TRIB2

Protein-coding gene in the species Homo sapiens
TRIB2
Identifiers
AliasesTRIB2, C5FW, GS3955, TRB2, tribbles pseudokinase 2
External IDsOMIM: 609462; MGI: 2145021; HomoloGene: 41445; GeneCards: TRIB2; OMA:TRIB2 - orthologs
Gene location (Human)
Chromosome 2 (human)
Chr.Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for TRIB2
Genomic location for TRIB2
Band2p24.3Start12,716,910 bp[1]
End12,742,734 bp[1]
Gene location (Mouse)
Chromosome 12 (mouse)
Chr.Chromosome 12 (mouse)[2]
Chromosome 12 (mouse)
Genomic location for TRIB2
Genomic location for TRIB2
Band12|12 A1.1Start15,841,728 bp[2]
End15,866,923 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • ganglionic eminence

  • tibial nerve

  • trigeminal ganglion

  • spleen

  • renal medulla

  • left adrenal gland

  • right adrenal gland

  • lymph node

  • spinal ganglia

  • frontal pole
Top expressed in
  • cumulus cell

  • vas deferens

  • medial ganglionic eminence

  • interventricular septum

  • atrioventricular valve

  • saccule

  • retina

  • endocardial cushion

  • left lung lobe

  • right lung lobe
More reference expression data
BioGPS


More reference expression data
Gene ontology
Molecular function
  • nucleotide binding
  • protein kinase activity
  • protein kinase inhibitor activity
  • transcription factor binding
  • mitogen-activated protein kinase kinase binding
  • ubiquitin protein ligase binding
  • ubiquitin-protein transferase regulator activity
Cellular component
  • cytoplasm
  • cytoskeleton
  • nucleus
Biological process
  • regulation of MAP kinase activity
  • protein phosphorylation
  • negative regulation of fat cell differentiation
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process
  • negative regulation of protein kinase activity
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

28951

217410

Ensembl

ENSG00000071575

ENSMUSG00000020601

UniProt

Q92519

Q8K4K3

RefSeq (mRNA)

NM_021643

NM_144551

RefSeq (protein)

NP_067675

NP_653134

Location (UCSC)Chr 2: 12.72 – 12.74 MbChr 12: 15.84 – 15.87 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Tribbles homolog 2 is an atypical protein kinase that is encoded in human by the TRIB2 gene.[5][6][7][8] TRIB2 is a pseudokinase member of the (pseudoenzyme) class of signaling/scaffold proteins, possessing very low vestigial catalytic output in vitro and critical scaffolding signaling functions in cells.[9] It is known to signal to canonical MAPK and AKT pathways and to regulate the ubiquitination of substrates with important functions in cell proliferation that control the cell ccyle. It has also been associated with various diseases, especially in human and murine blood and solid tumor models.[10] Like TRIB1 and TRIB3, TRIB2 has recently been considered as a potential allosteric drug target,[11] and its three dimensional structure has been solved with the aid of stabilizing nanobodies [12] corroborating the potential for new approaches for drug targeting outside the highly degraded ATP site [13] and is a putative regulator of cancer-associated signalling and survival through AKT pSer473 modulation.[14] Recent work has established a convincing link between targetable overexpression of TRIB2 and prostate cancer drug responses [15]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000071575 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020601 – 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. ^ Wu M, Xu LG, Zhai Z, Shu HB (Jul 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.
  6. ^ Keeshan K, He Y, Wouters BJ, Shestova O, Xu L, Sai H, Rodriguez CG, Maillard I, Tobias JW, Valk P, Carroll M, Aster JC, Delwel R, Pear WS (Nov 2006). "Tribbles homolog 2 inactivates C/EBPalpha and causes acute myelogenous leukemia". Cancer Cell. 10 (5): 401–11. doi:10.1016/j.ccr.2006.09.012. PMC 2839500. PMID 17097562.
  7. ^ 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. S2CID 24556931.
  8. ^ "Entrez Gene: TRIB2 tribbles homolog 2 (Drosophila)".
  9. ^ Bailey FP, et al. (2015). "The Tribbles 2 (TRB2) pseudokinase binds to ATP and autophosphorylate very weakly in a metal-independent manner". Biochemical Society Transactions. 467 (1): 47–62. doi:10.1042/BJ20141441. PMC 4844368. PMID 25583260.
  10. ^ 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.
  11. ^ 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.
  12. ^ Jamieson SA, Pudjihartono M, Horne CR, Viloria JS, Dunlop JL, McMillan HD, Day RC, Keeshan K, Murphy JM, Mace PD (2022). "Nanobodies identify an activated state of the TRIB2 pseudokinase". Structure. 30 (11): 1518–1529. doi:10.1016/j.str.2022.08.006. PMID 36108635.
  13. ^ Byrne DP, Foulkes DM, Eyers PA (2017). "Pseudokinases: update on their functions and evaluation as new drug targets". Future Medicinal Chemistry. 9 (2): 245–265. doi:10.4155/fmc-2016-0207. PMID 28097887.
  14. ^ Foulkes DM, Byrne DP, Yeun W, Shrestha S, Bailey FP, Ferries S, Eyers CE, Keeshan K, Wells C, Drewry DH, Zuercher WJ, Kannan N, Eyers PA (2018). "Covalent inhibitors of EGFR family protein kinases induce degradation of human Tribbles 2 (TRIB2) pseudokinase in cancer cells". Science Signaling. 11: 14687. doi:10.1126/scisignal.aat795. PMID 28276427.
  15. ^ Monga J, Valeriote F, Hwang C, Gadgeel S, Ghosh J (2023). "Daclatasvir, an Antiviral Drug, Downregulates Tribbles 2 Pseudokinase and Resensitizes Enzalutamide-Resistant Prostate Cancer Cells". Molecular Cancer Therapeutics. 22: 381–392. doi:10.1126/scisignal.aat795. PMID 28276427.

Further reading

  • 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.
  • Kiss-Toth E, Bagstaff SM, Sung HY, et al. (2004). "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades" (PDF). J. Biol. Chem. 279 (41): 42703–8. doi:10.1074/jbc.M407732200. PMID 15299019. S2CID 25829757.
  • 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.
  • Hillier LW, Graves TA, Fulton RS, et al. (2005). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4". Nature. 434 (7034): 724–31. Bibcode:2005Natur.434..724H. doi:10.1038/nature03466. PMID 15815621.
  • Zhang Y, Davis JL, Li W (2005). "Identification of tribbles homolog 2 as an autoantigen in autoimmune uveitis by phage display". Mol. Immunol. 42 (11): 1275–81. doi:10.1016/j.molimm.2004.11.020. PMID 15950723.
  • Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569. S2CID 13709685.
  • Lin KR, Lee SF, Hung CM, et al. (2007). "Survival factor withdrawal-induced apoptosis of TF-1 cells involves a TRB2-Mcl-1 axis-dependent pathway". J. Biol. Chem. 282 (30): 21962–72. doi:10.1074/jbc.M701663200. PMID 17545167.
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Non-specific serine/threonine protein kinases (EC 2.7.11.1)
Pyruvate dehydrogenase kinase (EC 2.7.11.2)
Dephospho-(reductase kinase) kinase (EC 2.7.11.3)
3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4)
(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)
(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)
Myosin-heavy-chain kinase (EC 2.7.11.7)
Fas-activated serine/threonine kinase (EC 2.7.11.8)
Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)
  • -
IκB kinase (EC 2.7.11.10)
cAMP-dependent protein kinase (EC 2.7.11.11)
cGMP-dependent protein kinase (EC 2.7.11.12)
Protein kinase C (EC 2.7.11.13)
Rhodopsin kinase (EC 2.7.11.14)
Beta adrenergic receptor kinase (EC 2.7.11.15)
G-protein coupled receptor kinases (EC 2.7.11.16)
Ca2+/calmodulin-dependent (EC 2.7.11.17)
Myosin light-chain kinase (EC 2.7.11.18)
Phosphorylase kinase (EC 2.7.11.19)
Elongation factor 2 kinase (EC 2.7.11.20)
Polo kinase (EC 2.7.11.21)
Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)
Polo kinase (EC 2.7.11.21)
Cyclin-dependent kinase (EC 2.7.11.22)
(RNA-polymerase)-subunit kinase (EC 2.7.11.23)
Mitogen-activated protein kinase (EC 2.7.11.24)
MAP3K (EC 2.7.11.25)
Tau-protein kinase (EC 2.7.11.26)
(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)
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Receptor protein serine/threonine kinase (EC 2.7.11.30)
MAP2K
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