ID   OTOP2_HUMAN             Reviewed;         562 AA.
AC   Q7RTS6;
DT   15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 3.
DT   03-AUG-2022, entry version 115.
DE   RecName: Full=Proton channel OTOP2 {ECO:0000305};
DE   AltName: Full=Otopetrin-2 {ECO:0000303|PubMed:12651873};
GN   Name=OTOP2 {ECO:0000303|PubMed:12651873, ECO:0000312|HGNC:HGNC:19657};
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 GENOMIC DNA].
RX   PubMed=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA   Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA   Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA   LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA   Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA   Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA   Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT   human lineage.";
RL   Nature 440:1045-1049(2006).
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   VARIANT [LARGE SCALE ANALYSIS] VAL-392.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Proton-selective channel that specifically transports protons
CC       into cells. Proton-selective channel activity is probably required in
CC       cell types that use changes in intracellular pH for cell signaling or
CC       to regulate biochemical or developmental processes.
CC       {ECO:0000250|UniProtKB:Q80SX5}.
CC   -!- INTERACTION:
CC       Q7RTS6; P11912: CD79A; NbExp=3; IntAct=EBI-7642372, EBI-7797864;
CC       Q7RTS6; Q969F0: FATE1; NbExp=4; IntAct=EBI-7642372, EBI-743099;
CC       Q7RTS6; P48165: GJA8; NbExp=3; IntAct=EBI-7642372, EBI-17458373;
CC       Q7RTS6; Q9NQG1: MANBAL; NbExp=3; IntAct=EBI-7642372, EBI-3867271;
CC       Q7RTS6; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-7642372, EBI-10982110;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q80VM9};
CC       Multi-pass membrane protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the otopetrin family. {ECO:0000305}.
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DR   EMBL; AC068874; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC087651; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BK000567; DAA00895.1; -; mRNA.
DR   CCDS; CCDS11708.1; -.
DR   RefSeq; NP_835454.1; NM_178160.2.
DR   RefSeq; XP_011523781.1; XM_011525479.1.
DR   AlphaFoldDB; Q7RTS6; -.
DR   SMR; Q7RTS6; -.
DR   BioGRID; 124972; 6.
DR   IntAct; Q7RTS6; 6.
DR   MINT; Q7RTS6; -.
DR   STRING; 9606.ENSP00000332528; -.
DR   TCDB; 1.A.110.1.3; the channel-forming otopetrin (otop) family.
DR   iPTMnet; Q7RTS6; -.
DR   PhosphoSitePlus; Q7RTS6; -.
DR   BioMuta; OTOP2; -.
DR   DMDM; 296439281; -.
DR   jPOST; Q7RTS6; -.
DR   MassIVE; Q7RTS6; -.
DR   PaxDb; Q7RTS6; -.
DR   PeptideAtlas; Q7RTS6; -.
DR   PRIDE; Q7RTS6; -.
DR   ProteomicsDB; 68894; -.
DR   Antibodypedia; 32060; 95 antibodies from 16 providers.
DR   DNASU; 92736; -.
DR   Ensembl; ENST00000331427.9; ENSP00000332528.4; ENSG00000183034.13.
DR   GeneID; 92736; -.
DR   KEGG; hsa:92736; -.
DR   MANE-Select; ENST00000331427.9; ENSP00000332528.4; NM_178160.3; NP_835454.1.
DR   UCSC; uc010wrp.2; human.
DR   CTD; 92736; -.
DR   DisGeNET; 92736; -.
DR   GeneCards; OTOP2; -.
DR   HGNC; HGNC:19657; OTOP2.
DR   HPA; ENSG00000183034; Tissue enriched (intestine).
DR   MalaCards; OTOP2; -.
DR   MIM; 607827; gene.
DR   neXtProt; NX_Q7RTS6; -.
DR   OpenTargets; ENSG00000183034; -.
DR   PharmGKB; PA134930692; -.
DR   VEuPathDB; HostDB:ENSG00000183034; -.
DR   eggNOG; KOG4740; Eukaryota.
DR   GeneTree; ENSGT00940000156691; -.
DR   HOGENOM; CLU_032913_0_0_1; -.
DR   InParanoid; Q7RTS6; -.
DR   OMA; IHRTHYS; -.
DR   OrthoDB; 524642at2759; -.
DR   PhylomeDB; Q7RTS6; -.
DR   TreeFam; TF313428; -.
DR   PathwayCommons; Q7RTS6; -.
DR   SignaLink; Q7RTS6; -.
DR   BioGRID-ORCS; 92736; 14 hits in 1067 CRISPR screens.
DR   GenomeRNAi; 92736; -.
DR   Pharos; Q7RTS6; Tdark.
DR   PRO; PR:Q7RTS6; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q7RTS6; protein.
DR   Bgee; ENSG00000183034; Expressed in mucosa of transverse colon and 22 other tissues.
DR   ExpressionAtlas; Q7RTS6; baseline and differential.
DR   GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0015252; F:proton channel activity; ISS:UniProtKB.
DR   GO; GO:1902600; P:proton transmembrane transport; ISS:UniProtKB.
DR   InterPro; IPR004878; Otopetrin.
DR   PANTHER; PTHR21522; PTHR21522; 1.
DR   Pfam; PF03189; Otopetrin; 3.
PE   1: Evidence at protein level;
KW   Cell membrane; Hydrogen ion transport; Ion channel; Ion transport;
KW   Membrane; Reference proteome; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..562
FT                   /note="Proton channel OTOP2"
FT                   /id="PRO_0000313820"
FT   TRANSMEM        30..50
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        62..82
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        100..120
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        137..157
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        169..189
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        241..261
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        289..309
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        324..344
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        371..391
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        402..422
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        495..515
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        527..547
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          1..20
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         392
FT                   /note="A -> V (in a colorectal cancer sample; somatic
FT                   mutation; dbSNP:rs148548570)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_037760"
FT   VARIANT         465
FT                   /note="G -> W (in dbSNP:rs6501741)"
FT                   /id="VAR_037761"
SQ   SEQUENCE   562 AA;  62236 MW;  07B46C4A06C655D3 CRC64;
     MSEELAQGPK ESPPAPRAGP REVWKKGGRL LSVLLAVNVL LLACTLISGG AFNKVAVYDT
     DVFALLTAMM LLATLWILFY LLRTVRCPCA VPYRDAHAGP IWLRGGLVLF GICTLIMDVF
     KTGYYSSFFE CQSAIKILHP LIQAVFVIIQ TYFLWVSAKD CVHVHLDLTW CGLMFTLTTN
     LAIWMAAVVD ESVHQSHSYS SSHSNASHAR LISDQHADNP VGGDSCLCST AVCQIFQQGY
     FYLYPFNIEY SLFASTMLYV MWKNVGRFLA STPGHSHTPT PVSLFRETFF AGPVLGLLLF
     VVGLAVFIIY EVQVSGDGSR TRQALVIYYS FNIVCLGLTT LVSLSGSIIY RFDRRAMDHH
     KNPTRTLDVA LLMGAALGQY AISYYSIVAV VAGTPQDLLA GLNLTHALLM IAQHTFQNMF
     IIESLHRGPP GAEPHSTHPK EPCQDLTFTN LDALHTLSAC PPNPGLVSPS PSDQREAVAI
     VSTPRSQWRR QCLKDISLFL LLCNVILWIM PAFGARPHFS NTVEVDFYGY SLWAVIVNIC
     LPFGIFYRMH AVSSLLEVYV LS