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FLASH GENE
Symbol RPS6KA3 contributors: mct - updated : 13-10-2017
HGNC name ribosomal protein S6 kinase, 90kDa, polypeptide 3
HGNC id 10432
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • two non identical catalytic domains, respectively located in N and C terminal regions (respectively NTK and CTK) connected by an ~100 AA linker
  • C-terminal sequences that bind PDZ-containing proteins
    • HOMOLOGY
    interspecies homolog to murine Rps6ka2
    intraspecies homolog to rps6ka2
    Homologene
    FAMILY
  • protein kinase superfamily
  • AGC Ser/Thr protein kinase family
  • S6 kinase subfamily
    • CATEGORY enzyme , signaling , receptor membrane serine/threonine kinase phosphatase
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,cytoplasm,cytoskeleton,intermed filament
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,kinetochore
    text
  • cytoplasmic retention also required for PEA15 to impair kinase activity of RPS6KA3
  • localizes at the kinetochores under spindle checkpoint conditions, and during mitosis, associated with the centrosomes, the spindle and at the mid-body
    • basic FUNCTION
  • involved in the activation of glycogen synthesis and playing important role in learning and memory
  • required for epidermal growth factor activated phosphorylation of histone H3, which may cause chromatin remodeling and facilitate gene transcription
  • involved in cell proliferation and differentiation but not in vivo in the phosphorylation of RPS6
  • mediating protein synthesis initiation and elongation induced by hormones or growth factors
  • noteworthy required for growth factor stimulated transcription of FOS
  • maybe playing an essential regulatory role in protein synthesis during cell proliferation
  • required for osteoblast differentiation and function through its ability to phosphorylate specific transcription factors
  • critical upstream signaling element in the activation of PLD1 to produce the lipids required for exocytosis
  • pivotal factor linking the stress response to survival and proliferation
  • is a critical mediator of inhibitory cross-talk between receptor tyrosine kinases and 5-hydroxytryptamine 2A receptors (5-HT2AR) by phosphorylating 5-HT2AR
  • novel role for RPS6KA3 in cognitive processes , suggesting the critical implication of an intriguing brain structure in place aversion learning
  • is a key regulator of integrin activity, suggesting a novel mechanism by which it may promote cell migration and cancer metastasis
  • promotes G2/M transition in mammalian cells through activating phosphorylation of CDC25A and CDC25B
  • plays a key role in cell proliferation and transformation induced by tumor promoters such as epidermal growth factor (EGF) in human skin cells
  • plays an important role in stress-tolerance and cell survival, resulting in cell proliferation and cancer development
  • is a modulator of craniofacial development
  • is a critical regulator of cementoblast function
  • is a nonredundant regulator of cementum homeostasis, alveolar bone maintenance, and periodontal health, with all these features being independent of RPS6KA3 function in systemic bone formation
  • downstream kinase of the mitogen-activated protein kinase (MAPK) pathway, which is important in regulating survival, transcription, growth and proliferation
  • affects mitotic progression by regulating the distribution, basal level and the stability of mitotic spindles
    • CELLULAR PROCESS protein, translation/synthesis
    PHYSIOLOGICAL PROCESS development
    text skeletal development
    PATHWAY
    metabolism
    signaling
  • FGFR2-RPS6KA3 signalling pathway is involved in pathophysiology of breast cancer
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
  • ATP
    • protein
  • RPS6 binding
  • interacting with PEA15
  • interacts with and stimulates PLD activity through the phosphorylation of Thr-147 in the PLD1 amino-terminal phox homology domain
  • interacting with SCRIB (Scribble might be implicated in the recruitment of RPS6KA3 to the plasma membrane)
  • interacting with TIA1(the RPS6KA3 N-terminal kinase domain controls the direct interaction with the prion-related domain of TIA1)
  • interacting with FGFR3 (association is critical for FGFR3-dependent tyrosine phosphorylation at Y529 and Y707 of RPS6KA3 as well as its subsequent activation and RPS6KA3 is important for FGFR3-induced hematopoietic transformation)
  • preferentially phosphorylates CDC25A and CDC25B in mitotic cells
  • RPS6KA3 is a potential FGFR1 interaction partner, and activated RPS6KA3 directly interacts with and phosphorylates FGFR1, thereby modulating receptor signaling through regulation of endocytosis
    • cell & other
    REGULATION
    activated by a high K+-induced rise in cytosolic calcium
    inhibited by PEA15
    Other in response to TNF, PDPK1 could phosphorylate RPS6KA3 and activated RPS6KA3, then promoting the activation of NFKB1
    ASSOCIATED DISORDERS
    corresponding disease(s) CLS , MRX19
    related resource Coffin-Lowry Syndrome
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Rsk2-deficient mice display hypomineralization of cellular cementum with accumulation of nonmineralized cementoid (pMID: 26927527)