ID T2R38_HUMAN Reviewed; 333 AA. AC P59533; A4D1U6; P59552; Q2M3E8; Q645W3; Q86UK3; DT 11-APR-2003, integrated into UniProtKB/Swiss-Prot. DT 21-JUN-2005, sequence version 3. DT 12-AUG-2020, entry version 152. DE RecName: Full=Taste receptor type 2 member 38; DE Short=T2R38; DE AltName: Full=PTC bitter taste receptor; DE AltName: Full=Taste receptor type 2 member 61; DE Short=T2R61; GN Name=TAS2R38; Synonyms=PTC; 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], AND VARIANT VAL-262. 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 [2] 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 [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PRO-49 AND VAL-296. RX PubMed=12595690; DOI=10.1126/science.1080190; RA Kim U.-K., Jorgenson E., Coon H., Leppert M., Risch N., Drayna D.T.; RT "Positional cloning of the human quantitative trait locus underlying taste RT sensitivity to phenylthiocarbamide."; RL Science 299:1221-1225(2003). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-262. 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-262. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-262. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-262. 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 [8] 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 [9] 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 [10] 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 [11] RP TISSUE SPECIFICITY. RX PubMed=16720576; DOI=10.1074/jbc.m513637200; RA Behrens M., Bartelt J., Reichling C., Winnig M., Kuhn C., Meyerhof W.; RT "Members of RTP and REEP gene families influence functional bitter taste RT receptor expression."; RL J. Biol. Chem. 281:20650-20659(2006). 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). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. CC -!- TISSUE SPECIFICITY: Expressed in subsets of taste receptor cells of the CC tongue and exclusively in gustducin-positive cells. Expressed in testis CC (PubMed:16720576). {ECO:0000269|PubMed:16720576}. CC -!- POLYMORPHISM: Variations in TAS2R38 are associated with the ability to CC taste phenylthiocarbamide (PTC tasting) [MIM:171200]; also called CC thiourea tasting. The ability to taste the substance PTC and a number CC of related substances is genetically controlled. Genetic studies have CC demonstrated complex inheritance for this trait. For some people (and CC some chimpanzees also), the chemical PTC tastes very bitter. For CC others, it is tasteless. Actually, substantial variation in taste CC sensitivity exists in human. Five haplotypes arising from three coding CC SNPs in the TAS2R38 gene are associated with distinct phenotypes of PTC CC taste sensitivity. 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; AF494231; AAM19322.1; -; Genomic_DNA. DR EMBL; AY114095; AAM63545.1; -; Genomic_DNA. DR EMBL; AY258598; AAP14667.1; -; Genomic_DNA. DR EMBL; AY724960; AAU21156.1; -; Genomic_DNA. DR EMBL; CH236950; EAL24011.1; -; Genomic_DNA. DR EMBL; CH471070; EAW83993.1; -; Genomic_DNA. DR EMBL; BC104933; AAI04934.1; -; mRNA. DR EMBL; BC104937; AAI04938.1; -; mRNA. DR CCDS; CCDS34765.1; -. DR RefSeq; NP_789787.4; NM_176817.4. DR BioGRID; 111698; 2. DR STRING; 9606.ENSP00000448219; -. DR TCDB; 9.A.14.17.5; the g-protein-coupled receptor (gpcr) family. DR GlyGen; P59533; 2 sites. DR iPTMnet; P59533; -. DR PhosphoSitePlus; P59533; -. DR BioMuta; TAS2R38; -. DR DMDM; 68068016; -. DR MassIVE; P59533; -. DR PaxDb; P59533; -. DR PRIDE; P59533; -. DR ProteomicsDB; 57140; -. DR Antibodypedia; 50262; 135 antibodies. DR Ensembl; ENST00000547270; ENSP00000448219; ENSG00000257138. DR GeneID; 5726; -. DR KEGG; hsa:5726; -. DR UCSC; uc003vwx.1; human. DR CTD; 5726; -. DR