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Q3V3I2

- GNAT3_MOUSE

UniProt

Q3V3I2 - GNAT3_MOUSE

Protein

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

Gene

Gnat3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 84 (01 Oct 2014)
      Sequence version 2 (01 Jul 2008)
      Previous versions | rss
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    Functioni

    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.4 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi47 – 471MagnesiumBy similarity
    Metal bindingi181 – 1811MagnesiumBy similarity
    Binding sitei326 – 3261GTP; via amide nitrogenBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi40 – 478GTPBy similarity
    Nucleotide bindingi175 – 1817GTPBy similarity
    Nucleotide bindingi200 – 2045GTPBy similarity
    Nucleotide bindingi269 – 2724GTPBy similarity

    GO - Molecular functioni

    1. G-protein beta/gamma-subunit complex binding Source: RefGenome
    2. G-protein coupled photoreceptor activity Source: RefGenome
    3. G-protein coupled receptor binding Source: RefGenome
    4. GTPase activity Source: MGI
    5. GTP binding Source: UniProtKB-KW
    6. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: RefGenome
    2. detection of chemical stimulus involved in sensory perception of bitter taste Source: RefGenome
    3. detection of visible light Source: GOC
    4. G-protein coupled receptor signaling pathway Source: MGI
    5. response to nicotine Source: Ensembl
    6. sensory perception of bitter taste Source: MGI
    7. sensory perception of sweet taste Source: MGI
    8. sensory perception of taste Source: MGI
    9. sensory perception of umami taste Source: MGI

    Keywords - Molecular functioni

    Transducer

    Keywords - Ligandi

    GTP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_205726. G-protein activation.
    REACT_222824. Adenylate cyclase inhibitory pathway.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Guanine nucleotide-binding protein G(t) subunit alpha-3
    Alternative name(s):
    Gustducin alpha-3 chain
    Gene namesi
    Name:Gnat3
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 5

    Organism-specific databases

    MGIiMGI:3588268. Gnat3.

    Subcellular locationi

    Cytoplasm By similarity

    GO - Cellular componenti

    1. acrosomal vesicle Source: Ensembl
    2. apical plasma membrane Source: Ensembl
    3. axoneme Source: Ensembl
    4. cytoplasm Source: MGI
    5. heterotrimeric G-protein complex Source: MGI
    6. photoreceptor inner segment Source: RefGenome
    7. photoreceptor outer segment Source: RefGenome
    8. protein complex Source: MGI

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Disruption phenotypei

    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.8 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 354353Guanine nucleotide-binding protein G(t) subunit alpha-3PRO_0000342672Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi2 – 21N-myristoyl glycineBy similarity

    Post-translational modificationi

    Potential N-myristoylation may anchor alpha-subunit to the inner surface of plasma membrane.By similarity

    Keywords - PTMi

    Lipoprotein, Myristate

    Proteomic databases

    MaxQBiQ3V3I2.
    PaxDbiQ3V3I2.
    PRIDEiQ3V3I2.

    PTM databases

    PhosphoSiteiQ3V3I2.

    Expressioni

    Tissue specificityi

    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.5 Publications

    Developmental stagei

    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 E10.5.2 Publications

    Gene expression databases

    BgeeiQ3V3I2.
    GenevestigatoriQ3V3I2.

    Interactioni

    Subunit structurei

    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 GNG13.1 Publication

    Structurei

    3D structure databases

    ProteinModelPortaliQ3V3I2.
    SMRiQ3V3I2. Positions 14-354.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the G-alpha family. G(i/o/t/z) subfamily.Curated

    Phylogenomic databases

    eggNOGiNOG322962.
    GeneTreeiENSGT00690000102007.
    HOGENOMiHOG000038730.
    HOVERGENiHBG063184.
    InParanoidiQ3V3I2.
    KOiK04631.
    OMAiKVHLSVC.
    OrthoDBiEOG72C50B.
    PhylomeDBiQ3V3I2.
    TreeFamiTF300673.

