TRIB2

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TRIB2
Identifiers
AliasesTRIB2, C5FW, GS3955, TRB2, tribbles pseudokinase 2
External IDsMGI: 2145021 HomoloGene: 41445 GeneCards: TRIB2
Gene location (Human)
Chromosome 2 (human)
Chr.Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for TRIB2
Genomic location for TRIB2
Band2p24.3Start12,716,889 bp[1]
End12,742,734 bp[1]
RNA expression pattern
PBB GE TRIB2 202478 at fs.png

PBB GE TRIB2 202479 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_021643

NM_144551

RefSeq (protein)

NP_067675

NP_653134

Location (UCSC)Chr 2: 12.72 – 12.74 MbChr 12: 15.79 – 15.82 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 little vestigial catalytic output in vitro.[9] It is known to signal to canonical MAPK pathways and to regulate the ubiquitination of substrates with important functions in the immune system. It has also been associated with various diseases, especially in vertebrate leukaemia models.[10] Like TRIB1 and TRIB3, TRIB2 has recently been considered as a potential allosteric drug target,[11][12] and is a putative regulator of cancer-associated signalling and survival through AKT pSer473 modulation [13]


References[edit]

  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:".
  4. ^ "Mouse PubMed Reference:".
  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.
  8. ^ "Entrez Gene: TRIB2 tribbles homolog 2 (Drosophila)".
  9. ^ Bailey FP, et al. (2015). "The Tribbles 2 (TRB2) pseudokinase binds to ATP and autophosphorylates 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. In Press (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. ^ 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.
  13. ^ Hill R, Madureira PA, Ferreira B, Baptista I, Machado S, Colaço L, Dos Santos M, Liu N, Dopazo A, Ugurel S, Adrienn A, Kiss-Toth E, Isbilen M, Gure AO, Link W (2017). "TRIB2 confers resistance to anti-cancer therapy by activating the serine/threonine protein kinase AKT". Nature Communications. 8 (5): 14687. doi:10.1038/ncomms14687. PMC 5347136. PMID 28276427.

Further reading[edit]