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T2R46_HUMAN
ID   T2R46_HUMAN             Reviewed;         309 AA.
AC   P59540; P59548; Q645X6;
DT   11-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 2.
DT   03-AUG-2022, entry version 137.
DE   RecName: Full=Taste receptor type 2 member 46;
DE            Short=T2R46;
DE   AltName: Full=Taste receptor type 2 member 54;
DE            Short=T2R54;
GN   Name=TAS2R46;
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 [GENOMIC DNA].
RX   PubMed=12584440; DOI=10.1159/000068546;
RA   Conte C., Ebeling M., Marcuz A., Nef P., Andres-Barquin P.J.;
RT   "Identification and characterization of human taste receptor genes
RT   belonging to the TAS2R family.";
RL   Cytogenet. Genome Res. 98:45-53(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-228.
RX   PubMed=15496549; DOI=10.1093/molbev/msi027;
RA   Fischer A., Gilad Y., Man O., Paeaebo S.;
RT   "Evolution of bitter taste receptors in humans and apes.";
RL   Mol. Biol. Evol. 22:432-436(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-299.
RX   PubMed=12379855; DOI=10.1038/ng1014;
RA   Bufe B., Hofmann T., Krautwurst D., Raguse J.-D., Meyerhof W.;
RT   "The human TAS2R16 receptor mediates bitter taste in response to beta-
RT   glucopyranosides.";
RL   Nat. Genet. 32:397-401(2002).
RN   [4]
RP   REVIEW.
RX   PubMed=12139982; DOI=10.1016/s0959-4388(02)00345-8;
RA   Montmayeur J.-P., Matsunami H.;
RT   "Receptors for bitter and sweet taste.";
RL   Curr. Opin. Neurobiol. 12:366-371(2002).
RN   [5]
RP   REVIEW.
RX   PubMed=11696554; DOI=10.1074/jbc.r100054200;
RA   Margolskee R.F.;
RT   "Molecular mechanisms of bitter and sweet taste transduction.";
RL   J. Biol. Chem. 277:1-4(2002).
RN   [6]
RP   REVIEW.
RX   PubMed=12581520; DOI=10.1016/s0092-8674(03)00071-0;
RA   Zhang Y., Hoon M.A., Chandrashekar J., Mueller K.L., Cook B., Wu D.,
RA   Zuker C.S., Ryba N.J.;
RT   "Coding of sweet, bitter, and umami tastes: different receptor cells
RT   sharing similar signaling pathways.";
RL   Cell 112:293-301(2003).
RN   [7]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=19628819; DOI=10.1126/science.1173869;
RA   Shah A.S., Ben-Shahar Y., Moninger T.O., Kline J.N., Welsh M.J.;
RT   "Motile cilia of human airway epithelia are chemosensory.";
RL   Science 325:1131-1134(2009).
CC   -!- FUNCTION: Receptor that may play a role in the perception of bitterness
CC       and is gustducin-linked. May play a role in sensing the chemical
CC       composition of the gastrointestinal content. The activity of this
CC       receptor may stimulate alpha gustducin, mediate PLC-beta-2 activation
CC       and lead to the gating of TRPM5 (By similarity). In airway epithelial
CC       cells, binding of bitter compounds increases the intracellular calcium
CC       ion concentration and stimulates ciliary beat frequency (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:19628819}; Multi-
CC       pass membrane protein {ECO:0000269|PubMed:19628819}. Cell projection,
CC       cilium membrane {ECO:0000269|PubMed:19628819}. Note=In airway
CC       epithelial cells, localizes to motile cilia.
CC   -!- TISSUE SPECIFICITY: Expressed in subsets of taste receptor cells of the
CC       tongue and exclusively in gustducin-positive cells. Expressed on
CC       ciliated airway epithelium. {ECO:0000269|PubMed:19628819}.
CC   -!- MISCELLANEOUS: Most taste cells may be activated by a limited number of
CC       bitter compounds; individual taste cells can discriminate among bitter
CC       stimuli.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor T2R family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=A tail of protection - Issue
CC       119 of July 2010;
CC       URL="https://web.expasy.org/spotlight/back_issues/119";
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DR   EMBL; AY114091; AAM63541.1; -; Genomic_DNA.
DR   EMBL; AY724941; AAU21143.1; -; Genomic_DNA.
DR   EMBL; AF494227; AAM19318.1; -; Genomic_DNA.
DR   CCDS; CCDS53748.1; -.
DR   RefSeq; NP_795368.2; NM_176887.2.
DR   AlphaFoldDB; P59540; -.
DR   SMR; P59540; -.
DR   STRING; 9606.ENSP00000436450; -.
DR   ChEMBL; CHEMBL4523253; -.
