Q3V3I2 (GNAT3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Guanine nucleotide-binding protein G(t) subunit alpha-3

Alternative name(s):
Gustducin alpha-3 chain

Gene names

Name:

Gnat3

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	354 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Guanine nucleotide-binding protein (G protein) alpha subunit playing a prominent role in bitter and sweet taste transduction as well as in umami (monosodium glutamate, monopotassium glutamate, and inosine monophosphate) taste transduction. Transduction by this alpha subunit involves coupling of specific cell-surface receptors with a cGMP-phosphodiesterase; Activation of phosphodiesterase lowers intracellular levels of cAMP and cGMP which may open a cyclic nucleotide-suppressible cation channel leading to influx of calcium, ultimately leading to release of neurotransmitter. Indeed, denatonium and strychnine induce transient reduction in cAMP and cGMP in taste tissue, whereas this decrease is inhibited by GNAT3 antibody. Gustducin heterotrimer transduces response to bitter and sweet compounds via regulation of phosphodiesterase for alpha subunit, as well as via activation of phospholipase C for beta and gamma subunits, with ultimate increase inositol trisphosphate and increase of intracellular Calcium. GNAT3 can functionally couple to taste receptors to transmit intracellular signal: receptor heterodimer TAS1R2/TAS1R3 senses sweetness and TAS1R1/TAS1R3 transduces umami taste, whereas the T2R family GPCRs act as bitter sensors. Functions also as lumenal sugar sensors in the gut to control the expression of the Na+-glucose transporter SGLT1 in response to dietaty sugar, as well as the secretion of Glucagon-like peptide-1, GLP-1 and glucose-dependent insulinotropic polypeptide, GIP. Thus, may modulate the gut capacity to absorb sugars, with implications in malabsorption syndromes and diet-related disorders including diabetes and obesity. Ref.5 Ref.6 Ref.17 Ref.18
Subunit structure	G proteins are composed of 3 units; alpha, beta and gamma, respectively GNAT3, GNB1 and GNG13 for Gustducin heterotrimer for bitter taste transduction. The alpha chain contains the guanine nucleotide binding site. Gustducin heterotrimer may also be composed of GNAT3, GNB3 and GNG13. Ref.5
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Expressed in taste buds (sensory organs of clustered epithelial cells) of the circumvallate and fungiform papillae of the tongue as well as in palatal taste buds at protein level. Expressed in enteroendocrine cells of the gut, such as in subsets of enteroendocrine cells in the midjejunum and brush cells. Detected also in spermatozoa. Ref.8 Ref.14 Ref.15 Ref.16 Ref.18
Developmental stage	From week 1 to 7, the number of cells expressing GNAT3 in single taste buds increases within fungiform papilla; by week 7, the number reached the value found in adults. Expressed in cell bodies and axons of facial motor neurons at E10.5. Ref.10 Ref.12
Post-translational modification	Potential N-myristoylation may anchor alpha-subunit to the inner surface of plasma membrane By similarity.
Disruption phenotype	Mice are not affected in their tasting ability for salty (NaCl) and sour (HCl) stimuli, which are known not to be mediated by G proteins; but, they exhibit a significant reduction in the ability to taste the bitter compounds denatonium and quinine as well as the sweet compounds sucrose and SC45647, a guanidine sweetener. The incidence of cells responding to bitter stimulus is also reduced by seventy per cent. The residual behavorial response to bitter and sweet taste in these deficient mice suggests that there is alternative mechanism to compensate. However, transgenic expression of Gnat3 in these deficient mice restores responsiveness to both bitter and sweet compounds, whereas expression of mutated 'Gly-352' transgene do not. Furthermore, in wild-type mice, this mutated transgene acts as dominant-negative by inhibition of endogenous Gnat3 interactions with taste receptors. Mice show less preference for acesulfame-K, dulcin, fructose, D-phenylalanine, L-proline, D-tryptophan, saccharin, sweetener SC45647 and sucrose; Furthermore, in their gut, sugar or sweeteners do not increase SGLT1 expression and glucose-absorptive capacity compared to wild-type mice and the ingestion of glucose reveals deficiencies in secretion of GLP-1 and regulation of plasma insulin and glucose. Mice lacking GNAT3 show less preference for umami compounds such as monosodium glutamate (MSG) and no preference for inosine monophosphate (IMP) whereas wild-type mice strongly prefer IMP. The response to umami signals implicates the anteriorly placed taste buds of the tongue, and not the posterior part. Ref.3 Ref.4 Ref.7 Ref.9 Ref.11 Ref.13 Ref.17 Ref.18
