Serine/threonine-protein kinase pim-2

UniProt Q9P1W9 Organism Homo sapiens Gene PIM2 EC 2.7.11.1

Also known as: PIM2

Function

Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression, the regulation of cap-dependent protein translation and through survival signaling by phosphorylation of a pro-apoptotic protein, BAD. Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase transcriptional activity. The stabilization of MYC exerted by PIM2 might explain partly the strong synergism between these 2 oncogenes in tumorigenesis. Regulates cap-dependent protein translation in a mammalian target of rapamycin complex 1 (mTORC1)-independent manner and in parallel to the PI3K-Akt pathway. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Promotes cell survival in response to a variety of proliferative signals via positive regulation of the I-kappa-B kinase/NF-kappa-B cascade; this process requires phosphorylation of MAP3K8/COT. Promotes growth factor-independent proliferation by phosphorylation of cell cycle factors such as CDKN1A and CDKN1B. Involved in the positive regulation of chondrocyte survival and autophagy in the epiphyseal growth plate.

Classification

Family (Pfam): PF00069 Pkinase
InterPro: Kinase-like_dom_sf, PIM1/2/3, PIM_Ser/Thr_kinase, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
Functional cluster: Secreted Growth Factors & Cytokines

Experimental structures · PDB · 2

2IWI X-ray 2.80A
4X7Q X-ray 2.33A

A predicted model is available from AlphaFold.

Gene Ontology · 15

Drugs targeting this protein · 3

SGI-1776 inhibitor
AZD-1208 inhibitor
LGH-447 inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Cyclin-dependent kinase inhibitor 1 1 shared papers
Serine/threonine-protein kinase pim-3 1 shared papers
Serine/threonine-protein kinase pim-1 1 shared papers
Forkhead box protein O3 1 shared papers
Cyclin-dependent kinase inhibitor 1B 1 shared papers
Serine/threonine-protein kinase DCLK1 1 shared papers
AP-1 complex subunit sigma-1A 1 shared papers
Elongation factor 1-gamma 1 shared papers
Stathmin 1 shared papers
Translationally-controlled tumor protein 1 shared papers
Actin, aortic smooth muscle 1 shared papers
Ornithine decarboxylase 1 shared papers

Literature · 10 cited papers

Pim-2 phosphorylation of p21(Cip1/WAF1) enhances its stability and inhibits cell proliferation in HCT116 cells. Int. J. Biochem. Cell Biol. · 2010
Crystal structure of the PIM2 kinase in complex with an organoruthenium inhibitor. PLoS ONE · 2009
Serine/threonine kinase Pim-2 promotes liver tumorigenesis induction through mediating survival and preventing apoptosis of liver cell. J. Surg. Res. · 2009
Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels. Cancer Res. · 2008
Patterns of somatic mutation in human cancer genomes. Nature · 2007
Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection. Cell. Microbiol. · 2006
The DNA sequence of the human X chromosome. Nature · 2005
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
The human Pim-2 proto-oncogene and its testicular expression. Biochim. Biophys. Acta · 1998

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