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FLASH GENE
Symbol MARK4 contributors: mct - updated : 21-08-2017
HGNC name MAP/microtubule affinity-regulating kinase 4
HGNC id 13538
DNA
TYPE functioning gene
STRUCTURE 54.03 kb     18 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
17 - 5163 - 752 expressed in brain neurogenic regions 2014 25123532
  • MARK4L
  • co-localisation of vimentin and MARK4L suggests that MARK4 has a wide-ranging influence on cytoskeleton
  • exhibits an additional nucleolar localisation in tumour cells
  • 18 - 5243 75.2 688 - 2014 25123532
  • MARK4S
  • MARK4S levels are significantly decreased in glioma and show an inverse correlation with tumour grade
  • in MARK4S silenced cells, centrosomes were duplicated and positioned apically to the nucleus, indicating that the centrosome cycle was altered and the cells arrested in G1 phase
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
    Nervousbrain   predominantly
    Reproductivemale systemtestis    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    ReproductiveSertoli cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • catalytic domain
  • ubiquitin associated domain
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Emk2
    intraspecies homolog to MARK3
    Homologene
    FAMILY
  • MARK family of serine-threonine protein kinase
  • microtubule-affinity regulating kinase (MARK) family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    text
  • localized prominently at the tips of neurite-like processes
  • associated with the basal body and ciliary axoneme
  • expressed throughout the cell cycle and preferentially activated during mitosis
  • basic FUNCTION
  • playing a role in hepatocellular carcinogenesis
  • directly involved in microtubule organization in neuronal cells and may contribute to the pathological phosphorylation of tau in Alzheimer disease
  • MARK1, MARK2, MARK3, MARK4 phosphorylate MAPT in its repeat domain and thereby regulate its affinity for microtubules and affect the aggregation of tau into Alzheimer paired helical filaments
  • is a new negative regulator of MTOR
  • MARK4 kinase activity was required for initiation of axoneme extension 9)
  • is a critical positive regulator of early steps in ciliogenesis
  • MARK1, MARK2, MARK3, MARK4 are implicated in phosphorylation of tau protein, causing formation of neurofibrillary tangles in Alzheimer disease (AD)
  • promotes adipogenesis in adipocytes by activating the MAP2K1 and inhibiting the MAPK14 pathway, and triggers apoptosis by activating the MAP2K1 pathway
  • serine-threonine kinase that phosphorylates MAP proteins, increasing microtubule dynamics
  • MARK2 and MARK4 regulate Sertoli cell blood-testis barrier (BTB) Dynamics through microtubule and actin cytoskeletons
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, nucleotide,
    protein
  • PNMA1
  • phosphorylates tau and the related microtubule-associated protein 2 (MAP2) and MAP4
  • phosphorylates Raptor, a key component of MTOR, and this phosphorylation may interfere with Raptor-Rag interaction (increases Raptor Ser-792 phosphorylation, an inhibitory site, to inhibit MTOR)
  • ODF2 is an interaction partner of MARK4 and ODF2 localization to the centriole partially depended on MARK4
  • cell & other
    REGULATION
    Other regulated by 14-3-3 scaffolding proteins, as well as the LKB1 tumour suppressor kinase and atypical protein kinase C (PKC)(Göransson 2006)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene target for pharmacological intervention in focal cerebral ischaemia
    Marker
  • MARK4L is a nucleolus-associated tumour marker
  • Therapy target
    SystemTypeDisorderPubmed
    diabetemetabolic syndrom 
    anti-Mark4 therapy targetted to inhibit lipid accumulation and apoptosis of adipocytes shows potential as a novel therapeutic strategy for treatment of obesity-associated metabolic complications
    neurologyneurodegenerative 
    promising target for AD therapy
    ANIMAL & CELL MODELS