Tbio TRIB3 Tribbles homolog 3

Protein Summary

Description

Disrupts insulin signaling by binding directly to Akt kinases and blocking their activation. May bind directly to and mask the 'Thr-308' phosphorylation site in AKT1. Binds to ATF4 and inhibits its transcriptional activation activity. Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity. Interacts with MAPK kinases and regulates activation of MAP kinases. May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells. Does not display kinase activity. Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress. Can inhibit APOBEC3A editing of nuclear DNA. The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. The encoded protein is a negative regulator of NF-kappaB and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein can negatively regulate the cell survival serine-threonine kinase AKT1. Differential promoter usage and alternate splicing result in multiple transcript variants. [provided by RefSeq, Jul 2014]

Uniprot Accession IDs

• Q96RU7
• Q53GU4
• Q53ZW7
• Q6I9Y9
• Q8TAI6
• Q9H5M8
• Q9NUD2
• TRB-3

Gene Name

• TRIB3

Ensembl ID

• ENST00000217233
• ENSP00000217233
• ENSG00000101255

Symbol

• C20orf97
• NIPK
• SKIP3
• TRB3
• NIPK
• SINK
• TRB3
• SKIP3
• C20orf97

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
biological process	0.99
gene perturbation	0.99
small molecule perturbation	0.99
PubMedID	0.93

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: 163.6   (req: < 5)

Gene RIFs: 82   (req: <= 3)

Antibodies: 525   (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: 163.6   (req: >= 5)

Gene RIFs: 82   (req: > 3)

Antibodies: 525   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 23

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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Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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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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Protein-Protein Interactions (86)

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1 – 10 of 86

• See Interactions on String-DB

STK40

Tbio

Family:  Kinase

Novelty:  0.10461675

p_int:  0.996005606

p_ni:  0.003991817

p_wrong:  0.000002577

Score:  0.879

Data Source:  BioPlex,STRINGDB

COP1

Tbio

Family:  Enzyme

Novelty:  0.10908534

p_int:  0.967971339

p_ni:  0.032028661

Score:  0.896

Data Source:  BioPlex,STRINGDB

AKT1

Tchem

Family:  Kinase

Novelty:  0.00003185

Score:  0.962

Data Source:  Reactome,STRINGDB

AKT2

Tchem

Family:  Kinase

Novelty:  0.00167027

Score:  0.948

Data Source:  Reactome,STRINGDB

PDPK1

Tchem

Family:  Kinase

Novelty:  0.00430458

Score:  0.915

Data Source:  STRINGDB

AKT3

Tchem

Family:  Kinase

Novelty:  0.00308931

Score:  0.915

Data Source:  STRINGDB

ATF4

Tbio

Family:  TF

Novelty:  0.00253408

Score:  0.912

Data Source:  STRINGDB

PPARA

Tclin

Family:  NR

Novelty:  0.00017403

Score:  0.91

Data Source:  STRINGDB

FABP1

Tchem

Novelty:  0.00192691

Score:  0.909

Data Source:  STRINGDB

HELZ2

Tdark

Family:  Enzyme

Novelty:  0.1810765

Score:  0.908

Data Source:  STRINGDB

Pathways (34)

Reactome (29)

KEGG (1)

PathwayCommons (1)

WikiPathways (3)

Activation of AKT2 (R-HSA-165158)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of AKT2	4 targets	R-HSA-165158
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	CD28 co-stimulation	33 targets	R-HSA-389356
Reactome	CD28 dependent PI3K/Akt signaling	22 targets	R-HSA-389357
Reactome	Costimulation by the CD28 family	88 targets	R-HSA-388841

Name	Explore in Pharos	Explore in Source
Activation of AKT2	4 targets	R-HSA-165158
Adaptive Immune System	894 targets	R-HSA-1280218
CD28 co-stimulation	33 targets	R-HSA-389356
CD28 dependent PI3K/Akt signaling	22 targets	R-HSA-389357
Costimulation by the CD28 family	88 targets	R-HSA-388841

Gene Ontology Terms (26)

Functions (7)

Components (3)

Processes (16)

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1 – 7 of 7

GO Term	Evidence	Assigned by
protein kinase binding	Inferred from Physical Interaction (IPI)	UniProtKB
mitogen-activated protein kinase kinase binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
transcription corepressor activity	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
ubiquitin protein ligase binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
ubiquitin-protein transferase regulator activity	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
ATP binding	Inferred from Electronic Annotation (IEA)	InterPro
protein kinase inhibitor activity	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

GWAS Traits (1)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
low density lipoprotein cholesterol measurement	EFO_0004611	1	1	1		49.5

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
low density lipoprotein cholesterol measurement	EFO_0004611	1		49.5

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UniProt Keyword Find Similar Targets

No Header	No Header
Apoptosis
Complete proteome
Nucleus
Phosphoprotein
Polymorphism
Protein kinase inhibitor
Reference proteome
Stress response
Transcription
Transcription regulation

GWAS Trait Find Similar Targets

No Header	No Header
low density lipoprotein cholesterol measurement

MGI Phenotype Find Similar Targets

No Header	No Header
cellular phenotype
endocrine/exocrine gland phenotype
hematopoietic system phenotype
immune system phenotype

Orthologs (9)

1 – 5 of 9

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	tribbles pseudokinase 3	VGNC:14143	745623
Macaque	tribbles pseudokinase 3		714636
Mouse	tribbles pseudokinase 3	MGI:1345675	228775
Rat	tribbles pseudokinase 3	RGD:708432	246273
Dog	tribbles pseudokinase 3	VGNC:47802	485819

Species	Name	OMA	EggNOG	Inparanoid
Chimp	tribbles pseudokinase 3
Macaque	tribbles pseudokinase 3
Mouse	tribbles pseudokinase 3
Rat	tribbles pseudokinase 3
Dog	tribbles pseudokinase 3

Publication Statistics

PubMed Score 163.60

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PubTator Score 180.86

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