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RPS6KA3 Gene

protein-coding   GIFtS: 76
GCID: GC0XM020168

Ribosomal Protein S6 Kinase, 90kDa, Polypeptide 3

(Previous names: ribosomal protein S6 kinase, 90kD, polypeptide 3, mental...)
(Previous symbols: MRX19, CLS)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Ribosomal Protein S6 Kinase, 90kDa, Polypeptide 31 2     pp90RSK22 3
MRX191 2 5     EC 2.7.11.13 8
RSK22 3 5     Coffin-Lowry Syndrome1
CLS1 2     Mental Retardation, X-Linked 191
Insulin-Stimulated Protein Kinase 12 3     Ribosomal Protein S6 Kinase, 90kD, Polypeptide 31
Ribosomal S6 Kinase 22 3     HU-32
ISPK-12 3     RSK2
MAPKAPK-1b2 3     S6K-alpha32
MAPKAPK1B2 3     p90-RSK22
RSK-22 3     Ribosomal Protein S6 Kinase Alpha-32
S6K-alpha-32 3     90 KDa Ribosomal Protein S6 Kinase 33
MAP Kinase-Activated Protein Kinase 1b2 3     ISPK13
MAPK-Activated Protein Kinase 1b2 3     p90RSK33
MAPKAP Kinase 1b2 3     EC 2.7.118
P90-RSK 32 3     

External Ids:    HGNC: 104321   Entrez Gene: 61972   Ensembl: ENSG000001771897   OMIM: 3000755   UniProtKB: P518123   

Export aliases for RPS6KA3 gene to outside databases

Previous GC identifers: GC0XU990207 GC0XM018839 GC0XM019371 GC0XM019534 GC0XM019933 GC0XM020077 GC0XM017910


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for RPS6KA3 Gene:
This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase
contains 2 non-identical kinase catalytic domains and phosphorylates various substrates, including members of the
mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in
controlling cell growth and differentiation. Mutations in this gene have been associated with Coffin-Lowry
syndrome (CLS). (provided by RefSeq, Jul 2008)

GeneCards Summary for RPS6KA3 Gene:
RPS6KA3 (ribosomal protein S6 kinase, 90kDa, polypeptide 3) is a protein-coding gene. Diseases associated with RPS6KA3 include coffin-lowry syndrome, and estrogen resistance. GO annotations related to this gene include protein serine/threonine kinase activity and magnesium ion binding. An important paralog of this gene is RPS6KA6.

UniProtKB/Swiss-Prot: KS6A3_HUMAN, P51812
Function: Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and
mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77,
regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and
differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In
fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in
the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation
(EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor
CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by
phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via
an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation
complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and
stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly
phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates
phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling
independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD
and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by
phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle
regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins
and prevents its translocation to the nucleus and inhibition of G1 progression. In LPS-stimulated dendritic
cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated
transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3. Phosphorylates DAPK1

summary for RPS6KA3 Gene:
p90 ribosomal S6 kinases (RSKs) are a family of protein serine/threonine kinases that regulate diverse
cellular processes such as cell growth, motility, survival and proliferation. There are four isoforms of
this enzyme; RSK1-4, which are directly activated by ERK1/2 in response to growth factors, many polypeptide
hormones, neurotransmitters and chemokines. p90 RSKs phosphorylate numerous cytosolic and nuclear targets
and act as downstream effectors of the ERK/MAPK signaling cascade. They are expressed ubiquitously in human
tissues and exist in multiple subcellular compartments. Abberant activation of p90 RSKs has been linked to
many human diseases, including breast and prostate cancers.

