GNAT3_HUMAN
ID GNAT3_HUMAN Reviewed; 354 AA.
AC A8MTJ3; A4D1B2; A4D1B3; B9EJG5;
DT 01-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Guanine nucleotide-binding protein G(t) subunit alpha-3;
DE AltName: Full=Gustducin alpha-3 chain;
GN Name=GNAT3;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=8015379; DOI=10.1016/0169-328x(94)90047-7;
RA Takami S., Getchell T.V., McLaughlin S.K., Margolskee R.F., Getchell M.L.;
RT "Human taste cells express the G protein alpha-gustducin and neuron-
RT specific enolase.";
RL Brain Res. Mol. Brain Res. 22:193-203(1994).
RN [6]
RP FUNCTION.
RX PubMed=11917125; DOI=10.1073/pnas.072090199;
RA Li X., Staszewski L., Xu H., Durick K., Zoller M., Adler E.;
RT "Human receptors for sweet and umami taste.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:4692-4696(2002).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=16728727; DOI=10.1152/ajpgi.00074.2006;
RA Rozengurt N., Wu S.V., Chen M.C., Huang C., Sternini C., Rozengurt E.;
RT "Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L
RT cells of human colon.";
RL Am. J. Physiol. 291:G792-G802(2006).
RN [8]
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).
RN [9]
RP FUNCTION.
RX PubMed=17724330; DOI=10.1073/pnas.0706890104;
RA Jang H.-J., Kokrashvili Z., Theodorakis M.J., Carlson O.D., Kim B.-J.,
RA Zhou J., Kim H.H., Xu X., Chan S.L., Juhaszova M., Bernier M., Mosinger B.,
RA Margolskee R.F., Egan J.M.;
RT "Gut-expressed gustducin and taste receptors regulate secretion of
RT glucagon-like peptide-1.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:15069-15074(2007).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=17724332; DOI=10.1073/pnas.0706678104;
RA Margolskee R.F., Dyer J., Kokrashvili Z., Salmon K.S., Ilegems E., Daly K.,
RA Maillet E.L., Ninomiya Y., Mosinger B., Shirazi-Beechey S.P.;
RT "T1R3 and gustducin in gut sense sugars to regulate expression of Na+-
RT glucose cotransporter 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:15075-15080(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 in malabsorption syndromes and diet-related disorders including
CC diabetes and obesity. {ECO:0000269|PubMed:11917125,
CC ECO:0000269|PubMed:17724330}.
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:8015379}. Note=Dual
CC distribution pattern; plasmalemmal pattern with apical region
CC localization and cytosolic pattern with localization throughout the
CC cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in taste buds (sensory organs of
CC clustered epithelial cells) of the circumvallate and foliate papillae
CC of the tongue at protein level. Expressed in enteroendocrine L cells of
CC the gut. Detected also in spermatozoa. {ECO:0000269|PubMed:16728727,
CC ECO:0000269|PubMed:17021831, ECO:0000269|PubMed:17724332,
CC ECO:0000269|PubMed:8015379}.
CC -!- PTM: Potential N-myristoylation may anchor alpha-subunit to the inner
CC surface of plasma membrane. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the G-alpha family. G(i/o/t/z) subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAL24192.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=EAL24193.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AC004862; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236949; EAL24192.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH236949; EAL24193.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471091; EAW77007.1; -; Genomic_DNA.
DR EMBL; BC147016; AAI47017.1; -; mRNA.
DR EMBL; BC147017; AAI47018.1; -; mRNA.
DR CCDS; CCDS47625.1; -.
DR RefSeq; NP_001095856.1; NM_001102386.2.
DR AlphaFoldDB; A8MTJ3; -.
DR SMR; A8MTJ3; -.
DR BioGRID; 131390; 15.
DR IntAct; A8MTJ3; 5.
DR STRING; 9606.ENSP00000381339; -.
DR GlyGen; A8MTJ3; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; A8MTJ3; -.
DR PhosphoSitePlus; A8MTJ3; -.
DR SwissPalm; A8MTJ3; -.
DR BioMuta; GNAT3; -.
DR jPOST; A8MTJ3; -.
DR MassIVE; A8MTJ3; -.
DR MaxQB; A8MTJ3; -.
