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Details on Person UniProt:Q96RU7 TRIB3

Class:Id	ReferenceGeneProduct:60223
_chainChangeLog	chain:1-358 added on Fri February 6 2015
_displayName	UniProt:Q96RU7 TRIB3
_timestamp	2024-11-03 20:03:44
chain	chain:1-358
checksum	CE15FD89A81E8D63
comment	FUNCTION Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15775988, PubMed:15781252). Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress (PubMed:15775988, PubMed:15781252). May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells (PubMed:15775988, PubMed:15781252). 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 (By similarity). Disrupts insulin signaling by binding directly to Akt kinases and blocking their activation (By similarity). May bind directly to and mask the 'Thr-308' phosphorylation site in AKT1 (By similarity). Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity (PubMed:12736262). Interacts with MAPK kinases and regulates activation of MAP kinases (PubMed:15299019). Can inhibit APOBEC3A editing of nuclear DNA (PubMed:22977230).SUBUNIT Interacts with AKT1, AKT2, MAP2K1 and MAP2K7 (PubMed:15299019). Interacts with ATF4 (PubMed:12743605). Interacts with DDIT3/CHOP and inhibits its interaction with EP300/P300 (PubMed:15775988, PubMed:17872950). Interacts with APOBEC3C (PubMed:22977230). Interacts (via N-terminus) with APOBEC3A (PubMed:22977230). Interacts with RELA (PubMed:12736262).INTERACTION 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.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 down-regulate its own induction by repression of ATF4-DDIT3/CHOP functions.DOMAIN The protein kinase domain is predicted to be catalytically inactive.SIMILARITY Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Tribbles subfamily.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.
description	recommendedName: Tribbles homolog 3 shortName: TRB-3 alternativeName: Neuronal cell death-inducible putative kinase alternativeName: SINK alternativeName: p65-interacting inhibitor of NF-kappa-B
geneName	TRIB3 C20orf97 NIPK SKIP3 TRB3
identifier	Q96RU7
isSequenceChanged	FALSE
keyword	Apoptosis Nucleus Phosphoprotein Protein kinase inhibitor Proteomics identification Reference proteome Stress response Transcription Transcription regulation
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
name	TRIB3
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:5649895] ENSEMBL:ENSG00000101255 TRIB3 [Homo sapiens]
secondaryIdentifier	TRIB3_HUMAN Q53GU4 Q53ZW7 Q6I9Y9 Q8TAI6 Q9H5M8 Q9NUD2
sequenceLength	358
species	[Species:48887] Homo sapiens
(referenceEntity)	[EntityWithAccessionedSequence:162411] TRIB3 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:199447] TRIB3 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:9635877] TRIB3 [nucleoplasm] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:Q96RU7 TRIB3 (60223)