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Q62070

- PIM2_MOUSE

UniProt

Q62070 - PIM2_MOUSE

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Protein

Serine/threonine-protein kinase pim-2

Gene

Pim2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei120 – 1201ATPPROSITE-ProRule annotation
Active sitei222 – 2221Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi97 – 1059ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. protein kinase activity Source: MGI
  3. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. apoptotic mitochondrial changes Source: MGI
  2. G1/S transition of mitotic cell cycle Source: UniProtKB
  3. negative regulation of apoptotic process Source: MGI
  4. negative regulation of cell proliferation Source: UniProtKB
  5. positive regulation of autophagy Source: UniProtKB
  6. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  7. positive regulation of transcription, DNA-templated Source: UniProtKB
  8. protein phosphorylation Source: UniProtKB
  9. protein stabilization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase pim-2 (EC:2.7.11.1)
Gene namesi
Name:Pim2
Synonyms:Pim-2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Unplaced

Organism-specific databases

MGIiMGI:97587. Pim2.

Pathology & Biotechi

Disruption phenotypei

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.2 Publications

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 370370Serine/threonine-protein kinase pim-2PRO_0000024366Add
BLAST

Post-translational modificationi

Autophosphorylated.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiQ62070.

PTM databases

PhosphoSiteiQ62070.

Expressioni

Tissue specificityi

Widely expressed, with highest expression in spleen, thymus and brain. Expressed in epiphyseal chondrocytes.2 Publications

Inductioni

Induced by a wide range of growth factors and mitogens; IL2, IL3, IL4, IL7,IL9 and by interferon-gamma (IFNG).3 Publications

Gene expression databases

CleanExiMM_PIM2.
GenevestigatoriQ62070.

Interactioni

Subunit structurei

Interacts with MYC.1 Publication

Protein-protein interaction databases

BioGridi202167. 1 interaction.
MINTiMINT-232729.

Structurei

3D structure databases

ProteinModelPortaliQ62070.
SMRiQ62070. Positions 49-364.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini91 – 345255Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000231357.
HOVERGENiHBG106681.
InParanoidiQ62070.
KOiK08806.
PhylomeDBiQ62070.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative initiation. Align

Isoform 1 (identifier: Q62070-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MARATNLNAA PSAGASGPPD SLPSTLAPPS PGSPAALPRA STPCGLSGFS
60 70 80 90 100
GLNIRSTSSM LTKPLQGHPS PPVTPTQPPG GKDRAAFEAE YRLGPLLGKG
110 120 130 140 150
GFGTVFAGHR VTDRRQVAIK VISRNRVLGW STVSDSVTCP LEVALLWKVG
160 170 180 190 200
EGNGHPGVIR LLDWFETPEG FMLVLERPMP AQDLFDYITE KGPLGESCSR
210 220 230 240 250
SFFTQVVAAV QHCHARGVVH RDIKDENILI DLCRGSIKLI DFGSGALLHD
260 270 280 290 300
EPYTDFDGTR VYSPPEWISR HQYHALPATV WSLGVLLYDM VCGDIPFERD
310 320 330 340 350
QEILEAELHF PAHVSPDCCA LIRRCLAPKP CSRPSLEEIL LDPWMQSPAE
360 370
EKPINSSKGS PTPLPWSLLP

Note: Initiates from CTG codon.

Length:370
Mass (Da):40,060
Last modified:November 1, 1996 - v1
Checksum:i12BB70BFD04DBE8A
GO
Isoform 2 (identifier: Q62070-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.
     26-26: L → M

Note: Initiates from CTG codon.

Show »
Length:345
Mass (Da):37,741
Checksum:iEA5EA9E7718C74E3
GO
Isoform 3 (identifier: Q62070-3) [UniParc]FASTAAdd to Basket

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).

Show »
Length:311
Mass (Da):34,487
Checksum:iF7B770908D23A710
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5959Missing in isoform 3. 2 PublicationsVSP_018856Add
BLAST
Alternative sequencei1 – 2525Missing in isoform 2. 1 PublicationVSP_018854Add
BLAST
Alternative sequencei26 – 261L → M in isoform 2. 1 PublicationVSP_018855

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS29976.1. [Q62070-1]
PIRiS55333.
RefSeqiNP_613072.1. NM_138606.2. [Q62070-1]
UniGeneiMm.347478.

Genome annotation databases

GeneIDi18715.
KEGGimmu:18715.
UCSCiuc009smz.1. mouse. [Q62070-1]

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS29976.1. [Q62070-1 ]
PIRi S55333.
RefSeqi NP_613072.1. NM_138606.2. [Q62070-1 ]
UniGenei Mm.347478.

3D structure databases

ProteinModelPortali Q62070.
SMRi Q62070. Positions 49-364.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 202167. 1 interaction.
MINTi MINT-232729.

PTM databases

PhosphoSitei Q62070.

Proteomic databases

PRIDEi Q62070.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 18715.
KEGGi mmu:18715.
UCSCi uc009smz.1. mouse. [Q62070-1 ]

Organism-specific databases

CTDi 11040.
MGIi MGI:97587. Pim2.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000231357.
HOVERGENi HBG106681.
InParanoidi Q62070.
KOi K08806.
PhylomeDBi Q62070.

Miscellaneous databases

NextBioi 294801.
PROi Q62070.
SOURCEi Search...

Gene expression databases

CleanExi MM_PIM2.
Genevestigatori Q62070.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiPIM2_MOUSE
AccessioniPrimary (citable) accession number: Q62070
Secondary accession number(s): A2AER1
, Q62071, Q62072, Q8R2P0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: November 1, 1996
Last modified: October 29, 2014
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3