CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-005174
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ribosomal protein S6 kinase beta-1 
Protein Synonyms/Alias
 S6K-beta-1; S6K1; 70 kDa ribosomal protein S6 kinase 1; P70S6K1; p70-S6K 1; Ribosomal protein S6 kinase I; Serine/threonine-protein kinase 14A; p70 ribosomal S6 kinase alpha; p70 S6 kinase alpha; p70 S6K-alpha; p70 S6KA 
Gene Name
 RPS6KB1 
Gene Synonyms/Alias
 STK14A 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
99ELLRVLGKGGYGKVFubiquitination[1]
104LGKGGYGKVFQVRKVubiquitination[1]
304NRKKTIDKILKCKLNacetylation[2]
450RTPVSPVKFSPGDFWubiquitination[1]
516QAFPMISKRPEHLRMacetylation[3]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [3] S6K1 is acetylated at lysine 516 in response to growth factor stimulation.
 Fenton TR, Gwalter J, Cramer R, Gout IT.
 Biochem Biophys Res Commun. 2010 Jul 30;398(3):400-5. [PMID: 20599721] 
Functional Description
 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. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the preinitiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. 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. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1- 2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin. 
Sequence Annotation
 DOMAIN 91 352 Protein kinase.
 DOMAIN 353 423 AGC-kinase C-terminal.
 NP_BIND 97 105 ATP (By similarity).
 REGION 424 525 Autoinhibitory domain.
 MOTIF 28 32 TOS motif.
 ACT_SITE 218 218 Proton acceptor (By similarity).
 BINDING 123 123 ATP (By similarity).
 MOD_RES 252 252 Phosphothreonine; by PDPK1.
 MOD_RES 304 304 N6-acetyllysine.
 MOD_RES 394 394 Phosphoserine.
 MOD_RES 412 412 Phosphothreonine; by MTOR, NEK6 and NEK7
 MOD_RES 434 434 Phosphoserine (By similarity).
 MOD_RES 441 441 Phosphoserine.
 MOD_RES 444 444 Phosphothreonine.
 MOD_RES 447 447 Phosphoserine.
 MOD_RES 452 452 Phosphoserine.
 MOD_RES 516 516 N6-acetyllysine (By similarity).  
Keyword
 3D-structure; Acetylation; Alternative initiation; Apoptosis; ATP-binding; Cell cycle; Cell junction; Complete proteome; Cytoplasm; Kinase; Membrane; Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Synapse; Synaptosome; Transferase; Translation regulation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 525 AA 
Protein Sequence
MRRRRRRDGF YPAPDFRDRE AEDMAGVFDI DLDQPEDAGS EDELEEGGQL NESMDHGGVG 60
PYELGMEHCE KFEISETSVN RGPEKIRPEC FELLRVLGKG GYGKVFQVRK VTGANTGKIF 120
AMKVLKKAMI VRNAKDTAHT KAERNILEEV KHPFIVDLIY AFQTGGKLYL ILEYLSGGEL 180
FMQLEREGIF MEDTACFYLA EISMALGHLH QKGIIYRDLK PENIMLNHQG HVKLTDFGLC 240
KESIHDGTVT HTFCGTIEYM APEILMRSGH NRAVDWWSLG ALMYDMLTGA PPFTGENRKK 300
TIDKILKCKL NLPPYLTQEA RDLLKKLLKR NAASRLGAGP GDAGEVQAHP FFRHINWEEL 360
LARKVEPPFK PLLQSEEDVS QFDSKFTRQT PVDSPDDSTL SESANQVFLG FTYVAPSVLE 420
SVKEKFSFEP KIRSPRRFIG SPRTPVSPVK FSPGDFWGRG ASASTANPQT PVEYPMETSG 480
IEQMDVTMSG EASAPLPIRQ PNSGPYKKQA FPMISKRPEH LRMNL 525 
Gene Ontology
 GO:0030054; C:cell junction; IEA:UniProtKB-KW.
 GO:0009986; C:cell surface; IEA:Compara.
 GO:0005737; C:cytoplasm; IDA:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
 GO:0005739; C:mitochondrion; IDA:UniProtKB.
 GO:0043005; C:neuron projection; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
 GO:0045202; C:synapse; IEA:UniProtKB-KW.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0042277; F:peptide binding; IEA:Compara.
 GO:0004672; F:protein kinase activity; IDA:UniProtKB.
 GO:0004711; F:ribosomal protein S6 kinase activity; IEA:Compara.
 GO:0007568; P:aging; IEA:Compara.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0016477; P:cell migration; IEA:Compara.
 GO:0071363; P:cellular response to growth factor stimulus; IDA:UniProtKB.
 GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:UniProtKB.
 GO:0007281; P:germ cell development; IEA:Compara.
 GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
 GO:0007616; P:long-term memory; IEA:Compara.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:UniProtKB.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:UniProtKB.
 GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB.
 GO:0048633; P:positive regulation of skeletal muscle tissue growth; IEA:Compara.
 GO:0014911; P:positive regulation of smooth muscle cell migration; IEA:Compara.
 GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Compara.
 GO:0045948; P:positive regulation of translational initiation; IMP:UniProtKB.
 GO:0043491; P:protein kinase B signaling cascade; IEA:Compara.
 GO:0046324; P:regulation of glucose import; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0014878; P:response to electrical stimulus involved in regulation of muscle adaptation; IEA:Compara.
 GO:0045471; P:response to ethanol; IEA:Compara.
 GO:0033762; P:response to glucagon stimulus; IEA:Compara.
 GO:0051384; P:response to glucocorticoid stimulus; IEA:Compara.
 GO:0009749; P:response to glucose stimulus; IEA:Compara.
 GO:0009408; P:response to heat; IEA:Compara.
 GO:0043201; P:response to leucine; IEA:Compara.
 GO:0032496; P:response to lipopolysaccharide; IEA:Compara.
 GO:0009612; P:response to mechanical stimulus; IEA:Compara.
 GO:0007584; P:response to nutrient; IEA:Compara.
 GO:0033574; P:response to testosterone stimulus; IEA:Compara.
 GO:0009636; P:response to toxic substance; IEA:Compara.
 GO:0034612; P:response to tumor necrosis factor; IEA:Compara.
 GO:0009611; P:response to wounding; IEA:Compara.
 GO:0014732; P:skeletal muscle atrophy; IEA:Compara.
 GO:0003009; P:skeletal muscle contraction; IEA:Compara.
 GO:0031929; P:TOR signaling cascade; IDA:UniProtKB. 
Interpro
 IPR000961; AGC-kinase_C.
 IPR011009; Kinase-like_dom.
 IPR017892; Pkinase_C.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR016238; Ribosomal_S6_kinase.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00069; Pkinase
 PF00433; Pkinase_C 
SMART
 SM00133; S_TK_X
 SM00220; S_TKc 
PROSITE
 PS51285; AGC_KINASE_CTER
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS