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FLASH GENE
Symbol MAP3K12 contributors: mct/npt - updated : 24-08-2012
HGNC name mitogen-activated protein kinase kinase kinase 12
HGNC id 6851
Location 12q13.13      Physical location : 53.874.276 - 53.893.444
Synonym name
  • dual leucine zipper kinase DLK
  • protein kinase MUK
  • zipper protein kinase
    • Synonym symbol(s) ZPK, DLK, MUK, ZPKP1
    EC.number 2.7.11.25
    DNA
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem
    STRUCTURE 19.17 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence cytosine-phosphate-guanine/HTF
    Binding site   transcription factor
    text structure
  • core promoter region is TATA-less, but contains several potential transcription factor-binding motifs such as a GC-box, positively regulated by SP3
    • MAPPING cloned Y linked N status provisional
    Physical map
    KRT8 12q13 keratin 8 KRT18 12q13 keratin 18 EIF4B 12q13.13 eukaryotic translation initiation factor 4B PRO1843 12q13.13 hypothetical protein PRO1843 TENC1 12q12 tensin like C1 domain-containing phosphatase FLJ14800 12q13.13 hypothetical protein FLJ14800 IGFBP6 12q13 insulin-like growth factor binding protein 6 SOAT2 12q13.13 sterol O-acyltransferase 2 LOC387862 12 hypothetical gene supported by AK130082; NM_001416 CSAD 12q13.11-q14.3 cysteine sulfinic acid decarboxylase LOC390316 12 similar to oriLyt TD-element binding protein 7 ITGB7 12q13.2 integrin, beta 7 MGC11308 12q13.13 hypothetical protein MGC11308 ESPL1 8 extra spindle poles like 1 (S. cerevisiae) PFDN5 12q13.1 prefoldin 5 C12orf10 12q13 chromosome 12 open reading frame 10 AAAS 12q13 achalasia, adrenocortical insufficiency, alacrimia (Allgrove, triple-A) SP7 12q12 Sp7 transcription factor SP1 12q13.1 Sp1 transcription factor AMHR2 12q13 anti-Mullerian hormone receptor, type II DKFZP564J157 12q12 DKFZp564J157 protein PCBP2 12q13.12-q13.13 poly(rC) binding protein 2 MAP3K12 12q13 mitogen-activated protein kinase kinase kinase 12 TARBP2 12q12-q13 TAR (HIV) RNA binding protein 2 NPFF 12q13.13 neuropeptide FF-amide peptide precursor FLJ30317 12q13.13 hypothetical protein FLJ30317 ATF7 12q13 activating transcription factor 7 LOC341412 12q13.13 similar to ribosomal protein L31 ATP5G2 12q13.13 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit c (subunit 9), isoform 2 KIAA1536 12q13.13 KIAA1536 protein HOXC13 12q13.3 homeo box C13 HOXC12 12q13.3 homeo box C12
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 3640 - 892 - 2005 15695824
    15 - 3541 93 859 - 2005 15695824
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Respiratorylung   highly
     respiratory tractlarynx  highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    Muscularstriatumskeletal  
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    Skin/Tegumentkeratinocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain
    PROTEIN
    PHYSICAL PROPERTIES basic
    STRUCTURE
    motifs/domains
  • N terminal kinase catalytic domain, hybrid between those of serine/threonine and tyrosine protein kinases
  • a double leucine zipper domain
  • a large C terminal glycine and proline rich region
    • conjugated HemoP
    mono polymer dimer
    HOMOLOGY
    interspecies homolog to murine Map3k12
    Homologene
    FAMILY
  • MAP (mitogen activated protein) kinase family
  • Mixed lineage kinase family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    text phosphorylated and dephosphorylated in cytosol and dephosphorylated only when membrane-associated
    basic FUNCTION
  • serine/threonine protein kinase contributing in the developing brain to cytodifferentiation, apoptotic elimination, and migration
  • acting in the epidermis to promote the terminal differentiation of keratinocytes
  • acting as a signaling molecule implicated in the regulation of keratinocyte terminal differentiation and cornification
  • plays a significant role in the coordinated regulation of radial migration and axon projection by modulating JNK activity
  • potential role in PDGF signaling
  • potentially involved in regenerative responses of mammalian dorsal root ganglion neurons to axonal injury through activation of c-JUN
  • plays a significant role in the coordinated regulation of radial migration and axon projection by modulating JNK activity
  • key regulator of development, cell differentiation and apoptosis
  • critical role in naturally occurring programmed cell death of motoneurons
  • selectively regulates the JNK-based stress response pathway to mediate axon degeneration and neuronal apoptosis without influencing other aspects of JNK signaling
  • participates in cell proliferation and/or survival, at least in part, by modulating the expression of cell cycle regulatory proteins
  • appears to be important for proper cell proliferation and/or cell survival
  • cell cycle-regulated protein whose depletion by RNA interference causes proliferation arrest concomitantly with senescence
  • essential component of the neuronal response to axon damage, broadly regulating the transcriptional response to axonal injury
  • is required for both the proapoptotic and proregenerative responses that occur after optic nerve lesion through broad regulation of injury-induced alterations in gene expression
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
  • JNK cascade
  • MAP3K12-JNK pathway facilitates axon formation in neocortical neurons via stage-specific regulation of microtubule stability
  • MAP3K12-ERK signaling pathway may act as a regulator of the interaction that occurs between HSPB1 and the cytoskeleton during the formation of the cornified cell envelope, a process conferring to the skin its crucial barrier function (PMIDS:
    • a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Mg2+
    • protein
  • interacting with the GTP bound form of RAC and CDC42, regulators of JNK pathway
  • induces activation of c-Jun N-terminal kinase (JNK), a molecule that regulates morphogenesis in various organisms
  • its expression, is sufficient by itself to induce HSPB1 phosphorylation, cell periphery localization, and redistribution to the insoluble protein fraction (cytoskeleton) in poorly differentiated keratinocytes (PMIDS:
  • novel transcriptional target of PPARG with functional PPARG-binding sites in its promoter
    • cell & other
    REGULATION
    activated by phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    MAP3K12 depletion interrupts progression of the cell cycle from the G1 to S phase
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neuromuscularspinal muscular atrophy 
    could become a strategic therapeutic target in motor neuron diseases in which aberrant activation of the apoptogenic cascade is involved
    ANIMAL & CELL MODELS
  • Map3k12-null mice displayed reduced apoptosis in multiple neuronal populations during development, demonstrating that prodegenerative Map3k12 signaling is required in vivo