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FLASH GENE
Symbol STK4 contributors: mct - updated : 16-12-2012
HGNC name serine/threonine kinase 4
HGNC id 11408
DNA
TYPE functioning gene
STRUCTURE 113.47 kb     11 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Map cen - HNF4A - SERINC3 - PKIG - ADA ADA - KCNS1 - STK4 - SEMG1 - SEMG2 - PI3 - TOMM34 - YWHAB - PABPC1L - WFDC2 - SDC4 - TNNC2 - qter
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
11 - 6344 - 487 - 2007 17932490
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Hearing/Equilibriumear   highly
Lymphoid/Immunelymph node   predominantly
 spleen   highly
 thymus   highly
Nervousbrain   lowly
Respiratorylung   lowly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  moderately
Epithelialbarrier liningretinal pigment epithelium (RPE)  
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/ImmuneB cell
Lymphoid/ImmuneT cell
cell lineage
cell lines
fluid/secretion highly in blood
at STAGE
PROTEIN
PHYSICAL PROPERTIES acid
STRUCTURE
motifs/domains
  • eleven subdomains typical of STK in the N terminus, N-terminal kinase domain, and N-terminal catalytic domain
  • SARAH domains acting as a platform to mediate homodimerization and hetero-interaction with a range of adaptors including RASSFs and Salvador, which also possess SARAH domains
  • two caspase cleavage sites situated between its N-terminal kinase domain and its C-terminal regulatory domain
  • C-terminal regulatory and dimerization regions that are cleaved upon nuclear transport, autophosphorylation sites within the regulatory region and both regulatory region phosphorylation and MST1 dimerization contribute to FoxO phosphorylation
  • conjugated PhosphoP
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to rattus Stk4 (95.9pc)
    ortholog to murine Stk4 (97.3pc)
    ortholog to Drosophila hippo
    intraspecies homolog to DM protein kinase,highly
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • STE20 (Sterile-20) subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    text
  • caspase-cleaved form cycles between the nucleus and cytoplasm
  • full-length STK4 is excluded from the nucleus and localized to the cytoplasm
  • basic FUNCTION
  • inducing chromatin condensation followed by internucleosomal DNA fragmentation
  • with STK3, are activated in mitosis and catalyze the mitotic phosphorylation of MOBKL1A/MOBKL1B
  • serine/threonine protein kinase that is activated in response to a variety of apoptotic stimuli and causes apoptosis when over-expressed in mammalian cells
  • playing an important role in cancer progression
  • phosphorylates FOXO transcription factors in the cytosol and histone H2B in the nucleus to promote cellular apoptosis
  • plays crucial roles in lymphocyte trafficking
  • key enzyme involved in lymphocyte entry and interstitial migration
  • phosphorylating TNNI3 in the heart and may contribute to the modulation of myofilament function
  • serine/threonine kinase that is cleaved and activated by caspases during apoptosis, and induces apoptotic chromatin condensation through its phosphorylation of histone H2FAX at Ser-139
  • caspase-mediated cleavage is responsible for the phosphorylation of H2FAX
  • stimulates transcription of the proapoptotic mediator PMAIP1 in a FOXO1-dependent manner
  • STK3, STK4 control Rho GTPase activation and the migratory responses of single-positive (SP) thymocytes
  • hydrogen peroxide-stimulated STK4 activates a positive feedback loop to sustain an oxidizing cellular state
  • STK3/STK4 are required for proper cardiac lineage cell development and teratoma formation
  • STK3, STK4 are key players in mammalian Hippo pathway
  • STK3/STK4 regulate potentially placental development by control of trophoblast cell differentiation and labyrinthine vasculature at midgestation and STK3/STK4 control labyrinth morphogenesis in trophoblast- and fetal endothelial-dependent manners
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    text upregulated in apoptotic cells
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • homodimerization mediated via the coiled-coil region
  • common component of apoptosis initiated by various stresses
  • INTERACTION
    DNA
    RNA
    small molecule metal binding, cofactor, nucleotide,
  • Mg2+
  • ATP
  • protein
  • NORE1
  • RASSF1A
  • FOXO3
  • pro-apoptotic kinase, that is a physiological AKT1 interaction partner
  • binds and phosphorylates SAV1 (the stabilizing effect of STK4 on SAV1 requires its interaction with SAV1 but is probably not due to phosphorylation of SAV1 by STK4)
  • interacting with RASSF1 (RASSF1 facilitates STK4 activation and thereby promotes apoptosis induced by death receptor signaling)
  • H2AFX is a substrate of STK4, which functions to induce apoptotic chromatin condensation and DNA fragmentation
  • important caspase substrate that induces chromatin compaction during apoptosis
  • RASSF1 interacts with and activates STK3/STK4 kinases by preventing their dephosphorylation
  • MICAL1 competes with STK4 for NDR binding and thereby antagonizes MST1-induced NDR activation
  • STK3/STK4 timulated the binding of SAV1 to PPARG, a transcription factor that plays a key role in adipogenesis
  • ABL1 mediates oxidative stress-induced neuronal cell death through phosphorylating STK4 at Y433
  • cell & other
    REGULATION
    activated by catalase and caspase, generating a 36 kDa catalytic fragment and correlating with eosinophil but not neutrophil apoptosis
    by phosphorylation at several sites
    homodimerization
    autophosphorylation of Thr-183
    protein phosphatase-2A treatment
    stress
    cleaved and activated by a process that involves both phosphorylation and removal of the C-terminal inhibitory domain by caspases
    RASSF1(activates STK3 and STK4 by promoting their autophosphorylation and phosphorylation of the downstream LATS1 kinase)
    inhibited by the C-terminal non-catalytic region
    epidermal growth factor (EGF) treatment
    Other phosphorylated by AKT1 on the Thr(387) (protects STK4 from apoptotic cleavage in apoptotic cells, prevents its proteolytic activation, blocking FOXO3 phosphorylation and nuclear translocation)
    ASSOCIATED DISORDERS
    corresponding disease(s) TIIAC
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS