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FLASH GENE
Symbol MAPK14 contributors: mct/npt/pgu - updated : 19-03-2015
HGNC name mitogen-activated protein kinase 14
HGNC id 6876
Location 6p21.31      Physical location : 35.995.453 - 36.079.012
Synonym name
  • stress-activated protein kinase 2A
  • CSAID (cytokine suppressive and anti-inflammatory drugs), binding protein 1
  • p38 MAP kinase
  • cytokine suppressive anti-inflammatory drug binding protein
  • MAP kinase MXI2
  • MAX-interacting protein 2
  • p38alpha Exip
  • stress-activated protein kinase 2A
    • Synonym symbol(s) SAPK2A, p38MAPK, CSBP1, RK, p38, EXIP, Mxi2, CSBP2, PRKM14, PRKM15, CSPB1, p38ALPHA
    EC.number 2.7.11.24
    DNA
    TYPE functioning gene
    SPECIAL FEATURE head to head
    STRUCTURE 83.56 kb     12 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map pter - D6S1611 - D6S1645 - MAPK14 - D6S3801 - D6S291 - cen
    Physical map
    LOC391916 6 hypothetical gene supported by BC001032; NM_001014 SNRPC 6p21.2 small nuclear ribonucleoprotein polypeptide C C6orf107 6p21 chromosome 6 open reading frame 107 TAF11 6p21 TAF11 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 28kDa ANKS1 6p21.31 ankyrin repeat and SAM domain containing 1 TCP11 6p21.2 t-complex 11 (mouse) CEGF3 6p21.3 CUB domain and EGF-like repeat containing 3 ZNF76 6p21.2 zinc finger protein 76 (expressed in testis) DEF6 6p21.33-p21.1 differentially expressed in FDCP 6 homolog (mouse) PPARD 6p21.2-p21.1 peroxisome proliferative activated receptor, delta MKRNP2 6p21.1 makorin, ring finger protein, pseudogene 2 FANCE 6p22-p21 Fanconi anemia, complementation group E RPL10A 6p21.3 ribosomal protein L10a TEAD3 6p21.2 TEA domain family member 3 TULP1 6p21.3 tubby like protein 1 LOC389382 6 similar to Rps15a protein FKBP5 6p21.3-p21.2 FK506 binding protein 5 C6orf81 6p21.31 chromosome 6 open reading frame 81 LOC389383 6 similar to AAAL3045 LOC340204 6p21.31 similar to precursor peptide CLPS 6p22-p21.1 colipase, pancreatic MGC33835 6p21.31 hypothetical protein MGC33835 SRPK1 6p213-p21.2 SFRS protein kinase 1 SLC26A8 6p21 solute carrier family 26, member 8 MAPK14 6p21.2 mitogen-activated protein kinase 14 MAPK13 6p21.1 mitogen-activated protein kinase 13 BRPF3 6p21 bromodomain and PHD finger containing, 3 PNPLA1 6p21.31 patatin-like phospholipase domain containing 1 LOC389384 6 similar to RIKEN cDNA 4930539E08 ETV7 6p21 ets variant gene 7 (TEL2 oncogene ) STEPP 6p21.31 small testis-specific peroxisomal protein C6orf69 6p21.31 chromosome 6 open reading frame 69 STK38 6p21 serine/threonine kinase 38 SFRS3 11p15.1 splicing factor, arginine/serine-rich 3 LOC389385 6 similar to Cytosol aminopeptidase (Leucine aminopeptidase) (LAP) (Leucyl aminopeptidase) (Proline aminopeptidase) (Prolyl aminopeptidase) LOC389386 6 similar to Cytosol aminopeptidase (Leucine aminopeptidase) (LAP) (Leucyl aminopeptidase) (Proline aminopeptidase) (Prolyl aminopeptidase) CDKN1A 6p21.2 cyclin-dependent kinase inhibitor 1A (p21, Cip1) LOC346190 6p21.31 similar to hypothetical protein FLJ31614 LOC391917 6 similar to putative G-protein coupled receptor CPNE5 6p21.1 copine V PPIL1 6p21.1 peptidylprolyl isomerase (cyclophilin)-like 1 C6orf89 6p21.31 chromosome 6 open reading frame 89 PI16 6p21.31 protease inhibitor 16 MTCH1 6pter-p24.1 mitochondrial carrier homolog 1 (C. elegans) FGD2 6p21.2 FGD1 family, member 2 LOC285849 6p21.31 similar to cytochrome c oxidase subunit VIa polypeptide 1 precursor; cytochrome C oxidase subunit VIa homolog LOC389387 6 similar to 60S ribosomal protein L12 PIM1 6p21.2 pim-1 oncogene C6orf128 6p21.31-p21.2 chromosome 6 open reading frame 128 C6orf197 6p21.2 chromosome 6 open reading frame 197
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 splicing 4353 41.4 360 - 1995 7696354
  • also called CSBP1
    • 12 splicing 4353 41.2 360 - 1995 7696354
    10 splicing 1431 34 297 - 1995 7696354
  • loss of exon 10,11,11'
