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FLASH GENE
Symbol BRSK2 contributors: shn/npt - updated : 24-02-2015
HGNC name BR serine/threonine kinase 2
HGNC id 11405
DNA
TYPE functioning gene
STRUCTURE 72.80 kb     20 Exon(s)
MAPPING cloned Y linked N status provisional
Map pter - D11S1363 - BRSK2 - D11S4177 - D11S1984 - cen
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
20 - 4520 - 766 - 2005 15705853
20 - 4140 - 674 - 2005 15705853
20 - 4563 - 735 - 2005 15705853
20 - 4093 - 668 - 2005 15705853
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrinepancreas   moderately Homo sapiens
Nervousbrain   specific Homo sapiens
Reproductivemale systemtestis  moderately Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Endocrineislet cell (alpha,beta...) Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
IMPRINTING maternally
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a kinase domain related to that of PAR-1
  • HOMOLOGY
    interspecies ortholog to BRSK2, Pan troglodytes
    ortholog to Brsk2, Rattus noorvegicus
    ortholog to Brsk2, Mus musculus
    intraspecies paralog to BRSK1
    Homologene
    FAMILY
  • protein kinase superfamily
  • CAMK Ser/Thr protein kinase family
  • AMPK subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text
  • BRSK2 co-localizes with CDK16 in the cytoplasm and phosphorylates one of its serine residues, Ser-12
  • ER stress induces endogenous BRSK2 to localize to the ER
  • basic FUNCTION
  • serine/threonine kinase
  • acting as a checkpoint kinase upon DNA damage induced by UV irradiation or methyl methane sulfonate (Lu 2004)
  • may be an autoantigen involved in the pathogenesis of small-cell lung cancer -associated limbic encephalitis
  • required for neuronal polarization (Kishi 2005)
  • an alternative splice form of SadB encoding a short SADB Ser-Thr kinase is localized to centrosomes, and controls centrosome duplication through phosphorylation of gamma-tubulin (Alvarado-Kristensson et al, 2009)
  • controls centrosome homeostasis by regulating phosphorylation of gamma-tubulin and regulates cell cycle progression (Alvarado-Kristensson et al, 2009)
  • BRSK2 and BRSK1 (its homologue, SAD-B) kinases may regulate neuronal polarization, presynaptic vesicle clustering and axon termination
  • BRSK1, BRSK2 are crucial for establishing neuronal polarity, and BRSK1 has also been shown to regulate neurotransmitter release presynaptically
  • ER stress may reduce BRSK2 protein and change BRSK2 subcellular localization, which in turn alleviate ER stress-induced apoptosis
  • BRSK2 level is elevated in response to ER stress, providing an example of ER stress-mediated transcription of a kinase
  • play an essential role in neuronal polarization
  • is a pancreas-specific mediator of incretin response in islet beta cells
  • stimulates cytoskeletal remodeling of F-actin, which is required for the trafficking and fusion of insulin secretory granules to the plasma membrane
  • function as the “yin and yang” of MTOR signaling in pancreatic islet beta cells
  • may also play a role in controlling satiety
  • BRSK1, BRSK2 are required for axon specification and arborization in subsets of neurons
  • involved in axonogenesis and the polarization of cortical neurons
  • CELLULAR PROCESS cell cycle, checkpoint
    cell cycle, progression
    PHYSIOLOGICAL PROCESS development , nervous system
    text neuronal polarization
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • BRSK2, BRSK1 are required to initiate WEE1 downregulation in polarized neurons
  • COPS5 promoted the ubiquitination and proteasome-dependent degradation of BRSK2
  • the elevated cellular DDIT3 levels could contribute to ER stress-mediated apoptosis after change of BRSK2 protein
  • interacts with CDK-related protein kinase CDK16, a kinase involved in neurite outgrowth and neurotransmitter release
  • is a unique pancreas-specific effector protein of MTOR signaling
  • AMPK-related kinases NUAK2 and BRSK2 regulate autophagy through WDR45
  • genetically and/or biochemically interact with several genes that are robustly associated with developmental disease (TSC2, PTEN)
  • cell & other
    REGULATION
    Other activated early in the program of neuronal differentiation
    is regulated by ER stress in protein level and it is involved in apoptosis induced by ER stress
    ASSOCIATED DISORDERS
    corresponding disease(s) NDDASDS
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabete  
    attractive target for developing novel diabetic drugs
    cancer  
    may be a potential target of antitumor therapies based on enhancing ER stress
    ANIMAL & CELL MODELS
  • Mouse embryonic fibroblasts from SADB–/– mice manifested no obvious centrosome defects (Alvarado-Kristensson et al, 2009)