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FLASH GENE
Symbol MARK2 contributors: mct/pgu - updated : 04-08-2012
HGNC name MAP/microtubule affinity-regulating kinase 2
HGNC id 3332
Location 11q13.1      Physical location : 63.606.399 - 63.678.491
Synonym name
  • ELKL motif kinase
  • murine Emk1 (ELKL Motif Kinase) homolog
  • protein-serine/threonine kinase
  • Ser/Thr protein kinase PAR-1B
  • PAR1 homolog
  • partitioning-defective 1 b
  • serine/threonine kinase
  • Synonym symbol(s) D11S1226, EMK1, PAR-1, Par1b, MGC99619
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 70.16 kb     18 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    TMSL5 11 thymosin-like 5 RARRES3 11q23 retinoic acid receptor responder (tazarotene induced) 3 HRASLS2 11q13.1 HRAS-like suppressor 2 HRASLS3 11q13.1 HRAS-like suppressor 3 LOC283241 11q13.1 hypothetical protein LOC283241 DKFZP564J0863 11q13.1 DKFZP564J0863 protein RTN3 11q13 reticulon 3 LOC144097 11q13.1 hypothetical protein BC007540 MARK2 11q12-q13 MAP/microtubule affinity-regulating kinase 2 LOC283248 11q13.1 hypothetical protein LOC283248 FLJ13848 11q13.1 hypothetical protein FLJ13848 COX8 11q13.1 cytochrome c oxidase subunit VIII OTUB1 11q13.1 OTU domain, ubiquitin aldehyde binding 1 LRP16 11q11 LRP16 protein LOC387776 11 LOC387776 FLRT1 11q12-q13 fibronectin leucine rich transmembrane protein 1 STIP1 11q13.2 stress-induced-phosphoprotein 1 (Hsp70/Hsp90-organizing protein) URP2 11q13.1 UNC-112 related protein 2 short form
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - - 2784 77.5 691 - 1998 9730619
    19 - 2965 83 745 - 1998 9730619
    18 - 4556 81.07 724 - 1998 9730619
    18 - 4748 - 788 - 1998 9730619
    - - 4541 - 719 - 1998 9730619
    - - 4511 - 709 - 1998 9730619
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunethymus   highly
    Nervousbrain   highly
    Reproductivefemale systemuteruscervix highly
    Respiratoryrespiratory tractlarynx  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • ubiquitin-associated domain (UBA) domain, attached via a taut linker to the large lobe of the kinase domain and leans against a hydrophobic patch on the small lobe
  • mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to murine Emk1 (ELKL Motif Kinase)
    Homologene
    FAMILY
  • Par-1 protein kinases family
  • CAMK Ser/Thr protein kinase family
  • microtubule affinity-regulating kinase (MARK)/Par-1 family
  • CATEGORY enzyme , receptor membrane serine/threonine
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text membrane accumulation of MARK2 induced by DVL1L1 is regulated by its phosphorylation status, which is important for MARK2 to regulate the microtubule dynamics
    basic FUNCTION
  • potentially involved in the control of cell polarity
  • involved in microtubule stability and cancer
  • adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathway
  • phosphorylates tau protein at sites that cause detachment from microtubules in Alzheimer neurofibrillary degeneration
  • conserved kinase that plays crucial roles in cell polarity
  • specifically regulates development of dendrites in hippocampal neurons
  • with MARK3, phosphorylate class IIa HDACs on one of their multiple 14-3-3 binding sites and alter their subcellular localization and repressive function
  • negatively regulates dendrite development through phosphorylation of MAP2
  • 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
  • regulates axon formation via phosphorylation of a kinesin superfamily protein KIF13B
  • potentially a positive regulator for lipogenesis in adipocytes and hepatocytes
  • plays key roles in the development of cell polarity
  • may contribute to cell polarization by regulating the turnover of ARHGEF2 at microtubules
  • appears to regulate cell polarization via several microtubule-associating proteins, such as KIF13B and ARHGEF2
  • is thought to regulate microtubule dynamics by inhibiting microtubule binding of microtubule-associated proteins
  • potential novel function in the maintenance of mature dendritic spine morphology by regulating microtubule growth and the accumulation of SRCIN1 in dendritic spines
  • ROCK1/MARK2-dependent regulation of basement membrane placement is required for the coordination of tissue polarity and the elaboration of tissue structure in the developing submandibular salivary gland
  • 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
  • interacts with CDK16
  • binds to the C-terminal part of WEE1
  • interacts with SSH1
  • interacting with FLOT2 (binds to MARK2, a known upstream mediator of major signal transduction pathways implicated in cell growth and metastasis, and may thereby influence tumor progression)
  • MARK2 is negatively regulated by PAK7, a neuronal member of the p21-activated kinase family
  • RAB11FIP2 is phosphorylated on serine 227 by MARK2, regulating an alternative pathway modulating the establishment of epithelial polarity
  • substrate for ARHGEF2
  • GAB1 brings MARK2 and PARD3 into a transient complex, stimulating PARD3 phosphorylation by MARK2
  • increase in MAPT phosphorylation at Ser262 through MARK2 contributes to MAPT-mediated neurodegeneration under a pathological condition in which axonal mitochondria is depleted
  • cell & other
    REGULATION
    Other regulated by atypical protein kinase C (aPKC) and another arm of the PKC pathway, one that involves novel PKCs (nPKC) and protein kinase D
    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
  • in Par-1b null mice, decrease in the adipose tissue due to decreases in total adipocyte cell number, not cell size
  • Par-1b/Par-1a double mutants are not viable, and at least one allele is necessary for embryonic survival