Gene Wiki entry for RPS6KA3 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000023.11  NT_167197.2  NC_018934.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the RPS6KA3 gene promoter:
         E2F-3a   E2F-4   SRF   E2F-5   SRF (504 AA)   E2F-2   E2F-1   E2F   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidRPS6KA3 promoter sequence
   Search Chromatin IP Primers for RPS6KA3

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat RPS6KA3


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: Xp22.2-p22.1   Ensembl cytogenetic band:  Xp22.12   HGNC cytogenetic band: Xp22.2-p22.1

RPS6KA3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
RPS6KA3 gene location

GeneLoc information about chromosome X         GeneLoc Exon Structure

GeneLoc location for GC0XM020168:  view genomic region     (about GC identifiers)

Start:
20,168,029 bp from pter      End:
20,285,523 bp from pter
Size:
117,495 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: KS6A3_HUMAN, P51812 (See protein sequence)
Recommended Name: Ribosomal protein S6 kinase alpha-3  
Size: 740 amino acids; 83736 Da
Cofactor: Magnesium (By similarity)
Subunit: Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells. Transiently dissociates
following mitogenic stimulation (By similarity). Interacts with NFATC4, ETV1/ER81 and FGFR1
Sequence caution: Sequence=BAD92170.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
5 PDB 3D structures from and Proteopedia for RPS6KA3:
4D9T (3D)        4D9U (3D)        4JG6 (3D)        4JG7 (3D)        4JG8 (3D)    
Secondary accessions: B2R9V4 Q4VAP3 Q59H26 Q5JPK8 Q7Z3Z7

Explore the universe of human proteins at neXtProt for RPS6KA3: NX_P51812

Explore proteomics data for RPS6KA3 at MOPED

Post-translational modifications: 

  • Activated by phosphorylation at Ser-227 by PDPK1. Autophosphorylated on Ser-386, as part of the activation
    process. May be phosphorylated at Thr-365 and Ser-369 by MAPK1/ERK2 and MAPK3/ERK1. Can also be activated via
    phosphorylation at Ser-386 by MAPKAPK21
  • N-terminal myristoylation results in an activated kinase in the absence of added growth factors1
  • Ubiquitination2 at Lys72, Lys81, Lys504, Lys566, Lys591, Lys658
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for RPS6KA3 (P51812) (see all 40)
     VVHRDLK  DKILRQK  CDIWSLG  KLTDFGL 


    See RPS6KA3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_004577.1  
    ENSEMBL proteins: 
     ENSP00000368884   ENSP00000407655   ENSP00000388512   ENSP00000440220   ENSP00000444837  
     ENSP00000368865  
    Reactome Protein details: P51812

    RPS6KA3 Human Recombinant Protein Products:

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    Novus Biologicals RPS6KA3 Proteins
    Novus Biologicals RPS6KA3 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

    RPS6KA3 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of RPS6KA3
    R&D Systems Antibodies for RPS6KA3 (RSK2)
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    OriGene Custom Antibody Services for RPS6KA3
    Novus Biologicals RPS6KA3 Antibodies
    Abcam antibodies for RPS6KA3
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    ThermoFisher Antibody for RPS6KA3
    LSBio Antibodies in human, mouse, rat for RPS6KA3

    RPS6KA3 Assay Products:

    EMD Millipore Kits and Assays for the Analysis of RPS6KA3
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    R&D Systems ELISAs for RPS6KA3 (RSK2)         (see all)
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    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    IUPHAR Guide to PHARMACOLOGY protein family classification: ribosomal protein S6 kinase, 90kDa, polypeptide 3
    RSK subfamily
    Other AGC kinases

    Selected InterPro protein domains (see all 8):
     IPR017441 Protein_kinase_ATP_BS
     IPR002290 Ser/Thr_dual-sp_kinase_dom
     IPR000961 AGC-kinase_C
     IPR011009 Kinase-like_dom
     IPR017892 Pkinase_C

    Graphical View of Domain Structure for InterPro Entry P51812

    ProtoNet protein and cluster: P51812

    1 Blocks protein domain: IPB000961 Protein kinase C-terminal domain

    UniProtKB/Swiss-Prot: KS6A3_HUMAN, P51812
    Similarity: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily
    Similarity: Contains 1 AGC-kinase C-terminal domain
    Similarity: Contains 2 protein kinase domains


    RPS6KA3 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: KS6A3_HUMAN, P51812
    Function: Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and
    mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77,
    regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and
    differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In
    fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in
    the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation
    (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor
    CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by
    phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via
    an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation
    complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and
    stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly
    phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates
    phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling
    independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD
    and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by
    phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle
    regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins
    and prevents its translocation to the nucleus and inhibition of G1 progression. In LPS-stimulated dendritic
    cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated
    transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3. Phosphorylates DAPK1
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    Enzyme regulation: Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-577 in the C-terminal
    kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-386, allowing
    binding of PDPK1, which in turn phosphorylates Ser-227 in the N-terminal kinase domain (NTDK) leading to the full
    activation of the protein and subsequent phosphorylation of the substrates by the NTKD

         Genatlas biochemistry entry for RPS6KA3:
    ribosomal S6 kinase,polypeptide 3,growth factor regulated serine /threonine kinase family,responsive for the
    activation of glycogen synthesis,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,maybe playing an essentilal regulatory role in protein synthesis during cell proliferation,required for
    epidermal growth factor activated phosphorylation of histone H3

         Enzyme Numbers (IUBMB): EC 2.7.11.11 2 EC 2.7.112

         Gene Ontology (GO): Selected molecular function terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000287magnesium ion binding IEA--
    GO:0004672protein kinase activity TAS10436156
    GO:0004674protein serine/threonine kinase activity IEA--
    GO:0004713protein tyrosine kinase activity ----
    GO:0005524ATP binding IEA--
         
    RPS6KA3 for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for RPS6KA3:
     Decreased melanin production  Increased mitotic index 

         Selected MGI mutant phenotypes (inferred from 3 alleles(MGI details for Rps6ka3) (see all 23):
     adipose tissue  behavior/neurological  cardiovascular system  craniofacial  digestive/alimentary 
     endocrine/exocrine gland  growth/size/body  hearing/vestibular/ear  hematopoietic system  homeostasis/metabolism 
     immune system  integument  liver/biliary system  muscle  nervous system 

    RPS6KA3 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for RPS6KA3: Rps6ka3tm1Kry Rps6ka3tm1Ljg Rps6ka3tm1.1Kry

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for RPS6KA3
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for RPS6KA3

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for RPS6KA3
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for RPS6KA3

    miRNA
    Products:
        
    miRTarBase miRNAs that target RPS6KA3:
    hsa-mir-1296-5p (MIRT036103), hsa-mir-503-5p (MIRT041136), hsa-mir-320a (MIRT044599), hsa-mir-29a-3p (MIRT049971), hsa-mir-16-5p (MIRT031564), hsa-mir-21-5p (MIRT030861)

    Block miRNA regulation of human, mouse, rat RPS6KA3 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate RPS6KA3 (see all 206):
    hsa-miR-579 hsa-miR-140-5p hsa-miR-3938 hsa-miR-520f hsa-miR-1224-3p hsa-miR-106a hsa-miR-1260b hsa-miR-3653
    Browse SwitchGear 3'UTR luciferase reporter plasmids
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for RPS6KA3


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    KS6A3_HUMAN, P51812: Nucleus (By similarity). Cytoplasm (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol4
    nucleus4
    golgi apparatus1
    mitochondrion1

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005654nucleoplasm TAS--
    GO:0005829cytosol TAS--
    GO:0005840ribosome ----
    GO:0016020membrane ----

    RPS6KA3 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for RPS6KA3 About   (see all 41)  
    See pathways by source

    SuperPathContained pathways About
    1MAPK targets/ Nuclear events mediated by MAP kinases
    ERK/MAPK targets0.88
    MAP kinase activation in TLR cascade0.61
    Nuclear Events (kinase and transcription factor activation)0.88
    MAP Kinase Signaling0.31
    MAPK targets/ Nuclear events mediated by MAP kinases0.80
    CREB phosphorylation0.00
    2Post NMDA receptor activation events
    Post NMDA receptor activation events0.90
    Long-term potentiation0.35
    Activation of NMDA receptor upon glutamate binding and postsynaptic events0.90
    RSK activation0.00
    CREB phosphorylation through the activation of Ras0.78
    3Development EGFR signaling pathway
    Development GDNF family signaling0.45
    BDNF Pathway0.39
    GDNF-Family Ligands and Receptor Interactions0.41
    4MAPK signaling pathway
    MAPK signaling pathway0.50
    MAPK signaling pathway0.50
    5Development IGF 1 receptor signaling
    Development IGF RI signaling0.49
    Development IGF 1 receptor signaling0.48

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for RPS6KA3 (see all 19)
        FLT3 Signaling
    MAPK Signaling
    UVB-Induced MAPK Signaling
    Mitochondrial Apoptosis
    CNTF Signaling

    1 Cell Signaling Technology (CST) Pathway for RPS6KA3
        MAP Kinase Signaling

    5 Tocris Bioscience Pathways for RPS6KA3
        Insulin Pathway
    Apoptosis Pathway
    NF-kappaB Pathway
    MAPK Pathway
    mTOR Pathway

    Selected GeneGo (Thomson Reuters) Pathways for RPS6KA3 (see all 8)
        Development A2A receptor signaling
    Apoptosis and survival BAD phosphorylation
    Development Thrombopoietin-regulated cell processes
    Development IGF-1 receptor signaling
    Development GDNF family signaling

    Selected BioSystems Pathways for RPS6KA3 (see all 7)
        MAPK signaling pathway
    EGFR1 Signaling Pathway
    Insulin Signaling
    BDNF signaling pathway
    Cytoplasmic Ribosomal Proteins


    Selected Reactome Pathways for RPS6KA3 (see all 7)
        CREB phosphorylation
    Recycling pathway of L1
    Senescence-Associated Secretory Phenotype (SASP)
    RSK activation
    Gastrin-CREB signalling pathway via PKC and MAPK


    Selected Kegg Pathways  (Kegg details for RPS6KA3) (see all 6):
        MAPK signaling pathway
    Oocyte meiosis
    mTOR signaling pathway
    Long-term potentiation
    Neurotrophin signaling pathway


    RPS6KA3 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Array including RPS6KA3: 
              Epigenetic Chromatin Modification Enzymes in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for RPS6KA3

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for RPS6KA3 (P518122, 3 ENSP000003688844) via UniProtKB, MINT, STRING, and/or I2D (see all 105)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    BARX1Q9HBU12, 3, ENSP000002539684MINT-8269516 I2D: score=2 STRING: ENSP00000253968
    EIF3CQ996132, 3, ENSP000003326044MINT-8269527 I2D: score=2 STRING: ENSP00000332604
    MASP1P487402, 3MINT-8269538 I2D: score=2 
    ENSG00000232960P678703, ENSP000003955464I2D: score=1 STRING: ENSP00000395546
    CSNK2BP678703I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 32):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001501skeletal system development TAS8955270
    GO:0002224toll-like receptor signaling pathway TAS--
    GO:0002755MyD88-dependent toll-like receptor signaling pathway TAS--
    GO:0002756MyD88-independent toll-like receptor signaling pathway TAS--
    GO:0006468protein phosphorylation ----

    RPS6KA3 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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      Browse compounds at ApexBio 

    Compounds for RPS6KA3 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    BRD 7389p90 ribosomal S6 kinase inhibitor[376382-11-5]
    PF 4708671S6K1 inhibitor[1255517-76-0]
    SL 0101-1Selective p90 ribosomal S6 kinase (RSK) inhibitor[77307-50-7]

    3 HMDB Compounds for RPS6KA3    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    MagnesiumMagnesium (see all 2)7439-95-4--

    Selected Novoseek inferred chemical compound relationships for RPS6KA3 gene (see all 14)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    threonine 62.3 27 18855572 (2), 14678837 (1), 9315666 (1), 10480933 (1) (see all 15)
    serine 50.6 27 18855572 (2), 9315666 (1), 10480933 (1), 16879200 (1) (see all 15)
    rapamycin 40.3 3 17678899 (1), 17786541 (1), 12087098 (1)
    wortmannin 33 1 15608143 (1)
    pd 98,059 32.9 1 15608143 (1)
    tyrosine 23.4 37 18156174 (4), 19223461 (3), 17785202 (2), 16369048 (1) (see all 5)
    salicylic acid 15.8 6 15738002 (3), 11189448 (1)
    alanine 10.4 3 15206906 (1), 19956600 (1)
    phosphoinositide 4.94 1 11108711 (1)
    lysine 4.56 1 19956600 (1)



    RPS6KA3 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for RPS6KA3 gene: 
    NM_004586.2  

    Unigene Cluster for RPS6KA3:

