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FLASH GENE
Symbol PIM1 contributors: mct/pgu - updated : 10-10-2016
HGNC name pim-1 oncogene
HGNC id 8986
Location 6p21.2      Physical location : 37.137.921 - 37.143.202
Synonym name
  • pim-1 kinase 44 kDa isoform
  • pim-1 oncogene (proviral integration site 1)
  • non-specific serine/threonine protein kinase
  • Oncogene PIM1
  • Synonym symbol(s) PIM
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 5.28 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map pter - F13A1 F13A1 - HLA - (D6S29 , PIM1 ) - (D6S5 , D6S19 ) - (MUT MUT , D6S4 ) - cen
    Authors (PMID: 1968423)
    RNA
    TRANSCRIPTS type messenger
    text one short isoform of 34 Kd and a large form of 44 Kd
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 2751 - 313 - 2012 22451912
    6 - 2751 - 404 - 2012 22451912
    PIM1L
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly Homo sapiens
    Lymphoid/Immunespleen   highly Homo sapiens
     thymus   highly Homo sapiens
    Nervousbrainlimbic systemhippocampus   Homo sapiens
    Reproductivemale systemprostate    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly Homo sapiens
    Nervouscentral    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmature hematopoietic Homo sapiens
    Blood/Hematopoieticprogenitor cell Homo sapiensFetal
    cell lineage necessary and sufficient for polyploisisation, not critical for cytoplasmic differentiation on megakaryoporesis
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a serine threonine kinase domain
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Pim1 (94.2pc)
    homolog to rattus Pim1 (97.1pc)
    Homologene
    FAMILY
  • protein kinase superfamily
  • Pim family, related to the calcium-calmodulin family
  • CATEGORY enzyme , protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus
    text cytoplasmic and nuclear in interphase, moving to the spindle pole at mitosis
    basic FUNCTION
  • serine/threonine kinase
  • mediator of cytokine-dependent survival signals in hematopoietic cells
  • has a role in cardioprotection downstream of AKT activation
  • PIM1 and PIM2 play a key role in the v-Abl transformation, possibly via participating in modulation of SOCS1 and via regulating the apoptotic signaling
  • promote cell cycle progression and tumorigenesis by down-regulating CDKN1B expression at both transcriptional and posttranslational levels
  • phosphorylates MAP3K5 and thus decreases its kinase activity and negatively regulates apoptosis
  • contributes to viral reactivation oby phosphorylating KSHV latency-associated nuclear antigen, LANA
  • implicated in the control of cell cycle progression and apoptosis
  • may act as a sensor for ribosomal stress independently of or in concert with the known TP53-dependent mechanisms
  • contributes to hematopoietic cell growth and survival, although its role is probably secondary to other signaling pathways
  • serine-threonine kinase that has antiapoptotic activity and is involved in cell survival, proliferation, differentiation, transformation, tumor progression, as well as angiogenesis
  • BCL6 and PIM1 are both protooncogenes that play roles in the pathogenesis of lymphoma
  • PIM1 oncogene is required for normal visual function
  • PIM1 activity prevents DNM1L compartmentalization to the mitochondria and preserves reticular mitochondrial morphology in response to simulated ischemia (sI)
  • PIM1, PIM2, PIM3 have been implicated in the regulation of apoptosis, metabolism, cell cycle, and homing and migration, which has led to the postulation of these proteins as interesting targets for anticancer drug discovery
  • involved in several signalling pathways such as the regulation of cell cycle progression and apoptosis
  • CELLULAR PROCESS cell cycle, division, mitosis
    cell life, proliferation/growth
    cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • promoting complex formation between NuMA, HP1beta, dynein and dynactin, a complex that is necessary for mitosis
  • INTERACTION
    DNA
    RNA
    small molecule metal binding, nucleotide,
  • ATP binding
  • Mn2+ binding
  • protein
  • regulated by heat shock proteins and the ubiquitin-proteasome pathway
  • phosphorylating RUNX family transcription factors and enhancing their activity
  • phosphorylating BAD while inhibiting its pro-apoptoic activities
  • phosphorylated PIM1 binds PIN1 allowing the interaction of PPP2R5B, and dephosphorylation of PIM1 then allows for ubiquitinylation and protein degradation of PIM1
  • interacts with ribosomal protein RPS19 and cosediments with ribosomes
  • PIM1 is a gene that cooperates with BCL6 to promote the development of lymphomas
  • modulation of the degradation of ISCU by the PIM1 protease is a regulatory mechanism serving to rapidly help balance the cell need for critical iron-requiring processes under changing environmental conditions
  • is an important regulator of MET receptor tyrosine kinase levels and signaling
  • negatively regulates FOXP3 chromatin binding activity by specifically phosphorylating FOXP3 at Ser(422)
  • PIM1 specifically inhibits DDX58- and IFIH1-mediated IFNB1 signaling
  • cell & other
  • may interact preferentially with active ribosomes
  • REGULATION
    activated by upregulated by BCR/ABL, requiring STAT5 activation, involved in theBCR/ABL mediated cell protection against apoptosis
    induced by hypoxia
    Other autoregulated by phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    in Burkitt's lymphoma
    tumoral     --over  
    upregulated by the Kaposi sarcoma-associated herpes virus in infected B cells
    tumoral     --over  
    protein kinase up-regulated in prostate cancer
    tumoral     --over  
    up-regulation of PIM1 might be a tumor marker for gastric cancer
    tumoral     --over  
    prognostic marker in pancreatic ductal adenocarcinoma
    tumoral     --low  
    significant association between PIM1 down-regulation and occurence of lymph node metastases in non-small cell lung cancer
    constitutional       loss of function
    induces a strong adhesive phenotype by enhancing endothelial cell-cell and cell-matrix adhesion by the deposition of a specific extracellular matrix
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhead and neck 
    may be used as a novel predictive marker of radiation response in patients with squamocellular cancers of head and neck
    cancerhemopathy 
    PIM1 specific kinase inhibitors may be promising therapies for BCL6/PIM1-associated lymphomas
    immunologyautoimmune 
    could be a new potential therapeutic target in the prevention and treatment of human-specific autoimmune diseases because of its ability to modulate the immunosuppressive activity of human Tregs
    ANIMAL & CELL MODELS
    compound Pim knockhout mice show a profound reduction of body size and non efficient proliferation of peripheral T lymphocytes