Sequence similarities	Belongs to the G-alpha family. G(i/o/t/z) subfamily.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	GTP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Transducer
PTM	Lipoprotein Myristate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	G-protein signaling, coupled to cAMP nucleotide second messenger Inferred from Biological aspect of Ancestor. Source: RefGenome detection of chemical stimulus involved in sensory perception of bitter taste Inferred from Biological aspect of Ancestor. Source: RefGenome rhodopsin mediated phototransduction Inferred from Biological aspect of Ancestor. Source: RefGenome sensory perception of sweet taste Inferred from mutant phenotype Ref.11. Source: MGI sensory perception of umami taste Inferred from mutant phenotype Ref.11. Source: MGI
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell heterotrimeric G-protein complex Inferred from physical interaction Ref.5. Source: MGI photoreceptor inner segment Inferred from Biological aspect of Ancestor. Source: RefGenome photoreceptor outer segment Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular function	G-protein beta/gamma-subunit complex binding Inferred from Biological aspect of Ancestor. Source: RefGenome G-protein coupled receptor binding Inferred from Biological aspect of Ancestor. Source: RefGenome GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Inferred from direct assay Ref.5. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW signal transducer activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 354	353	Guanine nucleotide-binding protein G(t) subunit alpha-3		PRO_0000342672
Regions
	Nucleotide binding	40 – 47	8	GTP By similarity
	Nucleotide binding	175 – 181	7	GTP By similarity
	Nucleotide binding	200 – 204	5	GTP By similarity
	Nucleotide binding	269 – 272	4	GTP By similarity
Sites
	Metal binding	47	1	Magnesium By similarity
	Metal binding	181	1	Magnesium By similarity
	Binding site	326	1	GTP; via amide nitrogen By similarity
Amino acid modifications
	Lipidation	2	1	N-myristoyl glycine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q3V3I2 [UniParc]. Last modified July 1, 2008. Version 2. Checksum: 05DBC95DAC356CEF	FASTA	354	40,316
	10 20 30 40 50 60 MGSGISSESK ESARRSKELE KKLQEDAERD ARTVKLLLLG AGESGKSTIV KQMKIIHKNG 70 80 90 100 110 120 YSKQECMEFK AVIYSNTLQS ILAIVKAMAT LGIDYVNPRS REDQEQLHSM ANTLEDGDMT 130 140 150 160 170 180 PQLAEIIKRL WGDPGIQACF ERASEYQLND SAAYYLNDLD RLTAPGYVPN EQDVLHSRVK 190 200 210 220 230 240 TTGIIETQFS FKDLNFRMFD VGGQRSERKK WIHCFEGVTC IIFCAALSAY DMVLVEDEEV 250 260 270 280 290 300 NRMHESLHLF NSICNHKYFA TTSIVLFLNK KDLFQEKVAK VHLSICFPEY TGPNTFEDAG 310 320 330 340 350 NYIKNQFLDL NLKKEDKEIY SHMTCATDTQ NVKFVFDAVT DIIIKENLKD CGLF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-310. Strain: C57BL/6J. Tissue: Thymus.
[3]	"Transduction of bitter and sweet taste by gustducin." Wong G.T., Gannon K.S., Margolskee R.F. Nature 381:796-800(1996) [PubMed: 8657284] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[4]	"Directing gene expression to gustducin-positive taste receptor cells." Wong G.T., Ruiz-Avila L., Margolskee R.F. J. Neurosci. 19:5802-5809(1999) [PubMed: 10407021] [Abstract] Cited for: DISRUPTION PHENOTYPE, TRANSGENE.
[5]	"Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium." Huang L., Shanker Y.G., Dubauskaite J., Zheng J.Z., Yan W., Rosenzweig S., Spielman A.I., Max M., Margolskee R.F. Nat. Neurosci. 2:1055-1062(1999) [PubMed: 10570481] [Abstract] Cited for: FUNCTION, SUBUNIT.
[6]	"Bitter taste transduced by PLC-beta(2)-dependent rise in IP(3) and alpha-gustducin-dependent fall in cyclic nucleotides." Yan W., Sunavala G., Rosenzweig S., Dasso M., Brand J.G., Spielman A.I. Am. J. Physiol. 280:C742-C751(2001) [PubMed: 11245589] [Abstract] Cited for: FUNCTION.
[7]	"Dominant loss of responsiveness to sweet and bitter compounds caused by a single mutation in alpha-gustducin." Ruiz-Avila L., Wong G.T., Damak S., Margolskee R.F. Proc. Natl. Acad. Sci. U.S.A. 98:8868-8873(2001) [PubMed: 11447270] [Abstract] Cited for: DISRUPTION PHENOTYPE, TRANSGENE.
[8]	"Regional expression patterns of taste receptors and gustducin in the mouse tongue." Kim M.-R., Kusakabe Y., Miura H., Shindo Y., Ninomiya Y., Hino A. Biochem. Biophys. Res. Commun. 312:500-506(2003) [PubMed: 14637165] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter stimuli." Caicedo A., Pereira E., Margolskee R.F., Roper S.D. J. Neurosci. 23:9947-9952(2003) [PubMed: 14586025] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[10]	"Dynamic expression of RGS4 in the developing nervous system and regulation by the neural type-specific transcription factor Phox2b." Grillet N., Dubreuil V., Dufour H.D., Brunet J.-F. J. Neurosci. 23:10613-10621(2003) [PubMed: 14627646] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[11]	"Umami taste responses are mediated by alpha-transducin and alpha-gustducin." He W., Yasumatsu K., Varadarajan V., Yamada A., Lem J., Ninomiya Y., Margolskee R.F., Damak S. J. Neurosci. 24:7674-7680(2004) [PubMed: 15342734] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[12]	"Developmental change of alpha-gustducin expression in the mouse fungiform papilla." Zhang G.-H., Deng S.-P., Li L.-L., Li H.-T. Anat. Embryol. (Berl.) 211:625-630(2006) [PubMed: 16933139] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[13]	"Taste responses to sweet stimuli in alpha-gustducin knockout and wild-type mice." Danilova V., Damak S., Margolskee R.F., Hellekant G. Chem. Senses 31:573-580(2006) [PubMed: 16740645] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[14]	"Phenotypic characterization of taste cells of the mouse small intestine." Sutherland K., Young R.L., Cooper N.J., Horowitz M., Blackshaw L.A. Am. J. Physiol. 292:G1420-G1428(2007) [PubMed: 17290008] [Abstract] Cited for: TISSUE SPECIFICITY.
[15]	"Expression of T1Rs and gustducin in palatal taste buds of mice." Stone L.M., Barrows J., Finger T.E., Kinnamon S.C. Chem. Senses 32:255-262(2007) [PubMed: 17229761] [Abstract] Cited for: TISSUE SPECIFICITY.
[16]	"Expression of the G-protein alpha-subunit gustducin in mammalian spermatozoa." Fehr J., Meyer D., Widmayer P., Borth H.C., Ackermann F., Wilhelm B., Gudermann T., Boekhoff I. J. Comp. Physiol. A 193:21-34(2007) [PubMed: 17021831] [Abstract] Cited for: TISSUE SPECIFICITY.
[17]	"Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1." Jang H.-J., Kokrashvili Z., Theodorakis M.J., Carlson O.D., Kim B.-J., Zhou J., Kim H.H., Xu X., Chan S.L., Juhaszova M., Bernier M., Mosinger B., Margolskee R.F., Egan J.M. Proc. Natl. Acad. Sci. U.S.A. 104:15069-15074(2007) [PubMed: 17724330] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[18]	"T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1." Margolskee R.F., Dyer J., Kokrashvili Z., Salmon K.S., Ilegems E., Daly K., Maillet E.L., Ninomiya Y., Mosinger B., Shirazi-Beechey S.P. Proc. Natl. Acad. Sci. U.S.A. 104:15075-15080(2007) [PubMed: 17724332] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AC129572 Genomic DNA. No translation available. AK040065 mRNA. Translation: BAE20568.1.
IPI	IPI00347770.
RefSeq	NP_001074612.1. NM_001081143.1.
UniGene	Mm.332230.
3D structure databases
HSSP	HSSP built from PDB template 1AGR based on UniProtKB P10824.
ProteinModelPortal	Q3V3I2.
SMR	Q3V3I2. Positions 12-354.
ModBase	Search...
Protein-protein interaction databases
STRING	Q3V3I2.
PTM databases
PhosphoSite	Q3V3I2.
Proteomic databases
PRIDE	Q3V3I2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000030561; ENSMUSP00000030561; ENSMUSG00000028777.
GeneID	242851.
KEGG	mmu:242851.
Organism-specific databases
CTD	346562.
MGI	MGI:3588268. Gnat3.
Phylogenomic databases
eggNOG	maNOG05766.
GeneTree	ENSGT00560000076725.
HOGENOM	HBG444960.
HOVERGEN	HBG063184.
InParanoid	Q3V3I2.
OMA	IIHKNGY.
OrthoDB	EOG47D9GD.
PhylomeDB	Q3V3I2.
Gene expression databases
Bgee	Q3V3I2.
Genevestigator	Q3V3I2.
Family and domain databases
InterPro	IPR001408. Gprotein_alpha_I. IPR001019. Gprotein_alpha_su. IPR011025. GproteinA_insert. [Graphical view]
Gene3D	G3DSA:1.10.400.10. GproteinA_insert. 1 hit.
KO	K04631.
PANTHER	PTHR10218. Gprotein_alph_bd. 1 hit.
Pfam	PF00503. G-alpha. 1 hit. [Graphical view]
PRINTS	PR00318. GPROTEINA. PR00441. GPROTEINAI.
SMART	SM00275. G_alpha. 1 hit. [Graphical view]
SUPFAM	SSF47895. Transducn_insert. 1 hit.
ProtoNet	Search...
Other
NextBio	385586.
SOURCE	Search...

Entry information

Entry name

GNAT3_MOUSE

Accession

Primary (citable) accession number: Q3V3I2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 2008
Last sequence update:	July 1, 2008
Last modified:	January 25, 2012
This is version 60 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program