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FLASH GENE
Symbol MAP2K1 contributors: mct/pgu - updated : 14-04-2017
HGNC name mitogen-activated protein kinase kinase 1
HGNC id 6840
Corresponding disease
CFC3 cardio-facio-cutaneous syndrome 3
Location 15q22.31      Physical location : 66.679.210 - 66.783.881
Synonym name
  • MAPK/ERK kinase 1
  • protein kinase, mitogen-activated, kinase 1 (MAP kinase kinase 1)
  • ERK activator kinase 1
  • MAP-extracellular signal-regulated kinase 1
  • dual specificity mitogen-activated protein kinase kinase 1
    • Synonym symbol(s) MAPKK1, MEK1, PRKMK1, MKK1, CFC3
    EC.number 2.7.12.2
    DNA
    TYPE functioning gene
    STRUCTURE 104.67 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 splicing 2603 43.4 393 - 1995 7624324
    - splicing - 40.7 - - 1995 7601337
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • serine/threonine kinase, mitogen associated protein kinase (MAPK)
  • a leucine-rich nuclear export signal (NES)
  • a docking site, a stretch of about 20 amino acids immediately on the C-terminal side of the MAPKK catalytic domain
    • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Map2k1
    homolog to C.elegans Y54e10bl.6
    intraspecies homolog to MEK2/MAP2K2
    Homologene
    FAMILY
  • protein kinase superfamily
  • STE Ser/Thr protein kinase family
  • MAP kinase kinase subfamily
    • CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • nucleocytoplasmic shuttling protein
  • required for Golgi fragmentation in G2 and for the entry of cells into mitosis
    • basic FUNCTION
  • implicated in regulation of a parallel but distinct cascade that leads to phosphorylation of N-terminal sites on c-Jun
  • stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals
  • activating the MAP kinase ERK1 (PRKM3)
  • playing an essential role in extra-embryonic ectoderm during placentogenesis
  • dual-specificity kinase that mediate ERK1 and ERK2 activation during adhesion and growth factor signaling
  • mediates the regulation of MAP2K2 in the context of a previously undiscovered MAP2K1/MAP2K2 complex
  • crucial modulator of Mek and Erk signaling and have potential implications for the role of MAP2K1 and MAP2K2 in tumorigenesis
  • may contribute to the stability of the NEK10/RAF1 interaction
  • negatively regulates TLR2 signaling in endothelial cell, MAP2K1 promotes TLR2 signaling in monocytes
  • is necessary for PTEN membrane recruitment as part of a ternary complex containing the multidomain adaptor MAGI1
  • Treg cell-specific expression of activated MAP2K1 led to dysregulation of Treg function and instability of FOXP3 expression
  • plays an important role in the RAS/MAPK signaling pathway that controls numerous cellular and developmental processes
  • MAP2K1 levels are upregulated at transcriptional level whereas MAP2K2 levels are downregulated at posttranslational level
    • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    nucleotide, transcription, regulation
    cell communication
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
    MAP kinase signal transduction pathway
    a component
  • components of the two MAPK cascades, MAP3K5-MAP2K4-MAPK10 and RAF1-MAPK1-MAP2K1 interacting with arrestins
  • MAP2K1/MAP2K2 heterodimerize and form a stable complex in fibroblasts
    • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
    • protein
  • interacting with TRIB1
  • binding directly to ARRB1, influencing both its phosphorylation by ERK and the timing of its isoprenaline-stimulated internalization
  • substrate of KSR1, and the catalytic activities of both proteins are required for eliciting cell survival responses downstream of TNF
  • MAP2K1 conditionally compensates for loss of MAP2K2 only in the presence of other mitogen-activated protein kinase kinases
  • MED28 regulates cellular migration in a MAP2K1-dependent manner in breast cancer cells, reinforcing the important cellular roles of MED28
  • inhibits cardiac PPARA activity by direct interaction and prevents its nuclear localization
  • interacts with the nuclear receptor corepressor silencing mediator of retinoid and thyroid hormone receptor (NCOR2)
  • PKMYT1 mediates MAP2K1 effects on the Golgi complex
  • activates RAF1 through a Ras-independent mechanism
  • essential regulator of lipid/protein phosphatase PTEN, through which it controls phosphatidylinositol-3-phosphate accumulation and AKT signaling
  • PAK1 can stimulate MAP2K1/MAP2K2 activity in a kinase-independent manner, probably by serving as a scaffold to facilitate interaction of RAF1
  • nuclear enrichment of MAP2K1 physically sequesters PPARG, the master regulator of adipogenesis, from its target genes and thus inhibits adipogenesis while also disrupting the MAP2K1-extracellular-signal regulated kinase (ERK) signaling cascade
  • regulatory role for BRAF in the MAPK pathway independent of its kinase activity but dependent on interaction with MAP2K1
  • is required for TLR4 mediated ERK activation and in turn regulates the production of IL10 and IL12A
    • cell & other
    REGULATION
    activated by phosphorylation
    inhibited by two-(2-chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3;4-difluoro-benzamide
    Other acetylation of MAP2K1 stimulates its kinase activity, and acetylated MAP2K1 is under the regulatory control of the sirtuin family members SIRT1 and SIRT2
    ASSOCIATED DISORDERS
    corresponding disease(s) CFC3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    missense mutation in CFC
    tumoral somatic mutation      
    in melanomas
    constitutional somatic mutation      
    are a common cause of extracranial arteriovenous malformation (AVM)
    tumoral somatic mutation      
    in BRAF V600E-negative Langerhans cell histiocytosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • is a promising prognostic biomarker candidate correlated to response to platinum based chemotherapy in ovarian cancer
    • Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousvascular 
    . MEK1 inhibitors, which are approved to treat several forms of cancer, are potential therapeutic agents for individuals with extracranial Arteriovenous malformation (AVM)
    diabetetype 2 
    MAP2K1 signaling pathway could be a novel therapeutic target for novel antidiabetic agents
    ANIMAL & CELL MODELS
    The null mutation of the mouse Mek1 gene by insertional mutagenesis was recessive lethal, and homozygous mutant embryos died at 10.5 days of gestation. Histopathologic analysis revealed a marked decrease of vascular endothelial cells in the labyrinthine region, resulting in reduced vascularization of the placenta. Failure to establish a functional placenta was considered a likely cause of embryonic death.