TRIB3

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Tribbles homolog 3 is a protein that in humans is encoded by the TRIB3 gene.[1][2][3]

## Contents

* 1 Function
* 2 Interactions
* 3 References
* 4 Further reading

## 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.[3] TRIB3 has recently been associated with neuronal signalling, and like TRIB1 and TRIB2, could be considered as a potential allosteric drug target.[4][5]

## Interactions

TRIB3 has been shown to interact with:

* AKT1,[1]
* CSNK2B,[6]
* Fibronectin[6]
* MCM3AP,[7]
* RELA,[8]
* SIAH1,[6] and
* TIAF1.[6]

## References

1. ↑ 1.0 1.1 "TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver". Science 300 (5625): 1574–7. Jun 2003. doi:10.1126/science.1079817. PMID 12791994. Bibcode: 2003Sci...300.1574D.
2. ↑ "Tribbles: novel regulators of cell function; evolutionary aspects". Cell Mol Life Sci 63 (14): 1632–41. Aug 2006. doi:10.1007/s00018-006-6007-9. PMID 16715410.
3. ↑ 3.0 3.1 "Entrez Gene: TRIB3 tribbles homolog 3 (Drosophila)". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=57761.
4. ↑ "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. 2016. doi:10.1016/j.tcb.2016.11.002. PMID 27908682.
5. ↑ "Tribbles pseudokinases: novel targets for chemical biology and drug discovery?". Biochemical Society Transactions 43 (5): 1095–1103. 2015. doi:10.1042/BST20150109. PMID 26517930.
6. ↑ 6.0 6.1 6.2 6.3 "E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3". Cell. Signal. 20 (5): 942–8. May 2008. doi:10.1016/j.cellsig.2008.01.010. PMID 18276110.
7. ↑ "SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia". Oncogene 22 (18): 2823–35. May 2003. doi:10.1038/sj.onc.1206367. PMID 12743605.
8. ↑ "SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription". J. Biol. Chem. 278 (29): 27072–9. July 2003. doi:10.1074/jbc.M209814200. PMID 12736262.

## Further reading

* "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1–2): 171–4. 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
* "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1–2): 149–56. 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
* "The DNA sequence and comparative analysis of human chromosome 20.". Nature 414 (6866): 865–71. 2002. doi:10.1038/414865a. PMID 11780052. Bibcode: 2001Natur.414..865D.
* "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. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
* "SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription.". J. Biol. Chem. 278 (29): 27072–9. 2003. doi:10.1074/jbc.M209814200. PMID 12736262.
* "SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia.". Oncogene 22 (18): 2823–35. 2003. doi:10.1038/sj.onc.1206367. PMID 12743605.
* "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. 2003. doi:10.1016/j.bbrc.2003.08.069. PMID 13679039. Bibcode: 2003BBRC..309..774H.
* "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. 2004. doi:10.1038/ng1285. PMID 14702039.
* "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades.". J. Biol. Chem. 279 (41): 42703–8. 2004. doi:10.1074/jbc.M407732200. PMID 15299019.
* "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
* "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. 2005. doi:10.1038/sj.emboj.7600596. PMID 15775988.
* "Characterization of human NIPK (TRB3, SKIP3) gene activation in stressful conditions.". Biochem. Biophys. Res. Commun. 330 (1): 210–8. 2005. doi:10.1016/j.bbrc.2005.02.149. PMID 15781252. Bibcode: 2005BBRC..330..210O.
* "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. 2005. doi:10.2337/diabetes.54.9.2807. PMID 16123373.
* "TRB3 is a PI 3-kinase dependent indicator for nutrient starvation.". Cell. Signal. 18 (6): 899–909. 2006. doi:10.1016/j.cellsig.2005.08.002. PMID 16129579.
* "A human protein-protein interaction network: a resource for annotating the proteome.". Cell 122 (6): 957–68. 2005. doi:10.1016/j.cell.2005.08.029. PMID 16169070.
* "Effect of TRB3 on insulin and nutrient-stimulated hepatic p70 S6 kinase activity.". J. Biol. Chem. 281 (40): 29719–29. 2006. doi:10.1074/jbc.M511636200. PMID 16887816.
* "Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis, and decreases TRB3.". Mol. Cell. Biol. 26 (22): 8217–27. 2007. doi:10.1128/MCB.00979-06. PMID 16966378.

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Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

| Non-specific serine/threonine protein kinases (EC 2.7.11.1)|

* LATS1
* LATS2
* MAST1
* MAST2
* STK38
* STK38L
* CIT
* ROCK1
* SGK
* SGK2
* SGK3
* Protein kinase B
* AKT1
* AKT2
* AKT3
* Ataxia telangiectasia mutated
* mTOR
* EIF-2 kinases
* PKR
* HRI
* EIF2AK3
* EIF2AK4
* Wee1
* WEE1

|

Pyruvate dehydrogenase kinase (EC 2.7.11.2)|

* PDK1
* PDK2
* PDK3
* PDK4

Dephospho-(reductase kinase) kinase (EC 2.7.11.3)|

* AMP-activated protein kinase α
* PRKAA1
* PRKAA2
* β
* PRKAB1
* PRKAB2
* γ
* PRKAG1
* PRKAG2
* PRKAG3

3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4)|

* BCKDK
* BCKDHA
* BCKDHB

(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)|

* IDH2
* IDH3A
* IDH3B
* IDH3G

(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)|

* STK4

Myosin-heavy-chain kinase (EC 2.7.11.7)|

* Aurora kinase
* Aurora A kinase
* Aurora B kinase
* Aurora C kinase

Fas-activated serine/threonine kinase (EC 2.7.11.8)|

* FASTK
* STK10

Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)|

* -

IκB kinase (EC 2.7.11.10)|

* CHUK
* IKK2
* TBK1
* IKBKE
* IKBKG
* IKBKAP

cAMP-dependent protein kinase (EC 2.7.11.11)|

* Protein kinase A
* PRKACG
* PRKACB
* PRKACA
* PRKY

cGMP-dependent protein kinase (EC 2.7.11.12)|

* Protein kinase G
* PRKG1

Protein kinase C (EC 2.7.11.13)|

* Protein kinase C
* Protein kinase Cζ
* PKC alpha
* PRKCB1
* PRKCD
* PRKCE
* PRKCH
* PRKCG
* PRKCI
* PRKCQ
* Protein kinase N1
* PKN2
* PKN3

Rhodopsin kinase (EC 2.7.11.14)|

* Rhodopsin kinase

Beta adrenergic receptor kinase (EC 2.7.11.15)|

* Beta adrenergic receptor kinase
* Beta adrenergic receptor kinase-2

G-protein coupled receptor kinases (EC 2.7.11.16)|

* GRK4
* GRK5
* GRK6

Ca2+/calmodulin-dependent (EC 2.7.11.17)|

* BRSK2
* CAMK1
* CAMK1A
* CAMK1B
* CAMK1D
* CAMK1G
* CAMK2
* CAMK2A
* CAMK2B
* CAMK2D
* CAMK2G
* CAMK4
* MLCK
* CASK
* CHEK1
* CHEK2
* DAPK1
* DAPK2
* DAPK3
* STK11
* MAPKAPK2
* MAPKAPK3
* MAPKAPK5
* MARK1
* MARK2
* MARK3
* MARK4
* MELK
* MKNK1
* MKNK2
* NUAK1
* NUAK2
* OBSCN
* PASK
* PHKG1
* PHKG2
* PIM1
* PIM2
* PKD1
* PRKD2
* PRKD3
* PSKH1
* SNF1LK2
* KIAA0999
* STK40
* SNF1LK
* SNRK
* SPEG
* TSSK2
* Kalirin
* TRIB1
* TRIB2
* TRIB3
* TRIO
* Titin
* DCLK1

Myosin light-chain kinase (EC 2.7.11.18)|

* MYLK
* MYLK2
* MYLK3
* MYLK4

Phosphorylase kinase (EC 2.7.11.19)|

* PHKA1
* PHKA2
* PHKB
* PHKG1
* PHKG2

Elongation factor 2 kinase (EC 2.7.11.20)|

* EEF2K
* STK19

Polo kinase (EC 2.7.11.21)|

* PLK1
* PLK2
* PLK3
* PLK4

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

| Polo kinase (EC 2.7.11.21)|

* PLK1
* PLK2
* PLK3
* PLK4

|

Cyclin-dependent kinase (EC 2.7.11.22)|

* CDK1
* CDK2
* CDKL2
* CDK3
* CDK4
* CDK5
* CDKL5
* CDK6
* CDK7
* CDK8
* CDK9
* CDK10
* CDK12
* CDC2L5
* PCTK1
* PCTK2
* PCTK3
* PFTK1
* CDC2L1

(RNA-polymerase)-subunit kinase (EC 2.7.11.23)|

* RPS6KA5
* RPS6KA4
* P70S6 kinase
* P70-S6 Kinase 1
* RPS6KB2
* RPS6KA2
* RPS6KA3
* RPS6KA1
* RPS6KC1

Mitogen-activated protein kinase (EC 2.7.11.24)|

* Extracellular signal-regulated
* MAPK1
* MAPK3
* MAPK4
* MAPK6
* MAPK7
* MAPK12
* MAPK15
* C-Jun N-terminal
* MAPK8
* MAPK9
* MAPK10
* P38 mitogen-activated protein
* MAPK11
* MAPK13
* MAPK14

MAP3K (EC 2.7.11.25)|

* MAP kinase kinase kinases
* MAP3K1
* MAP3K2
* MAP3K3
* MAP3K4
* MAP3K5
* MAP3K6
* MAP3K7
* MAP3K8
* RAFs
* ARAF
* BRAF
* KSR1
* KSR2
* MLKs
* MAP3K12
* MAP3K13
* MAP3K9
* MAP3K10
* MAP3K11
* MAP3K7
* ZAK
* CDC7
* MAP3K14

Tau-protein kinase (EC 2.7.11.26)|

* TPK1
* TTK
* GSK-3

(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)|

* -

Tropomyosin kinase (EC 2.7.11.28)|

* -

Low-density-lipoprotein receptor kinase (EC 2.7.11.29)|

* -

Receptor protein serine/threonine kinase (EC 2.7.11.30)|

* Bone morphogenetic protein receptors
* BMPR1
* BMPR1A
* BMPR1B
* BMPR2
* ACVR1
* ACVR1B
* ACVR1C
* ACVR2A
* ACVR2B
* ACVRL1
* Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

| MAP2K|

* MAP2K1
* MAP2K2
* MAP2K3
* MAP2K4
* MAP2K5
* MAP2K6
* MAP2K7

|

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Enzymes

Activity|

* Active site
* Binding site
* Catalytic triad
* Oxyanion hole
* Enzyme promiscuity
* Catalytically perfect enzyme
* Coenzyme
* Cofactor
* Enzyme catalysis

Regulation|

* Allosteric regulation
* Cooperativity
* Enzyme inhibitor
* Enzyme activator

Classification|

* EC number
* Enzyme superfamily
* Enzyme family
* List of enzymes

Kinetics|

* Enzyme kinetics
* Eadie–Hofstee diagram
* Hanes–Woolf plot
* Lineweaver–Burk plot
* Michaelis–Menten kinetics

Types|

* EC1 Oxidoreductases (list)
* EC2 Transferases (list)
* EC3 Hydrolases (list)
* EC4 Lyases (list)
* EC5 Isomerases (list)
* EC6 Ligases (list)
* EC7 Translocases (list)

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