    Ribosomal protein S6 kinase, 90kDa, polypeptide 3
    Hs.445387  [show with all ESTs]
    Unigene Representative Sequence: NM_004586
    9 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000379565(uc011mjk.2 uc004czu.3 uc004czv.3 uc011mjl.2 uc011mjm.2)
    ENST00000479809 ENST00000457145 ENST00000492128 ENST00000438357 ENST00000474266
    ENST00000544447 ENST00000540702 ENST00000379548
    miRNA
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    hsa-miR-579 hsa-miR-140-5p hsa-miR-3938 hsa-miR-520f hsa-miR-1224-3p hsa-miR-106a hsa-miR-1260b hsa-miR-3653
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    Additional mRNA sequence: 

    AB102662.1 AB208933.1 AK022869.1 AK294373.1 AK296775.1 AK313932.1 AK316482.1 BC015451.1 
    BC096301.1 BC096302.3 BC096303.1 L07599.1 U08316.1 

    12 DOTS entries:

    DT.95158418  DT.91955088  DT.121308692  DT.204635  DT.86821215  DT.100746782  DT.121308705  DT.40215819 
    DT.99969413  DT.100825755  DT.433587  DT.95348295 

    Selected AceView cDNA sequences (see all 200):

    AL048274 BM834578 AA046164 AW073800 BX108073 BM697290 AW298782 CB157416 
    CF136261 AI561193 BQ082753 BE502112 AA045847 BU620678 BG680701 BG775542 
    AI242997 BX474710 BC015451 BM834712 AI475476 BX486316 AI278229 AA578676 

    GeneLoc Exon Structure

    4 Alternative Splicing Database (ASD) splice patterns (SP) for RPS6KA3    About this scheme

    ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23a · 23b
    SP1:              -     -                 -                                                                                                                     
    SP2:              -     -                 -                                                                                                                     
    SP3:                                      -                                                                                                                     
    SP4:                                                                                                                                                            


    ECgene alternative splicing isoforms for RPS6KA3

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    RPS6KA3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AATAATCCTG
    RPS6KA3 Expression
    About this image


    RPS6KA3 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 9) fully expand
     
     Brain (Nervous System)    fully expand to see all 4 entries
             Cerebral Cortex
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Somite (Muscoskeletal System)
             Muscle Progenitor Cells Thoracic Ventrolateral Dermomyotome Lip
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
     
     Testis (Reproductive System)
             Leydig Cells Testis Interstitium
    RPS6KA3 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    RPS6KA3 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.445387

    UniProtKB/Swiss-Prot: KS6A3_HUMAN, P51812
    Tissue specificity: Expressed in many tissues, highest levels in skeletal muscle

        Pathway & Disease-focused RT2 Profiler PCR Array including RPS6KA3: 
              Epigenetic Chromatin Modification Enzymes in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for RPS6KA3 gene from Selected species (see all 21)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Rps6ka31 , 5 ribosomal protein S6 kinase polypeptide 31, 5 94.41(n)1
    99.86(a)1
      X (73.27 cM)5
    1106511  NM_148945.11  NP_683747.11 
     1592103075 
    chicken
    (Gallus gallus)
    Aves RPS6KA31 ribosomal protein S6 kinase, 90kDa, polypeptide 3 86.43(n)
    96.81(a)
      418605  XM_004934672.1  XP_004934729.1 
    lizard
    (Anolis carolinensis)
    Reptilia RPS6KA36
    ribosomal protein S6 kinase, 90kDa, polypeptide 3
    97(a)
    1 ↔ 1
    3(123939285-123988467)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.331752 Xenopus laevis Rsk-2 (RSK2) mRNA, complete cds 83.38(n)    AF165162.1 
    zebrafish
    (Danio rerio)
    Actinopterygii Dr.210392 Danio rerio mRNA similar to ribosomal protein S6 kinase more 76.87(n)    BC045856.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta S6kII1 , 3 protein amino acid phosphorylation
    protein serine/threonine more3
    Ribosomal protein S6 kinase II1
    57(a)
    (best of 2)3
    57.85(n)1
    63.08(a)1
      20B13
    331391  NM_078713.31  NP_523437.21 
    worm
    (Caenorhabditis elegans)
    Secernentea T01H8.1b3 Protein kinase C terminal domain 62(a)
    (best of 3)
      I(8582453-8585937)   --
    soybean
    (Glycine max)
    eudicotyledons Gma.38352 Transcribed sequence with moderate similarity to protein more 74.05(n)    BI973364.1 
    rice
    (Oryza sativa)
    Liliopsida Os.110682 Oryza sativa (japonica cultivar-group) mRNA for hypothetical more 71.77(n)    AK062218.1 


