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Aliases for RPS6KA4 Gene

Aliases for RPS6KA4 Gene

  • Ribosomal Protein S6 Kinase, 90kDa, Polypeptide 4 2 3
  • MSK2 3 4 6
  • RSKB 3 4 6
  • Nuclear Mitogen- And Stress-Activated Protein Kinase 2 3 4
  • 90 KDa Ribosomal Protein S6 Kinase 4 3 4
  • Ribosomal Protein Kinase B 3 4
  • S6K-Alpha-4 3 4
  • EC 2.7.11.1 4 64
  • Ribosomal Protein S6 Kinase, 90kD, Polypeptide 4 2
  • Mitogen- And Stress-Activated Protein Kinase 2 3
  • Ribosomal Protein S6 Kinase Alpha 4 3
  • Ribosomal Protein S6 Kinase Alpha-4 3
  • EC 2.7.11 64
  • RSK-B 3

External Ids for RPS6KA4 Gene

Summaries for RPS6KA4 Gene

Entrez Gene Summary for RPS6KA4 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 CREB1 and c-fos. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

GeneCards Summary for RPS6KA4 Gene

RPS6KA4 (Ribosomal Protein S6 Kinase, 90kDa, Polypeptide 4) is a Protein Coding gene. Among its related pathways are MAPK signaling pathway and L1CAM interactions. GO annotations related to this gene include protein serine/threonine kinase activity and ribosomal protein S6 kinase activity. An important paralog of this gene is MKNK2.

UniProtKB/Swiss-Prot for RPS6KA4 Gene

  • Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates Ser-10 of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate Ser-28 of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors.

Tocris Summary for RPS6KA4 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 RPS6KA4 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RPS6KA4 Gene

Genomics for RPS6KA4 Gene

Genomic Location for RPS6KA4 Gene

Start:
64,359,148 bp from pter
End:
64,372,215 bp from pter
Size:
13,068 bases
Orientation:
Plus strand

Genomic View for RPS6KA4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for RPS6KA4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RPS6KA4 Gene

Regulatory Elements for RPS6KA4 Gene

Transcription factor binding sites by QIAGEN in the RPS6KA4 gene promoter:

Proteins for RPS6KA4 Gene

  • Protein details for RPS6KA4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O75676-KS6A4_HUMAN
    Recommended name:
    Ribosomal protein S6 kinase alpha-4
    Protein Accession:
    O75676
    Secondary Accessions:
    • A8K7Z8
    • O75585
    • Q53ES8

    Protein attributes for RPS6KA4 Gene

    Size:
    772 amino acids
    Molecular mass:
    85606 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells which transiently dissociates following mitogenic stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA4 associates with and phosphorylates the NF-kappa-B p65 subunit RELA
    Miscellaneous:
    • Enzyme activity requires the presence of both kinase domains.

    Alternative splice isoforms for RPS6KA4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RPS6KA4 Gene

Proteomics data for RPS6KA4 Gene at MOPED

Post-translational modifications for RPS6KA4 Gene

  • Ser-343 and Thr-568 phosphorylation is required for kinase activity. Ser-343 and Ser-196 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain. Phosphorylated at Ser-343, Thr-568 and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha. Autophosphorylated at Ser-737 and Ser-745 by the N-terminal kinase domain (By similarity).
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys37 and Lys440

Other Protein References for RPS6KA4 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for RPS6KA4 Gene

UniProtKB/Swiss-Prot:

KS6A4_HUMAN
Domain:
  • Contains 1 AGC-kinase C-terminal domain.:
    • O75676
  • Contains 2 protein kinase domains.:
    • O75676
Family:
  • Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.:
    • O75676
genes like me logo Genes that share domains with RPS6KA4: view

Function for RPS6KA4 Gene

Molecular function for RPS6KA4 Gene

UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot EnzymeRegulation: Activated by phosphorylation at Ser-343, Thr-568 and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-196, Ser-360 and Ser-365 by the activated C-terminal kinase domain.
UniProtKB/Swiss-Prot Function: Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates Ser-10 of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate Ser-28 of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors.

