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FLASH GENE
Symbol MARK3 contributors: mct/pgu - updated : 21-08-2010
HGNC name MAP/microtubule affinity-regulating kinase 3
HGNC id 6897
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a conserved N-terminal kinase domain
  • a conserved region of about 40 amino acids at their extreme C-termini, with a ubiquitin-associated (UBA) domain located C-terminal to the kinase domain, forming a stable intramolecular interaction with the N-terminal lobe of the kinase domain (Murphy 2007), and a highly conserved C-terminal domain, which has been termed kinase-associated domain-1 (KA-1)
  • HOMOLOGY
    Homologene
    FAMILY
  • microtubule affinity-regulating kinase (MARK)/Par-1 family
  • CATEGORY enzyme , receptor membrane kinase
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    text membrane localisation of MARK3 required a highly conserved C-terminal domain
    basic FUNCTION
  • kinase involved in the phosphorylation of microtubule-associated proteins
  • may be involved in cell cycle regulation, and its alterations may lead to carcinogenesis
  • positive regulator of the WNT-beta catenin signaling pathway
  • play a pivotal role in establishing cellular polarity
  • with MARK2, phosphorylate class IIa HDACs on one of their multiple 14-3-3 binding sites and alter their subcellular localization and repressive function
  • 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
  • potentially a positive regulator for lipogenesis in adipocytes and hepatocytes
  • MARK1, MARK2, MARK3, MARK4 are implicated in phosphorylation of tau protein, causing formation of neurofibrillary tangles in Alzheimer disease (AD)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds to CDC25C and phosphorylates CDC25C on serine-216
  • cell & other
    REGULATION
    Other phosphorylated by STK11
    regulated by 14-3-3 scaffolding proteins, as well as the LKB1 tumour suppressor kinase and atypical protein kinase C (PKC)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Par-1a/ mice are viable and develop normally, and adult mice are hypermetabolic, have decreased white and brown adipose tissue mass, and unaltered glucose/insulin handling, but show resistance to glucose intolerance on high-fat diet, and diet-dependent reduced adiposity
  • Par-1b/Par-1a double mutants are not viable, and at least one allele is necessary for embryonic survival