TRIB3

TRIB3
Identifiers
Aliases	TRIB3, C20orf97, NIPK, SINK, SKIP3, TRB3, tribbles pseudokinase 3
External IDs	OMIM: 607898; MGI: 1345675; HomoloGene: 10902; GeneCards: TRIB3; OMA:TRIB3 - orthologs
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20p13 Start 362,835 bp[1] End 397,559 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 G3|2 74.83 cM Start 152,179,342 bp[2] End 152,185,952 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver pancreatic ductal cell gonad islet of Langerhans stromal cell of endometrium upper lobe of left lung optic nerve body of pancreas parotid gland anterior pituitary Top expressed in lumbar spinal ganglion endothelial cell of lymphatic vessel calvaria yolk sac submandibular gland seminal vesicula ascending aorta semi-lunar valve aortic valve olfactory epithelium More reference expression data BioGPS More reference expression data
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 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 by RNA polymerase II 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 transmembrane transport positive regulation of proteasomal ubiquitin-dependent protein catabolic process apoptotic process regulation of lipid metabolic process negative regulation of protein kinase B signaling regulation of autophagy Sources:Amigo / QuickGO
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 NP_001288119 NP_001288122 NP_001288125 NP_001288130 NP_066981 NP_780302 Location (UCSC) Chr 20: 0.36 – 0.4 Mb Chr 2: 152.18 – 152.19 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Tribbles homolog 3 is a protein that in humans is encoded by the TRIB3 gene.^[5][6][7]

Function

The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. It is a pseudoenzyme that is thought to be a negative regulator of NF-kappaB, and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein has been reported to negatively regulate the cell survival serine-threonine kinase AKT1.^[7] TRIB3 has recently been associated with neuronal signalling, and like TRIB1 and TRIB2, could be considered as a potential allosteric drug target.^[8][9]

Interactions

TRIB3 has been shown to interact with:

• AKT1,^[5]
• CSNK2B,^[10]
• Fibronectin^[10]
• MCM3AP,^[11]
• RELA,^[12]
• SIAH1,^[10] and
• TIAF1.^[10]

References

1. GRCh38: Ensembl release 89: ENSG00000101255 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000032715 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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. Bibcode:2003Sci...300.1574D. doi:10.1126/science.1079817. PMID 12791994. S2CID 43360696.
6. 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. PMC 11136108. PMID 16715410. S2CID 24556931.
7. "Entrez Gene: TRIB3 tribbles homolog 3 (Drosophila)".
8. Eyers PA, Keeshan K, Kannan N (2016). "Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease". Trends in Cell Biology. 27 (9): S0962-8924(16)30178-7. doi:10.1016/j.tcb.2016.11.002. PMC 5382568. PMID 27908682.
9. Foulkes DM, Byrne DP, Eyers PA (2015). "Tribbles pseudokinases: novel targets for chemical biology and drug discovery?". Biochemical Society Transactions. 43 (5): 1095–1103. doi:10.1042/BST20150109. PMID 26517930.
10. 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.
11. 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.
12. 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. Bibcode:2001Natur.414..865D. 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. Bibcode:2002PNAS...9916899M. 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. hdl:2262/33449. 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. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923.
• 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.