ID:KS6A1_HUMAN DESCRIPTION: RecName: Full=Ribosomal protein S6 kinase alpha-1; Short=S6K-alpha-1; EC=2.7.11.1; AltName: Full=90 kDa ribosomal protein S6 kinase 1; Short=p90-RSK 1; Short=p90RSK1; Short=p90S6K; AltName: Full=MAP kinase-activated protein kinase 1a; Short=MAPK-activated protein kinase 1a; Short=MAPKAP kinase 1a; Short=MAPKAPK-1a; AltName: Full=Ribosomal S6 kinase 1; Short=RSK-1; 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, 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium. ENZYME REGULATION: Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-573 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-380, allowing binding of PDPK1, which in turn phosphorylates Ser-221 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD. SUBUNIT: Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells. Transiently dissociates following mitogenic stimulation. Interacts with ETV1/ER81 and FGFR1. INTERACTION: P50552:VASP; NbExp=4; IntAct=EBI-963034, EBI-748201; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. PTM: Activated by phosphorylation at Ser-221 by PDPK1. Autophosphorylated on Ser-380, as part of the activation process. May be phosphorylated at Thr-359 and Ser-363 by MAPK1/ERK2 and MAPK3/ERK1. PTM: N-terminal myristoylation results in an activated kinase in the absence of added growth factors. 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. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/RPS6KA1ID43477ch1p36.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00069 - Protein kinase domain PF00433 - Protein kinase C terminal domain PF06293 - Lipopolysaccharide kinase (Kdo/WaaP) family PF07714 - Protein tyrosine and serine/threonine kinase PF14531 - Kinase-like
SCOP Domains: 56112 - Protein kinase-like (PK-like)
ModBase Predicted Comparative 3D Structure on Q15418
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000166 nucleotide binding GO:0000287 magnesium ion binding GO:0004672 protein kinase activity GO:0004674 protein serine/threonine kinase activity GO:0004712 protein serine/threonine/tyrosine kinase activity GO:0005515 protein binding GO:0005524 ATP binding GO:0016301 kinase activity GO:0016740 transferase activity GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process GO:0046872 metal ion binding
Biological Process: GO:0006468 protein phosphorylation GO:0006915 apoptotic process GO:0007049 cell cycle GO:0007165 signal transduction GO:0016310 phosphorylation GO:0030307 positive regulation of cell growth GO:0035556 intracellular signal transduction GO:0043066 negative regulation of apoptotic process GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043555 regulation of translation in response to stress GO:0043620 regulation of DNA-templated transcription in response to stress GO:0045597 positive regulation of cell differentiation GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0072574 hepatocyte proliferation GO:2000491 positive regulation of hepatic stellate cell activation
AK225672 - Homo sapiens mRNA for ribosomal protein S6 kinase, 90kDa, polypeptide 1 isoform a variant, clone: STM07387. BC014966 - Homo sapiens ribosomal protein S6 kinase, 90kDa, polypeptide 1, mRNA (cDNA clone MGC:23062 IMAGE:4867373), complete cds. AK315730 - Homo sapiens cDNA, FLJ96835, Homo sapiens ribosomal protein S6 kinase, 90kDa, polypeptide 1(RPS6KA1), mRNA. L07597 - Homo sapiens ribosomal protein S6 kinase 1 (RPS6KA1) mRNA, complete cds. AB385042 - Synthetic construct DNA, clone: pF1KB5107, Homo sapiens RPS6KA1 gene for ribosomal protein S6 kinase alpha-1, complete cds, without stop codon, in Flexi system. DQ892242 - Synthetic construct clone IMAGE:100004872; FLH184445.01X; RZPDo839G01144D ribosomal protein S6 kinase, 90kDa, polypeptide 1 (RPS6KA1) gene, encodes complete protein. DQ895443 - Synthetic construct Homo sapiens clone IMAGE:100009903; FLH184441.01L; RZPDo839G01143D ribosomal protein S6 kinase, 90kDa, polypeptide 1 (RPS6KA1) gene, encodes complete protein. KJ897502 - Synthetic construct Homo sapiens clone ccsbBroadEn_06896 RPS6KA1 gene, encodes complete protein. KJ905309 - Synthetic construct Homo sapiens clone ccsbBroadEn_14830 RPS6KA1 gene, encodes complete protein. AK299007 - Homo sapiens cDNA FLJ54535 complete cds, highly similar to Ribosomal protein S6 kinase alpha-1 (EC 2.7.11.1). AK294818 - Homo sapiens cDNA FLJ53289 complete cds, highly similar to Ribosomal protein S6 kinase alpha-1 (EC 2.7.11.1). AK092955 - Homo sapiens cDNA FLJ35636 fis, clone SPLEN2011820, highly similar to RIBOSOMAL PROTEIN S6 KINASE II ALPHA 1 (EC 2.7.1.-). AK292722 - Homo sapiens cDNA FLJ76963 complete cds, highly similar to Homo sapiens ribosomal protein S6 kinase, 90kDa, polypeptide 1 (RPS6KA1), transcript variant 2, mRNA. DL491958 - Novel nucleic acids. DL490515 - Novel nucleic acids. BC039069 - Homo sapiens ribosomal protein S6 kinase, 90kDa, polypeptide 1, mRNA (cDNA clone IMAGE:5180915), with apparent retained intron. JD343135 - Sequence 324159 from Patent EP1572962. JD407702 - Sequence 388726 from Patent EP1572962. JD538131 - Sequence 519155 from Patent EP1572962. JD118418 - Sequence 99442 from Patent EP1572962. JD180448 - Sequence 161472 from Patent EP1572962. JD085807 - Sequence 66831 from Patent EP1572962. JD189565 - Sequence 170589 from Patent EP1572962. JD376943 - Sequence 357967 from Patent EP1572962. JD520862 - Sequence 501886 from Patent EP1572962. JD196940 - Sequence 177964 from Patent EP1572962. JD385259 - Sequence 366283 from Patent EP1572962. JD392899 - Sequence 373923 from Patent EP1572962. JD466402 - Sequence 447426 from Patent EP1572962. JD190669 - Sequence 171693 from Patent EP1572962. JD286127 - Sequence 267151 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_ghPathway - Growth Hormone Signaling Pathway h_igf1rPathway - Multiple antiapoptotic pathways from IGF-1R signaling lead to BAD phosphorylation h_mPRPathway - How Progesterone Initiates the Oocyte Maturation h_badPathway - Regulation of BAD phosphorylation h_erkPathway - Erk1/Erk2 Mapk Signaling pathway h_melanocytepathway - Melanocyte Development and Pigmentation Pathway h_erk5Pathway - Role of Erk5 in Neuronal Survival h_mapkPathway - MAPKinase Signaling Pathway h_crebPathway - Transcription factor CREB and its extracellular signals h_g2Pathway - Cell Cycle: G2/M Checkpoint
Reactome (by CSHL, EBI, and GO)
Protein Q15418 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
