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Q62070 (PIM2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase pim-2

EC=2.7.11.1
Gene names
Name:Pim2
Synonyms:Pim-2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length370 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 of 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. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

Interacts with MYC. Ref.12

Tissue specificity

Widely expressed, with highest expression in spleen, thymus and brain. Expressed in epiphyseal chondrocytes. Ref.4 Ref.11

Induction

Induced by a wide range of growth factors and mitogens; IL2, IL3, IL4, IL7,IL9 and by interferon-gamma (IFNG). Ref.4 Ref.6 Ref.10

Post-translational modification

Autophosphorylated. Ref.5 Ref.6 Ref.7

Disruption phenotype

Mice are viable and fertile. Deficient mice shown reduced T-cell activation and expansion in the presence of the serine/threonine protein kinase mTOR inhibitor rapamycin. Triple knockout mice PIM1/PIM2/PIM3 shown a profound reduction in body size at birth and throughout postnatal life due to a reduction in the number of cells rather than cell size. Ref.8 Ref.10

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
   Coding sequence diversityAlternative initiation
   DiseaseProto-oncogene
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic mitochondrial changes

Inferred from direct assay Ref.5. Source: MGI

negative regulation of apoptotic process

Inferred from direct assay Ref.5. Source: MGI

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay Ref.7. Source: UniProtKB

positive regulation of autophagy

Inferred from mutant phenotype Ref.11. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype Ref.12. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.7. Source: UniProtKB

protein stabilization

Inferred from direct assay Ref.12. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.12. Source: UniProtKB

protein kinase activity

Inferred from direct assay PubMed 11854514. Source: MGI

protein serine/threonine kinase activity

Inferred from direct assay Ref.12. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative initiation. [Align] [Select]
Isoform 1 (identifier: Q62070-1)

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: Q62070-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.
     26-26: L → M
Note: Initiates from CTG codon.
Isoform 3 (identifier: Q62070-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: Missing.
Note: Mutagen in position: 61:K->A (loss of kinase activity).

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 370370Serine/threonine-protein kinase pim-2
PRO_0000024366

Regions

Domain91 – 345255Protein kinase
Nucleotide binding97 – 1059ATP By similarity

Sites

Active site2221Proton acceptor By similarity
Binding site1201ATP By similarity

Natural variations

Alternative sequence1 – 5959Missing in isoform 3.
VSP_018856
Alternative sequence1 – 2525Missing in isoform 2.
VSP_018854
Alternative sequence261L → M in isoform 2.
VSP_018855

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 12BB70BFD04DBE8A

FASTA37040,060
        10         20         30         40         50         60 
MARATNLNAA PSAGASGPPD SLPSTLAPPS PGSPAALPRA STPCGLSGFS GLNIRSTSSM 

        70         80         90        100        110        120 
LTKPLQGHPS PPVTPTQPPG GKDRAAFEAE YRLGPLLGKG GFGTVFAGHR VTDRRQVAIK 

       130        140        150        160        170        180 
VISRNRVLGW STVSDSVTCP LEVALLWKVG EGNGHPGVIR LLDWFETPEG FMLVLERPMP 

       190        200        210        220        230        240 
AQDLFDYITE KGPLGESCSR SFFTQVVAAV QHCHARGVVH RDIKDENILI DLCRGSIKLI 

       250        260        270        280        290        300 
DFGSGALLHD EPYTDFDGTR VYSPPEWISR HQYHALPATV WSLGVLLYDM VCGDIPFERD 

       310        320        330        340        350        360 
QEILEAELHF PAHVSPDCCA LIRRCLAPKP CSRPSLEEIL LDPWMQSPAE EKPINSSKGS 

       370 
PTPLPWSLLP 

« Hide

Isoform 2 [UniParc].

Checksum: EA5EA9E7718C74E3
Show »

FASTA34537,741
Isoform 3 [UniParc].

