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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
Corresponding disease
CLS Coffin-Lowry syndrome
MRX19 mental retardation, 19
Location Xp22.12      Physical location : 20.168.029 - 20.284.750
Synonym name
  • insulin stimulated protein kinase 1
  • mitogen-activated protein (MAP) kinase-activated protein (KAP) kinase-1
  • ribosomal S6 kinase 2
  • Synonym symbol(s) RSK2, ISPK1, MAPKAPK1B, HU-3, ISPK-1, RSK, S6K-alpha3, p90-RSK2, pp90RSK2, CLS, MRX19
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 116.72 kb     22 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map see CLS
    Physical map
    GRPR Xp22.2-p22.13 gastrin-releasing peptide receptor LOC139451 Xp22.22 similar to melanoma antigen, family B, 4; melanoma-associated antigen B4 LOC139452 Xp22.22 similar to 60S ribosomal protein L6 (TAX-responsive enhancer element binding protein 107) (TAXREB107) (Neoplasm-related protein C140) LOC392429 X similar to Hspcb protein CTPS2 Xp22 CTP synthase II CALB3 Xp22.2 calbindin 3, (vitamin D-dependent calcium binding protein) SYAP1 Xp22.31 synapse associated protein 1, SAP47 homolog (Drosophila) CXorf15 Xp22.22 chromosome X open reading frame 15 RBBP7 Xp22.31 retinoblastoma binding protein 7 RNU4P6 Xp22.22 RNA, U4 small nuclear pseudogene 6 REPS2 Xp22.22 RALBP1 associated Eps domain containing 2 PRO0386 Xp22.22 hypothetical protein PRO0386 NHS Xp22.13 Nance-Horan syndrome (congenital cataracts and dental anomalies) SCML1 Xp22 sex comb on midleg-like 1 (Drosophila) LOC392430 X similar to dJ40E16.3 (novel gene similar to D. melanogaster CG5327 ) RAI2 Xp22 retinoic acid induced 2 LOC392431 X similar to Mdm4, transformed 3T3 cell double minute 4, p53 binding protein (mouse) MGC33653 Xp22.22 hypothetical protein MGC33653 SCML2 Xp22 sex comb on midleg-like 2 (Drosophila) CDKL5 Xp22 cyclin-dependent kinase-like 5 RS1 Xp22.2 retinoschisis (X-linked, juvenile) 1 PPEF1 Xp22.2-p22.1 protein phosphatase, EF hand calcium-binding domain 1 PHKA2 Xp22.2-p22.13 phosphorylase kinase, alpha 2 (liver) GPR64 Xp22.22 G protein-coupled receptor 64 PDHA1 Xp22.1 pyruvate dehydrogenase (lipoamide) alpha 1 LOC389840 X similar to MAP/ERK kinase kinase 5; apoptosis signal regulating kinase SH3KBP1 Xp22.3-p11.3 SH3-domain kinase binding protein 1 LOC256643 Xp22.13 hypothetical protein LOC256643 FLJ14503  hypothetical protein FLJ14503 EIF1A Xp22.1 eukaryotic translation initiation factor 1A RPS6KA3 Xp22.13 ribosomal protein S6 kinase, 90kDa, polypeptide 3 CNK2 Xp22.13 ribosomal protein S6 kinase, 90kDa, polypeptide 3 FLJ34960 Xp22.13 hypothetical protein FLJ34960 SMPX Xp22.1 small muscle protein, X-linked MBTPS2 Xp22.1-p22.2 membrane-bound transcription factor protease, site 2 SMS Xp22.1 spermine synthase PHEX Xp22.2-p22.1 phosphate regulating gene with homologies to endopeptidases on the X chromosome (hypophosphatemia, vitamin D resistant rickets) FLJ25735 Xp22.13 hypothetical protein FLJ25735 LOC389841 X LOC389841 DDX53 Xp22 DEAD (Asp-Glu-Ala-Asp) box polypeptide 53 MGC45134 Xp22.13 hypothetical protein MGC45134 LOC392432 X similar to hypothetical protein MGC35083 FLJ30296 Xp22.13 hypothetical protein FLJ30296 PRDX4 Xp22.12-p21.3 peroxiredoxin 4 ACATE2 Xp22.13 likely ortholog of mouse acyl-Coenzyme A thioesterase 2, mitochondrial SAT Xp22.1 spermidine/spermine N1-acetyltransferase MGC4825 Xp22.13 hypothetical protein MGC4825 LOC317771 Xp22.1 ribosomal protein L9 pseudogene FLJ25444 Xp22.13 hypothetical protein FLJ25444 KIAA1677 Xp22.1-p21 KIAA1677 EIF2S3 Xp22.2-p22.1 eukaryotic translation initiation factor 2, subunit 3 gamma, 52kDa ZFX Xp22.13-p22.12 zinc finger protein, X-linked LOC347438 Xp22.13 similar to P38IP protein
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 7723 83.7 740 - 2017 28013489
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
     vesselsaorta  highly
    Endocrinepancreas   highly
     thyroid    
    Nervousbrainhindbraincerebellum  
     brainforebraincerebral cortexoccipital 
     brainforebraincerebral cortexfrontal 
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    NervousPurkinje cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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)