
**NCBI Gene Summary**: 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]

**GeneCards Summary**: TRIB3 (Tribbles Pseudokinase 3) is a Protein Coding gene. Diseases associated with TRIB3 include Type 2 Diabetes Mellitus and Geotrichosis. Among its related pathways are Insulin receptor signalling cascade and CD28 co-stimulation. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein kinase binding. An important paralog of this gene is TRIB1.

**UniProtKB/Swiss-Prot Summary**: Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress [PMID: 15781252, PMID: 15775988]. Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress [PMID: 15781252, PMID: 15775988]. May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells [PMID: 15781252, PMID: 15775988]. Acts as a negative feedback regulator of the ATF4-dependent transcription during the ISR: while TRIB3 expression is promoted by ATF4, TRIB3 protein interacts with ATF4 and inhibits ATF4 transcription activity. 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. Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity [PMID: 12736262]. Interacts with MAPK kinases and regulates activation of MAP kinases [PMID: 15299019]. Can inhibit APOBEC3A editing of nuclear DNA [PMID: 22977230].
