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FLASH GENE
Symbol MAPK8 contributors: shn - updated : 03-07-2011
HGNC name mitogen-activated protein kinase 8
HGNC id 6881
Location 10q11.22      Physical location : 49.609.686 - 49.643.182
Synonym name
  • stress-activated protein kinase 1
  • JNK1 alpha protein kinase
  • JNK1 beta protein kinase
  • c-Jun N-terminal kinase 1
  • Synonym symbol(s) JNK1, SAPK1, PRKM8, JNK, MKD8, JNK1A2, JNK21B1/2, JNK-46
    EC.number 2.7.11.24
    DNA
    TYPE functioning gene
    STRUCTURE 33.53 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D10S225 - D10S1754 - MAPK8 - D10S1787 - D10S1772 - qter
    Physical map
    PPYR1 10q11.2-q21.2 pancreatic polypeptide receptor 1 LOC387667 10 hypothetical gene supported by BC004945; NM_002136 LOC220466 10q11.22 similar to ARF GTPase-activating protein LOC340733 10q11.22 similar to Dual specificity phosphatase 8 CTSLL2 10q22 cathepsin L-like 2 LOC340844 10q11.22 similar to Ahcy protein LOC195977 10q11.22 hypothetical protein LOC195977 LOC387668 10 similar to ARF GTPase-activating protein ANXA8 10q11.2 annexin A8 FLJ10824 10q11.22 hypothetical protein FLJ10824 LOC389963 10 similar to Sodium/hydrogen exchanger 3 (Na(+)/H(+) exchanger 3) (NHE-3) LOC387669 10 LOC387669 LOC387670 10 hypothetical gene supported by NM_133446 ZNF488 10q11.22 zinc finger protein 488 RBP3 10q11.2 retinol binding protein 3, interstitial GDF2 10q11.22 growth differentiation factor 2 GDF10 10q21.1 growth differentiation factor 10 DKFZP566K0524 10q11.22 DKFZP566K0524 protein LOC387671 10 similar to ARF GTPase-activating protein LOC387672 10 similar to Ribosome biogenesis protein BMS1 homolog LOC387673 10 similar to Glutamate dehydrogenase, mitochondrial precursor (GDH) LOC338598 10q11.22 similar to hypothetical protein MGC5560 LOC118706 10q11.22 similar to ARF GTPase-activating protein LOC387674 10 similar to Ribosome biogenesis protein BMS1 homolog MGC35285 10q11.22 hypothetical protein MGC35285 MAPK8 10q11.2 mitogen-activated protein kinase 8 RhoGAP2 LOC387675 10 LOC387675 LOC159491 LOC389964 10 similar to ribosomal protein L13a; 60S ribosomal protein L13a; 23 kD highly basic protein KIAA1607 FLJ31737 LOC170370 10q11.23 hypothetical LOC170370 LOC170371 10q11.23 hypothetical protein LOC170371 LOC118461 DRG11 ERCC6 10q11 excision repair cross-complementing rodent repair deficiency, complementation group 6 PGBD3 10q11 piggyBac transposable element derived 3 CHAT 10q11.2 choline acetyltransferase SLC18A3 10q11.2 solute carrier family 18 (vesicular acetylcholine), member 3 LOC282966 10q11.23 hypothetical protein LOC282966 FLJ10851 10q11.23 hypothetical protein FLJ10851 MAPK6PS6 10q11.21 hypothetical protein FLJ10851 PARG 10q11.23 poly (ADP-ribose) glycohydrolase LOC387676 10 similar to KIAA0592 protein LOC387677 10 hypothetical gene supported by BC051717; NM_133446 LOC255319 10q11.23 similar to ARF GTPase-activating protein MSMB 10q11.2 microseminoprotein, beta- NCOA4 10q11.2 nuclear receptor coactivator 4 TIMM23 10q11.21-q11.23 translocase of inner mitochondrial membrane 23 homolog (yeast) LOC387678 10 similar to ARF GTPase-activating protein LOC389965 10 similar to Sodium/hydrogen exchanger 3 (Na(+)/H(+) exchanger 3) (NHE-3) LOC387679 10 similar to KIAA0592 protein LOC387680 10 similar to KIAA0592 protein LOC389966 10 similar to Sodium/hydrogen exchanger 3 (Na(+)/H(+) exchanger 3) (NHE-3) ASAH2 10q11.21 N-acylsphingosine amidohydrolase (non-lysosomal ceramidase) 2
    RNA
    TRANSCRIPTS type messenger
    text several alternatively spliced isoforms (PMID: 8654373)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 1412 55 427 - 1996 8654373
    transcript variant JNK1-b2
    11 - 1412 55 427 - 1996 8654373
    transcript variant JNK1-a2
    11 - 1417 46 384 - 1996 8654373
    transcript variant JNK1-a1
    11 - 1417 46 384 - 1996 8654373
    transcript variant JNK1-b1
    EXPRESSION
    Type widely
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
     vessel   moderately
    Digestivemouth   highly
     pharynx   moderately
    Endocrineparathyroid   moderately
    Lymphoid/Immunelymph node   moderately
     thymus   highly
     tonsils   moderately
    Nervousbrain   moderately
    Reproductivefemale systemuteruscervix highly
     female systembreastmammary gland moderately
    Respiratorylung    
     respiratory tractlarynx  moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneB cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • tyrosine kinase catalytic domain
  • RIO-like kinase domain
  • conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to MAPK8, Pan troglodytes
    ortholog to mapk8, Danio rerio
    ortholog to Mapk8, Mus musculus
    ortholog to Mapk8, Rattus norvegicus
    Homologene
    FAMILY
  • protein kinase superfamily
  • CMGC Ser/Thr protein kinase family
  • MAP (mitogen activated protein) kinase subfamily
  • CATEGORY enzyme , immunity/defense
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • responding to activation by environmental stress by phosphorylating a number of transcription factor(primarily components of Ap1, C-jun and ATF2)
  • crucial mediator of obesity and insulin resistance
  • required for effector T cell function but not for T cell activation
  • implicated in the immune response that is mediated by the activation and differentiation of CD4 helper T (TH) cells into TH1 and TH2 effector cells
  • JNK1 signaling pathway plays a key role in T cell receptor-initiated TH cell proliferation, apoptosis, and differentiation
  • implicated in the apoptotic response of cells exposed to stress
  • playing a necessary role for epithelial morphogenesis and essential regulator of signal transduction by the EGF receptor in the epidermis
  • promoting abnormal extracellular matrix metabolism in the tissue (in abdominal aortic aneurysm)through suppression of essential enzymes
  • acting with MAPK8 as sensor and downstream effectors of persistent DNA damage in transcribed genes
  • phosphorylating heat shock factor protein 4 (HSF4)
  • acting as a JUN kinase and MAP kinase (serine/threonine kinase)
  • involved in the activation of pro-apoptotic gene products
  • playong a role in cell mobility
  • involved in the negative regulation of apoptosis
  • involved in UV radiation induced apoptosis
  • playing a key role in T cell proliferation, apoptosis and differentiation
  • its activity is required for protection of liver from hepatic steatosis
  • required for IL-3-mediated cell survival through phosphorylation and inactivation of the proapoptotic Bcl-2 family protein BAD (
  • JNK pathway is critically involved in diabetes
  • play a role in the developing nervous system and T-cell-mediated immunity
  • necessary for epithelial morphogenesis and is an essential regulator of signal transduction by the EGF receptor in the epidermis
  • may play an important part in maintaining microtubule stability and efficient neurite elongation
  • both MAPK8 and MAPK9, have cytotoxic potential, however MAPK9 is the primary signal transducer
  • implicated in diet-induced obesity
  • role of neuronal and pituitary MAPK8 as a regulator of hypothalamic and peripheral insulin sensitivity as well as somatic growth
  • critical role in pituitary control of thyroid function
  • plays a key role in Ras-induced tumorigenesis
  • has dual roles in the regulation of SIRT1 activity; it induces and then decreases the SIRT1 activity through the phosphorylation-mediated processes
  • MAPK10 mediates potentially its effects mainly at the transcriptional level, while MAPK8 or MAPK9 appear to mediate their pro-apoptotic effect in the cytoplasm
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    cell migration & motility
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling signal transduction
  • response to UV and stress
  • MAPK8-SIRT1 pathway provides a new molecular mechanism for the pathogenesis of hepatic steatosis in obesity
  • a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor, nucleotide,
  • Mg2+
  • ATP
  • protein
  • Rho GTPase activating protein 1 (ARHGAP1)
  • four scaffolding proteins: MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4
  • ERK-2 and Elk1 (
  • tumor protein p53, TP53 (
  • mitogen-activated protein kinase kinase kinase 1, MEKK1 (
  • mitogen-activated protein kinase 5, MKP5 (
  • Jun N-terminal protein kinase (JNK)/stress-activated protein kinase-associated protein 1, JSAP1 (
  • c-Myc (
  • COP9 signalosome (
  • MEK kinase 2 and c-Jun N-terminal kinase (JNK) kinase 2 (
  • insulin receptor substrate 1, IRS1 (
  • heat shock transcription factor 1, HSF1 (
  • Mitogen-activated protein (MAP) kinase phosphatase 1, MKP-1/CL100 (
  • Glutathione S-transferase P1-1, GSTP1-1 (
  • v-crk sarcoma virus CT10 oncogene homolog (avian), CRK (
  • Jun dimerization protein 2, JDP2 (
  • Protein kinase D, PKD (
  • I kappa B kinase complex-associated protein, IKAP (
  • SH3-domain binding protein 5, SH3BP5 (
  • c-Jun NH2-terminal kinase-associated leucine zipper protein, JLP (
  • SH3-domain binding protein 5, SH3BP5 (
  • cyclin-dependent kinase inhibitor 2A, CDKN2A
  • JNK1/MAPK8-associated membrane protein, JAMP (
  • histone deacetylase-related protein, HDRP (
  • mitogen-activated protein kinase 8 interacting protein 2 (MAPK8IP2)
  • synuclein, gamma (breast cancer-specific protein 1) (SNCG)
  • mitogen-activated protein kinase 3 (MAPK3)
  • Protein kinase D (PKD)
  • mitogen-activated protein kinase 9 (MAPK9 also known as JNK2)
  • sirtuin 1, SIRT1 (
  • mediates the up-regulation of proinflammatory genes in lipin-2-deficient macrophages
  • mediates the expression of CTGF and corneal scarring in corneal wound healing
  • cell & other
    REGULATION
    activated by PIAS1 (protein inhibitor of activated STAT1)
    TNF (TNF-alpha) for TNF-induced preferential release of DIABLO
    threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7
    mitogen-activated protein kinase kinase 7 (MKK7)
    NLR family, apoptosis inhibitory protein (NAIP) and baculoviral IAP repeat-containing 7 (BIRC7 also known as ML-IAP)
    TGF-beta in a SMAD-independent manner
    a high-fat diet and triggers development of insulin resistance
    COP9 (
    JKAP (
    I kappa B kinase complex-associated protein, IKAP (
    inhibited by dual specificity phosphatases (DUSP), such as DU
    CYLD
    Glutathione S-transferase P1-1, GSTP1-1 (
    repressed by cyclin-dependent kinase inhibitor 2A, CDKN2A
    Other regulation of its activity by NF-kappaB during TGF-beta1 signaling
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    in obesity
    constitutional       loss of function
    deficiency in the nervous system is sufficient to account for the role of MAPK8 in the regulation of high-fat diet-induced weight gain
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
  • JNK-related therapeutic strategies for RP1 diseases
  • SystemTypeDisorderPubmed
    diabete  
    a potential new therapy for diabetes using cell-permeable JNK-inhibitory peptide
    miscelleaneousvascular 
    therapeutic target in abdominal aortic aneurysm
    ANIMAL & CELL MODELS
    JNK activity observed in wild-type activated TH cells was severely reduced in TH cells from Jnk1-/- mice
  • MAPK8 deficient mice display a progressive loss of axonal and dendritic microtubules and MAP1B and MAP2 are hypophosphorylated in MAPK8/ brains compromising their ability to bind to microtubules and promote their assembly and stability
  • Mice lacking both of the ubiquitously expressed isoforms JNK1 and -2 die during midgestation with neural tube closure defects and brain abnormalities
  • JNK-deficient mice exhibit delayed epithelial development in the epidermis, intestines, lungs, an eyelid closure defect associated with markedly reduced epidermal growth factor (EGF) receptor function, and loss of expression of the ligand EGF
  • genetic loss of the MAPK, c-Jun N-terminal kinase 1 in a mouse model of multiple sclerosis, enhances IL-10 production, rendering innate myeloid cells unresponsive to certain microbes and less capable of generating IL-17-roducing, encephalitogenic T cells