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FLASH GENE
Symbol MELK contributors: mct/pgu - updated : 28-04-2020
HGNC name maternal embryonic leucine zipper kinase
HGNC id 16870
Location 9p13.2      Physical location : 36.572.904 - 36.677.678
Synonym name
  • xenopus protein kinase p69EG3 homolog
  • pEg3 kinase
  • protein kinase PK38
  • Synonym symbol(s) KIAA0175, HPK38, MPK38
    EC.number 2.7.11.1/ 2.7.10.2
    DNA
    TYPE functioning gene
    STRUCTURE 104.82 kb     18 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • a TP53-responsive region within the MELK promoter that did not map to the TP53 consensus response elements, but to a region containing a FOXM1-binding site
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 - 2486 74.5 651 - 2002 11802789
    17 - 2363 - 610 - 2002 11802789
    17 - 2342 - 603 - 2002 11802789
    16 - 2273 - 580 - 2002 11802789
    17 - 2400 - 619 - 2002 11802789
    16 - 2256 - 571 - 2002 11802789
    16 - 2283 - 580 - 2002 11802789
    16 - 2300 - 457 - 2002 11802789
    15 - 2160 - 520 - 2002 11802789
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveintestinelarge intestinecolon  
     stomach    
    Lymphoid/Immunethymus    
     tonsils    
    Reproductivefemale systemplacenta   
     female systemuterus   
     female systemovary   
     male systemtestis   
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    Lymphoid    
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, interphase
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • putative transmembrane domain
  • an N-terminal serine/threonine kinase domain, and a mitochondrial targeting signal at the N-terminus of the MC domain
  • a leucine zipper motif
  • an UBA domain, a kinase active site, with key residues for achieving high potency, laying the groundwork for structure-based drug design efforts
  • catalytic domain
  • HOMOLOGY
    interspecies homolog to Xenopus protein kinase p69EG3
    homolog to murine Mpk38
    intraspecies paralog to maternal embryomic leucine zipper kinase
    Homologene
    FAMILY
  • protein kinase superfamily
  • CAMK Ser/Thr protein kinase family
  • SNF1 subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • localized in the cytoplasm and the nucleus during interphase and at the cell cortex during anaphase and telophase
  • basic FUNCTION
  • may play a role in the signal transduction events in the egg and early embryo
  • FAU, BCLG and MELK, are crucially important in breast cancer
  • responsible for various cellular functions, including early T cell activation, embryonic development, apoptosis, and oncogenesis
  • serine/threonine kinase involved in several cell processes, including the cell cycle, proliferation, apoptosis and mRNA processing
  • is primarily required for proper proliferation, and might play multiple roles in retinal development
  • functions as a modulator of intracellular signaling and affects various cellular and biological processes, including cell cycle, cell proliferation, apoptosis, spliceosome assembly, gene expression, embryonic development, hematopoiesis, and oncogenesis
  • plays a prominent role in cell cycle control, cell proliferation, apoptosis, cell migration, cell renewal, embryogenesis, oncogenesis, and cancer treatment resistance and recurrence
  • is an oncogenic kinase involved in the pathogenesis and recurrence of Hepatocellular carcinoma (HCC)
  • play critical roles in human carcinogenesis through activation of cell proliferation, inhibition of apoptosis and maintenance of stemness
  • MELK is dispensable for the proliferation of cancer cells
  • MELK levels reflect mitotic activity in diverse cell types
  • observed pattern of MELK expression in cancer can be explained by the fact that MELK is up-regulated in mitotic cells
  • serve critical roles in the maintenance of stemness of cancer cells
  • functions likely as a positive regulator of CDKN1A, regulating apoptosis, cell cycle arrest, and metabolism during obesity
  • MELK enhances tumorigenesis, migration, invasion and metastasis of Esophageal squamous cell carcinoma (ESCC) cells via activation of FOXM1 signaling pathway
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • MELK-EIF4B signaling axis that regulates protein synthesis during mitosis, and consequently influences cancer cell survival
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ZNF622
  • FAU modifies apoptosis-controller BCL2L14, which is also a key target for candidate oncoprotein maternal embryonic leucine zipper kinase (MELK)
  • co-localizes and interacts with anillin an important regulator of cytokinesis
  • phosphorylates STRAP at Ser(188) via direct interaction
  • EIF4B is a MELK-interacting protein during mitosis and a bona fide substrate of MELK
  • ZNF622 is an activator of MELK, and activation of MELK may participate in obesity
  • MELK serves a key role in cancer stem cells (CSCs) through the regulation of SOX2
  • MELK is an interacting partner of CDKN1A (interaction through the cyclin-dependent kinase (CDK) binding region of CDKN1A and the C-terminal domain of MELK)
  • MELK induces EZH2 phosphorylation, which subsequently binds to and methylates NFKB1, leading to tumor proliferation and persistence of stemnessin glioma
  • important role of MELK and USP36 in mediating EZH2 stability in natural killer/T-cell lymphoma (NKTL)
  • ability of BUB1B to regulate MELK was found to be essential for its ability to promote prostate cancer cell proliferation
  • TP53 represses MELK expression by inhibiting E2F1A-dependent transcription of FOXM1 and mutation-driven loss of wild-type TP53, which frequently occurs in TNBCs, induces MELK expression by suppressing FOXM1 expression and activity in TP53-mutant breast cancers
  • cell & other
    REGULATION
    Phosphorylated by MSLN and MAPK (MELK phosphorylation by MSLN and MAPK enhance its activity during M-phase)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    dysregulated expression of FAU and MELK is associated with poor prognosis in breast cancer
    tumoral     --over  
    correlated with poor overall survival (OS) and disease-free survival (DFS) of Pancreatic cancer patients
    tumoral     --over  
    in TNBCs (Triple-negative breast cancer) as compared with ER-positive breast cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • attractive target for improvements in breast cancer risk prediction and prognosis
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    considered as a potential therapeutic target for cancers
    cancerreproductivebreast
    attractive targets for improvements in breast cancer therapy
    cancerdigestiveoesophagus
    is a potential therapeutic target for ESCC patients, even those in an advanced stage
    cancerhead and neck 
    MELK inhibition may also be promising for clinical applications in the treatment of HNSCC
    cancerbrainglioma/neuroblstoma
    is a novel therapeutic target for NB and its inhibitor OTSSP167 is a promising drug for further clinical development
    cancer  
    MELK inhibition may be effective for human cancers even if TP53 is mutated
    immunologyinfectious 
    potential target for anti-HIV therapy
    cancerdigestiveliver
    promising molecular target to develop therapeutic strategies for patients with advanced HCC
    ANIMAL & CELL MODELS