DR   DrugCentral; P59540; -.
DR   GlyGen; P59540; 2 sites.
DR   iPTMnet; P59540; -.
DR   PhosphoSitePlus; P59540; -.
DR   BioMuta; TAS2R46; -.
DR   DMDM; 55977809; -.
DR   PaxDb; P59540; -.
DR   PeptideAtlas; P59540; -.
DR   PRIDE; P59540; -.
DR   Antibodypedia; 23423; 20 antibodies from 10 providers.
DR   DNASU; 259292; -.
DR   Ensembl; ENST00000533467.1; ENSP00000436450.1; ENSG00000226761.3.
DR   Ensembl; ENST00000574263.1; ENSP00000460229.1; ENSG00000262525.3.
DR   GeneID; 259292; -.
DR   KEGG; hsa:259292; -.
DR   MANE-Select; ENST00000533467.1; ENSP00000436450.1; NM_176887.2; NP_795368.2.
DR   UCSC; uc001qzp.1; human.
DR   CTD; 259292; -.
DR   DisGeNET; 259292; -.
DR   GeneCards; TAS2R46; -.
DR   HGNC; HGNC:18877; TAS2R46.
DR   HPA; ENSG00000226761; Not detected.
DR   MIM; 612774; gene.
DR   neXtProt; NX_P59540; -.
DR   OpenTargets; ENSG00000226761; -.
DR   PharmGKB; PA38731; -.
DR   VEuPathDB; HostDB:ENSG00000226761; -.
DR   eggNOG; ENOG502TE6U; Eukaryota.
DR   GeneTree; ENSGT00960000186648; -.
DR   HOGENOM; CLU_072337_2_0_1; -.
DR   InParanoid; P59540; -.
DR   OMA; IMISSWS; -.
DR   OrthoDB; 1339037at2759; -.
DR   PhylomeDB; P59540; -.
DR   TreeFam; TF335891; -.
DR   PathwayCommons; P59540; -.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   Reactome; R-HSA-420499; Class C/3 (Metabotropic glutamate/pheromone receptors).
DR   Reactome; R-HSA-9717207; Sensory perception of sweet, bitter, and umami (glutamate) taste.
DR   BioGRID-ORCS; 259292; 54 hits in 1028 CRISPR screens.
DR   GeneWiki; TAS2R46; -.
DR   GenomeRNAi; 259292; -.
DR   Pharos; P59540; Tchem.
DR   PRO; PR:P59540; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; P59540; protein.
DR   Bgee; ENSG00000226761; Expressed in adrenal tissue and 35 other tissues.
DR   GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0033038; F:bitter taste receptor activity; IDA:UniProtKB.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR   GO; GO:0001580; P:detection of chemical stimulus involved in sensory perception of bitter taste; IDA:UniProtKB.
DR   InterPro; IPR007960; TAS2R.
DR   Pfam; PF05296; TAS2R; 1.
PE   2: Evidence at transcript level;
KW   Cell membrane; Cell projection; Cilium; G-protein coupled receptor;
KW   Glycoprotein; Membrane; Receptor; Reference proteome; Sensory transduction;
KW   Taste; Transducer; Transmembrane; Transmembrane helix.
FT   CHAIN           1..309
FT                   /note="Taste receptor type 2 member 46"
FT                   /id="PRO_0000082318"
FT   TOPO_DOM        1
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2..22
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        23..46
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        47..67
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        68..86
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        87..107
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        108..126
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        127..147
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        148..178
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        179..199
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        200..229
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        230..250
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        251..259
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        260..280
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        281..309
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        161
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        176
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         228
FT                   /note="L -> M (in dbSNP:rs2708380)"
FT                   /evidence="ECO:0000269|PubMed:15496549"
FT                   /id="VAR_062091"
FT   CONFLICT        296..297
FT                   /note="HV -> QM (in Ref. 3)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   309 AA;  35523 MW;  FF4D7747F0CE47EF CRC64;
     MITFLPIIFS ILIVVTFVIG NFANGFIALV NSIEWFKRQK ISFADQILTA LAVSRVGLLW
     VLVLNWYATE LNPAFNSIEV RITAYNVWAV INHFSNWLAT SLSIFYLLKI ANFSNLIFLH
     LKRRVKSVVL VILLGPLLFL VCHLFVINMN QIIWTKEYEG NMTWKIKLRS AMYLSNTTVT
     ILANLVPFTL TLISFLLLIC SLCKHLKKMQ LHGKGSQDPS MKVHIKALQT VTSFLLLCAI
     YFLSIIMSVW SFESLENKPV FMFCEAIAFS YPSTHPFILI WGNKKLKQTF LSVLWHVRYW
     VKGEKPSSS
 
 
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