TRIB3

TRIB3
Identifiers
Aliases	TRIB3, C20orf97, NIPK, SINK, SKIP3, TRB3, tribbles pseudokinase 3
External IDs	MGI: 1345675 HomoloGene: 10902 GeneCards: TRIB3
Gene ontology Molecular function • transcription corepressor activity • ubiquitin-protein transferase regulator activity • protein kinase inhibitor activity • kinase activity • protein binding • mitogen-activated protein kinase kinase binding • ATP binding • protein kinase binding • ubiquitin protein ligase binding Cellular component • cytosol • plasma membrane • nucleoplasm • nucleus Biological process • negative regulation of fat cell differentiation • regulation of transcription, DNA-templated • negative regulation of fatty acid biosynthetic process • negative regulation of protein kinase activity • negative regulation of transcription from RNA polymerase II promoter • transcription, DNA-templated • response to endoplasmic reticulum stress • protein phosphorylation • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress • positive regulation of ubiquitin-protein transferase activity • cellular response to insulin stimulus • regulation of MAP kinase activity • positive regulation of protein binding • negative regulation of transcription, DNA-templated • regulation of glucose transport • positive regulation of proteasomal ubiquitin-dependent protein catabolic process • apoptotic process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	57761	228775
Ensembl	ENSG00000101255	ENSMUSG00000032715
UniProt	Q96RU7	Q8K4K2
RefSeq (mRNA)	NM_021158 NM_001301188 NM_001301190 NM_001301193 NM_001301196 NM_001301201	NM_144554 NM_175093
RefSeq (protein)	NP_001288117.1 NP_001288119.1 NP_001288122.1 NP_001288125.1 NP_001288130.1 NP_066981.2	NP_780302.2
Location (UCSC)	Chr 20: 0.36 – 0.4 Mb	Chr 2: 152.34 – 152.34 Mb
PubMed search	[1]	[2]
Wikidata

View/Edit Human

View/Edit Mouse

Tribbles homolog 3 is a protein that in humans is encoded by the TRIB3 gene.^[3][4][5]

Function

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.^[5]

Interactions

TRIB3 has been shown to interact with:

• AKT1,^[3]
• CSNK2B,^[6]
• Fibronectin^[6]
• MCM3AP,^[7]
• RELA,^[8]
• SIAH1,^[6] and
• TIAF1.^[6]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Du K, Herzig S, Kulkarni RN, Montminy M (Jun 2003). "TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver". Science. 300 (5625): 1574–7. doi:10.1126/science.1079817. PMID 12791994.
4. Hegedus Z, Czibula A, Kiss-Toth E (Aug 2006). "Tribbles: novel regulators of cell function; evolutionary aspects". Cell Mol Life Sci. 63 (14): 1632–41. doi:10.1007/s00018-006-6007-9. PMID 16715410.
5. "Entrez Gene: TRIB3 tribbles homolog 3 (Drosophila)".
6. Zhou Y, Li L, Liu Q, Xing G, Kuai X, Sun J, Yin X, Wang J, Zhang L, He F (May 2008). "E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3". Cell. Signal. 20 (5): 942–8. doi:10.1016/j.cellsig.2008.01.010. PMID 18276110.
7. Bowers AJ, Scully S, Boylan JF (May 2003). "SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia". Oncogene. 22 (18): 2823–35. doi:10.1038/sj.onc.1206367. PMID 12743605.
8. Wu M, Xu LG, Zhai Z, Shu HB (July 2003). "SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription". J. Biol. Chem. 278 (29): 27072–9. doi:10.1074/jbc.M209814200. PMID 12736262.

Further reading

• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene. 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene. 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20.". Nature. 414 (6866): 865–71. doi:10.1038/414865a. PMID 11780052.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Wu M, Xu LG, Zhai Z, Shu HB (2003). "SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription.". J. Biol. Chem. 278 (29): 27072–9. doi:10.1074/jbc.M209814200. PMID 12736262.
• Bowers AJ, Scully S, Boylan JF (2003). "SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia.". Oncogene. 22 (18): 2823–35. doi:10.1038/sj.onc.1206367. PMID 12743605.
• Huang J, Teng L, Liu T, et al. (2003). "Identification of a novel serine/threonine kinase that inhibits TNF-induced NF-kappaB activation and p53-induced transcription.". Biochem. Biophys. Res. Commun. 309 (4): 774–8. doi:10.1016/j.bbrc.2003.08.069. PMID 13679039.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Kiss-Toth E, Bagstaff SM, Sung HY, et al. (2004). "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades.". J. Biol. Chem. 279 (41): 42703–8. doi:10.1074/jbc.M407732200. PMID 15299019.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Ohoka N, Yoshii S, Hattori T, et al. (2005). "TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death.". EMBO J. 24 (6): 1243–55. doi:10.1038/sj.emboj.7600596. PMC 556400. PMID 15775988.
• Ord D, Ord T (2005). "Characterization of human NIPK (TRB3, SKIP3) gene activation in stressful conditions.". Biochem. Biophys. Res. Commun. 330 (1): 210–8. doi:10.1016/j.bbrc.2005.02.149. PMID 15781252.
• Prudente S, Hribal ML, Flex E, et al. (2005). "The functional Q84R polymorphism of mammalian Tribbles homolog TRB3 is associated with insulin resistance and related cardiovascular risk in Caucasians from Italy.". Diabetes. 54 (9): 2807–11. doi:10.2337/diabetes.54.9.2807. PMID 16123373.
• Schwarzer R, Dames S, Tondera D, et al. (2006). "TRB3 is a PI 3-kinase dependent indicator for nutrient starvation.". Cell. Signal. 18 (6): 899–909. doi:10.1016/j.cellsig.2005.08.002. PMID 16129579.
• Stelzl U, Worm U, Lalowski M, et al. (2005). "A human protein-protein interaction network: a resource for annotating the proteome.". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070.
• Matsushima R, Harada N, Webster NJ, et al. (2006). "Effect of TRB3 on insulin and nutrient-stimulated hepatic p70 S6 kinase activity.". J. Biol. Chem. 281 (40): 29719–29. doi:10.1074/jbc.M511636200. PMID 16887816.
• Koh HJ, Arnolds DE, Fujii N, et al. (2007). "Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis, and decreases TRB3.". Mol. Cell. Biol. 26 (22): 8217–27. doi:10.1128/MCB.00979-06. PMC 1636784. PMID 16966378.