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FLASH GENE
Symbol SIK2 contributors: mct - updated : 14-06-2016
HGNC name salt-inducible kinase 2
HGNC id 21680
Location 11q23.1      Physical location : 111.473.169 - 111.597.630
Synonym name
  • SNF1-like kinase 2
  • KIAA0781 protein
  • salt-inducible serine/threonine kinase 2
  • Qin-induced kinase
  • Synonym symbol(s) KIAA0781, LOH11CR1I, QIK, SNF1LK2, DKFZp434K1115, SIK-2
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 124.47 kb     15 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 5694 - 926 - 2004 15511237
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
    Endocrinepancreas    
    Nervousbrain   highly Homo sapiens
    Reproductivefemale systemovary   
     male systemtestis   
    Visualeyeretina    Homo sapiensAdult
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly Homo sapiens
    Muscularsmooth   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    not specificadipocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain, liver
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one UBA domain
  • HOMOLOGY
    Homologene
    FAMILY
  • protein kinase superfamily
  • CAMK Ser/Thr protein kinase family
  • AMPK subfamily
  • salt-inducible kinase (SIK) family
  • CATEGORY enzyme , receptor membrane serine/threonine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text
  • SIK2 co-localizes with VCP in the ER membrane
  • localizes at the centrosome
  • basic FUNCTION
  • protein serine/threonine kinase activity
  • SIK2-CRTC2 cascade may be important for the regulation of PPARGC1A and UCP1 gene expression in insulin signaling in brown adipose tissue (BAT)
  • SIK2 plays a key role in the initiation of mitosis, and regulates the localization of the centrosome linker protein, CEP250, through S2392 phosphorylation
  • function in the insulin-signaling pathway during adipocyte differentiation and to modulate CREB-mediated gene expression in response to hormones and nutrients
  • is a critical determinant in autophagy progression, suggesting a mechanism in which the interplay among kinase and deacetylase activities contributes to cellular protein pool homeostasis
  • SIK2 activates MEF2-dependent transcription and relieves repression of myogenesis by the deacetylases
  • could serve likely a similar role during the development of diabetic retinopathy
  • SIK2 is shown to be stabilized in pancreatic beta-cells following glucose stimulation, leading to improved systemic glucose homeostasis by regulating cellular calcium flux and insulin secretion
  • SIK2 is critical in regulating whole-body glucose metabolism primarily by controlling the CRTC2-CREB function of the white adipocytes
  • regulates mitotic progression and transcription in prostate cancer
  • plays a role in CREB1-mediated gene transcription
  • SIK3, rather than SIK1, SIK2, or AMPKs, acts as the predominant suppressor in gluconeogenic gene expression in the hepatocytes
  • disrupts EP300-PPARA interaction by direct phosphorylation of EP300 at Ser89, which in turn decreases PPARA-mediated ketogenic gene expression
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • STK11-SIK pathway functions as a key gluconeogenic gatekeeper in the liver
  • a component
  • SIK2-EP300-PPARA cascade mediates glucagon effect on ketogenesis
  • SIK2-CDK5R1-PJA2 complex is essential for glucose homeostasis and provides a link between CDK5R1-CDK5 and the AMPK family in excitable cells
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • plays critical roles in neuronal survival, is modulated by CaMKI/IV, and regulates CREB1 via CRTC1
  • STK11 acts through SIK2 and SIK3 to promote nucleocytoplasmic trafficking of class IIa HDACs
  • SIK2 co-localizes with VCP in the ER membrane and stimulates its ATPase activity through direct phosphorylation
  • SIK2 attenuates the association of the PPP2CA repressor, the protein phosphatase methylesterase-1 (PPME1), thus preserving the methylation status of the PPP2CA catalytic subunit
  • SIK2 increases SLC2A4 levels, regulates CRTC2, CRTC3, HDAC4 and glucose uptake in adipocytes
  • cell & other
    REGULATION
    Other is regulated by cAMP via phosphorylation at Ser358 in adipocytes
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    targeting SIK2 therapeutically will have pleiotropic effects on cell-cycle progression and transcription factor activation, which should be accounted for when characterizing SIK2 inhibitors
    cancerreproductiveovary
    as a plausible target for therapy in ovarian cancers
    ANIMAL & CELL MODELS