P06803 (PIM1_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 129. History...
Names and origin
|Protein names||Recommended name:|
Serine/threonine-protein kinase pim-1
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||397 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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 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 By similarity. Ref.2 Ref.6 Ref.7 Ref.8 Ref.9
ATP + a protein = ADP + a phosphoprotein.
Magnesium By similarity.
Binds to RP9. Interacts with CDKN1B and FOXO3 By similarity. Isoform 2 is isolated as a monomer whereas isoform 1 complexes with other proteins. Isoform 2 is isolated as a monomer whereas isoform 1 complexes with other proteins. Isoform 1, but not isoform 2, binds BMX. Interacts with BAD. Interacts with PPP2CA; this interaction promotes dephosphorylation of PIM1, ubiquitination and proteasomal degradation By similarity. Interacts with HSP90, this interaction stabilizes PIM1 protein levels. Interacts (ubiquitinated form) with HSP70 and promotes its proteosomal degradation By similarity. Interacts with CDKN1A By similarity. Interacts with CDC25C By similarity. Interacts (via N-terminal 96 residues) with CDC25A By similarity. Interacts with MAP3K5 By similarity. Interacts with MYC By similarity. Ref.5 Ref.6 Ref.8
Autophosphorylated on both serine/threonine and tyrosine residues. Phosphorylated. Interaction with PPP2CA promotes dephosphorylation By similarity. Ref.2
Ubiquitinated, leading to proteasomal degradation By similarity.
|Involvement in disease|
Frequently activated by provirus insertion in murine leukemia virus-induced T-cell lymphomas.
Deficient mice are viable and fertile however they have a specific defect in interleukin-7 (IL7)-driven growth of pre-B cells, as well as IL3-dependent growth of bone marrow-derived mast cells. Triple knockout mice PIM1/PIM2/PIM3 are viable and fertile too, but their body size is reduced at birth and throughout postnatal life due to a reduction in the number of cells rather than cell size. Ref.3 Ref.4 Ref.7
Contains 1 protein kinase domain.
|This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]|
|Isoform 1 (identifier: P06803-1) |
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
|Note: Initiates from CTG codon.|
|Isoform 2 (identifier: P06803-2) |
The sequence of this isoform differs from the canonical sequence as follows:
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 397||397||Serine/threonine-protein kinase pim-1||PRO_0000043351|
|Domain||122 – 374||253||Protein kinase|
|Nucleotide binding||128 – 136||9||ATP By similarity|
|Active site||251||1||Proton acceptor By similarity|
|Binding site||205||1||ATP; via carbonyl oxygen By similarity|
|Binding site||212||1||ATP By similarity|
Amino acid modifications
|Modified residue||92||1||Phosphoserine By similarity|
|Modified residue||107||1||Phosphothreonine By similarity|
|Modified residue||182||1||Phosphoserine By similarity|
|Modified residue||345||1||Phosphoserine By similarity|
|Alternative sequence||1 – 84||84||Missing in isoform 2.||VSP_018853|
|Mutagenesis||151||1||K → M: Loss of autophosphorylation and kinase activity. Ref.2|
|||"The primary structure of the putative oncogene pim-1 shows extensive homology with protein kinases."|
Selten G., Cuypers H.T., Boelens W., Robanus-Maandag E., Verbeek J., Domen J., van Beveren C., Berns A.
Cell 46:603-611(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
|||"The pim-1 oncogene encodes two related protein-serine/threonine kinases by alternative initiation at AUG and CUG."|
Saris C.J., Domen J., Berns A.
EMBO J. 10:655-664(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE INITIATION, FUNCTION, COMPLEX FORMATION, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-151.
|||"Impaired interleukin-3 response in Pim-1-deficient bone marrow-derived mast cells."|
Domen J., van der Lugt N.M., Laird P.W., Saris C.J., Clarke A.R., Hooper M.L., Berns A.
Blood 82:1445-1452(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
|||"Pim-1 levels determine the size of early B lymphoid compartments in bone marrow."|
Domen J., van der Lugt N.M., Acton D., Laird P.W., Linders K., Berns A.
J. Exp. Med. 178:1665-1673(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
|||"PAP-1, a novel target protein of phosphorylation by Pim-1 kinase."|
Maita H., Harada Y., Nagakubo D., Kitaura H., Ikeda M., Tamai K., Takahashi K., Ariga H., Iguchi-Ariga S.M.M.
Eur. J. Biochem. 267:5168-5178(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RP9.
|||"Pim-1 kinase promotes inactivation of the pro-apoptotic Bad protein by phosphorylating it on the Ser112 gatekeeper site."|
Aho T.L., Sandholm J., Peltola K.J., Mankonen H.P., Lilly M., Koskinen P.J.
FEBS Lett. 571:43-49(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BAD, INTERACTION WITH BAD.
|||"Mice deficient for all PIM kinases display reduced body size and impaired responses to hematopoietic growth factors."|
Mikkers H., Nawijn M., Allen J., Brouwers C., Verhoeven E., Jonkers J., Berns A.
Mol. Cell. Biol. 24:6104-6115(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
|||"Pim kinase-dependent inhibition of c-Myc degradation."|
Zhang Y., Wang Z., Li X., Magnuson N.S.
Oncogene 27:4809-4819(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF MYC, INTERACTION WITH MYC.
|||"Dissection of PIM serine/threonine kinases in FLT3-ITD-induced leukemogenesis reveals PIM1 as regulator of CXCL12-CXCR4-mediated homing and migration."|
Grundler R., Brault L., Gasser C., Bullock A.N., Dechow T., Woetzel S., Pogacic V., Villa A., Ehret S., Berridge G., Spoo A., Dierks C., Biondi A., Knapp S., Duyster J., Schwaller J.
J. Exp. Med. 206:1957-1970(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CXCR4, FUNCTION IN CELL MIGRATION.
|M13945 Genomic DNA. Translation: AAA39930.1.|
|PIR||TVMSP1. A24169. |
3D structure databases
|SMR||P06803. Positions 92-392. |
Protocols and materials databases
Genome annotation databases
|UCSC||uc008bta.1. mouse. |
|MGI||MGI:97584. Pim1. |
Gene expression databases
Family and domain databases
|InterPro||IPR011009. Kinase-like_dom. |
|Pfam||PF00069. Pkinase. 1 hit. |
|PIRSF||PIRSF037993. STPK_Pim-1. 1 hit. |
|SMART||SM00220. S_TKc. 1 hit. |
|SUPFAM||SSF56112. SSF56112. 1 hit. |
|PROSITE||PS00107. PROTEIN_KINASE_ATP. 1 hit. |
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
|Accession||Primary (citable) accession number: P06803|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|