Ribosomal protein S6 kinase alpha-1

Details

Name
Ribosomal protein S6 kinase alpha-1
Synonyms
  • 2.7.11.1
  • 90 kDa ribosomal protein S6 kinase 1
  • MAP kinase-activated protein kinase 1a
  • MAPK-activated protein kinase 1a
  • MAPKAP kinase 1a
  • MAPKAPK-1a
  • MAPKAPK1A
  • p90-RSK 1
  • p90RSK1
  • p90S6K
  • Ribosomal S6 kinase 1
  • RSK-1
  • RSK1
  • S6K-alpha-1
Gene Name
RPS6KA1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008126|Ribosomal protein S6 kinase alpha-1
MPLAQLKEPWPLMELVPLDPENGQTSGEEAGLQPSKDEGVLKEISITHHVKAGSEKADPS
HFELLKVLGQGSFGKVFLVRKVTRPDSGHLYAMKVLKKATLKVRDRVRTKMERDILADVN
HPFVVKLHYAFQTEGKLYLILDFLRGGDLFTRLSKEVMFTEEDVKFYLAELALGLDHLHS
LGIIYRDLKPENILLDEEGHIKLTDFGLSKEAIDHEKKAYSFCGTVEYMAPEVVNRQGHS
HSADWWSYGVLMFEMLTGSLPFQGKDRKETMTLILKAKLGMPQFLSTEAQSLLRALFKRN
PANRLGSGPDGAEEIKRHVFYSTIDWNKLYRREIKPPFKPAVAQPDDTFYFDTEFTSRTP
KDSPGIPPSAGAHQLFRGFSFVATGLMEDDGKPRAPQAPLHSVVQQLHGKNLVFSDGYVV
KETIGVGSYSECKRCVHKATNMEYAVKVIDKSKRDPSEEIEILLRYGQHPNIITLKDVYD
DGKHVYLVTELMRGGELLDKILRQKFFSEREASFVLHTIGKTVEYLHSQGVVHRDLKPSN
ILYVDESGNPECLRICDFGFAKQLRAENGLLMTPCYTANFVAPEVLKRQGYDEGCDIWSL
GILLYTMLAGYTPFANGPSDTPEEILTRIGSGKFTLSGGNWNTVSETAKDLVSKMLHVDP
HQRLTAKQVLQHPWVTQKDKLPQSQLSHQDLQLVKGAMAATYSALNSSKPTPQLKPIESS
ILAQRRVRKLPSTTL
Number of residues
735
Molecular Weight
82722.36
Theoretical pI
7.94
GO Classification
Functions
ATP binding / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / magnesium ion binding / protein serine/threonine kinase activity / protein serine/threonine/tyrosine kinase activity / ribosomal protein S6 kinase activity
Processes
axon guidance / cell cycle / hepatocyte proliferation / innate immune response / intracellular signal transduction / MyD88-dependent toll-like receptor signaling pathway / MyD88-independent toll-like receptor signaling pathway / negative regulation of apoptotic process / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / neurotrophin TRK receptor signaling pathway / positive regulation of cell differentiation / positive regulation of cell growth / positive regulation of hepatic stellate cell activation / positive regulation of transcription from RNA polymerase II promoter / protein phosphorylation / regulation of DNA-templated transcription in response to stress / regulation of translation in response to stress / signal transduction / stress-activated MAPK cascade / synaptic transmission / toll-like receptor 10 signaling pathway / toll-like receptor 2 signaling pathway / toll-like receptor 3 signaling pathway / toll-like receptor 4 signaling pathway / toll-like receptor 5 signaling pathway / toll-like receptor 9 signaling pathway / toll-like receptor signaling pathway / toll-like receptor TLR1 / toll-like receptor TLR6 / TRIF-dependent toll-like receptor signaling pathway
Components
cytoplasm / cytosol / nucleoplasm / nucleus / spindle
General Function
Ribosomal protein s6 kinase activity