    ENSEMBL Gene Tree for RPS6KA3 (if available)
    TreeFam Gene Tree for RPS6KA3 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for RPS6KA3 gene
    RPS6KA62  MAPKAPK32  MAPKAPK52  RPS6KA12  RPS6KA52  MAPKAPK22  RPS6KA42  MKNK12  
    MKNK22  RPS6KA22  
    Selected SIMAP similar genes for RPS6KA3 using alignment to 10 protein entries:     KS6A3_HUMAN (see all proteins) (see all similar genes):
    RPS6KA2    RPS6KA6    RPS6KA1    PKN2    KIN27    SGK2
    RPS6KB1    RPS6KB2    PRKCA    PRKCZ    PRKACB    PRKACA
    DKFZp564L2416    PRKACG    PRKY    CDC42BPA    RPS6KA5    DKFZp434B079

    RPS6KA3 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for RPS6KA3 (see all 1456)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr X posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs289351711,2,,4
    CCoffin-Lowry syndrome (CLS)4 pathogenic120173553(-) TCAGCA/GGAGAG 2 Q R mis1 ese30--------
    VAR_0061954
    Coffin-Lowry syndrome (CLS)4--see VAR_0061952 S A mis40--------
    VAR_0658974
    Mental retardation, X-linked 19 (MRX19)4--see VAR_0658972 R W mis40--------
    VAR_0658944
    Coffin-Lowry syndrome (CLS)4--see VAR_0658942 I K mis40--------
    VAR_0061904
    Coffin-Lowry syndrome (CLS)4--see VAR_0061902 V F mis40--------
    VAR_0061964
    Coffin-Lowry syndrome (CLS)4--see VAR_0061962 G D mis40--------
    VAR_0658964
    Coffin-Lowry syndrome (CLS)4--see VAR_0658962 F S mis40--------
    VAR_0061894
    Coffin-Lowry syndrome (CLS)4--see VAR_0061892 G V mis40--------
    VAR_0061934
    Coffin-Lowry syndrome (CLS)4--see VAR_0061932 D Y mis40--------
    VAR_0406294
    A gastric adenocarcinoma sample4--see VAR_0406292 Y C mis40--------

    HapMap Linkage Disequilibrium report for RPS6KA3 (20168029 - 20285523 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for RPS6KA3:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2672797CNV Deletion23128226
    nsv520690CNV Gain19592680
    nsv526033CNV Gain19592680

    Human Gene Mutation Database (HGMD): RPS6KA3
    Locus Specific Mutation Databases (LSDB): RPS6KA3

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing RPS6KA3
    DNA2.0 Custom Variant and Variant Library Synthesis for RPS6KA3

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 300075   
    OMIM disorders: 303600  300844  
    UniProtKB/Swiss-Prot: KS6A3_HUMAN, P51812
  • Coffin-Lowry syndrome (CLS) [MIM:303600]: A X-linked mental retardation associated with facial and
    digital dysmorphisms, progressive skeletal malformations, growth retardation, hearing deficit and paroxysmal
    movement disorders. Note=The disease is caused by mutations affecting the gene represented in this entry
  • Mental retardation, X-linked 19 (MRX19) [MIM:300844]: A non-syndromic form of mild to moderate mental
    retardation. Mental retardation is characterized by significantly below average general intellectual functioning
    associated with impairments in adaptive behavior and manifested during the developmental period. In contrast to
    syndromic or specific X-linked mental retardation which also present with associated physical, neurological
    and/or psychiatric manifestations, intellectual deficiency is the only primary symptom of non-syndromic X-linked
    mental retardation. Note=The disease is caused by mutations affecting the gene represented in this entry

  • Selected diseases for RPS6KA3 (see all 34):    
    About MalaCards
    coffin-lowry syndrome    estrogen resistance    partington syndrome    alpha-thalassemia/mental retardation syndrome
    fg syndrome    non-specific x-linked mental retardation    mental retardation, x-linked    alpha thalassemia
    mental retardation, x-linked 17/31, microduplication    mental retardation    prostate cancer    lactic acidosis
    thalassemia    lipodystrophy    intellectual disability    prostatitis
    ataxia telangiectasia    ataxia    insulin resistance    influenza

