   DisGeNET; 133060; -.
DR   GeneCards; OTOP1; -.
DR   HGNC; HGNC:19656; OTOP1.
DR   HPA; ENSG00000163982; Not detected.
DR   MIM; 607806; gene.
DR   neXtProt; NX_Q7RTM1; -.
DR   OpenTargets; ENSG00000163982; -.
DR   PharmGKB; PA134883507; -.
DR   VEuPathDB; HostDB:ENSG00000163982; -.
DR   eggNOG; KOG4740; Eukaryota.
DR   GeneTree; ENSGT00940000159350; -.
DR   HOGENOM; CLU_032913_1_0_1; -.
DR   InParanoid; Q7RTM1; -.
DR   OMA; GNVCMRE; -.
DR   OrthoDB; 3682573at2759; -.
DR   PhylomeDB; Q7RTM1; -.
DR   TreeFam; TF313428; -.
DR   PathwayCommons; Q7RTM1; -.
DR   Reactome; R-HSA-9729555; Sensory perception of sour taste.
DR   BioGRID-ORCS; 133060; 541 hits in 1142 CRISPR screens.
DR   GenomeRNAi; 133060; -.
DR   Pharos; Q7RTM1; Tbio.
DR   PRO; PR:Q7RTM1; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; Q7RTM1; Protein.
DR   Bgee; ENSG00000163982; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 7 other cell types or tissues.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
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; ISS:UniProtKB.
DR   GO; GO:0009590; P:detection of gravity; IEA:Ensembl.
DR   GO; GO:0042472; P:inner ear morphogenesis; IBA:GO_Central.
DR   GO; GO:0060336; P:negative regulation of type II interferon-mediated signaling pathway; ISS:UniProtKB.
DR   GO; GO:1902600; P:proton transmembrane transport; IDA:UniProtKB.
DR   InterPro; IPR004878; Otopetrin.
DR   PANTHER; PTHR21522; PROTON CHANNEL OTOP; 1.
DR   PANTHER; PTHR21522:SF19; PROTON CHANNEL OTOP1; 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..612
FT                   /note="Proton channel OTOP1"
FT                   /id="PRO_0000313816"
FT   TRANSMEM        67..87
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        92..112
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        137..157
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        168..188
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        201..221
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        269..289
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        311..331
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        346..366
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        393..413
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        424..444
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        545..565
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        576..596
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          1..50
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          499..525
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        505..519
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         241
FT                   /note="I -> V (in dbSNP:rs28394859)"
FT                   /id="VAR_037755"
FT   VARIANT         309
FT                   /note="D -> E (in dbSNP:rs2916414)"
FT                   /id="VAR_037756"
FT   VARIANT         434
FT                   /note="V -> M (in dbSNP:rs11736799)"
FT                   /id="VAR_037757"
FT   VARIANT         493
FT                   /note="K -> T (in dbSNP:rs34666677)"
FT                   /id="VAR_037758"
FT   VARIANT         516
FT                   /note="Q -> H (in dbSNP:rs35106142)"
FT                   /id="VAR_037759"
FT   CONFLICT        40
FT                   /note="E -> K (in Ref. 1; AAI30431/AAI30433)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   612 AA;  67353 MW;  7EF5C9F676D20D0F CRC64;
     MLEGLGSPAS PRAAASASVA GSSGPAACSP PSSSAPRSPE SPAPRRGGVR ASVPQKLAEM
     LSSQYGLIVF VAGLLLLLAW AVHAAGVSKS DLLCFLTALM LLQLLWMLWY VGRSSAHRRL
     FRLKDTHAGA GWLRGSITLF AVITVILGCL KIGYFIGFSE CLSATEGVFP VTHSVHTLLQ
     VYFLWGHAKD IIQSFKTLER FGVIHSVFTN LLLWANGVLN ESKHQLNEHK ERLITLGFGN
     ITTVLDDHTP QCNCTPPTLC TAISHGIYYL YPFNIEYQIL ASTMLYVLWK NIGRKVDSHQ
     HQKMQFKSDG VMVGAVLGLT VLAATIAVVV VYLIHIGRSK TKSESALIMF YLYAITLLML
     MGAAGLAGIR IYRIDEKSLD ESKNPARKLD SDLLVGTASG SWLISWGSIL AILCAEGHPR
     YTWYNLPYSI LAIVEKYIQN LFIFESIHRE PEKLSEDIQT LRVVTVCNGN TMPLASSCPK
     SGGVARDVAP QGKDMPPAAN GNVCMRESHD KEEEKQEESS WGGSPSPVRL PRFLQGNAKR
     KVLRNIAAFL FLCNISLWIP PAFGCRPEYD NGLEEIVFGF EPWIIVVNLA MPFSIFYRMH
     AAASLFEVYC KI
//