KS6B_CAEEL
ID KS6B_CAEEL Reviewed; 550 AA.
AC Q9NAH6;
DT 20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Ribosomal protein S6 kinase beta {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000255|PIRNR:PIRNR000605};
GN Name=rsks-1 {ECO:0000312|WormBase:Y47D3A.16};
GN ORFNames=Y47D3A.16 {ECO:0000312|WormBase:Y47D3A.16};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17266680; DOI=10.1111/j.1474-9726.2006.00266.x;
RA Pan K.Z., Palter J.E., Rogers A.N., Olsen A., Chen D., Lithgow G.J.,
RA Kapahi P.;
RT "Inhibition of mRNA translation extends lifespan in Caenorhabditis
RT elegans.";
RL Aging Cell 6:111-119(2007).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22560223; DOI=10.1016/j.cmet.2012.04.007;
RA Robida-Stubbs S., Glover-Cutter K., Lamming D.W., Mizunuma M.,
RA Narasimhan S.D., Neumann-Haefelin E., Sabatini D.M., Blackwell T.K.;
RT "TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf
RT and DAF-16/FoxO.";
RL Cell Metab. 15:713-724(2012).
RN [4] {ECO:0000305}
RP FUNCTION, DISRUPTION PHENOTYPE, PHOSPHORYLATION AT THR-404, AND MUTAGENESIS
RP OF THR-404.
RX PubMed=22278922; DOI=10.1242/dev.074047;
RA Korta D.Z., Tuck S., Hubbard E.J.;
RT "S6K links cell fate, cell cycle and nutrient response in C. elegans
RT germline stem/progenitor cells.";
RL Development 139:859-870(2012).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=23879233; DOI=10.1111/acel.12140;
RA Seo K., Choi E., Lee D., Jeong D.E., Jang S.K., Lee S.J.;
RT "Heat shock factor 1 mediates the longevity conferred by inhibition of TOR
RT and insulin/IGF-1 signaling pathways in C. elegans.";
RL Aging Cell 12:1073-1081(2013).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24332851; DOI=10.1016/j.celrep.2013.11.018;
RA Chen D., Li P.W., Goldstein B.A., Cai W., Thomas E.L., Chen F.,
RA Hubbard A.E., Melov S., Kapahi P.;
RT "Germline signaling mediates the synergistically prolonged longevity
RT produced by double mutations in daf-2 and rsks-1 in C. elegans.";
RL Cell Rep. 5:1600-1610(2013).
RN [7] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-404 AND SER-439, AND
RP MUTAGENESIS OF LYS-115; THR-404 AND SER-439.
RX PubMed=24431434; DOI=10.1523/jneurosci.2886-13.2014;
RA Hubert T., Wu Z., Chisholm A.D., Jin Y.;
RT "S6 kinase inhibits intrinsic axon regeneration capacity via AMP kinase in
RT Caenorhabditis elegans.";
RL J. Neurosci. 34:758-763(2014).
CC -!- FUNCTION: Serine/threonine-protein kinase which regulates mRNA
CC translation (PubMed:17266680). Negatively regulates lifespan and
CC resistance to starvation, oxidative stress, protein aggregation and
CC P.aeruginosa-mediated infection (PubMed:17266680, PubMed:23879233,
CC PubMed:24332851). May regulate these processes by preventing the
CC activation of transcription factor hif-1 (PubMed:23879233). Required,
CC probably downstream of let-363/TOR, for the establishment of the proper
CC number of germline progenitors by promoting cell cycle progression and
CC preventing differentiation during larval development. Regulates germ
CC cell size (PubMed:22278922). In addition required for sperm production
CC and embryo viability (PubMed:17266680, PubMed:22278922). Involved in
CC axon regeneration of PLM and ALM neurons by inhibiting growth cone
CC formation early after axotomy and later by inhibiting axon extension.
CC Functions in axon regeneration and lifespan probably by preventing aak-
CC 2/AMPK activation (PubMed:24332851, PubMed:24431434). Negatively
CC regulates autophagy (PubMed:22560223). {ECO:0000269|PubMed:17266680,
CC ECO:0000269|PubMed:22278922, ECO:0000269|PubMed:22560223,
CC ECO:0000269|PubMed:23879233, ECO:0000269|PubMed:24332851,
CC ECO:0000269|PubMed:24431434}.
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:0000255|PIRNR:PIRNR000605};
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:0000255|PIRNR:PIRNR000605};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305};
CC -!- SUBCELLULAR LOCATION: Cell projection, axon
CC {ECO:0000269|PubMed:24431434}. Perikaryon
CC {ECO:0000269|PubMed:24431434}. Note=Enriched in the synaptic branch of
CC PLM neurons. {ECO:0000269|PubMed:24431434}.
CC -!- PTM: May be phosphorylated on Thr-404 by let-363/TOR.
CC {ECO:0000305|PubMed:22278922}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes an increased
CC lifespan and resistance to starvation, slower growth and a decrease in
CC brood size (PubMed:17266680). Causes a decrease in the number of
CC germline progenitors (PubMed:22278922). RNAi-mediated knockdown in
CC adults causes increase in lgg-1 positive autophagic vesicles
CC (PubMed:22560223). RNAi-mediated knockdown in a daf-2 e1370 mutant
CC background results in daf-16-mediated up-regulation of stdh-1 reporter
CC expression in the intestine and a synergistic increase in lifespan.
CC RNAi-mediated knockdown in germ line, hypodermis and to a lesser extent
CC in intestine and daf-2 e1370 mutant background causes a synergistic
CC increase in lifespan (PubMed:24332851). {ECO:0000269|PubMed:17266680,
CC ECO:0000269|PubMed:22278922, ECO:0000269|PubMed:22560223,
CC ECO:0000269|PubMed:24332851}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. S6 kinase subfamily.
CC {ECO:0000255|PIRNR:PIRNR000605}.
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DR EMBL; BX284603; CAB55075.2; -; Genomic_DNA.
DR RefSeq; NP_499447.2; NM_067046.3.
DR AlphaFoldDB; Q9NAH6; -.
DR SMR; Q9NAH6; -.
DR STRING; 6239.Y47D3A.16; -.
DR iPTMnet; Q9NAH6; -.
DR EPD; Q9NAH6; -.
DR PaxDb; Q9NAH6; -.
DR PeptideAtlas; Q9NAH6; -.
DR EnsemblMetazoa; Y47D3A.16.1; Y47D3A.16.1; WBGene00012929.
DR GeneID; 176554; -.
DR KEGG; cel:CELE_Y47D3A.16; -.
DR UCSC; Y47D3A.16; c. elegans.
DR CTD; 176554; -.
DR WormBase; Y47D3A.16; CE46969; WBGene00012929; rsks-1.
DR eggNOG; KOG0598; Eukaryota.
DR GeneTree; ENSGT00940000170375; -.
DR HOGENOM; CLU_000288_63_5_1; -.
DR InParanoid; Q9NAH6; -.
DR OMA; XGELFTH; -.
DR OrthoDB; 1132245at2759; -.
DR PhylomeDB; Q9NAH6; -.
DR Reactome; R-CEL-166208; mTORC1-mediated signalling.
DR Reactome; R-CEL-198693; AKT phosphorylates targets in the nucleus.
DR PRO; PR:Q9NAH6; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00012929; Expressed in larva and 3 other tissues.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0004711; F:ribosomal protein S6 kinase activity; IBA:GO_Central.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0002119; P:nematode larval development; IGI:WormBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:2000786; P:positive regulation of autophagosome assembly; IMP:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:UniProtKB.
DR GO; GO:0031929; P:TOR signaling; IBA:GO_Central.
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 ATP-binding; Cell projection; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..550
FT /note="Ribosomal protein S6 kinase beta"
FT /evidence="ECO:0000305"
FT /id="PRO_0000435314"
FT DOMAIN 83..344
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 345..415
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 433..466
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 484..550
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 484..498
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 513..541
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 210
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 89..97
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 115
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 404
FT /note="Phosphothreonine"
FT /evidence="ECO:0000305|PubMed:22278922,
FT ECO:0000305|PubMed:24431434"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:24431434"
FT MUTAGEN 115
FT /note="K->Q: Probable loss of kinase activity. Enhanced
FT axonal regrowth following axotomy of PLM neurons."
FT /evidence="ECO:0000269|PubMed:24431434"
FT MUTAGEN 404
FT /note="T->A: Abolishes phosphorylation and causes a
FT decrease in the number of germline progenitors."
FT /evidence="ECO:0000269|PubMed:22278922"
FT MUTAGEN 404
FT /note="T->E: Phosphomimetic mutant which inhibits axon
FT regrowth following axotomy of PLM neurons."
FT /evidence="ECO:0000269|PubMed:24431434"
FT MUTAGEN 439
FT /note="S->D: Phosphomimetic mutant which inhibits axon
FT regrowth following axotomy of PLM neurons."
FT /evidence="ECO:0000269|PubMed:24431434"
SQ SEQUENCE 550 AA; 60424 MW; D207B4760CBCDC42 CRC64;
MADVFEFELE GHESQASPQR HAYHYDNCTE IMEDDHMYSN VADGQISAPP PSSSYMEDPM
MESIQLCASA INPPNVRVGP EDFQLLKVLG KGGYGKVFQV RKTTGSDNGQ IFAMKVLQKA
TIVRNQKDTA HTKAERNILE AVKSPFICDL LYAFQTGGKL YLILEYLSGG ELFMHLEREG
MFMENVAKFY LSEIVVSLEH LHQQGIIYRD LKPENILLDA YGHVKLTDFG LCKEEIEGDQ
KTHTFCGTIE YMAPEILMRC GHGKAVDWWS LGALMFDMLT GGPPFTAENR RKTIDKILKG
RLTLPAYLSN EARDLIKKLL KRHVDTRLGA GLSDAEEIKS HAFFKTTDWN LVYARQLEAP
FKPNIENDED TSLFDARFTK MTPVDSPCET NFSLNGDNPF VGFTYVAPSV LEMMNKGGHG
GISVAHLASS MSRAGAAKSP RKPGDPETAS ILHGGHSNLF GHGPNSEAPQ AFGYGIGSQM
TTTTAGGAGI QQPYQSFSGG YPEDDAMDTS TPRASESRET TTGNGSTTTT RPSNVGSSAS
TPIPLPKRVM
