Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q62070

- PIM2_MOUSE

UniProt

Q62070 - PIM2_MOUSE

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 113 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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 binding Source: UniProtKB
    3. protein kinase activity Source: MGI
    4. 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

    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.
    InParanoidiA2AER1.
    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_dom.
    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

    MARATNLNAA PSAGASGPPD SLPSTLAPPS PGSPAALPRA STPCGLSGFS    50
    GLNIRSTSSM LTKPLQGHPS PPVTPTQPPG GKDRAAFEAE YRLGPLLGKG 100
    GFGTVFAGHR VTDRRQVAIK VISRNRVLGW STVSDSVTCP LEVALLWKVG 150
    EGNGHPGVIR LLDWFETPEG FMLVLERPMP AQDLFDYITE KGPLGESCSR 200
    SFFTQVVAAV QHCHARGVVH RDIKDENILI DLCRGSIKLI DFGSGALLHD 250
    EPYTDFDGTR VYSPPEWISR HQYHALPATV WSLGVLLYDM VCGDIPFERD 300
    QEILEAELHF PAHVSPDCCA LIRRCLAPKP CSRPSLEEIL LDPWMQSPAE 350
    EKPINSSKGS PTPLPWSLLP 370

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 A2AER1.
    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_dom.
    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

    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 1, 2014
    This is version 113 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