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FLASH GENE
Symbol MAPKAPK2 contributors: mct - updated : 27-09-2016
HGNC name mitogen-activated protein kinase-activated protein kinase 2
HGNC id 6887
Location 1q32.1      Physical location : 206.858.288 - 206.907.626
Synonym symbol(s) MK2, MAPKAP-K2, MK-2
EC.number 2.7.11.1
DNA
TYPE functioning gene
STRUCTURE 49.27 kb     10 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
10 splicing 3534 - 370 - 2000 10964510
MAPKAPK2I1
10 splicing 2997 - 400 - 2000 10964510
  • MAPKAPK2I2
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Cardiovascularheart   highly
    Digestiveintestinelarge intestinecolon highly
     salivary gland   highly
    Reproductivemale systemprostate  highly
    Urinarykidney   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • proline-rich region with two putative SH3 binding sites
  • a tyrosine kinase catalytic domain
  • a threonine residue phosphorylated by MAP kinase
  • a nuclear localization signal (NLS)
  • conjugated sumoylated
    HOMOLOGY
    Homologene
    FAMILY SER/THR family of protein kinase
    CATEGORY enzyme , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • involved in many cellular processes including stress and inflammatory responses, nuclear export, gene expression regulation and cell proliferation
  • plays a role in neuroinflammatory and neurodegenerative pathology of relevance to Alzheimer disease
  • cell cycle checkpoint kinase that regulates the G2/M transition and S phase progression in response to UV irradiation
  • MAPKAPK2-mediated LIMK1 phosphorylation/activation plays an essential role in VEGFA-induced actin reorganization, migration, and tubule formation of endothelial cells
  • possible role in the cellular response after neuronal depolarization, in particular in excitotoxicity (
  • oncogenic and involved in tumor growth and invasion
  • emerges as a regulator of haematopoietic stem cells homeostasis, which could act through chromatin remodelling by the PcG (polycomb group complex)
  • critical role for the MAPKAPK2 pathway in the posttranscriptional regulation of gene expression as part of the DNA damage response in cancer cells
  • important role for MAPK14/MAPKAPK22 signaling in podocyte injury
  • RNA-binding protein that binds to AU-rich elements (AREs) in the 3prime-untranslated region of its target mRNAs and accelerates mRNA degradation
  • in human pulmonary microvascular endothelial cells, regulates TNF-induced expression of ICAM1 and IL8 via tristetraprolin at the mRNA decay level
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with RTN4 (NOGO-B)
  • LSP1 is a substrate of MAPKAPK2 in neutrophils (MAPKAPK2-regulated LSP1 phosphorylation is involved in stabilization of F-actin polarization during neutrophil chemotaxis)
  • TICAM1-signaling pathway promotes TNF-alpha mRNA translation through activation of the protein kinase MAPKAPK2
  • MAPKAPK2 and MAPK14 function in concert to phosphorylate Keratin 8, Keratin 18, and Keratin 20 in intestinal epithelia
  • interacting with TLR3 (TLR3 induces signaling mechanisms involving TICAM1, MAPK14 and MAPKAPK2 to enhance stabilization of IFNB mRNA contributing to enhanced IFNB levels during pathogen infections)
  • regulates tumor necrosis factor(TNF)-induced expression of intercellular adhesion molecule-1 (ICAM1) and interleukin-8 (IL8) in lung microvascular endothelial cells
  • PDE4A long isoforms can be phosphorylated by MAPKAPK2, which attenuates activation of such enzymes through their phosphorylation by protein kinase A
  • RNA helicase EIF4A1 is needed to ensure translation of the long and the known short isoforms of MAPKAPK2, of which the molecular properties were determined
  • cell & other
    REGULATION
    activated by MAP kinase
    Other its SUMOylation is a new mechanism for regulating actin filament dynamics in endothelial cells
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    common in various cancers
    Susceptibility to poor prognosis in individuals with lung cancer
    Variant & Polymorphism other g.CNV-30450 could increase risk and cause poor prognosis in individuals with lung cancer by enhancing the expression of MAPKAPK2
    Candidate gene
    Marker g.CNV-30450 in MAPKAPK2 may be a biomarker for susceptibility to and prognosis for lung cancer
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousurinarychronic kidney disease
    MAPKAPK2 inhibition is a promising potential therapeutic strategy to protect podocytes in various glomerular diseases
    neurologyacquired 
    may potentially be a useful target to treat acute spinal cord injury
    ANIMAL & CELL MODELS
  • MK2(-/-) mice showed reduced neuron and myelin loss, and increased sparing of serotonergic fibers in the ventral horn caudal to the injury site