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Protein

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

Gene

GNAT3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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.2 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

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-112043 PLC beta mediated events
R-HSA-170670 Adenylate cyclase inhibitory pathway
R-HSA-202040 G-protein activation
R-HSA-381771 Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
R-HSA-392170 ADP signalling through P2Y purinoceptor 12
R-HSA-418555 G alpha (s) signalling events
R-HSA-418594 G alpha (i) signalling events
R-HSA-418597 G alpha (z) signalling events
R-HSA-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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000214415.3
HGNCiHGNC:22800 GNAT3
MIMi139395 gene
neXtProtiNX_A8MTJ3

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

Organism-specific databases

DisGeNETi346562
OpenTargetsiENSG00000214415
PharmGKBiPA134931156

Polymorphism and mutation databases

BioMutaiGNAT3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00003426712 – 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

EPDiA8MTJ3
MaxQBiA8MTJ3
PaxDbiA8MTJ3
PRIDEiA8MTJ3
ProteomicsDBi2028
TopDownProteomicsiA8MTJ3

PTM databases

iPTMnetiA8MTJ3
PhosphoSitePlusiA8MTJ3
SwissPalmiA8MTJ3

Expressioni

Tissue specificityi

Expressed in taste buds (sensory organs of clustered epithelial cells) of the circumvallate and foliate papillae of the tongue at protein level. Expressed in enteroendocrine L cells of the gut. Detected also in spermatozoa.4 Publications

Gene expression databases

BgeeiENSG00000214415 Expressed in 12 organ(s), highest expression level in intestine
CleanExiHS_GNAT3
GenevisibleiA8MTJ3 HS

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.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi131390, 5 interactors
IntActiA8MTJ3, 1 interactor
STRINGi9606.ENSP00000381339

Structurei

3D structure databases

ProteinModelPortaliA8MTJ3
SMRiA8MTJ3
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
InParanoidiA8MTJ3
KOiK19729
OMAiHKYFATT
OrthoDBiEOG091G0VUT
PhylomeDBiA8MTJ3
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.

A8MTJ3-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGSGISSESK ESAKRSKELE KKLQEDAERD ARTVKLLLLG AGESGKSTIV
60 70 80 90 100
KQMKIIHKNG YSEQECMEFK AVIYSNTLQS ILAIVKAMTT LGIDYVNPRS
110 120 130 140 150
AEDQRQLYAM ANTLEDGGMT PQLAEVIKRL WRDPGIQACF ERASEYQLND
160 170 180 190 200
SAAYYLNDLD RITASGYVPN EQDVLHSRVK TTGIIETQFS FKDLHFRMFD
210 220 230 240 250
VGGQRSERKK WIHCFEGVTC IIFCAALSAY DMVLVEDEEV NRMHESLHLF
260 270 280 290 300
NSICNHKYFS TTSIVLFLNK KDIFQEKVTK VHLSICFPEY TGPNTFEDAG
310 320 330 340 350
NYIKNQFLDL NLKKEDKEIY SHMTCATDTQ NVKFVFDAVT DIIIKENLKD

CGLF
Length:354
Mass (Da):40,357
Last modified:July 1, 2008 - v2
Checksum:i47366FB99E9322AD
GO

Sequence cautioni

The sequence EAL24192 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAL24193 differs from that shown. Reason: Erroneous gene model prediction.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC004862 Genomic DNA No translation available.
CH236949 Genomic DNA Translation: EAL24192.1 Sequence problems.
CH236949 Genomic DNA Translation: EAL24193.1 Sequence problems.
CH471091 Genomic DNA Translation: EAW77007.1
BC147016 mRNA Translation: AAI47017.1
BC147017 mRNA Translation: AAI47018.1
CCDSiCCDS47625.1
RefSeqiNP_001095856.1, NM_001102386.2
UniGeneiHs.335049

Genome annotation databases

EnsembliENST00000398291; ENSP00000381339; ENSG00000214415
GeneIDi346562
KEGGihsa:346562
UCSCiuc011kgu.3 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC004862 Genomic DNA No translation available.
CH236949 Genomic DNA Translation: EAL24192.1 Sequence problems.
CH236949 Genomic DNA Translation: EAL24193.1 Sequence problems.
CH471091 Genomic DNA Translation: EAW77007.1
BC147016 mRNA Translation: AAI47017.1
BC147017 mRNA Translation: AAI47018.1
CCDSiCCDS47625.1
RefSeqiNP_001095856.1, NM_001102386.2
UniGeneiHs.335049

3D structure databases

ProteinModelPortaliA8MTJ3
SMRiA8MTJ3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi131390, 5 interactors
IntActiA8MTJ3, 1 interactor
STRINGi9606.ENSP00000381339

PTM databases

iPTMnetiA8MTJ3
PhosphoSitePlusiA8MTJ3
SwissPalmiA8MTJ3

Polymorphism and mutation databases

BioMutaiGNAT3

Proteomic databases

EPDiA8MTJ3
MaxQBiA8MTJ3
PaxDbiA8MTJ3
PRIDEiA8MTJ3
ProteomicsDBi2028
TopDownProteomicsiA8MTJ3

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000398291; ENSP00000381339; ENSG00000214415
GeneIDi346562
KEGGihsa:346562
UCSCiuc011kgu.3 human

Organism-specific databases

CTDi346562
DisGeNETi346562
EuPathDBiHostDB:ENSG00000214415.3
GeneCardsiGNAT3
HGNCiHGNC:22800 GNAT3
MIMi139395 gene
neXtProtiNX_A8MTJ3
OpenTargetsiENSG00000214415
PharmGKBiPA134931156
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0082 Eukaryota
ENOG410XNVQ LUCA
GeneTreeiENSGT00760000118851
HOGENOMiHOG000038730
HOVERGENiHBG063184
InParanoidiA8MTJ3
KOiK19729
OMAiHKYFATT
OrthoDBiEOG091G0VUT
PhylomeDBiA8MTJ3
TreeFamiTF300673

Enzyme and pathway databases

ReactomeiR-HSA-112043 PLC beta mediated events
R-HSA-170670 Adenylate cyclase inhibitory pathway
R-HSA-202040 G-protein activation
R-HSA-381771 Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
R-HSA-392170 ADP signalling through P2Y purinoceptor 12
R-HSA-418555 G alpha (s) signalling events
R-HSA-418594 G alpha (i) signalling events
R-HSA-418597 G alpha (z) signalling events
R-HSA-6814122 Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding

Miscellaneous databases

ChiTaRSiGNAT3 human
GeneWikiiGNAT3
GenomeRNAii346562
PROiPR:A8MTJ3
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000214415 Expressed in 12 organ(s), highest expression level in intestine
CleanExiHS_GNAT3
GenevisibleiA8MTJ3 HS

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_HUMAN
AccessioniPrimary (citable) accession number: A8MTJ3
Secondary accession number(s): A4D1B2, A4D1B3, B9EJG5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 2008
Last sequence update: July 1, 2008
Last modified: November 7, 2018
This is version 99 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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