{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q96RU7","secondaryAccessions":["Q53GU4","Q53ZW7","Q6I9Y9","Q8TAI6","Q9H5M8","Q9NUD2"],"uniProtkbId":"TRIB3_HUMAN","entryAudit":{"firstPublicDate":"2003-02-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2003-02-01","entryVersion":207,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Tribbles homolog 3"},"shortNames":[{"value":"TRB-3"}]},"alternativeNames":[{"fullName":{"value":"Neuronal cell death-inducible putative kinase"}},{"fullName":{"value":"SINK"}},{"fullName":{"value":"p65-interacting inhibitor of NF-kappa-B"}}]},"genes":[{"geneName":{"value":"TRIB3"},"synonyms":[{"value":"C20orf97"},{"value":"NIPK"},{"value":"SKIP3"},{"value":"TRB3"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8K4K2"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12736262"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15299019"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15775988"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15781252"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22977230"}],"value":"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)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12736262"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12743605"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15299019"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15775988"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17872950"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22977230"}],"value":"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)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q9ULX6","geneName":"AKAP8L","intActId":"EBI-357530"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q9NRW3","geneName":"APOBEC3C","intActId":"EBI-1044593"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q9H6L4","geneName":"ARMC7","intActId":"EBI-742909"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"P18848","geneName":"ATF4","intActId":"EBI-492498"},"numberOfExperiments":16,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"O95817","geneName":"BAG3","intActId":"EBI-747185"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"P41182","geneName":"BCL6","intActId":"EBI-765407"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q13515","geneName":"BFSP2","intActId":"EBI-10229433"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q0VAL7","geneName":"C21orf58","intActId":"EBI-10226774"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q6P5X5","geneName":"C22orf39","intActId":"EBI-7317823"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q9HC52","geneName":"CBX8","intActId":"EBI-712912"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q13111","geneName":"CHAF1A","intActId":"EBI-1020839"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"P51800-3","geneName":"CLCNKA","intActId":"EBI-11980535"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"P78358","geneName":"CTAG1B","intActId":"EBI-1188472"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"G5E9A7","geneName":"DMWD","intActId":"EBI-10976677"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q6W0C5","geneName":"DPPA3","intActId":"EBI-12082590"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q86UW9","geneName":"DTX2","intActId":"EBI-740376"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"O95967","geneName":"EFEMP2","intActId":"EBI-743414"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"O15197-2","geneName":"EPHB6","intActId":"EBI-10182490"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q9NQT4","geneName":"EXOSC5","intActId":"EBI-371876"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q6NZ36-4","geneName":"FAAP20","intActId":"EBI-12013806"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q3B820","geneName":"FAM161A","intActId":"EBI-719941"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q86YD7","geneName":"FAM90A1","intActId":"EBI-6658203"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q96RU7","intActId":"EBI-492476"},"interactantTwo":{"uniProtKBAccession":"Q8NEA6-2","geneName":"GLIS3","intActId":"EBI-12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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"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12736262"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12743605"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15775988"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16129579"}],"value":"By hypoxia, TNF, and by nutrient starvation. Expression is PI 3-kinase and/or NF-kappa-B-dependent. 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