Ribosomal protein S6 kinase beta-1

Details

Name
Ribosomal protein S6 kinase beta-1
Kind
protein
Synonyms
  • 2.7.11.1
  • 70 kDa ribosomal protein S6 kinase 1
  • p70 ribosomal S6 kinase alpha
  • p70 S6 kinase alpha
  • p70 S6K-alpha
  • p70 S6KA
  • p70-S6K 1
  • P70S6K1
  • Ribosomal protein S6 kinase I
  • S6K-beta-1
  • S6K1
  • Serine/threonine-protein kinase 14A
  • STK14A
Gene Name
RPS6KB1
UniProtKB Entry
P23443Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0053138|Ribosomal protein S6 kinase beta-1
MRRRRRRDGFYPAPDFRDREAEDMAGVFDIDLDQPEDAGSEDELEEGGQLNESMDHGGVG
PYELGMEHCEKFEISETSVNRGPEKIRPECFELLRVLGKGGYGKVFQVRKVTGANTGKIF
AMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYLSGGEL
FMQLEREGIFMEDTACFYLAEISMALGHLHQKGIIYRDLKPENIMLNHQGHVKLTDFGLC
KESIHDGTVTHTFCGTIEYMAPEILMRSGHNRAVDWWSLGALMYDMLTGAPPFTGENRKK
TIDKILKCKLNLPPYLTQEARDLLKKLLKRNAASRLGAGPGDAGEVQAHPFFRHINWEEL
LARKVEPPFKPLLQSEEDVSQFDSKFTRQTPVDSPDDSTLSESANQVFLGFTYVAPSVLE
SVKEKFSFEPKIRSPRRFIGSPRTPVSPVKFSPGDFWGRGASASTANPQTPVEYPMETSG
IEQMDVTMSGEASAPLPIRQPNSGPYKKQAFPMISKRPEHLRMNL
Number of residues
525
Molecular Weight
59139.09
Theoretical pI
Not Available
GO Classification
Processes
cellular response to nutrient / positive regulation of TORC1 signaling / response to L-leucine
General Function
Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:22017876, PubMed:23429703, PubMed:28178239). Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:22017876, PubMed:23429703, PubMed:28178239). Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex (PubMed:16286006). Upon mitogenic stimulation, phosphorylation by the mechanistic target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation (PubMed:16286006). The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B (PubMed:16286006). Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis (PubMed:17053147). Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR (PubMed:15341740). In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2 (PubMed:11500364). Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling (PubMed:19720745, PubMed:19935711, PubMed:19995915). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function (By similarity). Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex (PubMed:17936702). The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function (PubMed:17936702). Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1 (PubMed:18952604). In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B (PubMed:17052453). May be involved in cytoskeletal rearrangement through binding to neurabin (By similarity). Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (PubMed:23429703). Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition (PubMed:28178239)
Specific Function
Atp binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Synapse, synaptosome
Gene sequence
>lcl|BSEQ0053139|Ribosomal protein S6 kinase beta-1 (RPS6KB1)
ATGAGGCGACGAAGGAGGCGGGACGGCTTTTACCCAGCCCCGGACTTCCGAGACAGGGAA
GCTGAGGACATGGCAGGAGTGTTTGACATAGACCTGGACCAGCCAGAGGACGCGGGCTCT
GAGGATGAGCTGGAGGAGGGGGGTCAGTTAAATGAAAGCATGGACCATGGGGGAGTTGGA
CCATATGAACTTGGCATGGAACATTGTGAGAAATTTGAAATCTCAGAAACTAGTGTGAAC
AGAGGGCCAGAAAAAATCAGACCAGAATGTTTTGAGCTACTTCGGGTACTTGGTAAAGGG
GGCTATGGAAAGGTTTTTCAAGTACGAAAAGTAACAGGAGCAAATACTGGGAAAATATTT
GCCATGAAGGTGCTTAAAAAGGCAATGATAGTAAGAAATGCTAAAGATACAGCTCATACA
AAAGCAGAACGGAATATTCTGGAGGAAGTAAAGCATCCCTTCATCGTGGATTTAATTTAT
GCCTTTCAGACTGGTGGAAAACTCTACCTCATCCTTGAGTATCTCAGTGGAGGAGAACTA
TTTATGCAGTTAGAAAGAGAGGGAATATTTATGGAAGACACTGCCTGCTTTTACTTGGCA
GAAATCTCCATGGCTTTGGGGCATTTACATCAAAAGGGGATCATCTACAGAGACCTGAAG
CCGGAGAATATCATGCTTAATCACCAAGGTCATGTGAAACTAACAGACTTTGGACTATGC
AAAGAATCTATTCATGATGGAACAGTCACACACACATTTTGTGGAACAATAGAATACATG
GCCCCTGAAATCTTGATGAGAAGTGGCCACAATCGTGCTGTGGATTGGTGGAGTTTGGGA
GCATTAATGTATGACATGCTGACTGGAGCACCCCCATTCACTGGGGAGAATAGAAAGAAA
ACAATTGACAAAATCCTCAAATGTAAACTCAATTTGCCTCCCTACCTCACACAAGAAGCC
AGAGATCTGCTTAAAAAGCTGCTGAAAAGAAATGCTGCTTCTCGTCTGGGAGCTGGTCCT
GGGGACGCTGGAGAAGTTCAAGCTCATCCATTCTTTAGACACATTAACTGGGAAGAACTT
CTGGCTCGAAAGGTGGAGCCCCCCTTTAAACCTCTGTTGCAATCTGAAGAGGATGTAAGT
CAGTTTGATTCCAAGTTTACACGTCAGACACCTGTCGACAGCCCAGATGACTCAACTCTC
AGTGAAAGTGCCAATCAGGTCTTTCTGGGTTTTACATATGTGGCTCCATCTGTACTTGAA
AGTGTGAAAGAAAAGTTTTCCTTTGAACCAAAAATCCGATCACCTCGAAGATTTATTGGC
AGCCCACGAACACCTGTCAGCCCAGTCAAATTTTCTCCTGGGGATTTCTGGGGAAGAGGT
GCTTCGGCCAGCACAGCAAATCCTCAGACACCTGTGGAATACCCAATGGAAACAAGTGGC
ATAGAGCAGATGGATGTGACAATGAGTGGGGAAGCATCGGCACCACTTCCAATACGACAG
CCGAACTCTGGGCCATACAAAAAACAAGCTTTTCCCATGATCTCCAAACGGCCAGAGCAC
CTGCGTATGAATCTATGA
Chromosome Location
17
Locus
17q23.1
External Identifiers
ResourceLink
UniProtKB IDP23443
UniProtKB Entry NameKS6B1_HUMAN
GeneCard IDRPS6KB1
HGNC IDHGNC:10436
PDB ID(s)3A60, 3A61, 3A62, 3WE4, 3WF5, 3WF6, 3WF7, 3WF8, 3WF9, 4L3J, 4L3L, 4L42, 4L43, 4L44, 4L45, 4L46, 4RLO, 4RLP, 5WBH, 5WBK, 7N91, 7N93
KEGG IDhsa:6198
IUPHAR/Guide To Pharmacology ID1525
NCBI Gene ID6198
General References
Not Available

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
CI-1040investigationalyestargetinhibitorDetails
Tetrabromo-2-BenzotriazoleexperimentalyestargetinhibitorDetails
M-2698investigationalyestargetinhibitorDetails