You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP01426
Secondary Accession Numbers
  • 6722
Name Ribosomal protein S6 kinase beta-1
Synonyms
  1. 70 kDa ribosomal protein S6 kinase 1
  2. P70S6K1
  3. Ribosomal protein S6 kinase I
  4. S6K-beta-1
  5. S6K1
  6. Serine/threonine-protein kinase 14A
  7. p70 S6 kinase alpha
  8. p70 S6K-alpha
  9. p70 S6KA
  10. p70 ribosomal S6 kinase alpha
  11. p70-S6K 1
Gene Name RPS6KB1
Protein Type Enzyme
Biological Properties
General Function Involved in protein serine/threonine kinase activity
Specific Function Acts to integrate nutrient and growth factor signals in regulation of protein synthesis, cell proliferation, cell growth, cell cycle progression and cell survival. Downstream effector of the mTOR signaling pathway. Phosphorylates specifically ribosomal protein S6 in response to insulin or several classes of mitogens. During translation initiation, the inactive form associatess with the eIF-3 complex under conditions of nutrient depletion. Mitogenic stimulation leads to phosphorylation and dissociation from the eIF-3 complex and the free activated form can phosphorylate other translational targets including EIF4B. Promotes protein synthesis by phosphorylating PDCD4 at 'Ser-67' and targeting it for degradation. Phosphorylates RICTOR leading to regulation of mammalian target of rapamycin complex 2 (mTORC2) signaling; probably phosphorylates RICTOR at 'Thr-1135'. Phosphorylates IRS1 at multiple serine residues coupled with insulin resistance; probably phosphorylates IRS1 at 'Ser-270'. Required for TNF-alpha induced IRS-1 degradation. Phosphorylates EEF2K in response to IGF1 and inhibits EEF2K activity. Phosphorylates BAD at 'Ser-99' in response to IGF1 leading to BAD inactivation and inhibition of BAD-induced apoptosis. Phosphorylates mitochondrial RMP leading to dissociation of a RMP:PPP1CC complex; probably phosphorylates RMP at 'Ser-99'. The free mitochondrial PPP1CC can dephosphorylate RPS6KB1 at Thr-412 which is proposed to be a negative feed back mechanism for the RPS6KB1 antiapoptotic function. Phosphorylates GSK3B at 'Ser-9' under conditions leading to loss of the TSC1-TSC2 complex. Phosphorylates POLDIP3
Pathways
  • Bafetinib Inhibition of BCR-ABL
  • BCR-ABL Action in CML Pathogenesis
  • Bosutinib Inhibition of BCR-ABL
  • Dasatinib Inhibition of BCR-ABL
  • Imatinib Inhibition of BCR-ABL
  • Leucine Stimulation on Insulin Signaling
  • Nilotinib Inhibition of BCR-ABL
  • Ponatinib Inhibition of BCR-ABL
Reactions Not Available
GO Classification
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein kinase activity
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
biological regulation
regulation of biological process
cellular metabolic process
regulation of cellular process
signal transduction
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Isoform Alpha II:Cytoplasm
Gene Properties
Chromosome Location Chromosome:1
Locus 17q23.1
SNPs RPS6KB1
Gene Sequence
>1578 bp
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
Protein Properties
Number of Residues 525
Molecular Weight 59139.1
Theoretical pI 6.64
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Ribosomal protein S6 kinase beta-1
MRRRRRRDGFYPAPDFRDREAEDMAGVFDIDLDQPEDAGSEDELEEGGQLNESMDHGGVG
PYELGMEHCEKFEISETSVNRGPEKIRPECFELLRVLGKGGYGKVFQVRKVTGANTGKIF
AMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYLSGGEL
FMQLEREGIFMEDTACFYLAEISMALGHLHQKGIIYRDLKPENIMLNHQGHVKLTDFGLC
KESIHDGTVTHTFCGTIEYMAPEILMRSGHNRAVDWWSLGALMYDMLTGAPPFTGENRKK
TIDKILKCKLNLPPYLTQEARDLLKKLLKRNAASRLGAGPGDAGEVQAHPFFRHINWEEL
LARKVEPPFKPLLQSEEDVSQFDSKFTRQTPVDSPDDSTLSESANQVFLGFTYVAPSVLE
SVKEKFSFEPKIRSPRRFIGSPRTPVSPVKFSPGDFWGRGASASTANPQTPVEYPMETSG
IEQMDVTMSGEASAPLPIRQPNSGPYKKQAFPMISKRPEHLRMNL
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P23443
UniProtKB/Swiss-Prot Entry Name KS6B1_HUMAN
PDB IDs Not Available
GenBank Gene ID M60724
GeneCard ID RPS6KB1
GenAtlas ID RPS6KB1
HGNC ID HGNC:10436
References
General References
  1. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  2. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  3. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  4. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  5. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. [PubMed:16964243 ]
  6. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974 ]
  7. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846 ]
  8. Grove JR, Banerjee P, Balasubramanyam A, Coffer PJ, Price DJ, Avruch J, Woodgett JR: Cloning and expression of two human p70 S6 kinase polypeptides differing only at their amino termini. Mol Cell Biol. 1991 Nov;11(11):5541-50. [PubMed:1922062 ]
