GNAT3_RAT
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 03-AUG-2022, entry version 168.
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. Transduction by this alpha subunit
CC involves coupling of specific cell-surface receptors with a cGMP-
CC phosphodiesterase; Activation of phosphodiesterase lowers intracellular
CC levels of cAMP and cGMP which may open a cyclic nucleotide-suppressible
CC cation channel leading to influx of calcium, ultimately leading to
CC release of neurotransmitter. Indeed, denatonium and strychnine induce
CC transient reduction in cAMP and cGMP in taste tissue, whereas this
CC decrease is inhibited by GNAT3 antibody. Gustducin heterotrimer
CC transduces response to bitter and sweet compounds via regulation of
CC phosphodiesterase for alpha subunit, as well as via activation of
CC phospholipase C for beta and gamma subunits, with ultimate increase
CC inositol trisphosphate and increase of intracellular Calcium. GNAT3 can
CC functionally couple to taste receptors to transmit intracellular
CC signal: receptor heterodimer TAS1R2/TAS1R3 senses sweetness and
CC TAS1R1/TAS1R3 transduces umami taste, whereas the T2R family GPCRs act
CC as bitter sensors. Functions also as lumenal sugar sensors in the gut
CC to control the expression of the Na+-glucose transporter SGLT1 in
CC response to dietaty sugar, as well as the secretion of Glucagon-like
CC peptide-1, GLP-1 and glucose-dependent insulinotropic polypeptide, GIP.
CC Thus, may modulate the gut capacity to absorb sugars, with implications
CC for the prevention and treatment of malabsorption syndromes and diet-
CC related disorders including diabetes and obesity.
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,
CC respectively GNAT3, GNB1 and GNG13 for Gustducin heterotrimer for
CC bitter taste transduction. The alpha chain contains the guanine
CC nucleotide binding site. Gustducin heterotrimer may also be composed of
CC GNAT3, GNB3 and GNG13.
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 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}.
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DR EMBL; X65747; CAA46650.1; -; mRNA.
DR PIR; S24352; S24352.
DR RefSeq; NP_775162.1; NM_173139.1.
DR AlphaFoldDB; P29348; -.
DR SMR; P29348; -.
DR STRING; 10116.ENSRNOP00000007032; -.
DR iPTMnet; P29348; -.
DR PhosphoSitePlus; P29348; -.
DR jPOST; P29348; -.
DR PaxDb; P29348; -.
DR PRIDE; P29348; -.
DR Ensembl; ENSRNOT00000007032; ENSRNOP00000007032; ENSRNOG00000005268.
DR GeneID; 286924; -.
DR KEGG; rno:286924; -.
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; 754573at2759; -.
DR PhylomeDB; P29348; -.
DR Reactome; R-RNO-170670; Adenylate cyclase inhibitory pathway.
DR Reactome; R-RNO-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
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 tissues.
DR Genevisible; P29348; RN.
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; IDA:RGD.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; ISO:RGD.
DR GO; GO:0001917; C:photoreceptor inner segment; IBA:GO_Central.
DR GO; GO:0001750; C:photoreceptor outer segment; IBA:GO_Central.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0001580; P:detection of chemical stimulus involved in sensory perception of bitter taste; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
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 GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR CDD; cd00066; G-alpha; 1.
DR Gene3D; 1.10.400.10; -; 1.
DR Gene3D; 3.40.50.300; -; 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; PTHR10218; 1.
DR Pfam; PF00503; G-alpha; 1.
DR PRINTS; PR00318; GPROTEINA.
DR PRINTS; PR00441; GPROTEINAI.
DR SMART; SM00275; G_alpha; 1.
DR SUPFAM; SSF47895; SSF47895; 1.
DR SUPFAM; SSF52540; SSF52540; 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 10..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
