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Symbol RPS6KA3 contributors: mct - updated : 13-10-2017
HGNC name ribosomal protein S6 kinase, 90kDa, polypeptide 3
HGNC id 10432
  • 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
    interspecies homolog to murine Rps6ka2
    intraspecies homolog to rps6ka2
  • 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,cytoskeleton,microtubule,mitotic spindle
    intracellular,cytoplasm,cytoskeleton,intermed filament
  • 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
    text skeletal development
  • FGFR2-RPS6KA3 signalling pathway is involved in pathophysiology of breast cancer
  • a component
    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
    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
    corresponding disease(s) CLS , MRX19
    related resource Coffin-Lowry Syndrome
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • Rsk2-deficient mice display hypomineralization of cellular cementum with accumulation of nonmineralized cementoid (pMID: 26927527)