  9. Gout I, Minami T, Hara K, Tsujishita Y, Filonenko V, Waterfield MD, Yonezawa K: Molecular cloning and characterization of a novel p70 S6 kinase, p70 S6 kinase beta containing a proline-rich region. J Biol Chem. 1998 Nov 13;273(46):30061-4. [PubMed:9804755 ]
  10. Pullen N, Dennis PB, Andjelkovic M, Dufner A, Kozma SC, Hemmings BA, Thomas G: Phosphorylation and activation of p70s6k by PDK1. Science. 1998 Jan 30;279(5351):707-10. [PubMed:9445476 ]
  11. Wang X, Li W, Williams M, Terada N, Alessi DR, Proud CG: Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase. EMBO J. 2001 Aug 15;20(16):4370-9. [PubMed:11500364 ]
  12. Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K: Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell. 2002 Jul 26;110(2):177-89. [PubMed:12150926 ]
  13. Fleckenstein DS, Dirks WG, Drexler HG, Quentmeier H: Tumor necrosis factor receptor-associated factor (TRAF) 4 is a new binding partner for the p70S6 serine/threonine kinase. Leuk Res. 2003 Aug;27(8):687-94. [PubMed:12801526 ]
  14. Richardson CJ, Broenstrup M, Fingar DC, Julich K, Ballif BA, Gygi S, Blenis J: SKAR is a specific target of S6 kinase 1 in cell growth control. Curr Biol. 2004 Sep 7;14(17):1540-9. [PubMed:15341740 ]
  15. Raught B, Peiretti F, Gingras AC, Livingstone M, Shahbazian D, Mayeur GL, Polakiewicz RD, Sonenberg N, Hershey JW: Phosphorylation of eucaryotic translation initiation factor 4B Ser422 is modulated by S6 kinases. EMBO J. 2004 Apr 21;23(8):1761-9. Epub 2004 Apr 8. [PubMed:15071500 ]
  16. Fingar DC, Richardson CJ, Tee AR, Cheatham L, Tsou C, Blenis J: mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4E-BP1/eukaryotic translation initiation factor 4E. Mol Cell Biol. 2004 Jan;24(1):200-16. [PubMed:14673156 ]
  17. Holz MK, Ballif BA, Gygi SP, Blenis J: mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Cell. 2005 Nov 18;123(4):569-80. [PubMed:16286006 ]
  18. Zhang HH, Lipovsky AI, Dibble CC, Sahin M, Manning BD: S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt. Mol Cell. 2006 Oct 20;24(2):185-97. [PubMed:17052453 ]
  19. Dorrello NV, Peschiaroli A, Guardavaccaro D, Colburn NH, Sherman NE, Pagano M: S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science. 2006 Oct 20;314(5798):467-71. [PubMed:17053147 ]
  20. Hauge C, Antal TL, Hirschberg D, Doehn U, Thorup K, Idrissova L, Hansen K, Jensen ON, Jorgensen TJ, Biondi RM, Frodin M: Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation. EMBO J. 2007 May 2;26(9):2251-61. Epub 2007 Apr 19. [PubMed:17446865 ]
  21. Djouder N, Metzler SC, Schmidt A, Wirbelauer C, Gstaiger M, Aebersold R, Hess D, Krek W: S6K1-mediated disassembly of mitochondrial URI/PP1gamma complexes activates a negative feedback program that counters S6K1 survival signaling. Mol Cell. 2007 Oct 12;28(1):28-40. [PubMed:17936702 ]
  22. Garcia-Martinez JM, Alessi DR: mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem J. 2008 Dec 15;416(3):375-85. doi: 10.1042/BJ20081668. [PubMed:18925875 ]
  23. Zhang J, Gao Z, Yin J, Quon MJ, Ye J: S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2. J Biol Chem. 2008 Dec 19;283(51):35375-82. doi: 10.1074/jbc.M806480200. Epub 2008 Oct 24. [PubMed:18952604 ]
  24. Kim D, Akcakanat A, Singh G, Sharma C, Meric-Bernstam F: Regulation and localization of ribosomal protein S6 kinase 1 isoforms. Growth Factors. 2009 Feb;27(1):12-21. doi: 10.1080/08977190802556986. [PubMed:19085255 ]
  25. Keshwani MM, Gao X, Harris TK: Mechanism of PDK1-catalyzed Thr-229 phosphorylation of the S6K1 protein kinase. J Biol Chem. 2009 Aug 21;284(34):22611-24. doi: 10.1074/jbc.M109.032177. Epub 2009 Jul 1. [PubMed:19570988 ]
  26. Dibble CC, Asara JM, Manning BD: Characterization of Rictor phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1. Mol Cell Biol. 2009 Nov;29(21):5657-70. doi: 10.1128/MCB.00735-09. Epub 2009 Aug 31. [PubMed:19720745 ]
  27. Julien LA, Carriere A, Moreau J, Roux PP: mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling. Mol Cell Biol. 2010 Feb;30(4):908-21. doi: 10.1128/MCB.00601-09. Epub 2009 Dec 7. [PubMed:19995915 ]
  28. Treins C, Warne PH, Magnuson MA, Pende M, Downward J: Rictor is a novel target of p70 S6 kinase-1. Oncogene. 2010 Feb 18;29(7):1003-16. doi: 10.1038/onc.2009.401. Epub 2009 Nov 23. [PubMed:19935711 ]
  29. Sunami T, Byrne N, Diehl RE, Funabashi K, Hall DL, Ikuta M, Patel SB, Shipman JM, Smith RF, Takahashi I, Zugay-Murphy J, Iwasawa Y, Lumb KJ, Munshi SK, Sharma S: Structural basis of human p70 ribosomal S6 kinase-1 regulation by activation loop phosphorylation. J Biol Chem. 2010 Feb 12;285(7):4587-94. doi: 10.1074/jbc.M109.040667. Epub 2009 Oct 28. [PubMed:19864428 ]