P29348 (GNAT3_RAT) 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
Synonyms:	Gnat-3

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	354 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein 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 for the prevention and treatment of malabsorption syndromes and diet-related disorders including diabetes and obesity. Ref.1 Ref.2 Ref.3 Ref.6 Ref.10
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: Associated with microvilli, the presumed sites of sensory transduction in taste cells. Ref.9
Tissue specificity	Expressed in taste buds (sensory organs of clustered epithelial cells) of the circumvallate, foliate and fungiform papillae of the tongue, as well as in nasoincisor, palatal and epiglottal taste buds at protein level. Expressed in enteroendocrine of the gut, in the lumenal pole of a subset of brush cells lining the stomach and the intestine at protein level. Detected in solitary cells troughout the respiratory track. Expressed also in spermatozoa. Ref.1 Ref.4 Ref.5 Ref.11 Ref.12 Ref.13
Developmental stage	Expressed in scattered solitary ovoid or bipolar cells among the oral epithelium from day 1-7, but with higher frequency in the soft palate as compared with the nasoincisor, circumvallate, and foliate papillae at day 1. During the second week, the solitary cells could no longer be recognized while cells expressing GNAT3 within the taste buds gradually increased. The onset of taste transduction accomplished by the palatal taste buds developed earlier than that achieved by taste buds in the circumvallate and foliate papillae. Ref.7
Induction	By bitter compounds denatonium and quinine. Ref.3
Post-translational modification	Potential N-myristoylation may anchor alpha-subunit to the inner surface of plasma membrane.
Miscellaneous	Transgenic expression of GNAT3 restores responsiveness of GNAT3 deficient mice 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.
Sequence similarities	Belongs to the G-alpha family. G(i/o/t/z) subfamily.

Ontologies

Keywords
Biological process	Sensory transduction Taste Vision
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	G-protein signaling, coupled to cAMP nucleotide second messenger 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 expression pattern. Source: RGD rhodopsin mediated phototransduction Inferred from Biological aspect of Ancestor. Source: RefGenome 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 direct assay. Source: RGD cytoplasm Inferred from direct assay. Source: RGD 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 direct assay Ref.2. Source: RGD GTPase activity Inferred from direct assay Ref.2. Source: RGD 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
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 354	353	Guanine nucleotide-binding protein G(t) subunit alpha-3		PRO_0000203743
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
Experimental info
	Mutagenesis	352	1	G → P: Loss of activation by both bitter and sweet compounds due to disruption of interaction with taste receptors. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	P29348 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 3B7260BBCB0448D6	FASTA	354	40,294
	10 20 30 40 50 60 MGSGISSESK ESAKRSKELE KKLQEDAERD ARTVKLLLLG AGESGKSTIV KQMKIIHKNG 70 80 90 100 110 120 YSKQECMEFK AVVYSNTLQS ILAIVKAMTT LGIDYVNPRS REDQQLLLSM ANTLEDGDMT 130 140 150 160 170 180 PQLAEIIKRL WGDPGIQACF ERASEYQLND SAAYYLNDLD RLTAPGYVPN EQDVLHSRVK 190 200 210 220 230 240 TTGIIETQFS FKDLNFRMFD VGGQRSERKK WIHCFEGVTC IIFCAALSAY DMVLVEDEEV 250 260 270 280 290 300 NRMHESLHLF NSICNHKYFA TTSIVLFLNK KDLFQEKVTK VHLSICFPEY TGPNTFEDAG 310 320 330 340 350 NYIKNQFLDL NLKKEDKEIY SHMTCATDTQ NVKFVFDAVT DIIIKENLKD CGLF

References

[1]	"Gustducin is a taste-cell-specific G protein closely related to the transducins." McLaughlin S.K., McKinnon P.J., Margolskee R.F. Nature 357:563-569(1992) [PubMed: 1608467] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY. Strain: Sprague-Dawley. Tissue: Tongue.
[2]	"Functional expression of the taste specific G-protein, alpha-gustducin." Hoon M.A., Northup J.K., Margolskee R.F., Ryba N.J.P. Biochem. J. 309:629-636(1995) [PubMed: 7626029] [Abstract] Cited for: FUNCTION.
[3]	"Coupling of bitter receptor to phosphodiesterase through transducin in taste receptor cells." Ruiz-Avila L., McLaughlin S.K., Wildman D., McKinnon P.J., Robichon A., Spickofsky N., Margolskee R.F. Nature 376:80-85(1995) [PubMed: 7596440] [Abstract] Cited for: FUNCTION, INDUCTION.
[4]	"Taste receptor-like cells in the rat gut identified by expression of alpha-gustducin." Hoefer D., Pueschel B., Drenckhahn D. Proc. Natl. Acad. Sci. U.S.A. 93:6631-6634(1996) [PubMed: 8692869] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"Differential expression of alpha-gustducin in taste bud populations of the rat and hamster." Boughter J.D. Jr., Pumplin D.W., Yu C., Christy R.C., Smith D.V. J. Neurosci. 17:2852-2858(1997) [PubMed: 9092606] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity." Hoon M.A., Adler E., Lindemeier J., Battey J.F., Ryba N.J.P., Zuker C.S. Cell 96:541-551(1999) [PubMed: 10052456] [Abstract] Cited for: FUNCTION.
[7]	"Alpha-gustducin-immunoreactive solitary chemosensory cells in the developing chemoreceptorial epithelium of the rat vallate papilla." Sbarbati A., Crescimanno C., Bernardi P., Osculati F. Chem. Senses 24:469-472(1999) [PubMed: 10576254] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[8]	"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: 10407021] [Abstract] Cited for: TRANSGENE.
[9]	"Ultrastructural localization of gustducin immunoreactivity in microvilli of type II taste cells in the rat." Yang R., Tabata S., Crowley H.H., Margolskee R.F., Kinnamon J.C. J. Comp. Neurol. 425:139-151(2000) [PubMed: 10940948] [Abstract] Cited for: SUBCELLULAR LOCATION.
[10]	"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: 11447270] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLY-352.
[11]	"Alpha-gustducin immunoreactivity in the airways." Merigo F., Benati D., Tizzano M., Osculati F., Sbarbati A. Cell Tissue Res. 319:211-219(2005) [PubMed: 15654652] [Abstract] Cited for: TISSUE SPECIFICITY.
[12]	"Co-expression patterns of the neuropeptides vasoactive intestinal peptide and cholecystokinin with the transduction molecules alpha-gustducin and T1R2 in rat taste receptor cells." Shen T., Kaya N., Zhao F.-L., Lu S.-G., Cao Y., Herness S. Neuroscience 130:229-238(2005) [PubMed: 15561439] [Abstract] Cited for: TISSUE SPECIFICITY.
[13]	"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: 17021831] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X65747 mRNA. Translation: CAA46650.1.
IPI	IPI00231001.
PIR	S24352.
RefSeq	NP_775162.1. NM_173139.1.
UniGene	Rn.10456.
3D structure databases
ProteinModelPortal	P29348.
SMR	P29348. Positions 5-353.
ModBase	Search...
Protein-protein interaction databases
STRING	P29348.
Proteomic databases
PRIDE	P29348.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	286924.
KEGG	rno:286924.
Organism-specific databases
CTD	346562.
RGD	727817. Gnat3.
Phylogenomic databases
eggNOG	maNOG05766.
GeneTree	ENSGT00560000076725.
HOVERGEN	HBG063184.
OrthoDB	EOG47D9GD.
PhylomeDB	P29348.
Gene expression databases
Genevestigator	P29348.
Family and domain databases
InterPro	IPR001408. Gprotein_alpha_I. IPR001019. Gprotein_alpha_su. IPR011025. GproteinA_insert. [Graphical view]
Gene3D	G3DSA:1.10.400.10. GproteinA_insert. 1 hit.
KO	K04631.
PANTHER	PTHR10218. Gprotein_alph_bd. 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
NextBio	625076.

Entry information

Entry name

GNAT3_RAT

Accession

Primary (citable) accession number: P29348

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 99 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program