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 24-JAN-2024, entry version 145. 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"; 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; 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 PDB; 7XP4; EM; 3.01 A; R=2-309. DR PDB; 7XP5; EM; 3.08 A; R=2-309. DR PDB; 7XP6; EM; 3.01 A; R=2-309. DR PDBsum; 7XP4; -. DR PDBsum; 7XP5; -. DR PDBsum; 7XP6; -. DR AlphaFoldDB; P59540; -. DR SMR; P59540; -. DR STRING; 9606.ENSP00000436450; -. DR ChEMBL; CHEMBL4523253; -. DR DrugCentral; P59540; -. DR GuidetoPHARMACOLOGY; 679; -. DR TCDB; 9.A.14.17.6; the g-protein-coupled receptor (gpcr) family. DR GlyCosmos; P59540; 2 sites, No reported glycans. DR GlyGen; P59540; 2 sites. DR iPTMnet; P59540; -. DR PhosphoSitePlus; P59540; -. DR BioMuta; TAS2R46; -. DR DMDM; 55977809; -. DR PaxDb; 9606-ENSP00000436450; -. DR PeptideAtlas; P59540; -. DR Antibodypedia; 23423; 27 antibodies from 11 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 AGR; HGNC:18877; -. 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; ENSGT01100000263477; -. DR HOGENOM; CLU_072337_2_0_1; -. DR InParanoid; P59540; -. DR OMA; IMISSWS; -. DR OrthoDB; 5306466at2759; -. 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 1106 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 male germ line stem cell (sensu Vertebrata) in testis and 36 other cell types or tissues. DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IC:UniProtKB. 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 CDD; cd15027; 7tm_TAS2R43-like; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR007960; TAS2R. DR PANTHER; PTHR11394; TASTE RECEPTOR TYPE 2; 1. DR PANTHER; PTHR11394:SF66; TASTE RECEPTOR TYPE 2 MEMBER 46; 1. DR Pfam; PF05296; TAS2R; 1. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Cell projection; Cilium; KW G-protein coupled receptor; Glycoprotein; Membrane; Receptor; KW Reference proteome; Sensory transduction; Taste; Transducer; Transmembrane; KW 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 //