OTOP1_HUMAN
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 03-AUG-2022, entry version 115.
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 PaxDb; Q7RTM1; -.
DR PeptideAtlas; Q7RTM1; -.
DR PRIDE; Q7RTM1; -.
DR ProteomicsDB; 68872; -.
DR Antibodypedia; 22553; 83 antibodies from 20 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 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; HPRYTWY; -.
DR OrthoDB; 524642at2759; -.
DR PhylomeDB; Q7RTM1; -.
DR TreeFam; TF313428; -.
DR PathwayCommons; Q7RTM1; -.
DR Reactome; R-HSA-9729555; Sensory perception of sour taste.
DR BioGRID-ORCS; 133060; 525 hits in 1064 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 skin of abdomen and 6 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of 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 interferon-gamma-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:1902600; P:proton transmembrane transport; IDA:UniProtKB.
DR InterPro; IPR004878; Otopetrin.
DR PANTHER; PTHR21522; PTHR21522; 2.
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