Enzyme Numbers (IUBMB) for RPS6KA4 Gene

Gene Ontology (GO) - Molecular Function for RPS6KA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IEA --
GO:0004672 protein kinase activity --
GO:0004674 protein serine/threonine kinase activity IMP 12773393
GO:0004711 ribosomal protein S6 kinase activity NAS 11035004
GO:0004713 protein tyrosine kinase activity --
genes like me logo Genes that share ontologies with RPS6KA4: view
genes like me logo Genes that share phenotypes with RPS6KA4: view

Animal Models for RPS6KA4 Gene

MGI Knock Outs for RPS6KA4:

miRNA for RPS6KA4 Gene

miRTarBase miRNAs that target RPS6KA4

No data available for Transcription Factor Targeting and HOMER Transcription for RPS6KA4 Gene

Localization for RPS6KA4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RPS6KA4 Gene

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for RPS6KA4 Gene COMPARTMENTS Subcellular localization image for RPS6KA4 gene
Compartment Confidence
nucleus 5
cytosol 4

Gene Ontology (GO) - Cellular Components for RPS6KA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 11035004
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IDA --
GO:0016020 membrane --
genes like me logo Genes that share ontologies with RPS6KA4: view

Pathways for RPS6KA4 Gene

genes like me logo Genes that share pathways with RPS6KA4: view

Pathways by source for RPS6KA4 Gene

1 GeneGo (Thomson Reuters Life Sciences Research) pathway for RPS6KA4 Gene
1 Cell Signaling Technology pathway for RPS6KA4 Gene

Gene Ontology (GO) - Biological Process for RPS6KA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001818 negative regulation of cytokine production TAS 18508628
GO:0006355 regulation of transcription, DNA-templated IDA 9792677
GO:0006468 protein phosphorylation IDA 9792677
GO:0006954 inflammatory response IEA --
GO:0007411 axon guidance TAS --
genes like me logo Genes that share ontologies with RPS6KA4: view

Compounds for RPS6KA4 Gene

(3) Tocris Compounds for RPS6KA4 Gene

Compound Action Cas Number
BRD 7389 p90 ribosomal S6 kinase inhibitor [376382-11-5]
PF 4708671 S6K1 inhibitor [1255517-76-0]
SL 0101-1 Selective p90 ribosomal S6 kinase (RSK) inhibitor [77307-50-7]

(3) HMDB Compounds for RPS6KA4 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
Magnesium
  • Magnesium
7439-95-4

(1) Drugbank Compounds for RPS6KA4 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Riboflavin Monophosphate
146-17-8 target
genes like me logo Genes that share compounds with RPS6KA4: view

Transcripts for RPS6KA4 Gene

Unigene Clusters for RPS6KA4 Gene

Ribosomal protein S6 kinase, 90kDa, polypeptide 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for RPS6KA4 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4a · 4b · 4c ^ 5a · 5b ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10a · 10b ^ 11a · 11b ^ 12 ^ 13 ^ 14 ^ 15a · 15b ^ 16 ^ 17a · 17b
SP1: - - -
SP2: - - - -
SP3: - - - -
SP4: - - - - - - - - - -
SP5: - - - - -
SP6: - - -
SP7: -
SP8:
SP9:

Relevant External Links for RPS6KA4 Gene

GeneLoc Exon Structure for
RPS6KA4
ECgene alternative splicing isoforms for
RPS6KA4

Expression for RPS6KA4 Gene

mRNA expression in normal human tissues for RPS6KA4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for RPS6KA4 Gene

SOURCE GeneReport for Unigene cluster for RPS6KA4 Gene Hs.105584

genes like me logo Genes that share expressions with RPS6KA4: view

Orthologs for RPS6KA4 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for RPS6KA4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RPS6KA4 36
  • 99.53 (n)
  • 99.74 (a)
RPS6KA4 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia RPS6KA4 36
  • 90.53 (n)
  • 94.68 (a)
RPS6KA4 37
  • 96 (a)
OneToOne
dog
(Canis familiaris)
Mammalia RPS6KA4 36
  • 91.09 (n)
  • 96.89 (a)
RPS6KA4 37
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Rps6ka4 36
  • 88.17 (n)
  • 96.11 (a)
Rps6ka4 16
Rps6ka4 37
  • 96 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia RPS6KA4 37
  • 88 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia RPS6KA4 37
  • 58 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Rps6ka4 36
  • 88.17 (n)
  • 96.37 (a)
lizard
(Anolis carolinensis)
Reptilia RPS6KA4 37
  • 75 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100486973 36
  • 62.98 (n)
  • 68.13 (a)
zebrafish
(Danio rerio)
Actinopterygii rps6ka4 36
  • 67.72 (n)
  • 72.18 (a)
rps6ka4 37
  • 70 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP006094 36
  • 56.12 (n)
  • 51.68 (a)
fruit fly
(Drosophila melanogaster)
Insecta JIL-1 37
  • 26 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea rskn-2 37
  • 47 (a)
OneToMany
R04A9.5 38
  • 44 (a)
C54G4.1 38
  • 47 (a)
corn
(Zea mays)
Liliopsida Zm.10489 36
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 49 (a)
OneToMany
Species with no ortholog for RPS6KA4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for RPS6KA4 Gene

ENSEMBL:
Gene Tree for RPS6KA4 (if available)
TreeFam:
Gene Tree for RPS6KA4 (if available)

Paralogs for RPS6KA4 Gene

genes like me logo Genes that share paralogs with RPS6KA4: view

Variants for RPS6KA4 Gene

Sequence variations from dbSNP and Humsavar for RPS6KA4 Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type MAF
rs478315 -- 64,364,156(-) AAAAT(A/T)AAAAA intron-variant
rs500265 -- 64,358,568(+) CAGGC(A/C)CCCCC upstream-variant-2KB
rs513264 -- 64,362,295(+) GCCCC(A/C)GACGG intron-variant
rs516124 -- 64,360,951(+) ACGGG(G/T)CCCTC intron-variant
rs521950 -- 64,360,272(+) ACGCA(A/C/G/T)GAGCA reference, missense, synonymous-codon

Structural Variations from Database of Genomic Variants (DGV) for RPS6KA4 Gene

Variant ID Type Subtype PubMed ID
dgv1156n71 CNV Loss 21882294
dgv1163n71 CNV Loss 21882294
dgv1166n71 CNV Loss 21882294
nsv832186 CNV Loss 17160897
nsv897685 CNV Loss 21882294
nsv358 CNV Insertion 18451855
dgv13n64 CNV Loss 17921354
dgv1169n71 CNV Loss 21882294
dgv1170n71 CNV Loss 21882294
nsv832187 CNV Loss 17160897

Relevant External Links for RPS6KA4 Gene

HapMap Linkage Disequilibrium report
RPS6KA4

Disorders for RPS6KA4 Gene

Relevant External Links for RPS6KA4

Genetic Association Database (GAD)
RPS6KA4
Human Genome Epidemiology (HuGE) Navigator
RPS6KA4
genes like me logo Genes that share disorders with RPS6KA4: view

No data available for UniProtKB/Swiss-Prot for RPS6KA4 Gene

Publications for RPS6KA4 Gene

  1. Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. (PMID: 9687510) Deak M. … Alessi D.R. (EMBO J. 1998) 2 3 4
  2. RSK-B, a novel ribosomal S6 kinase family member, is a CREB kinase under dominant control of p38alpha mitogen-activated protein kinase (p38alphaMAPK). (PMID: 9792677) Pierrat B. … Lesslauer W. (J. Biol. Chem. 1998) 2 3 4
  3. Differential regulation of mitogen- and stress-activated protein kinase-1 and -2 (MSK1 and MSK2) by CK2 following UV radiation. (PMID: 19933278) Jacks K.A. … Koch C.A. (J. Biol. Chem. 2010) 3 23
  4. C-terminal elements control location, activation threshold, and p38 docking of ribosomal S6 kinase B (RSKB). (PMID: 11035004) Tomas-Zuber M. … Lesslauer W. (J. Biol. Chem. 2001) 3 4
  5. MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14. (PMID: 12773393) Soloaga A. … Arthur J.S. (EMBO J. 2003) 3 4

Products for RPS6KA4 Gene

Sources for RPS6KA4 Gene

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