Checksum: F7B770908D23A710
Show »

FASTA31134,487

References

« Hide 'large scale' references
[1]"Proviral tagging in E mu-myc transgenic mice lacking the Pim-1 proto-oncogene leads to compensatory activation of Pim-2."
van der Lugt N.M., Domen J., Verhoeven E., Linders K., van der Gulden H., Allen J., Berns A.
EMBO J. 14:2536-2544(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), ALTERNATIVE INITIATION.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Strain: FVB/N.
Tissue: Mammary gland.
[4]"Pim-2 transgene induces lymphoid tumors, exhibiting potent synergy with c-myc."
Allen J.D., Verhoeven E., Domen J., van der Valk M., Berns A.
Oncogene 15:1133-1141(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, FUNCTION IN TUMORIGENESIS, INDUCTION BY IL2; IL3; IL4; IL7; IL9 AND INTERFERON-GAMMA.
[5]"The serine/threonine kinase Pim-2 is a transcriptionally regulated apoptotic inhibitor."
Fox C.J., Hammerman P.S., Cinalli R.M., Master S.R., Chodosh L.A., Thompson C.B.
Genes Dev. 17:1841-1854(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS APOPTOTIC INHIBITOR, AUTOPHOSPHORYLATION, PHOSPHORYLATION OF BAD, ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 3).
[6]"The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced cell death."
Yan B., Zemskova M., Holder S., Chin V., Kraft A., Koskinen P.J., Lilly M.
J. Biol. Chem. 278:45358-45367(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION BY IL3, FUNCTION AS APOPTOTIC INHIBITOR, PHOSPHORYLATION OF BAD, MUTAGENESIS.
[7]"Lymphocyte transformation by Pim-2 is dependent on nuclear factor-kappaB activation."
Hammerman P.S., Fox C.J., Cinalli R.M., Xu A., Wagner J.D., Lindsten T., Thompson C.B.
Cancer Res. 64:8341-8348(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A POSITIVE REGULATOR OF I-KAPPAB KINASE/NF-KAPPAB CASCADE, PHOSPHORYLATION OF MAP3K8/COT.
[8]"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.
[9]"Pim and Akt oncogenes are independent regulators of hematopoietic cell growth and survival."
Hammerman P.S., Fox C.J., Birnbaum M.J., Thompson C.B.
Blood 105:4477-4483(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE REGULATION OF CAP-DEPENDENT PROTEIN TRANSLATION.
[10]"The Pim kinases control rapamycin-resistant T cell survival and activation."
Fox C.J., Hammerman P.S., Thompson C.B.
J. Exp. Med. 201:259-266(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, INDUCTION BY IL4 AND IL7.
[11]"PIM-2 is an independent regulator of chondrocyte survival and autophagy in the epiphyseal growth plate."
Bohensky J., Shapiro I.M., Leshinsky S., Watanabe H., Srinivas V.
J. Cell. Physiol. 213:246-251(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[12]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L41495 mRNA. Translation: AAA98922.1.
L41495 mRNA. Translation: AAA98923.1.
L41495 mRNA. Translation: AAA98924.1.
AL671978 Genomic DNA. Translation: CAM24546.1.
BC027376 mRNA. Translation: AAH27376.1.
CCDSCCDS29976.1. [Q62070-1]
PIRS55333.
RefSeqNP_613072.1. NM_138606.2. [Q62070-1]
UniGeneMm.347478.

3D structure databases

ProteinModelPortalQ62070.
SMRQ62070. Positions 49-364.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202167. 1 interaction.
MINTMINT-232729.

PTM databases

PhosphoSiteQ62070.

Proteomic databases

PRIDEQ62070.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID18715.
KEGGmmu:18715.
UCSCuc009smz.1. mouse. [Q62070-1]

Organism-specific databases

CTD11040.
MGIMGI:97587. Pim2.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000231357.
HOVERGENHBG106681.
InParanoidA2AER1.
KOK08806.
PhylomeDBQ62070.

Gene expression databases

CleanExMM_PIM2.
GenevestigatorQ62070.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio294801.
PROQ62070.
SOURCESearch...

Entry information

Entry namePIM2_MOUSE
AccessionPrimary (citable) accession number: Q62070
Secondary accession number(s): A2AER1 expand/collapse secondary AC list , Q62071, Q62072, Q8R2P0
Entry history
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot