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Protein

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

Gene

Gnat3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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)DescriptionActionsGraphical viewLength
Metal bindingi47MagnesiumBy similarity1
Metal bindingi181MagnesiumBy similarity1
Binding sitei326GTP; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi40 – 47GTPBy similarity8
Nucleotide bindingi175 – 181GTPBy similarity7
Nucleotide bindingi200 – 204GTPBy similarity5
Nucleotide bindingi269 – 272GTPBy similarity4

GO - Molecular functioni

  • G-protein beta/gamma-subunit complex binding Source: GO_Central
  • G protein-coupled receptor binding Source: GO_Central
  • GTPase activity Source: MGI
  • GTP binding Source: MGI
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionTransducer
LigandGTP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-112043 PLC beta mediated events
R-MMU-170670 Adenylate cyclase inhibitory pathway
R-MMU-202040 G-protein activation
R-MMU-381771 Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
R-MMU-392170 ADP signalling through P2Y purinoceptor 12
R-MMU-418594 G alpha (i) signalling events
R-MMU-6814122 Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:3588268 Gnat3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00003426722 – 354Guanine nucleotide-binding protein G(t) subunit alpha-3Add BLAST353

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1

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

iPTMnetiQ3V3I2
PhosphoSitePlusiQ3V3I2

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

BgeeiENSMUSG00000028777 Expressed in 15 organ(s), highest expression level in vallate papilla
ExpressionAtlasiQ3V3I2 baseline and differential

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000030561

Structurei

3D structure databases

ProteinModelPortaliQ3V3I2
SMRiQ3V3I2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0082 Eukaryota
ENOG410XNVQ LUCA
GeneTreeiENSGT00760000118851
HOGENOMiHOG000038730
HOVERGENiHBG063184
InParanoidiQ3V3I2
KOiK19729
OMAiHKYFATT
OrthoDBiEOG091G0VUT
PhylomeDBiQ3V3I2
TreeFamiTF300673

Family and domain databases

CDDicd00066 G-alpha, 1 hit
Gene3Di1.10.400.10, 1 hit
InterProiView protein in InterPro
IPR001408 Gprotein_alpha_I
IPR001019 Gprotein_alpha_su
IPR011025 GproteinA_insert
IPR027417 P-loop_NTPase
PANTHERiPTHR10218 PTHR10218, 1 hit
PfamiView protein in Pfam
PF00503 G-alpha, 1 hit
PRINTSiPR00318 GPROTEINA
PR00441 GPROTEINAI
SMARTiView protein in SMART
SM00275 G_alpha, 1 hit
SUPFAMiSSF47895 SSF47895, 1 hit
SSF52540 SSF52540, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q3V3I2-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGSGISSESK ESARRSKELE KKLQEDAERD ARTVKLLLLG AGESGKSTIV
60 70 80 90 100
KQMKIIHKNG YSKQECMEFK AVIYSNTLQS ILAIVKAMAT LGIDYVNPRS
110 120 130 140 150
REDQEQLHSM ANTLEDGDMT PQLAEIIKRL WGDPGIQACF ERASEYQLND
160 170 180 190 200
SAAYYLNDLD RLTAPGYVPN EQDVLHSRVK TTGIIETQFS FKDLNFRMFD
210 220 230 240 250
VGGQRSERKK WIHCFEGVTC IIFCAALSAY DMVLVEDEEV NRMHESLHLF
260 270 280 290 300
NSICNHKYFA TTSIVLFLNK KDLFQEKVAK VHLSICFPEY TGPNTFEDAG
310 320 330 340 350
NYIKNQFLDL NLKKEDKEIY SHMTCATDTQ NVKFVFDAVT DIIIKENLKD

CGLF
Length:354
Mass (Da):40,316
Last modified:July 1, 2008 - v2
Checksum:i05DBC95DAC356CEF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC129572 Genomic DNA No translation available.
AK040065 mRNA Translation: BAE20568.1
CCDSiCCDS39017.1
RefSeqiNP_001074612.1, NM_001081143.1
UniGeneiMm.332230

3D structure databases

ProteinModelPortaliQ3V3I2
SMRiQ3V3I2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000030561

PTM databases

iPTMnetiQ3V3I2
PhosphoSitePlusiQ3V3I2

Proteomic databases

MaxQBiQ3V3I2
PaxDbiQ3V3I2
PRIDEiQ3V3I2

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi346562
MGIiMGI:3588268 Gnat3

Phylogenomic databases

eggNOGiKOG0082 Eukaryota
ENOG410XNVQ LUCA
GeneTreeiENSGT00760000118851
HOGENOMiHOG000038730
HOVERGENiHBG063184
InParanoidiQ3V3I2
KOiK19729
OMAiHKYFATT
OrthoDBiEOG091G0VUT
PhylomeDBiQ3V3I2
TreeFamiTF300673

Enzyme and pathway databases

ReactomeiR-MMU-112043 PLC beta mediated events
R-MMU-170670 Adenylate cyclase inhibitory pathway
R-MMU-202040 G-protein activation
R-MMU-381771 Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
R-MMU-392170 ADP signalling through P2Y purinoceptor 12
R-MMU-418594 G alpha (i) signalling events
R-MMU-6814122 Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding

Miscellaneous databases

PROiPR:Q3V3I2
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028777 Expressed in 15 organ(s), highest expression level in vallate papilla
ExpressionAtlasiQ3V3I2 baseline and differential

Family and domain databases

CDDicd00066 G-alpha, 1 hit
Gene3Di1.10.400.10, 1 hit
InterProiView protein in InterPro
IPR001408 Gprotein_alpha_I
IPR001019 Gprotein_alpha_su
IPR011025 GproteinA_insert
IPR027417 P-loop_NTPase
PANTHERiPTHR10218 PTHR10218, 1 hit
PfamiView protein in Pfam
PF00503 G-alpha, 1 hit
PRINTSiPR00318 GPROTEINA
PR00441 GPROTEINAI
SMARTiView protein in SMART
SM00275 G_alpha, 1 hit
SUPFAMiSSF47895 SSF47895, 1 hit
SSF52540 SSF52540, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGNAT3_MOUSE
AccessioniPrimary (citable) accession number: Q3V3I2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 2008
Last sequence update: July 1, 2008
Last modified: November 7, 2018
This is version 116 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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