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P06803

- PIM1_MOUSE

UniProt

P06803 - PIM1_MOUSE

Protein

Serine/threonine-protein kinase pim-1

Gene

Pim1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 133 (01 Oct 2014)
      Sequence version 2 (06 Dec 2005)
      Previous versions | rss
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    Functioni

    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.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei151 – 1511ATP
    Binding sitei205 – 2051ATP; via carbonyl oxygenPROSITE-ProRule annotation
    Binding sitei212 – 2121ATPPROSITE-ProRule annotation
    Active sitei251 – 2511Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi128 – 1369ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. manganese ion binding Source: UniProtKB
    3. protein binding Source: UniProtKB
    4. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. cell cycle Source: UniProtKB-KW
    3. cell proliferation Source: UniProtKB
    4. negative regulation of apoptotic process Source: UniProtKB
    5. positive regulation of transcription, DNA-templated Source: UniProtKB
    6. protein phosphorylation Source: UniProtKB
    7. protein stabilization Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, Cell cycle

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine/threonine-protein kinase pim-1 (EC:2.7.11.1)
    Gene namesi
    Name:Pim1
    Synonyms:Pim-1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:97584. Pim1.

    Subcellular locationi

    Cytoplasm 1 Publication. Nucleus 1 Publication. Cell membrane 1 Publication
    Note: Mainly located in the cytoplasm.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell
    3. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Frequently activated by provirus insertion in murine leukemia virus-induced T-cell lymphomas.

    Disruption phenotypei

    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.3 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi151 – 1511K → M: Loss of autophosphorylation and kinase activity. 1 Publication

    Keywords - Diseasei

    Proto-oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 397397Serine/threonine-protein kinase pim-1PRO_0000043351Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei92 – 921PhosphoserineBy similarity
    Modified residuei107 – 1071PhosphothreonineBy similarity
    Modified residuei182 – 1821PhosphoserineBy similarity
    Modified residuei345 – 3451PhosphoserineBy similarity

    Post-translational modificationi

    Autophosphorylated on both serine/threonine and tyrosine residues. Phosphorylated. Interaction with PPP2CA promotes dephosphorylation By similarity.By similarity
    Ubiquitinated, leading to proteasomal degradation.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiP06803.

    PTM databases

    PhosphoSiteiP06803.

    Expressioni

    Gene expression databases

    CleanExiMM_PIM1.
    GenevestigatoriP06803.

    Interactioni

    Subunit structurei

    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.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliP06803.
    SMRiP06803. Positions 92-392.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini122 – 374253Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000231357.
    HOVERGENiHBG106681.
    InParanoidiP06803.
    PhylomeDBiP06803.

    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.
    IPR017348. Ser/Thr_kinase_Pim-1.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    PIRSFiPIRSF037993. STPK_Pim-1. 1 hit.
    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 (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative initiation. Align

    Isoform 1 (identifier: P06803-1) [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

    MGPAAPLALP PPALPDPAGE PARGQPRQRP QSSSDSPSAL RASRSQSRNA    50
    TRSLSPGRRL SPSSLRRRCC SSRHRRRTDT LEVGMLLSKI NSLAHLRARP 100
    CNDLHATKLA PGKEKEPLES QYQVGPLLGS GGFGSVYSGI RVADNLPVAI 150
    KHVEKDRISD WGELPNGTRV PMEVVLLKKV SSDFSGVIRL LDWFERPDSF 200
    VLILERPEPV QDLFDFITER GALQEDLARG FFWQVLEAVR HCHNCGVLHR 250
    DIKDENILID LSRGEIKLID FGSGALLKDT VYTDFDGTRV YSPPEWIRYH 300
    RYHGRSAAVW SLGILLYDMV CGDIPFEHDE EIIKGQVFFR QTVSSECQHL 350
    IKWCLSLRPS DRPSFEEIRN HPWMQGDLLP QAASEIHLHS LSPGSSK 397

    Note: Initiates from CTG codon.

    Length:397
    Mass (Da):44,542
    Last modified:December 6, 2005 - v2
    Checksum:i2511AD77FD3DC837
    GO
    Isoform 2 (identifier: P06803-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-84: Missing.

    Show »
    Length:313
    Mass (Da):35,537
    Checksum:i79F4779E9DCBDC16
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 8484Missing in isoform 2. CuratedVSP_018853Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M13945 Genomic DNA. Translation: AAA39930.1.
    PIRiA24169. TVMSP1.
    UniGeneiMm.405293.
    Mm.485038.

    Genome annotation databases

    UCSCiuc008bta.1. mouse. [P06803-1]

    Keywords - Coding sequence diversityi

    Alternative initiation

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M13945 Genomic DNA. Translation: AAA39930.1 .
    PIRi A24169. TVMSP1.
    UniGenei Mm.405293.
    Mm.485038.

    3D structure databases

    ProteinModelPortali P06803.
    SMRi P06803. Positions 92-392.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei P06803.

    Proteomic databases

    PRIDEi P06803.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    UCSCi uc008bta.1. mouse. [P06803-1 ]

    Organism-specific databases

    MGIi MGI:97584. Pim1.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000231357.
    HOVERGENi HBG106681.
    InParanoidi P06803.
    PhylomeDBi P06803.

    Miscellaneous databases

    PROi P06803.
    SOURCEi Search...

    Gene expression databases

    CleanExi MM_PIM1.
    Genevestigatori P06803.

    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.
    IPR017348. Ser/Thr_kinase_Pim-1.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF037993. STPK_Pim-1. 1 hit.
    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. "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).
    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.
    3. "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.
    4. "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.
    5. Cited for: INTERACTION WITH RP9.
    6. "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.
    7. "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.
    8. "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.
    9. "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.

    Entry informationi

    Entry nameiPIM1_MOUSE
    AccessioniPrimary (citable) accession number: P06803
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1988
    Last sequence update: December 6, 2005
    Last modified: October 1, 2014
    This is version 133 of the entry and version 2 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