Tbio TRIB3 Tribbles homolog 3

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Tribbles Homolog 3

DTO Classes

Protein / Kinase / Protein Kinase / Camk Group / Trbl Family / 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

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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: 151.52   (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: 151.52   (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

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

Protein Structure (0 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

AF-Q96RU7-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

Pathways (34)

Reactome (29)

KEGG (1)

PathwayCommons (1)

WikiPathways (3)

Activation of AKT2 (R-HSA-165158)

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Items per page:

5

1 – 5 of 29

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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Items per page:

10

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

Protein-Protein Interactions (86)

Explore Interacting Targets

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

Publication Statistics

PubMed Score  151.52

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PubTator Score  180.86

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Amino Acid Sequence

Residue Counts

Protein Sequence

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Ortholog Sequence Conservation

WebLogo Color Code

PolarG S T Y C

NeutralQ N

BasicK R H

AcidicD E

HydrophobicA V L I P W F M

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Structural Annotations

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UniProt Keyword Find Similar Targets

Apoptosis
Complete proteome
Nucleus
Phosphoprotein
Polymorphism
Protein kinase inhibitor
Reference proteome
Stress response
Transcription
Transcription regulation

MGI Phenotype Find Similar Targets

cellular phenotype
endocrine/exocrine gland phenotype
hematopoietic system phenotype
immune system phenotype