Details for: GNAT3

Gene ID: 346562

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: GNAT3

Ensembl ID: ENSG00000214415

Description: G protein subunit alpha transducin 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • brush cell CL0002204
    CSI 6.77
    rCSI 13.39%
    PRS 99.85
  • intestinal tuft cell CL0019032
    CSI 6.09
    rCSI 9.31%
    PRS 99.85
  • sncg GABAergic cortical interneuron CL4023015
    CSI 2.37
    rCSI 3.81%
    PRS 99.79

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [GNAT3](/details-gene/346562) (G protein subunit alpha transducin 3), also known as gustducin, is a protein-coding gene located on chromosome 7q21.11. It encodes the alpha subunit of a heterotrimeric G protein that is a critical component of G protein-coupled receptor (GPCR) signaling cascades. Functionally, [GNAT3](/details-gene/346562) is best characterized for its central role in the sensory perception of sweet, umami, and bitter tastes. **Overall**, its expression is most significant in specialized chemosensory cells, such as the [brush cell](/details-cell/CL0002204) and [intestinal tuft cell](/details-cell/CL0019032), highlighting its function not only in oral taste perception but also in nutrient and chemical sensing within the gastrointestinal tract. Its involvement in these pathways has implications for metabolic regulation, including the secretion of incretin hormones like glucagon-like peptide-1 (GLP-1). ## Cellular Roles and Expression Landscape The expression profile of [GNAT3](/details-gene/346562) underscores its specialized function in chemosensation. The highest significance scores are observed in [brush cell](/details-cell/CL0002204) (CSI: 6.77) and its subtype, the [intestinal tuft cell](/details-cell/CL0019032) (CSI: 6.09). These cells are found in the epithelial linings of the respiratory and gastrointestinal tracts and act as sentinels, detecting luminal contents and initiating physiological responses. The presence of [GNAT3](/details-gene/346562) in these cells is consistent with studies demonstrating its role in gut-based sugar sensing and the subsequent regulation of glucose transporters and hormone secretion ([Link](https://doi.org/10.1073/pnas.0706890104), [Link](https://doi.org/10.1073/pnas.0706678104)). For example, [GNAT3](/details-gene/346562) has been shown to colocalize with GLP-1 in L cells of the human colon, directly linking it to metabolic hormone regulation ([Link](https://doi.org/10.1152/ajpgi.00074.2006)). Beyond the gut, [GNAT3](/details-gene/346562) shows significant expression in [sncg GABAergic cortical interneuron](/details-cell/CL4023015) (CSI: 2.37), suggesting a potential, albeit less characterized, role in the central nervous system. This is supported by its functional annotation in pathways related to neuronal signaling. Additionally, research has identified its expression in mammalian spermatozoa, particularly in the acrosomal vesicle, implicating it in processes related to fertilization ([Link](https://doi.org/10.1007/s00359-006-0168-8)). ## Pathways and Molecular Function [GNAT3](/details-gene/346562) functions as a classical G-alpha subunit involved in signal transduction. Its molecular functions are dominated by GTPase activity ([GO:0003924](https://www.ebi.ac.uk/QuickGO/term/GO:0003924)), GTP binding ([GO:0005525](https://www.ebi.ac.uk/QuickGO/term/GO:0005525)), and binding to GPCRs ([GO:0001664](https://www.ebi.ac.uk/QuickGO/term/GO:0001664)) and G-protein beta/gamma-subunits ([GO:0031683](https://www.ebi.ac.uk/QuickGO/term/GO:0031683)). The biological processes it mediates are centered on chemosensation and GPCR signaling. It is a key transducer in the detection of bitter ([GO:0001580](https://www.ebi.ac.uk/QuickGO/term/GO:0001580)), sweet ([GO:0050916](https://www.ebi.ac.uk/QuickGO/term/GO:0050916)), and umami ([GO:0050917](https://www.ebi.ac.uk/QuickGO/term/GO:0050917)) tastes, as detailed in the Reactome pathway 'Sensory perception of sweet, bitter, and umami (glutamate) taste' ([R-HSA-9717207](https://reactome.org/content/detail/R-HSA-9717207)). This function is consistent with its high expression in taste cells and intestinal chemosensory cells. Furthermore, its participation in 'G alpha (i) signalling events' ([R-HSA-418594](https://reactome.org/content/detail/R-HSA-418594)) and 'Adenylate cyclase-modulating g protein-coupled receptor signaling pathway' ([GO:0007188](https://www.ebi.ac.uk/QuickGO/term/GO:0007188)) underlies its broader role in cellular signaling. This includes pathways relevant to metabolism, such as the 'Synthesis, secretion, and inactivation of glucagon-like peptide-1 (glp-1)' ([R-HSA-381771](https://reactome.org/content/detail/R-HSA-381771)), and neuronal function, like 'GABA B receptor activation' ([R-HSA-977444](https://reactome.org/content/detail/R-HSA-977444)). ## Research Directions The well-defined role of [GNAT3](/details-gene/346562) in gut chemosensation and its link to metabolic hormones present clear avenues for translational research, while its expression in the nervous system suggests unexplored functions. **Proposed Hypotheses:** 1. Dysregulation of [GNAT3](/details-gene/346562) expression or function in [intestinal tuft cell](/details-cell/CL0019032)s contributes to the pathophysiology of metabolic syndrome. Specifically, reduced [GNAT3](/details-gene/346562) signaling in response to dietary nutrients may lead to blunted GLP-1 secretion, impairing glucose homeostasis and promoting obesity. 2. Within the central nervous system, [GNAT3](/details-gene/346562) in [sncg GABAergic cortical interneuron](/details-cell/CL4023015)s modulates inhibitory neurotransmission. It may act as a transducer for metabotropic receptors that fine-tune neuronal firing rates, thereby influencing cortical network activity and behavior. **Experimental Approach:** To test the first hypothesis regarding metabolic syndrome, a robust *in vitro* model could be employed. Human intestinal organoids, which contain functional [intestinal tuft cell](/details-cell/CL0019032)s, could be generated from induced pluripotent stem cells. Using CRISPR-Cas9, [GNAT3](/details-gene/346562) could be knocked out. A comparison between wild-type and knockout organoids' secretomes following stimulation with various tastants (e.g., sucralose, monosodium glutamate) would be performed. The concentration of secreted GLP-1 could be quantified by ELISA to directly assess whether [GNAT3](/details-gene/346562) is necessary for nutrient-induced incretin hormone release. **Therapeutic Potential:** [GNAT3](/details-gene/346562) represents a promising therapeutic target for metabolic diseases such as type 2 diabetes and obesity. As a G-protein, it belongs to a highly druggable class of proteins. The therapeutic strategy would likely involve **activation** rather than inhibition. Small-molecule agonists that specifically target and enhance [GNAT3](/details-gene/346562) signaling in enteroendocrine cells could amplify the body's natural incretin response to food intake. This approach could offer a novel mechanism to improve glycemic control and promote satiety, potentially complementing or providing an alternative to existing GLP-1 receptor agonist therapies.

Genular Protein ID: 1926130839

Symbol: GNAT3_HUMAN

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

UniProtKB Accession Codes:

A8MTJ3 A4D1B2 A4D1B3 B9EJG5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 7 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 6 EMDB 1 Ensembl 1 GO 19 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 10 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 SwissPalm 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

PubMed ID: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8015379

Title: Human taste cells express the G protein alpha-gustducin and neuron-specific enolase.

PubMed ID: 8015379

DOI: 10.1016/0169-328x(94)90047-7

PubMed ID: 11917125

Title: Human receptors for sweet and umami taste.

PubMed ID: 11917125

DOI: 10.1073/pnas.072090199

PubMed ID: 16728727

Title: Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon.

PubMed ID: 16728727

DOI: 10.1152/ajpgi.00074.2006

PubMed ID: 17021831

Title: Expression of the G-protein alpha-subunit gustducin in mammalian spermatozoa.

PubMed ID: 17021831

DOI: 10.1007/s00359-006-0168-8

PubMed ID: 17724330

Title: Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1.

PubMed ID: 17724330

DOI: 10.1073/pnas.0706890104

PubMed ID: 17724332

Title: T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1.

PubMed ID: 17724332

DOI: 10.1073/pnas.0706678104

Sequence Information:

  • Length: 354
  • Mass: 40357
  • Checksum: 47366FB99E9322AD
  • Sequence:
    • MGSGISSESK ESAKRSKELE KKLQEDAERD ARTVKLLLLG AGESGKSTIV KQMKIIHKNG 
YSEQECMEFK AVIYSNTLQS ILAIVKAMTT LGIDYVNPRS AEDQRQLYAM ANTLEDGGMT 
PQLAEVIKRL WRDPGIQACF ERASEYQLND SAAYYLNDLD RITASGYVPN EQDVLHSRVK 
TTGIIETQFS FKDLHFRMFD VGGQRSERKK WIHCFEGVTC IIFCAALSAY DMVLVEDEEV 
NRMHESLHLF NSICNHKYFS TTSIVLFLNK KDIFQEKVTK VHLSICFPEY TGPNTFEDAG 
NYIKNQFLDL NLKKEDKEIY SHMTCATDTQ NVKFVFDAVT DIIIKENLKD CGLF