PIM1 - Serine/threonine-protein kinase pim-1 - human protein (Function)
 
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PIM1 »  Serine/threonine-protein kinase pim-1
 
Gene name:  PIM1
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 163 2
GENE REF ISO

Function

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Overview 
Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.  
7
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • IDAUniProtKB
Manganese ion bindingdefinition[GO:0030145]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
4
  • IPIUniProtKB
  • IPIIntAct
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • IDAUniProtKB
Ribosomal small subunit bindingdefinition[GO:0043024]  
1
  • IPIUniProtKB
Transcription factor bindingdefinition[GO:0008134]  
1
  • IPIUniProtKB
GO biological process 
Apoptotic processdefinition[GO:0006915]  
  • IEAUniProtKB KW
Cell cycledefinition[GO:0007049]  
  • IEAUniProtKB KW
Cell proliferationdefinition[GO:0008283]  
1
  • IDAUniProtKB
Hyaluronan metabolic processdefinition[GO:0030212] silver  
  • IEAOrtholog Compara
Multicellular organismal developmentdefinition[GO:0007275]  
1
  • TASPINC
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • IDAUniProtKB
Negative regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0043433]  
1
  • IDAUniProtKB
Isoform  Iso 2   Positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycledefinition[GO:0031659]  
1
  • IDAUniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
2
  • IMPUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
3
  • IDAUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
3
  • CuratedUniProtKB
It requires the following cofactor
Magnesium.  
3
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Acute myeloid leukemia  hsa05221+5292  
Jak-STAT signaling pathway  hsa04630+5292  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Cell cycle  definition   [KW-0131]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: PIM1
GenomeRNAi: 5292
PRO: PR:P11309
Chemistry
GuidetoPHARMACOLOGY: 2158