    3 diseases from the University of Copenhagen DISEASES database for RPS6KA3:
    Coffin-Lowry syndrome     Intellectual disability     Partington syndrome

    RPS6KA3 for disorders           About GeneDecksing

    9 Novoseek inferred disease relationships for RPS6KA3 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    coffin-lowry syndrome 98.2 65 11180593 (3), 14973203 (2), 17586481 (2), 10528858 (2) (see all 33)
    mental retardation 64.2 11 7943043 (2), 15668050 (1), 10319851 (1), 16691578 (1) (see all 8)
    severe mental retardation 62.9 1 14678837 (1)
    cancer 3.63 22 16723234 (2), 17785199 (1), 19435896 (1), 15515167 (1) (see all 8)
    shock 0 5 11189448 (2)
    inflammation 0 1 18836586 (1)
    tumors 0 5 19435896 (1), 20045011 (1), 19956600 (1)
    prostate cancer 0 17 15833840 (4), 20045011 (1), 19822882 (1)
    disability 0 2 11160957 (1)

    GeneTests: RPS6KA3
    GeneReviews: RPS6KA3
    Genetic Association Database (GAD): RPS6KA3
    Human Genome Epidemiology (HuGE) Navigator: RPS6KA3 (4 documents)

    Export disorders for RPS6KA3 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for RPS6KA3 gene, integrated from 10 sources (see all 229):
    (articles sorted by number of sources associating them with RPS6KA3)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Human rsk isoforms: cloning and characterization of tissue-specific expression. (PubMed id 8141249)1, 2, 3, 9 Moller D.E.... Jakubowski M. (Am. J. Physiol. 1994)
    2. Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome. (PubMed id 8955270)1, 2, 4, 9 Trivier E.... Hanauer A. (Nature 1996)
    3. Identification of novel mutations in the RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome. (PubMed id 16879200)1, 3, 9 Delaunoy J.P....Hanauer A. (Clin. Genet. 2006)
    4. RSK2 mediates muscle cell differentiation through regulation of NFAT3. (PubMed id 17213202)1, 2, 9 Cho Y.-Y.... Dong Z. (J. Biol. Chem. 2007)
    5. X-linked Coffin-Lowry syndrome (CLS, MIM 303600, RPS6KA3 gene, protein product known under various names: pp90(rsk2), RSK2, ISPK, MAPKAP1). (PubMed id 11896450)1, 3, 9 Jacquot S....Hanauer A. (Eur. J. Hum. Genet. 2002)
    6. Rsk-2 activity is necessary for epidermal growth factor-induced phosphorylation of CREB protein and transcription of c-fos gene. (PubMed id 9770464)1, 2, 9 De Cesare D.... Sassone-Corsi P. (Proc. Natl. Acad. Sci. U.S.A. 1998)
    7. Nur77 is phosphorylated in cells by RSK in response to mitogenic stimulation. (PubMed id 16223362)1, 2, 9 Wingate A.D.... Arthur J.S. (Biochem. J. 2006)
    8. Intronic L1 insertion and F268S, novel mutations in RPS6KA3 (RSK2) causing Coffin-Lowry syndrome. (PubMed id 14986828)1, 2, 9 Martinez-Garay I.... Martinez F. (Clin. Genet. 2003)
    9. Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3. (PubMed id 10436156)1, 2, 9 Sassone-Corsi P.... Allis C.D. (Science 1999)
    10. Mutation analysis of the RSK2 gene in Coffin-Lowry patients: extensive allelic heterogeneity and a high rate of De novo mutations. (PubMed id 9837815)1, 2, 9 Jacquot S.... Hanauer A. (Am. J. Hum. Genet. 1998)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 6197 HGNC: 10432 AceView: RPS6KA3 Ensembl:ENSG00000177189 euGenes: HUgn6197
    ECgene: RPS6KA3 Kegg: 6197 H-InvDB: RPS6KA3

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for RPS6KA3 Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=RPS6KA3[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for RPS6KA3 gene:
    Search GeneIP for patents involving RPS6KA3

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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