KS6B1_BOVIN
ID KS6B1_BOVIN Reviewed; 527 AA.
AC Q6TJY3;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Ribosomal protein S6 kinase beta-1;
DE Short=S6K-beta-1;
DE Short=S6K1;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P23443};
DE AltName: Full=70 kDa ribosomal protein S6 kinase 1;
DE Short=P70S6K1;
DE Short=p70-S6K 1;
GN Name=RPS6KB1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Arvisais E.W., Davis J.S.;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
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 URI1 leading to dissociation of
CC a URI1-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. Following
CC activation by mTORC1, phosphorylates EPRS and thereby plays a key role
CC in fatty acid uptake by adipocytes and also most probably in
CC interferon-gamma-induced translation inhibition.
CC {ECO:0000250|UniProtKB:P23443}.
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:0000250|UniProtKB:P23443};
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:0000250|UniProtKB:P23443};
CC -!- ACTIVITY REGULATION: Inactivated by binding to URI1. Activation
CC requires multiple phosphorylation events on serine/threonine residues.
CC Activation appears to be first mediated by phosphorylation of multiple
CC sites in the autoinhibitory domain, which facilitates phosphorylation
CC at Thr-412, disrupting the autoinhibitory mechanism and allowing
CC phosphorylation of Thr-252 by PDPK1. The active conformation of the
CC kinase is believed to be stabilized by a mechanism involving three
CC conserved phosphorylation sites located in the kinase domain activation
CC loop (Thr-252) and in the AGC-kinase C-terminal domain (Ser-394 in the
CC middle of the tail/linker region and Thr-412 within a hydrophobic motif
CC at its end). Activated by mTORC1; isoform Alpha I and isoform Alpha II
CC are sensitive to rapamycin, which inhibits activating phosphorylation
CC at Thr-412. Activated by PDPK1 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PPP1R9A/neurabin-1. Interacts with RPTOR.
CC Interacts with IRS1. Interacts with EIF3B and EIF3C. Interacts with
CC TRAF4. Interacts with POLDIP3. Interacts (via N-terminus) with IER5.
CC {ECO:0000250|UniProtKB:P23443, ECO:0000250|UniProtKB:P67999}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Synapse, synaptosome
CC {ECO:0000250}. Mitochondrion outer membrane {ECO:0000250}.
CC Mitochondrion {ECO:0000250}. Note=Colocalizes with URI1 at
CC mitochondrion. {ECO:0000250}.
CC -!- DOMAIN: The autoinhibitory domain is believed to block phosphorylation
CC within the AGC-kinase C-terminal domain and the activation loop.
CC {ECO:0000250}.
CC -!- DOMAIN: The TOS (TOR signaling) motif is essential for activation by
CC mTORC1. {ECO:0000250}.
CC -!- PTM: 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. Dephosphorylation by PPP1CC at Thr-412 in mitochondrion (By
CC similarity). {ECO:0000250}.
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; AY396564; AAR01025.1; -; mRNA.
DR RefSeq; NP_991385.1; NM_205816.1.
DR AlphaFoldDB; Q6TJY3; -.
DR SMR; Q6TJY3; -.
DR STRING; 9913.ENSBTAP00000022415; -.
DR PaxDb; Q6TJY3; -.
DR PRIDE; Q6TJY3; -.
DR GeneID; 404181; -.
DR KEGG; bta:404181; -.
DR CTD; 6198; -.
DR eggNOG; KOG0598; Eukaryota.
DR HOGENOM; CLU_000288_63_5_1; -.
DR InParanoid; Q6TJY3; -.
DR OrthoDB; 1132245at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; ISS:UniProtKB.
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:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:AgBase.
DR GO; GO:0044539; P:long-chain fatty acid import into cell; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IDA:AgBase.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Acetylation; Apoptosis; ATP-binding; Cell cycle; Cytoplasm; Kinase;
KW Membrane; Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Synapse; Synaptosome; Transferase; Translation regulation.
FT CHAIN 1..527
FT /note="Ribosomal protein S6 kinase beta-1"
FT /id="PRO_0000248285"
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 1..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 424..527
FT /note="Autoinhibitory domain"
FT MOTIF 28..32
FT /note="TOS motif"
FT COMPBIAS 8..26
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 27..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:0000250|UniProtKB:P23443"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23443"
FT MOD_RES 412
FT /note="Phosphothreonine; by MTOR, NEK6 and NEK7"
FT /evidence="ECO:0000250|UniProtKB:P67999"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P67999"
FT MOD_RES 441
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23443"
FT MOD_RES 444
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P23443"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23443"
FT MOD_RES 452
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23443"
FT MOD_RES 516
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P67999"
SQ SEQUENCE 527 AA; 59352 MW; 094D904BA13CD1DF CRC64;
MRRRRRRDGF YPAPDFRDRE 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 PVDSPDDSAL SESANQVFLG FTYVAPSVLE
SVKEKFSFEP KIRSPRRFIG SPRTPVSPVK FSPGDFWGRG ASASTANPQT PVEYPMETSG
IEQMDVTMSG EASAPLPIRQ PNSGPYKKQA FPMISKRPEH LRMNLEL
