ID GNAT3_RAT Reviewed; 354 AA. AC P29348; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 02-SEP-2026, entry version 182. DE RecName: Full=Guanine nucleotide-binding protein G(t) subunit alpha-3; DE AltName: Full=Gustducin alpha-3 chain; GN Name=Gnat3; Synonyms=Gnat-3; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY. RC STRAIN=Sprague-Dawley; TISSUE=Tongue; RX PubMed=1608467; DOI=10.1038/357563a0; RA McLaughlin S.K., McKinnon P.J., Margolskee R.F.; RT "Gustducin is a taste-cell-specific G protein closely related to the RT transducins."; RL Nature 357:563-569(1992). RN [2] RP FUNCTION. RX PubMed=7626029; DOI=10.1042/bj3090629; RA Hoon M.A., Northup J.K., Margolskee R.F., Ryba N.J.P.; RT "Functional expression of the taste specific G-protein, alpha-gustducin."; RL Biochem. J. 309:629-636(1995). RN [3] RP FUNCTION, AND INDUCTION. RX PubMed=7596440; DOI=10.1038/376080a0; RA Ruiz-Avila L., McLaughlin S.K., Wildman D., McKinnon P.J., Robichon A., RA Spickofsky N., Margolskee R.F.; RT "Coupling of bitter receptor to phosphodiesterase through transducin in RT taste receptor cells."; RL Nature 376:80-85(1995). RN [4] RP TISSUE SPECIFICITY. RX PubMed=8692869; DOI=10.1073/pnas.93.13.6631; RA Hoefer D., Pueschel B., Drenckhahn D.; RT "Taste receptor-like cells in the rat gut identified by expression of RT alpha-gustducin."; RL Proc. Natl. Acad. Sci. U.S.A. 93:6631-6634(1996). RN [5] RP TISSUE SPECIFICITY. RX PubMed=9092606; DOI=10.1523/jneurosci.17-08-02852.1997; RA Boughter J.D. Jr., Pumplin D.W., Yu C., Christy R.C., Smith D.V.; RT "Differential expression of alpha-gustducin in taste bud populations of the RT rat and hamster."; RL J. Neurosci. 17:2852-2858(1997). RN [6] RP FUNCTION. RX PubMed=10052456; DOI=10.1016/s0092-8674(00)80658-3; RA Hoon M.A., Adler E., Lindemeier J., Battey J.F., Ryba N.J.P., Zuker C.S.; RT "Putative mammalian taste receptors: a class of taste-specific GPCRs with RT distinct topographic selectivity."; RL Cell 96:541-551(1999). RN [7] RP DEVELOPMENTAL STAGE. RX PubMed=10576254; DOI=10.1093/chemse/24.5.469; RA Sbarbati A., Crescimanno C., Bernardi P., Osculati F.; RT "Alpha-gustducin-immunoreactive solitary chemosensory cells in the RT developing chemoreceptorial epithelium of the rat vallate papilla."; RL Chem. Senses 24:469-472(1999). RN [8] RP TRANSGENE. RX PubMed=10407021; DOI=10.1523/jneurosci.19-14-05802.1999; RA Wong G.T., Ruiz-Avila L., Margolskee R.F.; RT "Directing gene expression to gustducin-positive taste receptor cells."; RL J. Neurosci. 19:5802-5809(1999). RN [9] RP SUBCELLULAR LOCATION. RX PubMed=10940948; RX DOI=10.1002/1096-9861(20000911)425:1<139::aid-cne12>3.0.co;2-#; RA Yang R., Tabata S., Crowley H.H., Margolskee R.F., Kinnamon J.C.; RT "Ultrastructural localization of gustducin immunoreactivity in microvilli RT of type II taste cells in the rat."; RL J. Comp. Neurol. 425:139-151(2000). RN [10] RP FUNCTION, AND MUTAGENESIS OF GLY-352. RX PubMed=11447270; DOI=10.1073/pnas.151235798; RA Ruiz-Avila L., Wong G.T., Damak S., Margolskee R.F.; RT "Dominant loss of responsiveness to sweet and bitter compounds caused by a RT single mutation in alpha-gustducin."; RL Proc. Natl. Acad. Sci. U.S.A. 98:8868-8873(2001). RN [11] RP TISSUE SPECIFICITY. RX PubMed=15654652; DOI=10.1007/s00441-004-1007-2; RA Merigo F., Benati D., Tizzano M., Osculati F., Sbarbati A.; RT "Alpha-gustducin immunoreactivity in the airways."; RL Cell Tissue Res. 319:211-219(2005). RN [12] RP TISSUE SPECIFICITY. RX PubMed=15561439; DOI=10.1016/j.neuroscience.2004.09.017; RA Shen T., Kaya N., Zhao F.-L., Lu S.-G., Cao Y., Herness S.; RT "Co-expression patterns of the neuropeptides vasoactive intestinal peptide RT and cholecystokinin with the transduction molecules alpha-gustducin and RT T1R2 in rat taste receptor cells."; RL Neuroscience 130:229-238(2005). RN [13] RP TISSUE SPECIFICITY. RX PubMed=17021831; DOI=10.1007/s00359-006-0168-8; RA Fehr J., Meyer D., Widmayer P., Borth H.C., Ackermann F., Wilhelm B., RA Gudermann T., Boekhoff I.; RT "Expression of the G-protein alpha-subunit gustducin in mammalian RT spermatozoa."; RL J. Comp. Physiol. A 193:21-34(2007). CC -!- FUNCTION: Guanine nucleotide-binding protein (G protein) alpha subunit CC playing a prominent role in bitter and sweet taste transduction as well CC as in umami (monosodium glutamate, monopotassium glutamate, and inosine CC monophosphate) taste transduction (PubMed:1608467, PubMed:7626029, CC PubMed:7596440, PubMed:10052456, PubMed:11447270). Transduction by this CC alpha subunit involves coupling of specific cell-surface receptors with CC a cGMP-phosphodiesterase; Activation of phosphodiesterase lowers CC intracellular levels of cAMP and cGMP which may open a cyclic CC nucleotide-suppressible cation channel leading to influx of calcium, CC ultimately leading to release of neurotransmitter. Indeed, denatonium CC and strychnine induce transient reduction in cAMP and cGMP in taste CC tissue, whereas this decrease is inhibited by GNAT3 antibody. Gustducin CC heterotrimer transduces response to bitter and sweet compounds via CC regulation of phosphodiesterase for alpha subunit, as well as via CC activation of phospholipase C for beta and gamma subunits, with CC ultimate increase inositol trisphosphate and increase of intracellular CC Calcium. GNAT3 can functionally couple to taste receptors to transmit CC intracellular signal: receptor heterodimer TAS1R2/TAS1R3 senses CC sweetness and TAS1R1/TAS1R3 transduces umami taste, whereas the T2R CC family GPCRs act as bitter sensors (By similarity). Also functions as CC lumenal sugar sensors in the gut to control the expression of the Na+- CC glucose transporter SGLT1 in response to dietaty sugar, as well as the CC secretion of Glucagon-like peptide-1, GLP-1 and glucose-dependent CC insulinotropic polypeptide, GIP. Thus, may modulate the gut capacity to CC absorb sugars, with implications for the prevention and treatment of CC malabsorption syndromes and diet-related disorders including diabetes CC and obesity. {ECO:0000250|UniProtKB:A8MTJ3, CC ECO:0000269|PubMed:10052456, ECO:0000269|PubMed:11447270, CC ECO:0000269|PubMed:1608467, ECO:0000269|PubMed:7596440, CC ECO:0000269|PubMed:7626029}. CC -!- SUBUNIT: G proteins are composed of 3 units; alpha, beta and gamma (By CC similarity). The alpha chain contains the guanine nucleotide binding CC site (By similarity). Component of the sweet taste receptor complex, CC consisting of TAS1R2, TAS1R3, GNAT3, GNB1 and GNG2; this complex CC mediates sweet taste transduction (By similarity). Component of the CC TAS2R14-GNAT3 complex, consisting of TAS2R14, GNAT3, GNB1 and GNG2; CC within the complex interacts with TAS2R14; this complex mediates bitter CC taste transduction (By similarity). Gustducin heterotrimer may also be CC composed of GNAT3, GNB3 and GNG13 (By similarity). CC {ECO:0000250|UniProtKB:A8MTJ3, ECO:0000250|UniProtKB:Q3V3I2}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10940948}. CC Note=Associated with microvilli, the presumed sites of sensory CC transduction in taste cells. CC -!- TISSUE SPECIFICITY: Expressed in taste buds (sensory organs of CC clustered epithelial cells) of the circumvallate, foliate and fungiform CC papillae of the tongue, as well as in nasoincisor, palatal and CC epiglottal taste buds at protein level. Expressed in enteroendocrine of CC the gut, in the lumenal pole of a subset of brush cells lining the CC stomach and the intestine at protein level. Detected in solitary cells CC throughout the respiratory track. Expressed also in spermatozoa. CC {ECO:0000269|PubMed:15561439, ECO:0000269|PubMed:15654652, CC ECO:0000269|PubMed:1608467, ECO:0000269|PubMed:17021831, CC ECO:0000269|PubMed:8692869, ECO:0000269|PubMed:9092606}. CC -!- DEVELOPMENTAL STAGE: Expressed in scattered solitary ovoid or bipolar CC cells among the oral epithelium from day 1-7, but with higher frequency CC in the soft palate as compared with the nasoincisor, circumvallate, and CC foliate papillae at day 1. During the second week, the solitary cells CC could no longer be recognized while cells expressing GNAT3 within the CC taste buds gradually increased. The onset of taste transduction CC accomplished by the palatal taste buds developed earlier than that CC achieved by taste buds in the circumvallate and foliate papillae. CC {ECO:0000269|PubMed:10576254}. CC -!- INDUCTION: By bitter compounds denatonium and quinine. CC {ECO:0000269|PubMed:7596440}. CC -!- PTM: Potential N-myristoylation may anchor alpha-subunit to the inner CC surface of plasma membrane. CC -!- MISCELLANEOUS: Transgenic expression of GNAT3 restores responsiveness CC of GNAT3 deficient mice to both bitter and sweet compounds, whereas CC expression of mutated Gly-352 transgene do not. Furthermore, in wild- CC type mice, this mutated transgene acts as a dominant-negative by CC inhibition of endogenous GNAT3 interactions with taste receptors. CC -!- SIMILARITY: Belongs to the G-alpha family. G(i/o/t/z) subfamily. CC {ECO:0000305}. 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; X65747; CAA46650.1; -; mRNA. DR PIR; S24352; S24352. DR RefSeq; NP_775162.1; NM_173139.2. DR AlphaFoldDB; P29348; -. DR SMR; P29348; -. DR FunCoup; P29348; 231. DR STRING; 10116.ENSRNOP00000007032; -. DR iPTMnet; P29348; -. DR PhosphoSitePlus; P29348; -. DR PaxDb; 10116-ENSRNOP00000007032; -. DR Ensembl; ENSRNOT00000007032.8; ENSRNOP00000007032.6; ENSRNOG00000005268.8. DR Ensembl; ENSRNOT00055037856; ENSRNOP00055030898; ENSRNOG00055022039. DR Ensembl; ENSRNOT00060021750; ENSRNOP00060017215; ENSRNOG00060012788. DR Ensembl; ENSRNOT00065028635; ENSRNOP00065022683; ENSRNOG00065017170. DR GeneID; 286924; -. DR KEGG; rno:286924; -. DR AGR; RGD:727817; -. DR CTD; 346562; -. DR RGD; 727817; Gnat3. DR eggNOG; KOG0082; Eukaryota. DR GeneTree; ENSGT00940000161422; -. DR HOGENOM; CLU_014184_6_0_1; -. DR InParanoid; P29348; -. DR OMA; EDQRQLC; -. DR OrthoDB; 5817230at2759; -. DR PhylomeDB; P29348; -. DR Reactome; R-RNO-170670; Adenylate cyclase inhibitory pathway. DR Reactome; R-RNO-392170; ADP signalling through P2Y purinoceptor 12. DR Reactome; R-RNO-418594; G alpha (i) signalling events. DR Reactome; R-RNO-9009391; Extra-nuclear estrogen signaling. DR Reactome; R-RNO-9717207; Sensory perception of sweet, bitter, and umami (glutamate) taste. DR PRO; PR:P29348; -. DR Proteomes; UP000002494; Chromosome 4. DR Bgee; ENSRNOG00000005268; Expressed in jejunum and 8 other cell types or tissues. DR ExpressionAtlas; P29348; baseline and differential. DR GO; GO:0001669; C:acrosomal vesicle; IDA:RGD. DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD. DR GO; GO:0005930; C:axoneme; IDA:RGD. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005834; C:heterotrimeric G-protein complex; ISO:RGD. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0032991; C:protein-containing complex; ISO:RGD. DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central. DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; IBA:GO_Central. DR GO; GO:0005525; F:GTP binding; IDA:RGD. DR GO; GO:0003924; F:GTPase activity; IDA:RGD. DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; IBA:GO_Central. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD. DR GO; GO:0007603; P:phototransduction, visible light; IBA:GO_Central. DR GO; GO:0035094; P:response to nicotine; IEP:RGD. DR GO; GO:0050913; P:sensory perception of bitter taste; ISO:RGD. DR GO; GO:0050916; P:sensory perception of sweet taste; ISO:RGD. DR GO; GO:0050909; P:sensory perception of taste; ISO:RGD. DR GO; GO:0050917; P:sensory perception of umami taste; ISO:RGD. DR CDD; cd00066; G-alpha; 1. DR FunFam; 1.10.400.10:FF:000001; Guanine nucleotide-binding protein G(I) subunit alpha; 1. DR FunFam; 3.40.50.300:FF:000720; Guanine nucleotide-binding protein G(k) subunit alpha; 1. DR FunFam; 3.40.50.300:FF:000256; Guanine nucleotide-binding protein G(t) subunit alpha; 1. DR Gene3D; 1.10.400.10; GI Alpha 1, domain 2-like; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR001408; Gprotein_alpha_I. DR InterPro; IPR001019; Gprotein_alpha_su. DR InterPro; IPR011025; GproteinA_insert. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR10218; GTP-BINDING PROTEIN ALPHA SUBUNIT; 1. DR PANTHER; PTHR10218:SF66; GUANINE NUCLEOTIDE-BINDING PROTEIN G(T) SUBUNIT ALPHA-3; 1. DR Pfam; PF00503; G-alpha; 1. DR PRINTS; PR00318; GPROTEINA. DR PRINTS; PR00441; GPROTEINAI. DR SMART; SM00275; G_alpha; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF47895; Transducin (alpha subunit), insertion domain; 1. DR PROSITE; PS51882; G_ALPHA; 1. PE 1: Evidence at protein level; KW Cytoplasm; GTP-binding; Lipoprotein; Magnesium; Metal-binding; Myristate; KW Nucleotide-binding; Reference proteome; Sensory transduction; Taste; KW Transducer; Vision. FT INIT_MET 1 FT /note="Removed" FT CHAIN 2..354 FT /note="Guanine nucleotide-binding protein G(t) subunit FT alpha-3" FT /id="PRO_0000203743" FT DOMAIN 32..354 FT /note="G-alpha" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230" FT REGION 1..27 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 35..48 FT /note="G1 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230" FT REGION 173..181 FT /note="G2 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230" FT REGION 196..205 FT /note="G3 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230" FT REGION 265..272 FT /note="G4 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230" FT REGION 324..329 FT /note="G5 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230" FT COMPBIAS 8..27 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 40..47 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250" FT BINDING 47 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT BINDING 175..181 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250" FT BINDING 181 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT BINDING 200..204 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250" FT BINDING 269..272 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250" FT BINDING 326 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000250" FT MUTAGEN 352 FT /note="G->P: Loss of activation by both bitter and sweet FT compounds due to disruption of interaction with taste FT receptors." FT /evidence="ECO:0000269|PubMed:11447270" SQ SEQUENCE 354 AA; 40294 MW; 3B7260BBCB0448D6 CRC64; MGSGISSESK ESAKRSKELE KKLQEDAERD ARTVKLLLLG AGESGKSTIV KQMKIIHKNG YSKQECMEFK AVVYSNTLQS ILAIVKAMTT LGIDYVNPRS REDQQLLLSM ANTLEDGDMT PQLAEIIKRL WGDPGIQACF ERASEYQLND SAAYYLNDLD RLTAPGYVPN EQDVLHSRVK TTGIIETQFS FKDLNFRMFD VGGQRSERKK WIHCFEGVTC IIFCAALSAY DMVLVEDEEV NRMHESLHLF NSICNHKYFA TTSIVLFLNK KDLFQEKVTK VHLSICFPEY TGPNTFEDAG NYIKNQFLDL NLKKEDKEIY SHMTCATDTQ NVKFVFDAVT DIIIKENLKD CGLF //