Specific 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 pre-initiation 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). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (By similarity). 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0017390|Ribosomal protein S6 kinase alpha-1 (RPS6KA1)
ATGGAGCAGGATCCCAAGCCGCCCCGTCTGCGGCTCTGGGCCCTGATCCCCTGGCTTCCC
AGGAAGCAGCGGCCCAGGATCAGCCAGACCTCTCTGCCTGTCCCTGGCCCTGGCTCTGGC
CCCCAGCGGGACTCGGATGAGGGCGTCCTCAAGGAGATCTCCATCACGCACCACGTCAAG
GCTGGCTCTGAGAAGGCTGATCCATCCCATTTCGAGCTCCTCAAGGTTCTGGGCCAGGGA
TCCTTTGGCAAAGTCTTCCTGGTGCGGAAAGTCACCCGGCCTGACAGTGGGCACCTGTAT
GCTATGAAGGTGCTGAAGAAGGCAACGCTGAAAGTACGTGACCGCGTCCGGACCAAGATG
GAGAGAGACATCCTGGCTGATGTAAATCACCCATTCGTGGTGAAGCTGCACTATGCCTTC
CAGACCGAGGGCAAGCTCTATCTCATTCTGGACTTCCTGCGTGGTGGGGACCTCTTCACC
CGGCTCTCAAAAGAGGTGATGTTCACGGAGGAGGATGTGAAGTTTTACCTGGCCGAGCTG
GCTCTGGGCCTGGATCACCTGCACAGCCTGGGTATCATTTACAGAGACCTCAAGCCTGAG
AACATCCTTCTGGATGAGGAGGGCCACATCAAACTCACTGACTTTGGCCTGAGCAAAGAG
GCCATTGACCACGAGAAGAAGGCCTATTCTTTCTGCGGGACAGTGGAGTACATGGCCCCT
GAGGTCGTCAACCGCCAGGGCCACTCCCATAGTGCGGACTGGTGGTCCTATGGGGTGTTG
ATGTTTGAGATGCTGACGGGCTCCCTGCCCTTCCAGGGGAAGGACCGGAAGGAGACCATG
ACACTGATTCTGAAGGCGAAGCTAGGCATGCCCCAGTTTCTGAGCACTGAAGCCCAGAGC
CTCTTGCGGGCCCTGTTCAAGCGGAATCCTGCCAACCGGCTCGGCTCCGGCCCTGATGGG
GCAGAGGAAATCAAGCGGCATGTCTTCTACTCCACCATTGACTGGAATAAGCTATACCGT
CGTGAGATCAAGCCACCCTTCAAGCCAGCAGTGGCTCAGCCTGATGACACCTTCTACTTT
GACACCGAGTTCACGTCCCGCACACCCAAGGATTCCCCAGGCATCCCCCCCAGCGCTGGG
GCCCATCAGCTGTTCCGGGGCTTCAGCTTCGTGGCCACCGGCCTGATGGAAGACGACGGC
AAGCCTCGTGCCCCGCAGGCACCCCTGCACTCGGTGGTACAGCAACTCCATGGGAAGAAC
CTGGTTTTTAGTGACGGCTACGTGGTAAAGGAGACAATTGGTGTGGGCTCCTACTCTGAG
TGCAAGCGCTGTGTCCACAAGGCCACCAACATGGAGTATGCTGTCAAGGTCATTGATAAG
AGCAAGCGGGATCCTTCAGAAGAGATTGAGATTCTTCTGCGGTATGGCCAGCACCCCAAC
ATCATCACTCTGAAAGATGTGTATGATGATGGCAAACACGTGTACCTGGTGACAGAGCTG
ATGCGGGGTGGGGAGCTGCTGGACAAGATCCTGCGGCAGAAGTTCTTCTCAGAGCGGGAG
GCCAGCTTTGTCCTGCACACCATTGGCAAAACTGTGGAGTATCTGCACTCACAGGGGGTT
GTGCACAGGGACCTGAAGCCCAGCAACATCCTGTATGTGGACGAGTCCGGGAATCCCGAG
TGCCTGCGCATCTGTGACTTTGGTTTTGCCAAACAGCTGCGGGCTGAGAATGGGCTCCTC
ATGACACCTTGCTACACAGCCAACTTTGTGGCGCCTGAGGTGCTGAAGCGCCAGGGCTAC
GATGAAGGCTGCGACATCTGGAGCCTGGGCATTCTGCTGTACACCATGCTGGCAGGATAT
ACTCCATTTGCCAACGGTCCCAGTGACACACCAGAGGAAATCCTAACCCGGATCGGCAGT
GGGAAGTTTACCCTCAGTGGGGGAAATTGGAACACAGTTTCAGAGACAGCCAAGGACCTG
GTGTCCAAGATGCTACACGTGGATCCCCACCAGCGCCTCACAGCTAAGCAGGTTCTGCAG
CATCCATGGGTCACCCAGAAAGACAAGCTTCCCCAAAGCCAGCTGTCCCACCAGGACCTA
CAGCTTGTGAAGGGAGCCATGGCTGCCACGTACTCCGCACTCAACAGCTCCAAGCCCACC
CCCCAGCTGAAGCCCATCGAGTCATCCATCCTGGCCCAGCGGCGAGTGAGGAAGTTGCCA
TCCACCACCCTGTGA
Chromosome Location
1
Locus
1p
External Identifiers
ResourceLink
UniProtKB IDQ15418
UniProtKB Entry NameKS6A1_HUMAN
GenBank Protein ID292457
GenBank Gene IDL07597
HGNC IDHGNC:10430
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04751Purvalanol AexperimentalunknownDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails