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Q3V3I2 (GNAT3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 80. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Guanine nucleotide-binding protein G(t) subunit alpha-3
Alternative name(s):
Gustducin alpha-3 chain
Gene names
Name:Gnat3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length354 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 behavioral 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 componentCytoplasm
   LigandGTP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionTransducer
   PTMLipoprotein
Myristate
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from direct assay Ref.5. Source: MGI

adenylate cyclase-modulating G-protein coupled receptor signaling pathway

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

response to nicotine

Inferred from electronic annotation. Source: Ensembl

rhodopsin mediated signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

sensory perception of bitter taste

Inferred from mutant phenotype PubMed 12379596Ref.11. Source: MGI

sensory perception of sweet taste

Inferred from mutant phenotype Ref.11. Source: MGI

sensory perception of taste

Inferred from direct assay Ref.5. Source: MGI

sensory perception of umami taste

Inferred from mutant phenotype PubMed 12379596Ref.11. Source: MGI

   Cellular_componentacrosomal vesicle

Inferred from electronic annotation. Source: Ensembl

apical plasma membrane

Inferred from electronic annotation. Source: Ensembl

axoneme

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 21606356. Source: MGI

extrinsic component of cytoplasmic side of plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

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

protein complex

Inferred from sequence orthology PubMed 18468998. Source: MGI

   Molecular_functionG-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 354353Guanine nucleotide-binding protein G(t) subunit alpha-3
PRO_0000342672

Regions

Nucleotide binding40 – 478GTP By similarity
Nucleotide binding175 – 1817GTP By similarity
Nucleotide binding200 – 2045GTP By similarity
Nucleotide binding269 – 2724GTP By similarity

Sites

Metal binding471Magnesium By similarity
Metal binding1811Magnesium By similarity
Binding site3261GTP; via amide nitrogen By similarity

Amino acid modifications

Lipidation21N-myristoyl glycine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q3V3I2 [UniParc].

Last modified July 1, 2008. Version 2.
Checksum: 05DBC95DAC356CEF

FASTA35440,316
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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.
RefSeqNP_001074612.1. NM_001081143.1.
UniGeneMm.332230.

3D structure databases

ProteinModelPortalQ3V3I2.
SMRQ3V3I2. Positions 14-354.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ3V3I2.

Proteomic databases

PaxDbQ3V3I2.
PRIDEQ3V3I2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000030561; ENSMUSP00000030561; ENSMUSG00000028777.
GeneID242851.
KEGGmmu:242851.
UCSCuc008wnr.1. mouse.

Organism-specific databases

CTD346562.
MGIMGI:3588268. Gnat3.

Phylogenomic databases

eggNOGNOG322962.
GeneTreeENSGT00690000102007.
HOGENOMHOG000038730.
HOVERGENHBG063184.
InParanoidQ3V3I2.
KOK04631.
OMAKVHLSVC.
OrthoDBEOG72C50B.
PhylomeDBQ3V3I2.
TreeFamTF300673.

Gene expression databases

BgeeQ3V3I2.
GenevestigatorQ3V3I2.

Family and domain databases

Gene3D1.10.400.10. 1 hit.
3.40.50.300. 2 hits.
InterProIPR001408. Gprotein_alpha_I.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERPTHR10218. PTHR10218. 1 hit.
PfamPF00503. G-alpha. 1 hit.
[Graphical view]
PRINTSPR00318. GPROTEINA.
PR00441. GPROTEINAI.
SMARTSM00275. G_alpha. 1 hit.
[Graphical view]
SUPFAMSSF47895. SSF47895. 1 hit.
SSF52540. SSF52540. 2 hits.
ProtoNetSearch...

Other

NextBio385586.
PROQ3V3I2.
SOURCESearch...

Entry information

Entry nameGNAT3_MOUSE
AccessionPrimary (citable) accession number: Q3V3I2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 2008
Last sequence update: July 1, 2008
Last modified: April 16, 2014
This is version 80 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot