Tbio GNAI3 Guanine nucleotide-binding protein G(k) subunit alpha

Protein Summary

Description

Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:8774883, PubMed:18434541, PubMed:19478087). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (PubMed:19478087). Stimulates the activity of receptor-regulated K(+) channels (PubMed:2535845). The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division (PubMed:17635935). Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling pathways. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes an alpha subunit and belongs to the G-alpha family. Mutation in this gene, resulting in a gly40-to-arg substitution, is associated with auriculocondylar syndrome, and shown to affect downstream targets in the G protein-coupled endothelin receptor pathway. [provided by RefSeq, Jun 2012]

Uniprot Accession IDs

• P08754
• P17539
• Q5TZX1

Gene Name

• GNAI3

Ensembl ID

• ENST00000369851
• ENSP00000358867
• ENSG00000065135

Symbol

• 87U6
• ARCND1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	1
interacting protein	1
molecular function	0.99
pathway	0.89
kinase perturbation	0.84

Protein Classes

PANTHER Classes

Protein / Enzyme Modulator / G-protein / Heterotrimeric G-protein / Guanine Nucleotide-binding Protein G(k) Subunit Alpha

DTO Classes

Protein / Enzyme Modulator / G-protein / Heterotrimeric G-protein / Guanine Nucleotide-binding Protein G(k) Subunit Alpha

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 29.1   (req: < 5)

Gene RIFs: 29   (req: <= 3)

Antibodies: 198   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 29.1   (req: >= 5)

Gene RIFs: 29   (req: > 3)

Antibodies: 198   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 25

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

Related Tools

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (432)

Explore Interacting Targets

1 – 10 of 432

• See Interactions on String-DB

GNAI1

Tbio

Novelty:  0.0488971

p_int:  0.999999997

p_ni:  3e-9

Score:  0.994

Data Source:  BioPlex,STRINGDB

RGS12

Tbio

Novelty:  0.02857864

p_int:  0.999999992

p_ni:  3e-9

p_wrong:  4e-9

Score:  0.98

Data Source:  BioPlex,STRINGDB

GNAO1

Tbio

Novelty:  0.00315097

p_int:  0.999999749

p_ni:  2.5e-7

Score:  0.938

Data Source:  BioPlex,STRINGDB

GNG4

Tbio

Novelty:  0.14371438

p_int:  0.999999514

p_ni:  4.86e-7

Score:  0.983

Data Source:  BioPlex,STRINGDB

RGS14

Tbio

Novelty:  0.01986201

p_int:  0.999999215

p_ni:  2.38e-7

p_wrong:  5.46e-7

Score:  0.996

Data Source:  BioPlex,STRINGDB

GPSM1

Tbio

Novelty:  0.03510582

p_int:  0.999999175

p_ni:  7.97e-7

p_wrong:  2.7e-8

Score:  0.984

Data Source:  BioPlex,STRINGDB

GNAT2

Tbio

Novelty:  0.01683655

p_int:  0.999998882

p_ni:  0.000001032

p_wrong:  8.7e-8

Score:  0.915

Data Source:  BioPlex,STRINGDB

ANKRD13B

Tdark

Novelty:  1.45055536

p_int:  0.99999845

p_ni:  4e-9

p_wrong:  0.000001546

Score:  0.316

Data Source:  BioPlex,STRINGDB

RAP1GAP

Tbio

Family:  Enzyme

Novelty:  0.0111232

p_int:  0.99999641

p_ni:  2.5e-8

p_wrong:  0.000003565

Score:  0.529

Data Source:  BioPlex,STRINGDB

GNB2

Tbio

Novelty:  0.08682553

p_int:  0.999979578

p_ni:  0.000020422

Score:  0.99

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (48)

Explore Nearest Tclin Targets

Upstream (38)

Downstream (10)

1 – 5 of 38

CXCR4

Tclin

Family:  GPCR

KEGG Distance:  1

Common Pathways:  6

1: Axon guidance

2: Chemokine signaling pathway

3: Pathways in cancer

4: Human immunodeficiency virus 1 infection

more:  2 more common pathways

P2RY12

Tclin

Family:  GPCR

KEGG Distance:  1

Common Pathways:  1

1: Platelet activation

EDNRB

Tclin

Family:  GPCR

KEGG Distance:  1

Common Pathways:  4

1: Relaxin signaling pathway

2: Pathways in cancer

3: cGMP-PKG signaling pathway

4: Melanogenesis

ADORA1

Tclin

Family:  GPCR

KEGG Distance:  1

Common Pathways:  6

1: Regulation of lipolysis in adipocytes

2: cAMP signaling pathway

3: Renin secretion

4: Sphingolipid signaling pathway

more:  2 more common pathways

ADRB2

Tclin

Family:  GPCR

KEGG Distance:  1

Common Pathways:  5

1: Regulation of lipolysis in adipocytes

2: Adrenergic signaling in cardiomyocytes

3: cAMP signaling pathway

4: Renin secretion

5: cGMP-PKG signaling pathway

Pathways (104)

Reactome (28)

KEGG (39)

PathwayCommons (30)

WikiPathways (7)

ADP signalling through P2Y purinoceptor 12 (R-HSA-392170)

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Items per page:

5

1 – 5 of 28

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	ADP signalling through P2Y purinoceptor 12	22 targets	R-HSA-392170
Reactome	Activation of GABAB receptors	39 targets	R-HSA-991365
Reactome	Adenylate cyclase inhibitory pathway	14 targets	R-HSA-170670
Reactome	Chaperonin-mediated protein folding	96 targets	R-HSA-390466
Reactome	Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	42 targets	R-HSA-6814122

Name	Explore in Pharos	Explore in Source
ADP signalling through P2Y purinoceptor 12	22 targets	R-HSA-392170
Activation of GABAB receptors	39 targets	R-HSA-991365
Adenylate cyclase inhibitory pathway	14 targets	R-HSA-170670
Chaperonin-mediated protein folding	96 targets	R-HSA-390466
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	42 targets	R-HSA-6814122

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (38)

Functions (9)

Components (13)

Processes (16)

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Items per page:

10

1 – 9 of 9

GO Term	Evidence	Assigned by
GDP binding	Inferred from Direct Assay (IDA)	UniProtKB
GTPase activity	Inferred from Direct Assay (IDA)	UniProtKB
G protein-coupled receptor binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
G-protein beta/gamma-subunit complex binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
GTP binding	Traceable Author Statement (TAS)	Reactome
G protein-coupled serotonin receptor binding	Inferred from Electronic Annotation (IEA)	Ensembl
GTPase activating protein binding	Inferred from Electronic Annotation (IEA)	Ensembl
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
protein domain specific binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (36)

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1 – 5 of 36

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
apolipoprotein B measurement	EFO_0004615	2	12	12		98.3
low density lipoprotein cholesterol measurement	EFO_0004611	2	9	10		96.7
body mass index	EFO_0004340	13	4	23		95.8
total cholesterol measurement	EFO_0004574	1	6	6		92.2
self reported educational attainment	EFO_0004784	4	4	3	6.3	90.3

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 36

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
apolipoprotein B measurement	EFO_0004615	12		98.3
low density lipoprotein cholesterol measurement	EFO_0004611	10		96.7
body mass index	EFO_0004340	23		95.8
total cholesterol measurement	EFO_0004574	6		92.2
self reported educational attainment	EFO_0004784	3	6.3	90.3

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
ADP-ribosylation
Cell cycle
Cell division
Cell membrane
Complete proteome
Cytoplasm
Cytoskeleton
Disease mutation
GTP-binding

GWAS Trait Find Similar Targets

No Header	No Header
anthropometric measurement
apolipoprotein A 1 measurement
apolipoprotein B measurement
appendicular lean mass
aspartate aminotransferase measurement
body fat percentage
body height
body mass index
breast carcinoma
chronotype measurement

MGI Phenotype Find Similar Targets

No Header	No Header
hematopoietic system phenotype
immune system phenotype
skeleton phenotype

IDG Resources

No IDG generated resources found

Orthologs (9)

1 – 5 of 9

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	G protein subunit alpha i3	VGNC:8327	457093
Macaque	G protein subunit alpha i3		699310
Mouse	guanine nucleotide binding protein (G protein), alpha inhibiting 3	MGI:95773	14679
Rat	G protein subunit alpha i3	RGD:2714	25643
Dog	G protein subunit alpha i3	VGNC:41303	611810

Species	Name	OMA	EggNOG	Inparanoid
Chimp	G protein subunit alpha i3
Macaque	G protein subunit alpha i3
Mouse	guanine nucleotide binding protein (G protein), alpha inhibiting 3
Rat	G protein subunit alpha i3
Dog	G protein subunit alpha i3

Publication Statistics

PubMed Score 29.10

PubMed score by year

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PubTator Score 42.50

PubTator score by year

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Related Publications

Text Mined References (97)

GeneRif Annotations (29)

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10

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PMID	Year	Title