DR PaxDb; A8MTJ3; -.
DR PeptideAtlas; A8MTJ3; -.
DR PRIDE; A8MTJ3; -.
DR ProteomicsDB; 2028; -.
DR TopDownProteomics; A8MTJ3; -.
DR Antibodypedia; 29521; 153 antibodies from 28 providers.
DR DNASU; 346562; -.
DR Ensembl; ENST00000398291.4; ENSP00000381339.3; ENSG00000214415.4.
DR GeneID; 346562; -.
DR KEGG; hsa:346562; -.
DR MANE-Select; ENST00000398291.4; ENSP00000381339.3; NM_001102386.3; NP_001095856.1.
DR UCSC; uc011kgu.3; human.
DR CTD; 346562; -.
DR DisGeNET; 346562; -.
DR GeneCards; GNAT3; -.
DR HGNC; HGNC:22800; GNAT3.
DR HPA; ENSG00000214415; Tissue enriched (intestine).
DR MIM; 139395; gene.
DR neXtProt; NX_A8MTJ3; -.
DR OpenTargets; ENSG00000214415; -.
DR PharmGKB; PA134931156; -.
DR VEuPathDB; HostDB:ENSG00000214415; -.
DR eggNOG; KOG0082; Eukaryota.
DR GeneTree; ENSGT00940000161422; -.
DR HOGENOM; CLU_014184_6_0_1; -.
DR InParanoid; A8MTJ3; -.
DR OMA; EDQRQLC; -.
DR OrthoDB; 754573at2759; -.
DR PhylomeDB; A8MTJ3; -.
DR TreeFam; TF300673; -.
DR PathwayCommons; A8MTJ3; -.
DR Reactome; R-HSA-170670; Adenylate cyclase inhibitory pathway.
DR Reactome; R-HSA-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR Reactome; R-HSA-392170; ADP signalling through P2Y purinoceptor 12.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-418597; G alpha (z) signalling events.
DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-HSA-9634597; GPER1 signaling.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR Reactome; R-HSA-9717207; Sensory perception of sweet, bitter, and umami (glutamate) taste.
DR SignaLink; A8MTJ3; -.
DR BioGRID-ORCS; 346562; 10 hits in 1066 CRISPR screens.
DR ChiTaRS; GNAT3; human.
DR GeneWiki; GNAT3; -.
DR GenomeRNAi; 346562; -.
DR Pharos; A8MTJ3; Tbio.
DR PRO; PR:A8MTJ3; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; A8MTJ3; protein.
DR Bgee; ENSG00000214415; Expressed in tibialis anterior and 15 other tissues.
DR Genevisible; A8MTJ3; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0005930; C:axoneme; IEA:Ensembl.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:GO_Central.
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; IDA:MGI.
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; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
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:0035094; P:response to nicotine; IEA:Ensembl.
DR GO; GO:0050916; P:sensory perception of sweet taste; IBA:GO_Central.
DR GO; GO:0050917; P:sensory perception of umami taste; IEA:Ensembl.
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 2: Evidence at transcript level;
KW Cytoplasm; GTP-binding; Lipoprotein; Magnesium; Metal-binding; Myristate;
KW Nucleotide-binding; Reference proteome; Transducer.
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_0000342671"
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"
SQ SEQUENCE 354 AA; 40357 MW; 47366FB99E9322AD CRC64;
MGSGISSESK ESAKRSKELE KKLQEDAERD ARTVKLLLLG AGESGKSTIV KQMKIIHKNG
YSEQECMEFK AVIYSNTLQS ILAIVKAMTT LGIDYVNPRS AEDQRQLYAM ANTLEDGGMT
PQLAEVIKRL WRDPGIQACF ERASEYQLND SAAYYLNDLD RITASGYVPN EQDVLHSRVK
TTGIIETQFS FKDLHFRMFD VGGQRSERKK WIHCFEGVTC IIFCAALSAY DMVLVEDEEV
NRMHESLHLF NSICNHKYFS TTSIVLFLNK KDIFQEKVTK VHLSICFPEY TGPNTFEDAG
NYIKNQFLDL NLKKEDKEIY SHMTCATDTQ NVKFVFDAVT DIIIKENLKD CGLF
