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A8MTJ3 (GNAT3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 65. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length354 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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.6 Ref.9

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.

Subcellular location

Cytoplasm. Note: Dual ditribution pattern; plasmalemmal pattern with apical region localization and cytosolic pattern with localization throughout the cytoplasm. Ref.5

Tissue specificity

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. Ref.5 Ref.7 Ref.8 Ref.10

Post-translational modification

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

Sequence similarities

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

Sequence caution

The sequence EAL24192.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence EAL24193.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Cellular componentCytoplasm
   LigandGTP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionTransducer
   PTMLipoprotein
Myristate
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

Traceable author statement. Source: Reactome

adenylate cyclase-modulating G-protein coupled receptor signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

blood coagulation

Traceable author statement. Source: Reactome

detection of chemical stimulus involved in sensory perception of bitter taste

Inferred from Biological aspect of Ancestor. Source: RefGenome

platelet activation

Traceable author statement. Source: Reactome

response to nicotine

Inferred from electronic annotation. Source: Ensembl

sensory perception of sweet taste

Inferred from Biological aspect of Ancestor. Source: RefGenome

sensory perception of umami taste

Inferred from Biological aspect of Ancestor. Source: RefGenome

synaptic transmission

Traceable author statement. Source: Reactome

   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

extrinsic component of cytoplasmic side of plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

heterotrimeric G-protein complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

photoreceptor inner segment

Inferred from Biological aspect of Ancestor. Source: RefGenome

photoreceptor outer segment

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Traceable author statement. Source: Reactome

protein complex

Inferred from direct assay 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 Biological aspect of Ancestor. Source: RefGenome

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_0000342671

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
A8MTJ3 [UniParc].

Last modified July 1, 2008. Version 2.
Checksum: 47366FB99E9322AD

FASTA35440,357
        10         20         30         40         50         60 
MGSGISSESK ESAKRSKELE KKLQEDAERD ARTVKLLLLG AGESGKSTIV KQMKIIHKNG 

        70         80         90        100        110        120 
YSEQECMEFK AVIYSNTLQS ILAIVKAMTT LGIDYVNPRS AEDQRQLYAM ANTLEDGGMT 

       130        140        150        160        170        180 
PQLAEVIKRL WRDPGIQACF ERASEYQLND SAAYYLNDLD RITASGYVPN EQDVLHSRVK 

       190        200        210        220        230        240 
TTGIIETQFS FKDLHFRMFD VGGQRSERKK WIHCFEGVTC IIFCAALSAY DMVLVEDEEV 

       250        260        270        280        290        300 
NRMHESLHLF NSICNHKYFS TTSIVLFLNK KDIFQEKVTK VHLSICFPEY TGPNTFEDAG 

       310        320        330        340        350 
NYIKNQFLDL NLKKEDKEIY SHMTCATDTQ NVKFVFDAVT DIIIKENLKD CGLF 

« Hide

References

« Hide 'large scale' references
[1]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Human taste cells express the G protein alpha-gustducin and neuron-specific enolase."
Takami S., Getchell T.V., McLaughlin S.K., Margolskee R.F., Getchell M.L.
Brain Res. Mol. Brain Res. 22:193-203(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[6]"Human receptors for sweet and umami taste."
Li X., Staszewski L., Xu H., Durick K., Zoller M., Adler E.
Proc. Natl. Acad. Sci. U.S.A. 99:4692-4696(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon."
Rozengurt N., Wu S.V., Chen M.C., Huang C., Sternini C., Rozengurt E.
Am. J. Physiol. 291:G792-G802(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"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.
[9]"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.
[10]"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: TISSUE SPECIFICITY.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS47625.1.
RefSeqNP_001095856.1. NM_001102386.1.
UniGeneHs.335049.

3D structure databases

ProteinModelPortalA8MTJ3.
SMRA8MTJ3. Positions 14-354.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid131390. 4 interactions.
IntActA8MTJ3. 1 interaction.
STRING9606.ENSP00000381339.

PTM databases

PhosphoSiteA8MTJ3.

Proteomic databases

MaxQBA8MTJ3.
PaxDbA8MTJ3.
PRIDEA8MTJ3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000398291; ENSP00000381339; ENSG00000214415.
GeneID346562.
KEGGhsa:346562.
UCSCuc011kgu.2. human.

Organism-specific databases

CTD346562.
GeneCardsGC07M080087.
HGNCHGNC:22800. GNAT3.
MIM139395. gene.
neXtProtNX_A8MTJ3.
PharmGKBPA134931156.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG322962.
HOGENOMHOG000038730.
HOVERGENHBG063184.
InParanoidA8MTJ3.
KOK04631.
OMAKVHLSVC.
OrthoDBEOG72C50B.
PhylomeDBA8MTJ3.
TreeFamTF300673.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_13685. Neuronal System.
REACT_604. Hemostasis.

Gene expression databases

BgeeA8MTJ3.
CleanExHS_GNAT3.
GenevestigatorA8MTJ3.

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

GeneWikiGNAT3.
GenomeRNAi346562.
NextBio98979.
PROA8MTJ3.
SOURCESearch...

Entry information

Entry nameGNAT3_HUMAN
AccessionPrimary (citable) accession number: A8MTJ3
Secondary accession number(s): A4D1B2, A4D1B3, B9EJG5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 2008
Last sequence update: July 1, 2008
Last modified: July 9, 2014
This is version 65 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM