KS6B1_RAT
ID KS6B1_RAT Reviewed; 525 AA.
AC P67999; P21425;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Ribosomal protein S6 kinase beta-1;
DE Short=S6K-beta-1;
DE Short=S6K1;
DE EC=2.7.11.1 {ECO:0000269|PubMed:12183455, ECO:0000269|PubMed:8524831};
DE AltName: Full=70 kDa ribosomal protein S6 kinase 1;
DE Short=P70S6K1;
DE Short=p70-S6K 1;
DE AltName: Full=Ribosomal protein S6 kinase I;
DE AltName: Full=p70 ribosomal S6 kinase alpha;
DE Short=p70 S6 kinase alpha;
DE Short=p70 S6K-alpha;
DE Short=p70 S6KA;
GN Name=Rps6kb1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2236064; DOI=10.1073/pnas.87.21.8550;
RA Banerjee P., Ahmad M.F., Grove J.R., Kozlosky C., Price D.J., Avruch J.;
RT "Molecular structure of a major insulin/mitogen-activated 70-kDa S6 protein
RT kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:8550-8554(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 24-525, AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=Sprague-Dawley;
RX PubMed=1699226; DOI=10.1073/pnas.87.19.7365;
RA Kozma S.C., Ferrari S., Bassand P., Siegmann M., Totty N., Thomas G.;
RT "Cloning of the mitogen-activated S6 kinase from rat liver reveals an
RT enzyme of the second messenger subfamily.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:7365-7369(1990).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP LYS-123; SER-434; SER-441; THR-444 AND SER-447.
RX PubMed=8524831; DOI=10.1073/pnas.92.25.11696;
RA Cheatham L., Monfar M., Chou M.M., Blenis J.;
RT "Structural and functional analysis of pp70S6k.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:11696-11700(1995).
RN [4]
RP ACTIVITY REGULATION.
RX PubMed=9427642; DOI=10.1016/s0960-9822(98)70037-5;
RA Alessi D.R., Kozlowski M.T., Weng Q.P., Morrice N., Avruch J.;
RT "3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and
RT activates the p70 S6 kinase in vivo and in vitro.";
RL Curr. Biol. 8:69-81(1998).
RN [5]
RP PHOSPHORYLATION AT THR-252; SER-394; THR-412; SER-434; THR-444 AND SER-447,
RP AND MUTAGENESIS OF LYS-123; THR-252; THR-256; SER-394 AND THR-412.
RX PubMed=9632736; DOI=10.1074/jbc.273.26.16621;
RA Weng Q.P., Kozlowski M., Belham C., Zhang A., Comb M.J., Avruch J.;
RT "Regulation of the p70 S6 kinase by phosphorylation in vivo. Analysis using
RT site-specific anti-phosphopeptide antibodies.";
RL J. Biol. Chem. 273:16621-16629(1998).
RN [6]
RP PHOSPHORYLATION AT THR-412 BY MTOR.
RX PubMed=9465032; DOI=10.1073/pnas.95.4.1432;
RA Burnett P.E., Barrow R.K., Cohen N.A., Snyder S.H., Sabatini D.M.;
RT "RAFT1 phosphorylation of the translational regulators p70 S6 kinase and
RT 4E-BP1.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:1432-1437(1998).
RN [7]
RP INTERACTION WITH NEURABIN-I, AND MUTAGENESIS.
RX PubMed=9653190; DOI=10.1073/pnas.95.14.8351;
RA Burnett P.E., Blackshaw S., Lai M.M., Qureshi I.A., Burnett A.F.,
RA Sabatini D.M., Snyder S.H.;
RT "Neurabin is a synaptic protein linking p70 S6 kinase and the neuronal
RT cytoskeleton.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8351-8356(1998).
RN [8]
RP PHOSPHORYLATION AT THR-412.
RX PubMed=11516946; DOI=10.1016/s0960-9822(01)00369-4;
RA Belham C., Comb M.J., Avruch J.;
RT "Identification of the NIMA family kinases NEK6/7 as regulators of the p70
RT ribosomal S6 kinase.";
RL Curr. Biol. 11:1155-1167(2001).
RN [9]
RP INTERACTION WITH RPTOR, TOS MOTIF, AND MUTAGENESIS OF PHE-28; ASP-29;
RP ILE-30; ASP-31 AND LEU-32.
RX PubMed=11967149; DOI=10.1016/s0960-9822(02)00762-5;
RA Schalm S.S., Blenis J.;
RT "Identification of a conserved motif required for mTOR signaling.";
RL Curr. Biol. 12:632-639(2002).
RN [10]
RP AUTOPHOSPHORYLATION, AND CATALYTIC ACTIVITY.
RX PubMed=12183455; DOI=10.1074/jbc.m205168200;
RA Romanelli A., Dreisbach V.C., Blenis J.;
RT "Characterization of phosphatidylinositol 3-kinase-dependent
RT phosphorylation of the hydrophobic motif site Thr(389) in p70 S6 kinase
RT 1.";
RL J. Biol. Chem. 277:40281-40289(2002).
RN [11]
RP INTERACTION WITH RPTOR, AND MUTAGENESIS OF PHE-28.
RX PubMed=12604610; DOI=10.1074/jbc.c200665200;
RA Nojima H., Tokunaga C., Eguchi S., Oshiro N., Hidayat S., Yoshino K.,
RA Hara K., Tanaka N., Avruch J., Yonezawa K.;
RT "The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR
RT substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS)
RT motif.";
RL J. Biol. Chem. 278:15461-15464(2003).
RN [12]
RP ACETYLATION AT LYS-516.
RX PubMed=20599721; DOI=10.1016/j.bbrc.2010.06.081;
RA Fenton T.R., Gwalter J., Cramer R., Gout I.T.;
RT "S6K1 is acetylated at lysine 516 in response to growth factor
RT stimulation.";
RL Biochem. Biophys. Res. Commun. 398:400-405(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-447 AND SER-452, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [14]
RP FUNCTION IN PHOSPHORYLATION OF EPRS.
RX PubMed=28178239; DOI=10.1038/nature21380;
RA Arif A., Terenzi F., Potdar A.A., Jia J., Sacks J., China A., Halawani D.,
RA Vasu K., Li X., Brown J.M., Chen J., Kozma S.C., Thomas G., Fox P.L.;
RT "EPRS is a critical mTORC1-S6K1 effector that influences adiposity in
RT mice.";
RL Nature 542:357-361(2017).
CC -!- FUNCTION: Serine/threonine-protein kinase that acts downstream of mTOR
CC signaling in response to growth factors and nutrients to promote cell
CC proliferation, cell growth and cell cycle progression. Regulates
CC protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and
CC contributes to cell survival by repressing the pro-apoptotic function
CC of BAD. Under conditions of nutrient depletion, the inactive form
CC associates with the EIF3 translation initiation complex. Upon mitogenic
CC stimulation, phosphorylation by the mammalian target of rapamycin
CC complex 1 (mTORC1) leads to dissociation from the EIF3 complex and
CC activation. The active form then phosphorylates and activates several
CC substrates in the pre-initiation complex, including the EIF2B complex
CC and the cap-binding complex component EIF4B. Also controls translation
CC initiation by phosphorylating a negative regulator of EIF4A, PDCD4,
CC targeting it for ubiquitination and subsequent proteolysis. Promotes
CC initiation of the pioneer round of protein synthesis by phosphorylating
CC POLDIP3/SKAR. In response to IGF1, activates translation elongation by
CC phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and
CC thus activation of EEF2. Also plays a role in feedback regulation of
CC mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition
CC of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating
CC the pro-apoptotic protein BAD and suppressing its pro-apoptotic
CC function. Phosphorylates mitochondrial RMP leading to dissociation of a
CC RMP:PPP1CC complex. The free mitochondrial PPP1CC can then
CC dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative
CC feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates
CC TNF-alpha-induced insulin resistance by phosphorylating IRS1 at
CC multiple serine residues, resulting in accelerated degradation of IRS1.
CC In cells lacking functional TSC1-2 complex, constitutively
CC phosphorylates and inhibits GSK3B. May be involved in cytoskeletal
CC rearrangement through binding to neurabin. Phosphorylates and activates
CC the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (By
CC similarity) (PubMed:8524831). Following activation by mTORC1,
CC phosphorylates EPRS and thereby plays a key role in fatty acid uptake
CC by adipocytes and also most probably in interferon-gamma-induced
CC translation inhibition (PubMed:28178239).
CC {ECO:0000250|UniProtKB:P23443, ECO:0000269|PubMed:28178239,
CC ECO:0000269|PubMed:8524831}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:12183455, ECO:0000269|PubMed:8524831};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:12183455,
CC ECO:0000269|PubMed:8524831};
CC -!- ACTIVITY REGULATION: Activation requires multiple phosphorylation
CC events on serine/threonine residues. Activation appears to be first
CC mediated by phosphorylation of multiple sites in the autoinhibitory
CC domain, which facilitates phosphorylation at Thr-412, disrupting the
CC autoinhibitory mechanism and allowing phosphorylation of Thr-252 by
CC PDPK1. The active conformation of the kinase is believed to be
CC stabilized by a mechanism involving three conserved phosphorylation
CC sites located in the kinase domain activation loop (Thr-252) and in the
CC AGC-kinase C-terminal domain (Ser-394 in the middle of the tail/linker
CC region and Thr-412 within a hydrophobic motif at its end). Activated by
CC mTORC1; isoform Alpha I and isoform Alpha II are sensitive to
CC rapamycin, which inhibits activating phosphorylation at Thr-412.
CC Activated by PDPK1 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PPP1R9A/neurabin-1 (PubMed:9653190). Interacts
CC with RPTOR (PubMed:11967149, PubMed:12604610). Interacts with IRS1 (By
CC similarity). Interacts with EIF3B and EIF3C (By similarity). Interacts
CC with POLDIP3 (By similarity). Interacts with TRAF4 (By similarity).
CC Interacts (via N-terminus) with IER5 (By similarity).
CC {ECO:0000250|UniProtKB:P23443, ECO:0000269|PubMed:11967149,
CC ECO:0000269|PubMed:12604610, ECO:0000269|PubMed:9653190}.
CC -!- INTERACTION:
CC P67999; O35867: Ppp1r9a; NbExp=4; IntAct=EBI-2639458, EBI-7092421;
CC P67999; P67999: Rps6kb1; NbExp=2; IntAct=EBI-2639458, EBI-2639458;
CC P67999; Q8N122: RPTOR; Xeno; NbExp=2; IntAct=EBI-2639458, EBI-1567928;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Synapse, synaptosome. Mitochondrion
CC outer membrane. Mitochondrion {ECO:0000250}. Note=Colocalizes with URI1
CC at mitochondrion. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Alpha I;
CC IsoId=P67999-1; Sequence=Displayed;
CC Name=Alpha II;
CC IsoId=P67999-2; Sequence=VSP_018842;
CC -!- TISSUE SPECIFICITY: Brain.
CC -!- DOMAIN: The autoinhibitory domain is believed to block phosphorylation
CC within the AGC-kinase C-terminal domain and the activation loop.
CC -!- DOMAIN: The TOS (TOR signaling) motif is essential for activation by
CC mTORC1.
CC -!- PTM: Dephosphorylation by PPP1CC at Thr-412 in mitochondrion (By
CC similarity). Phosphorylation at Thr-412 is regulated by mTORC1. The
CC phosphorylation at this site is maintained by an agonist-dependent
CC autophosphorylation mechanism. Activated by phosphorylation at Thr-252
CC by PDPK1. {ECO:0000250, ECO:0000269|PubMed:11516946,
CC ECO:0000269|PubMed:9465032, ECO:0000269|PubMed:9632736}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. S6 kinase subfamily. {ECO:0000305}.
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DR EMBL; M58340; AAA42104.1; -; mRNA.
DR EMBL; M57428; AAA42103.1; -; mRNA.
DR PIR; A36484; TVRTK6.
DR RefSeq; NP_114191.1; NM_031985.1.
DR AlphaFoldDB; P67999; -.
DR SMR; P67999; -.
DR BioGRID; 249866; 3.
DR ELM; P67999; -.
DR IntAct; P67999; 6.
DR MINT; P67999; -.
DR STRING; 10116.ENSRNOP00000005226; -.
DR iPTMnet; P67999; -.
DR PhosphoSitePlus; P67999; -.
DR jPOST; P67999; -.
DR PaxDb; P67999; -.
DR Ensembl; ENSRNOT00000118202; ENSRNOP00000078345; ENSRNOG00000003919. [P67999-1]
DR GeneID; 83840; -.
DR KEGG; rno:83840; -.
DR CTD; 6198; -.
DR RGD; 620683; Rps6kb1.
DR eggNOG; KOG0598; Eukaryota.
DR GeneTree; ENSGT00940000154203; -.
DR HOGENOM; CLU_000288_63_5_1; -.
DR InParanoid; P67999; -.
DR OMA; KGSIFAM; -.
DR OrthoDB; 1132245at2759; -.
DR PhylomeDB; P67999; -.
DR TreeFam; TF313438; -.
DR BRENDA; 2.7.11.1; 5301.
DR Reactome; R-RNO-166208; mTORC1-mediated signalling.
DR SABIO-RK; P67999; -.
DR PRO; PR:P67999; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000003919; Expressed in quadriceps femoris and 20 other tissues.
DR Genevisible; P67999; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0045202; C:synapse; IDA:SynGO.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0030165; F:PDZ domain binding; IPI:RGD.
DR GO; GO:0042277; F:peptide binding; IDA:RGD.
DR GO; GO:0004672; F:protein kinase activity; IDA:RGD.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IPI:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; ISO:RGD.
DR GO; GO:0004711; F:ribosomal protein S6 kinase activity; IMP:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0001662; P:behavioral fear response; ISO:RGD.
DR GO; GO:0016477; P:cell migration; IEP:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; ISO:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:RGD.
DR GO; GO:0071346; P:cellular response to interferon-gamma; ISO:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:RGD.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0007281; P:germ cell development; ISO:RGD.
DR GO; GO:0044539; P:long-chain fatty acid import into cell; ISS:UniProtKB.
DR GO; GO:0007616; P:long-term memory; IEP:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISO:RGD.
DR GO; GO:0048633; P:positive regulation of skeletal muscle tissue growth; IMP:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0045727; P:positive regulation of translation; ISO:RGD.
DR GO; GO:0045948; P:positive regulation of translational initiation; ISO:RGD.
DR GO; GO:0043491; P:protein kinase B signaling; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0046324; P:regulation of glucose import; IMP:UniProtKB.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:0014878; P:response to electrical stimulus involved in regulation of muscle adaptation; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0033762; P:response to glucagon; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0009749; P:response to glucose; IEP:RGD.
DR GO; GO:0009408; P:response to heat; IEP:RGD.
DR GO; GO:0032868; P:response to insulin; IMP:UniProtKB.
DR GO; GO:0043201; P:response to leucine; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; ISO:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0033574; P:response to testosterone; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0034612; P:response to tumor necrosis factor; IMP:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0014732; P:skeletal muscle atrophy; IEP:RGD.
DR GO; GO:0003009; P:skeletal muscle contraction; IEP:RGD.
DR GO; GO:0031929; P:TOR signaling; ISS:UniProtKB.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR016238; Ribosomal_S6_kinase.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000605; Ribsml_S6_kin_1; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative initiation; Apoptosis; ATP-binding; Cell cycle;
KW Cytoplasm; Direct protein sequencing; Kinase; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Synapse; Synaptosome;
KW Transferase; Translation regulation.
FT CHAIN 1..525
FT /note="Ribosomal protein S6 kinase beta-1"
FT /id="PRO_0000024348"
FT DOMAIN 91..352
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 353..423
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 28..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 380..399
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 424..525
FT /note="Autoinhibitory domain"
FT REGION 486..509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 28..32
FT /note="TOS motif"
FT COMPBIAS 28..48
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 218
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 97..105
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 123
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 252
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000269|PubMed:9632736"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:9632736"
FT MOD_RES 412
FT /note="Phosphothreonine; by MTOR, NEK6 and NEK7"
FT /evidence="ECO:0000269|PubMed:11516946,
FT ECO:0000269|PubMed:9465032, ECO:0000269|PubMed:9632736"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:9632736"
FT MOD_RES 441
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23443"
FT MOD_RES 444
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:9632736"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:9632736,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 452
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 516
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:20599721"
FT VAR_SEQ 1..23
FT /note="Missing (in isoform Alpha II)"
FT /evidence="ECO:0000305"
FT /id="VSP_018842"
FT MUTAGEN 28..32
FT /note="Missing: Almost complete loss of activity."
FT MUTAGEN 28
FT /note="F->A: Complete loss of activity. Abolishes
FT interaction with RPTOR. Reduces phosphorylation. Loss of
FT phosphorylation at T-412 and T-444."
FT /evidence="ECO:0000269|PubMed:11967149,
FT ECO:0000269|PubMed:12604610"
FT MUTAGEN 29
FT /note="D->A: Almost complete loss of activity; when
FT associated with A-31."
FT /evidence="ECO:0000269|PubMed:11967149"
FT MUTAGEN 30
FT /note="I->A: Almost complete loss of activity; when
FT associated with A-32."
FT /evidence="ECO:0000269|PubMed:11967149"
FT MUTAGEN 31
FT /note="D->A: Almost complete loss of activity; when
FT associated with A-29."
FT /evidence="ECO:0000269|PubMed:11967149"
FT MUTAGEN 32
FT /note="L->A: Almost complete loss of activity; when
FT associated with A-30."
FT /evidence="ECO:0000269|PubMed:11967149"
FT MUTAGEN 123
FT /note="K->M: Loss of activity towards ribosomal protein
FT S6."
FT /evidence="ECO:0000269|PubMed:8524831,
FT ECO:0000269|PubMed:9632736"
FT MUTAGEN 123
FT /note="K->R: Loss of activity."
FT /evidence="ECO:0000269|PubMed:8524831,
FT ECO:0000269|PubMed:9632736"
FT MUTAGEN 252
FT /note="T->A: Loss of activity towards ribosomal protein S6
FT and reduced phosphorylation at Thr-412."
FT /evidence="ECO:0000269|PubMed:9632736"
FT MUTAGEN 256
FT /note="T->A: Loss of activity towards ribosomal protein S6
FT without effect on phosphorylation status."
FT /evidence="ECO:0000269|PubMed:9632736"
FT MUTAGEN 394
FT /note="S->A,D: Loss of activity towards ribosomal protein
FT S6 and reduces phosphorylation at Thr-252."
FT /evidence="ECO:0000269|PubMed:9632736"
FT MUTAGEN 412
FT /note="T->A: Loss of activity towards ribosomal protein S6
FT and loss of phosphorylation at Thr-252."
FT /evidence="ECO:0000269|PubMed:9632736"
FT MUTAGEN 412
FT /note="T->E: Mimics phosphorylation. Constitutive active.
FT No effect on activity towards ribosomal protein S6."
FT /evidence="ECO:0000269|PubMed:9632736"
FT MUTAGEN 434
FT /note="S->D: No effect on sensitivity to wortmannin and
FT rapamycin; when associated with D-441, D-444 and D-447."
FT /evidence="ECO:0000269|PubMed:8524831"
FT MUTAGEN 441
FT /note="S->D: No effect on sensitivity to wortmannin and
FT rapamycin; when associated with D-434, D-D-444 and D-447."
FT /evidence="ECO:0000269|PubMed:8524831"
FT MUTAGEN 444
FT /note="T->D: No effect on sensitivity to wortmannin and
FT rapamycin; when associated with D-434, D-441, and D-447."
FT /evidence="ECO:0000269|PubMed:8524831"
FT MUTAGEN 447
FT /note="S->D: No effect on sensitivity to wortmannin and
FT rapamycin; when associated with D-434, D-441 and D-444."
FT /evidence="ECO:0000269|PubMed:8524831"
FT CONFLICT 367
FT /note="P -> R (in Ref. 1; AAA42104)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 525 AA; 59132 MW; 013BA13EFB3508D7 CRC64;
MRRRRRRDGF YPAPDFRHRE AEDMAGVFDI DLDQPEDAGS EDELEEGGQL NESMDHGGVG
PYELGMEHCE KFEISETSVN RGPEKIRPEC FELLRVLGKG GYGKVFQVRK VTGANTGKIF
AMKVLKKAMI VRNAKDTAHT KAERNILEEV KHPFIVDLIY AFQTGGKLYL ILEYLSGGEL
FMQLEREGIF MEDTACFYLA EISMALGHLH QKGIIYRDLK PENIMLNHQG HVKLTDFGLC
KESIHDGTVT HTFCGTIEYM APEILMRSGH NRAVDWWSLG ALMYDMLTGA PPFTGENRKK
TIDKILKCKL NLPPYLTQEA RDLLKKLLKR NAASRLGAGP GDAGEVQAHP FFRHINWEEL
LARKVEPPFK PLLQSEEDVS QFDSKFTRQT PVDSPDDSTL SESANQVFLG FTYVAPSVLE
SVKEKFSFEP KIRSPRRFIG SPRTPVSPVK FSPGDFWGRG ASASTANPQT PVEYPMETSG
IEQMDVTTSG EASAPLPIRQ PNSGPYKKQA FPMISKRPEH LRMNL