DisGeNET; 5726; -. DR EuPathDB; HostDB:ENSG00000257138.1; -. DR GeneCards; TAS2R38; -. DR HGNC; HGNC:9584; TAS2R38. DR HPA; ENSG00000257138; Tissue enhanced (intestine). DR MalaCards; TAS2R38; -. DR MIM; 171200; phenotype. DR MIM; 607751; gene. DR neXtProt; NX_P59533; -. DR OpenTargets; ENSG00000257138; -. DR PharmGKB; PA33936; -. DR eggNOG; ENOG502T15G; Eukaryota. DR GeneTree; ENSGT00960000186648; -. DR HOGENOM; CLU_072337_3_0_1; -. DR InParanoid; P59533; -. DR KO; K08474; -. DR OMA; VRADHMA; -. DR OrthoDB; 1010573at2759; -. DR PhylomeDB; P59533; -. DR TreeFam; TF335891; -. DR PathwayCommons; P59533; -. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR Reactome; R-HSA-420499; Class C/3 (Metabotropic glutamate/pheromone receptors). DR BioGRID-ORCS; 5726; 3 hits in 864 CRISPR screens. DR GeneWiki; TAS2R38; -. DR GenomeRNAi; 5726; -. DR Pharos; P59533; Tbio. DR PRO; PR:P59533; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P59533; protein. DR Bgee; ENSG00000257138; Expressed in sural nerve and 11 other tissues. DR Genevisible; P59533; HS. DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:CACAO. 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 GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome. DR InterPro; IPR007960; T2R. DR InterPro; IPR030050; TAS2R38. DR PANTHER; PTHR11394:SF52; PTHR11394:SF52; 1. DR Pfam; PF05296; TAS2R; 1. PE 2: Evidence at transcript level; KW G-protein coupled receptor; Glycoprotein; Membrane; Polymorphism; Receptor; KW Reference proteome; Sensory transduction; Taste; Transducer; Transmembrane; KW Transmembrane helix. FT CHAIN 1..333 FT /note="Taste receptor type 2 member 38" FT /id="PRO_0000082273" FT TOPO_DOM 1..17 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 18..38 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 39..55 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 56..76 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 77..94 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 95..115 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 116..142 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 143..163 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 164..190 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 191..211 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 212..251 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 252..272 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 273..276 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 277..297 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 298..333 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT CARBOHYD 89 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 178 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VARIANT 49 FT /note="A -> P (in dbSNP:rs713598)" FT /evidence="ECO:0000269|PubMed:12595690" FT /id="VAR_017860" FT VARIANT 262 FT /note="A -> V (in dbSNP:rs1726866)" FT /evidence="ECO:0000269|PubMed:12379855, FT ECO:0000269|PubMed:12690205, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:15496549, ECO:0000269|Ref.6" FT /id="VAR_017861" FT VARIANT 296 FT /note="I -> V (in dbSNP:rs10246939)" FT /evidence="ECO:0000269|PubMed:12595690" FT /id="VAR_017862" FT CONFLICT 186 FT /note="I -> N (in Ref. 1; AAM19322)" FT /evidence="ECO:0000305" SQ SEQUENCE 333 AA; 37892 MW; E3B5EDD5AB99994C CRC64; MLTLTRIRTV SYEVRSTFLF ISVLEFAVGF LTNAFVFLVN FWDVVKRQAL SNSDCVLLCL SISRLFLHGL LFLSAIQLTH FQKLSEPLNH SYQAIIMLWM IANQANLWLA ACLSLLYCSK LIRFSHTFLI CLASWVSRKI SQMLLGIILC SCICTVLCVW CFFSRPHFTV TTVLFMNNNT RLNWQIKDLN LFYSFLFCYL WSVPPFLLFL VSSGMLTVSL GRHMRTMKVY TRNSRDPSLE AHIKALKSLV SFFCFFVISS CAAFISVPLL ILWRDKIGVM VCVGIMAACP SGHAAILISG NAKLRRAVMT ILLWAQSSLK VRADHKADSR TLC //