InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TRIB3

Summary

InnateDB Protein

IDBP-37172.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TRIB3

Protein Name

tribbles homolog 3 (Drosophila)

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000217233

InnateDB Gene

IDBG-37170 (TRIB3)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:12736262, ECO:0000269PubMed:15299019, ECO:0000269PubMed:15775988, ECO:0000269PubMed:15781252, ECO:0000269PubMed:22977230}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:22977230}.

Disease Associations

Tissue Specificity

Highest expression in liver, pancreas, peripheral blood leukocytes and bone marrow. Also highly expressed in a number of primary lung, colon and breast tumors. Expressed in spleen, thymus, and prostate and is undetectable in other examined tissues, including testis, ovary, small intestine, colon, leukocyte, heart, brain, placenta, lung, skeletal muscle, and kidney. {ECO:0000269PubMed:12736262, ECO:0000269PubMed:12743605, ECO:0000269PubMed:15299019}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 49 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	49 [view]
Protein-Protein	48 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003714	transcription corepressor activity
GO:0004672	protein kinase activity
GO:0004860	protein kinase inhibitor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019899	enzyme binding
GO:0019901	protein kinase binding
GO:0031625	ubiquitin protein ligase binding
GO:0055106	ubiquitin-protein ligase regulator activity

Biological Process

GO:0006351	transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0006469	negative regulation of protein kinase activity
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0008286	insulin receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0010827	regulation of glucose transport
GO:0032092	positive regulation of protein binding
GO:0032869	cellular response to insulin stimulus
GO:0034976	response to endoplasmic reticulum stress
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0043405	regulation of MAP kinase activity
GO:0044255	cellular lipid metabolic process
GO:0044281	small molecule metabolic process
GO:0045087	innate immune response (InnateDB)
GO:0045599	negative regulation of fat cell differentiation
GO:0045717	negative regulation of fatty acid biosynthetic process
GO:0045892	negative regulation of transcription, DNA-templated
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0051443	positive regulation of ubiquitin-protein transferase activity
GO:0070059	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO:2001141	regulation of RNA biosynthetic process

Cellular Component

GO:0005634	nucleus
GO:0005829	cytosol
GO:0005886	plasma membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt