A8MTJ3 (GNAT3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Gustducin alpha-3 chain

Gene names

Name:

GNAT3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	354 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Cytoplasm
Ligand	GTP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Transducer
PTM	Lipoprotein Myristate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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: Compara 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
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Compara cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell 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
Molecular_function	G-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 354	354	Guanine nucleotide-binding protein G(t) subunit alpha-3		PRO_0000342671
Regions
	Nucleotide binding	40 – 47	8	GTP By similarity
	Nucleotide binding	175 – 181	7	GTP By similarity
	Nucleotide binding	200 – 204	5	GTP By similarity
	Nucleotide binding	269 – 272	4	GTP By similarity
Sites
	Metal binding	47	1	Magnesium By similarity
	Metal binding	181	1	Magnesium By similarity
	Binding site	326	1	GTP; via amide nitrogen By similarity
Amino acid modifications
	Lipidation	2	1	N-myristoyl glycine By similarity

Sequences

	Sequence		Length	Mass (Da)
	A8MTJ3 [UniParc]. Last modified July 1, 2008. Version 2. Checksum: 47366FB99E9322AD	FASTA	354	40,357
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
IPI	IPI00248911.
RefSeq	NP_001095856.1. NM_001102386.1.
UniGene	Hs.335049.
3D structure databases
ProteinModelPortal	A8MTJ3.
ModBase	Search...
Protein-protein interaction databases
IntAct	A8MTJ3. 1 interaction.
STRING	9606.ENSP00000381339.
PTM databases
PhosphoSite	A8MTJ3.
Proteomic databases
PaxDb	A8MTJ3.
PRIDE	A8MTJ3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000398291; ENSP00000381339; ENSG00000214415.
GeneID	346562.
KEGG	hsa:346562.
UCSC	uc011kgu.2. human.
Organism-specific databases
CTD	346562.
GeneCards	GC07M080087.
HGNC	HGNC:22800. GNAT3.
MIM	139395. gene.
neXtProt	NX_A8MTJ3.
PharmGKB	PA134931156.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG322962.
HOGENOM	HOG000038730.
HOVERGEN	HBG063184.
InParanoid	A8MTJ3.
KO	K04631.
OMA	RKEDKEI.
OrthoDB	EOG47D9GD.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	A8MTJ3.
CleanEx	HS_GNAT3.
Genevestigator	A8MTJ3.
Family and domain databases
Gene3D	1.10.400.10. 1 hit.
InterPro	IPR001408. Gprotein_alpha_I. IPR001019. Gprotein_alpha_su. IPR011025. GproteinA_insert. [Graphical view]
PANTHER	PTHR10218. PTHR10218. 1 hit.
Pfam	PF00503. G-alpha. 1 hit. [Graphical view]
PRINTS	PR00318. GPROTEINA. PR00441. GPROTEINAI.
SMART	SM00275. G_alpha. 1 hit. [Graphical view]
SUPFAM	SSF47895. Transducn_insert. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	346562.
NextBio	98979.
SOURCE	Search...

Entry information

Entry name

GNAT3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 54 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.