  • playing a role in the signal transduction pathway different from other isoforms
    • 11 splicing 4274 35.3 307 - 1995 7696354
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveintestinesmall intestine  highly
    Hearing/Equilibriumearinnercochlea highly
    Lymphoid/Immunethymus   highly
    Nervousbrain    
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    interspecies homolog to rattus Mapk14 (99,17 pc)
    homolog to murine Mapk14 (95,56 pc)
    Homologene
    FAMILY
  • protein kinase superfamily
  • CMGC Ser/Thr protein kinase family
  • MAP kinase subfamily
    • CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • serine/threonine kinase, may be playing a role in the early onset of apoptosis
  • involved in hypertrophic differentiation of chondrocytes
  • involved in cardiomyocyte proliferation and angiogenesis during development
  • involved in Sp1 phosphorylation
  • mediates IL1A-induced down-regulation of aggrecan gene expression in chondrocytes
  • may be regulating the early secretory pathway
  • substrates of this kinase include ATF2, MEF2C, MAX, CDC25B, p53, suggesting a role in stress related transcription and cell cycle regulation
  • controls myogenesis by antagonizing the activation of the JNK proliferation-promoting pathway, before its direct effect on muscle differentiation-specific gene transcription (fundamental role in muscle formation)
  • recruited to muscle-specific gene promoters during muscle development suggesting that indeed MAPK14 might play an important role at the chromatin
  • role in activating CREB1 metabolic pathway in the events leading to erythroid differentiation)
  • its activity promotes timely checkpoint satisfaction by indirectly influencing the motor proteins (e.g., Klp10, Klp67A) involved in regulating the dynamics of kinetochore microtubule ends
  • in intestinal epithelial cells contributes to the host immune responses against enteric bacteria by the recruitment of immune cells
  • MAPK14 recruitment to target genes appears to be a broad mechanism to regulate transcription
  • its activity is not just necessary for gene promoter activation but might also be necessary for the nascent mRNA elongation of MAPK14-dependent genes
  • regulates expression of osteoblast-specific genes by phosphorylation of osterix (SP7)
  • maintains CDH1 expression by suppressing MAP3K7-NFKB signaling, thus impeding the induction of EMT in human primary mesothelial cells
  • plays an important role in the regulation of hematopoietic stem cellself-renewal in vitro and inhibition of MAPK14 activation with a small molecule inhibitor may represent a novel approach to promote ex vivo expansion of hematopoietic stem cell
  • controls prothrombin expression by regulated RNA 3prime end processing
  • regulates G1-S transition in hypoxic cardiac fibroblasts
  • MAPK14-signaling is a central pathway for the integration of instructive signals in dendritic cells for T(H)17 differentiation and inflammation
  • MAPK14 and JNK pathways function downstream of ZAK during chondrogenesis
  • unexpected role of MAPK14 in cell cycle regulation in response to Aurora B inhibition, by promoting the transcriptional elongation of the cell cycle inhibitor CDKN1A
    • CELLULAR PROCESS cell cycle
    cell life, cell death/apoptosis
    nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • pathway of redox-sensitive signaling via NOX4 and MAPK14 in endothelial cells
  • MAPK14 pathway is an important contributor to the increased microglial production of proinflammatory cytokines induced by diverse stressors
  • MAPK14-dependent protective pathway might be able to be selectively modulated to enhance cardio-protection while not interfering with the inhibition of the better-known detrimental MAPK14-dependent pathways
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • regulate TEAD1 and CEBPB transcriptional activity in the absence of environmental stress and suggests a role for MAPK14 in the expression of extracellular matrix components that maintain organ architecture
  • SP7 (Osterix) is a novel substrate for MAPK14, and Ser-73 and Ser-77 are the regulatory sites phosphorylated by MAPK14
  • MAPKAPK2 and MAPK14 function in concert to phosphorylate Keratin 8, Keratin 18, and Keratin 20 in intestinal epithelia
  • interacting with MYCBP2 (modulates TRPV1 desensitization through MAPK14 signaling which presents not only a novel model for the modulation of TRPV1-mediated signals but also expands the role of MAPK14 in the regulation of activity-induced receptor internalization)
  • interaction between phosphorylated MAPK14 and cleaved N-terminal ATF6 could results in a protective effect against the vicious cycle of oxidative stress-ER stress by induction of ER chaperones and ERAD components
  • CDK5RAP3 binds MAPK14, alters its cellular localization, and inhibits basal and cytokine-stimulated MAPK14 activity
  • interplay between MAPK14 phosphorylation and DNAJC3 upregulation has key roles in modulating ERP29-induced cell-growth arrest and survival
  • SMAD7 and MAPK14 mitogen-activated protein kinase together regulate the expression of APC and cell migration in prostate cancer cells in response to TGFB1 stimulation
  • possible involvement of S100A12 in the development of osteoarthritis (OA) by up-regulating MMP13 and VEGFA via MAPK14 and NFKB1 pathways
  • PDGFB-induced activation of MAPK14 was significantly suppressed by SERPINA12
  • dual phosphorylation of PXN by JNK and MAPK14 is essential for T-cell activation, suggesting that NFATC1 is a functional target of the JNK/MAPK14 phosphorylated paxillin
  • OPRK1 activates MAPK14 through a phosphorylation and arrestin-dependent mechanism
  • cascade of posttranslational modifications involving MAPK14, KAT5, and MAPKAPK5, three proteins that are essential for RAS-induced senescence
  • CASP3, CASP9, and MAPK14 interacted with SLIT1-ROBO2 signaling
  • GSN induces cardiomyocyte hypertrophy and NPPB expression via MAPK14 signaling and GATA4 transcriptional factor activation
  • negative regulation of MAPK14 mediates the protective effects of SCD on ER homeostasis under distinct stress conditions
  • FNDC5 activated MAPK14 in an AMPK-dependent manner
  • TLR8, is involved in priming of human neutrophil ROS production by inducing the phosphorylation of NCF1 and MAPK14 and PIN1 is also involved in this process
  • TNFAIP8L2 inhibited the phosphorylation of AKT1, while promoting the phosphorylation of MAPK14, but had no effect on NFKBIA and ERK pathway
  • PGF may activate MMP9 via MAPK14 signaling pathway
  • TNFSF18 could promote Th17 cell differentiation by MAPK14 and STAT3 signaling in autoimmune arthritis
  • TNFAIP8L2 suppressed breast cancer tumorigenesis, growth and metastasis possibly via regulation of the AKT1 and MAPK14 signaling pathways
    • cell & other
    REGULATION
    activated by stresses and proinflammatory cytokines
    phosphorylation by MAP kinase kinase or by its autophosphorylation triggered by the interaction with MAP3K7IP1
    suppression of SRC activity (stimulates muscle differentiation by activating MAPK14 uni-directionally)
    GAS1 that promotes myogenic differentiation through regulation of cell cycle arrest and is critical to activate MAPK14, most likely via association with CDON/Cadherin multiprotein complexes
    Other regulated by MKK3 and MKK6
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in myoblasts that are unable to differentiate and form multinucleated myotubes
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularatheromacardiac
    FGF1/MAPK14 inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction
    cancerreproductiveovary
    pharmacological modulation of genes involved in cancer-specific homeostasis, such as MAPK14, might be exploited to design new therapeutic approaches to cancer treatment
    ANIMAL & CELL MODELS
  • Mapk14 activity is markedly reduced in the livers of obese mice compared with lean mice