    Family and domain databases

    Gene3Di1.10.400.10. 1 hit.
    3.40.50.300. 2 hits.
    InterProiIPR001408. Gprotein_alpha_I.
    IPR001019. Gprotein_alpha_su.
    IPR011025. GproteinA_insert.
    IPR027417. P-loop_NTPase.
    [Graphical view]
    PANTHERiPTHR10218. PTHR10218. 1 hit.
    PfamiPF00503. G-alpha. 1 hit.
    [Graphical view]
    PRINTSiPR00318. GPROTEINA.
    PR00441. GPROTEINAI.
    SMARTiSM00275. G_alpha. 1 hit.
    [Graphical view]
    SUPFAMiSSF47895. SSF47895. 1 hit.
    SSF52540. SSF52540. 2 hits.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q3V3I2-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGSGISSESK ESARRSKELE KKLQEDAERD ARTVKLLLLG AGESGKSTIV    50
    KQMKIIHKNG YSKQECMEFK AVIYSNTLQS ILAIVKAMAT LGIDYVNPRS 100
    REDQEQLHSM ANTLEDGDMT PQLAEIIKRL WGDPGIQACF ERASEYQLND 150
    SAAYYLNDLD RLTAPGYVPN EQDVLHSRVK TTGIIETQFS FKDLNFRMFD 200
    VGGQRSERKK WIHCFEGVTC IIFCAALSAY DMVLVEDEEV NRMHESLHLF 250
    NSICNHKYFA TTSIVLFLNK KDLFQEKVAK VHLSICFPEY TGPNTFEDAG 300
    NYIKNQFLDL NLKKEDKEIY SHMTCATDTQ NVKFVFDAVT DIIIKENLKD 350
    CGLF 354
    Length:354
    Mass (Da):40,316
    Last modified:July 1, 2008 - v2
    Checksum:i05DBC95DAC356CEF
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AC129572 Genomic DNA. No translation available.
    AK040065 mRNA. Translation: BAE20568.1.
    CCDSiCCDS39017.1.
    RefSeqiNP_001074612.1. NM_001081143.1.
    UniGeneiMm.332230.

    Genome annotation databases

    EnsembliENSMUST00000030561; ENSMUSP00000030561; ENSMUSG00000028777.
    GeneIDi242851.
    KEGGimmu:242851.
    UCSCiuc008wnr.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AC129572 Genomic DNA. No translation available.
    AK040065 mRNA. Translation: BAE20568.1 .
    CCDSi CCDS39017.1.
    RefSeqi NP_001074612.1. NM_001081143.1.
    UniGenei Mm.332230.

    3D structure databases

    ProteinModelPortali Q3V3I2.
    SMRi Q3V3I2. Positions 14-354.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei Q3V3I2.

    Proteomic databases

    MaxQBi Q3V3I2.
    PaxDbi Q3V3I2.
    PRIDEi Q3V3I2.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000030561 ; ENSMUSP00000030561 ; ENSMUSG00000028777 .
    GeneIDi 242851.
    KEGGi mmu:242851.
    UCSCi uc008wnr.1. mouse.

    Organism-specific databases

    CTDi 346562.
    MGIi MGI:3588268. Gnat3.

    Phylogenomic databases

    eggNOGi NOG322962.
    GeneTreei ENSGT00690000102007.
    HOGENOMi HOG000038730.
    HOVERGENi HBG063184.
    InParanoidi Q3V3I2.
    KOi K04631.
    OMAi KVHLSVC.
    OrthoDBi EOG72C50B.
    PhylomeDBi Q3V3I2.
    TreeFami TF300673.

    Enzyme and pathway databases

    Reactomei REACT_205726. G-protein activation.
    REACT_222824. Adenylate cyclase inhibitory pathway.

    Miscellaneous databases

    NextBioi 385586.
    PROi Q3V3I2.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q3V3I2.
    Genevestigatori Q3V3I2.

    Family and domain databases

    Gene3Di 1.10.400.10. 1 hit.
    3.40.50.300. 2 hits.
    InterProi IPR001408. Gprotein_alpha_I.
    IPR001019. Gprotein_alpha_su.
    IPR011025. GproteinA_insert.
    IPR027417. P-loop_NTPase.
    [Graphical view ]
    PANTHERi PTHR10218. PTHR10218. 1 hit.
    Pfami PF00503. G-alpha. 1 hit.
    [Graphical view ]
    PRINTSi PR00318. GPROTEINA.
    PR00441. GPROTEINAI.
    SMARTi SM00275. G_alpha. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47895. SSF47895. 1 hit.
    SSF52540. SSF52540. 2 hits.
    ProtoNeti Search...

    Publicationsi

    1. 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] [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. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    18. Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiGNAT3_MOUSE
    AccessioniPrimary (citable) accession number: Q3V3I2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 2008
    Last sequence update: July 1, 2008
    Last modified: October 1, 2014
    This is version 84 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3