ID   TA2R4_HUMAN             Reviewed;         299 AA.
AC   Q9NYW5; Q645W5; Q75MV8;
DT   11-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   24-JAN-2024, entry version 165.
DE   RecName: Full=Taste receptor type 2 member 4;
DE            Short=T2R4;
GN   Name=TAS2R4;
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 TOPOLOGY.
RX   PubMed=10761934; DOI=10.1016/s0092-8674(00)80705-9;
RA   Adler E., Hoon M.A., Mueller K.L., Chandrashekar J., Ryba N.J.P.,
RA   Zuker C.S.;
RT   "A novel family of mammalian taste receptors.";
RL   Cell 100:693-702(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [4]
RP   CHARACTERIZATION.
RX   PubMed=10761935; DOI=10.1016/s0092-8674(00)80706-0;
RA   Chandrashekar J., Mueller K.L., Hoon M.A., Adler E., Feng L., Guo W.,
RA   Zuker C.S., Ryba N.J.P.;
RT   "T2Rs function as bitter taste receptors.";
RL   Cell 100:703-711(2000).
RN   [5]
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   [6]
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   [7]
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   [8]
RP   FUNCTION, 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: Gustducin-coupled receptor for denatonium and N(6)-propyl-2-
CC       thiouracil implicated in the perception of bitter compounds in the oral
CC       cavity and the gastrointestinal tract. Signals through PLCB2 and the
CC       calcium-regulated cation channel TRPM5. In airway epithelial cells,
CC       binding of denatonium increases the intracellular calcium ion
CC       concentration and stimulates ciliary beat frequency.
CC       {ECO:0000269|PubMed:19628819}.
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 palate epithelium and exclusively in gustducin-positive
CC       cells. Expressed on airway ciliated epithelium.
CC       {ECO:0000269|PubMed:19628819}.
CC   -!- MISCELLANEOUS: Several bitter taste receptors are expressed in a single
CC       taste receptor cell.
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; AF227131; AAF43904.1; -; Genomic_DNA.
DR   EMBL; AY724958; AAU21154.1; -; Genomic_DNA.
DR   EMBL; AC004979; AAS02039.1; -; Genomic_DNA.
DR   CCDS; CCDS5868.1; -.
DR   RefSeq; NP_058640.1; NM_016944.1.
DR   AlphaFoldDB; Q9NYW5; -.
DR   SMR; Q9NYW5; -.
DR   STRING; 9606.ENSP00000247881; -.
DR   BindingDB; Q9NYW5; -.
DR   ChEMBL; CHEMBL3309107; -.
DR   GuidetoPHARMACOLOGY; 661; -.
DR   GlyCosmos; Q9NYW5; 3 sites, No reported glycans.
DR   GlyGen; Q9NYW5; 3 sites.
DR   BioMuta; TAS2R4; -.
DR   DMDM; 29839665; -.
DR   PaxDb; 9606-ENSP00000247881; -.
DR   PeptideAtlas; Q9NYW5; -.
DR   Antibodypedia; 32508; 44 antibodies from 17 providers.
DR   DNASU; 50832; -.
DR   Ensembl; ENST00000247881.4; ENSP00000247881.3; ENSG00000127364.4.
DR   GeneID; 50832; -.
DR   KEGG; hsa:50832; -.
DR   MANE-Select; ENST00000247881.4; ENSP00000247881.3; NM_016944.2; NP_058640.1.
DR   UCSC; uc003vwq.2; human.
DR   AGR; HGNC:14911; -.
DR   CTD; 50832; -.
DR   DisGeNET; 50832; -.
DR   GeneCards; TAS2R4; -.
DR   HGNC; HGNC:14911; TAS2R4.
DR   HPA; ENSG00000127364; Tissue enriched (brain).
DR   MIM; 604869; gene.
DR   neXtProt; NX_Q9NYW5; -.
DR   OpenTargets; ENSG00000127364; -.
DR   PharmGKB; PA37923; -.
DR   VEuPathDB; HostDB:ENSG00000127364; -.
DR   eggNOG; ENOG502S2SI; Eukaryota.
DR   GeneTree; ENSGT01100000263477; -.
DR   HOGENOM; CLU_072337_3_0_1; -.
DR   InParanoid; Q9NYW5; -.
DR   OMA; MKLMIYF; -.
DR   OrthoDB; 4631596at2759; -.
DR   PhylomeDB; Q9NYW5; -.
DR   TreeFam; TF335891; -.
DR   PathwayCommons; Q9NYW5; -.
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; 50832; 2 hits in 1137 CRISPR screens.
DR   GeneWiki; TAS2R4; -.
DR   GenomeRNAi; 50832; -.
DR   Pharos; Q9NYW5; Tchem.
DR   PRO; PR:Q9NYW5; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; Q9NYW5; Protein.
DR   Bgee; ENSG00000127364; Expressed in primordial germ cell in gonad and 102 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:0008527; F:taste receptor activity; TAS:UniProtKB.
DR   GO; GO:0001580; P:detection of chemical stimulus involved in sensory perception of bitter taste; IDA:UniProtKB.
DR   GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; IEA:Ensembl.
DR   CDD; cd15013; 7tm_TAS2R4; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR007960; TAS2R.
DR   InterPro; IPR030055; TAS2R4.
DR   PANTHER; PTHR11394; TASTE RECEPTOR TYPE 2; 1.
DR   PANTHER; PTHR11394:SF55; TASTE RECEPTOR TYPE 2 MEMBER 4; 1.
DR   Pfam; PF05296; TAS2R; 1.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   Genevisible; Q9NYW5; HS.
PE   1: Evidence at protein 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..299
FT                   /note="Taste receptor type 2 member 4"
FT                   /id="PRO_0000082205"
FT   TOPO_DOM        1..9
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        10..30
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        31..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..81
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        82..102
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        103..131
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        132..152
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        153..172
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        173..193
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        194..230
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        231..251
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        252..262
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        263..283
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        284..299
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        164
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        165
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        169
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         3
FT                   /note="R -> Q (in dbSNP:rs2233995)"
FT                   /id="VAR_034535"
FT   VARIANT         7
FT                   /note="F -> S (in dbSNP:rs2233998)"
FT                   /id="VAR_034536"
FT   VARIANT         62
FT                   /note="F -> L (in dbSNP:rs2233999)"
FT                   /id="VAR_053341"
FT   VARIANT         74
FT                   /note="T -> M (in dbSNP:rs2234000)"
FT                   /id="VAR_020200"
FT   VARIANT         96
FT                   /note="V -> L (in dbSNP:rs2234001)"
FT                   /id="VAR_020201"
FT   VARIANT         171
FT                   /note="S -> N (in dbSNP:rs2234002)"
FT                   /id="VAR_020202"
FT   VARIANT         191
FT                   /note="I -> V (in dbSNP:rs2234003)"
FT                   /id="VAR_053342"
SQ   SEQUENCE   299 AA;  33841 MW;  8265610092B19945 CRC64;
     MLRLFYFSAI IASVILNFVG IIMNLFITVV NCKTWVKSHR ISSSDRILFS LGITRFLMLG
     LFLVNTIYFV SSNTERSVYL SAFFVLCFMF LDSSSVWFVT LLNILYCVKI TNFQHSVFLL
     LKRNISPKIP RLLLACVLIS AFTTCLYITL SQASPFPELV TTRNNTSFNI SEGILSLVVS
     LVLSSSLQFI INVTSASLLI HSLRRHIQKM QKNATGFWNP QTEAHVGAMK LMVYFLILYI
     PYSVATLVQY LPFYAGMDMG TKSICLIFAT LYSPGHSVLI IITHPKLKTT AKKILCFKK
//