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MGP005676

UniProt Annotations

Entry Information

Gene Name	tribbles pseudokinase 3
Protein Entry	TRIB3_HUMAN
UniProt ID	Q96RU7
Species	Human

Comments

Comment type	Description
Caution	The role of this protein in Akt activation has been demonstrated by Du et al (PubMed:12791994) for the mouse ortholog but Iynedjian (PubMed:15469416) has not been able to reproduce the result in rat hepatocytes. {ECO:0000305}.
Domain	The protein kinase domain is predicted to be catalytically inactive.
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:0000269\|PubMed:12736262, ECO:0000269\|PubMed:15299019, ECO:0000269\|PubMed:15775988, ECO:0000269\|PubMed:15781252, ECO:0000269\|PubMed:22977230}.
Induction	By hypoxia, TNF, and by nutrient starvation. Expression is PI 3-kinase and/or NF-kappa-B-dependent. Induced by ER stress via ATF4-DDIT3/CHOP pathway and can downregulate its own induction by repression of ATF4-DDIT3/CHOP functions. {ECO:0000269\|PubMed:12736262, ECO:0000269\|PubMed:12743605, ECO:0000269\|PubMed:15775988, ECO:0000269\|PubMed:16129579}.
Interaction	P18848:ATF4; NbExp=2; IntAct=EBI-492476, EBI-492498; O14744:PRMT5; NbExp=2; IntAct=EBI-492476, EBI-351098;
Similarity	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Tribbles subfamily. {ECO:0000305}.
Similarity	Contains 1 protein kinase domain. {ECO:0000255\|PROSITE-ProRule:PRU00159}.
Subcellular Location	Nucleus {ECO:0000269\|PubMed:22977230}.
Subunit	Interacts with AKT1, AKT2, ATF4, MAP2K1 and MAP2K7. Interacts with DDIT3/CHOP and inhibits its interaction with EP300/P300. Interacts (via N-terminus) with APOBEC3A. Interacts with APOBEC3C. {ECO:0000269\|PubMed:12736262, ECO:0000269\|PubMed:12743605, ECO:0000269\|PubMed:15299019, ECO:0000269\|PubMed:15775988, ECO:0000269\|PubMed:17872950, ECO:0000269\|PubMed:22977230}.
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:0000269\|PubMed:12736262, ECO:0000269\|PubMed:12743605, ECO:0000269\|PubMed:15299019}.