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Protein

Ribosomal protein S6 kinase beta-1

Gene

Rps6kb1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 pre-initiation 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 RMP leading to dissociation of a RMP: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. Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (By similarity) (PubMed:11493700, PubMed:11500364, PubMed:15060135, PubMed:18952604). Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition (PubMed:28178239).By similarity5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Activity regulationi

Activation requires multiple phosphorylation events on serine/threonine residues. Activation appears to be first mediated by phosphorylation of multiple sites in the autoinhibitory domain, which facilitates phosphorylation at Thr-412, disrupting the autoinhibitory mechanism and allowing phosphorylation of Thr-252 by PDPK1. The active conformation of the kinase is believed to be stabilized by a mechanism involving three conserved phosphorylation sites located in the kinase domain activation loop (Thr-252) and in the AGC-kinase C-terminal domain (Ser-394 in the middle of the tail/linker region and Thr-412 within a hydrophobic motif at its end). Activated by mTORC1; isoform Alpha I and isoform Alpha II are sensitive to rapamycin, which inhibits activating phosphorylation at Thr-412. Activated by PDPK1 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei123ATPPROSITE-ProRule annotation1
Active sitei218Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi97 – 105ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Cell cycle, Translation regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-166208 mTORC1-mediated signalling

Names & Taxonomyi

Protein namesi
Recommended name:
Ribosomal protein S6 kinase beta-1 (EC:2.7.11.11 Publication)
Short name:
S6K-beta-1
Short name:
S6K1
Alternative name(s):
70 kDa ribosomal protein S6 kinase 1
Short name:
P70S6K1
Short name:
p70-S6K 1
Ribosomal protein S6 kinase I
Short name:
S6K
p70 ribosomal S6 kinase alpha
Short name:
p70 S6 kinase alpha
Short name:
p70 S6K-alpha
Short name:
p70 S6KA
Gene namesi
Name:Rps6kb1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1270849 Rps6kb1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cytoplasm, Membrane, Mitochondrion, Mitochondrion outer membrane, Synapse, Synaptosome

Pathology & Biotechi

Disruption phenotypei

Impairment of body growth. Lethal in combination with Rps6kb2 deficiency.1 Publication

Chemistry databases

ChEMBLiCHEMBL5429

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000243441 – 525Ribosomal protein S6 kinase beta-1Add BLAST525

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei252Phosphothreonine; by PDPK1By similarity1
Modified residuei394PhosphoserineBy similarity1
Modified residuei412Phosphothreonine; by MTOR, NEK6 and NEK7By similarity1
Modified residuei434PhosphoserineBy similarity1
Modified residuei441PhosphoserineBy similarity1
Modified residuei444PhosphothreonineBy similarity1
Modified residuei447PhosphoserineCombined sources1
Modified residuei452PhosphoserineCombined sources1
Modified residuei516N6-acetyllysineBy similarity1

Post-translational modificationi

Phosphorylation at Thr-412 is regulated by mTORC1. The phosphorylation at this site is maintained by an agonist-dependent autophosphorylation mechanism. Activated by phosphorylation at Thr-252 by PDPK1. Dephosphorylation by PPP1CC at Thr-412 in mitochondrion (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ8BSK8
PRIDEiQ8BSK8

PTM databases

iPTMnetiQ8BSK8
PhosphoSitePlusiQ8BSK8

Expressioni

Gene expression databases

BgeeiENSMUSG00000020516 Expressed in 297 organ(s), highest expression level in lacrimal gland
CleanExiMM_RPS6KB1
ExpressionAtlasiQ8BSK8 baseline and differential
GenevisibleiQ8BSK8 MM

Interactioni

Subunit structurei

Interacts with PPP1R9A/neurabin-1. Interacts with RPTOR. Interacts with IRS1. Interacts with EIF3B and EIF3C. Interacts with TRAF4. Interacts with POLDIP3. Interacts (via N-terminus) with IER5.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Mdm2P238042EBI-646423,EBI-641788

GO - Molecular functioni

Protein-protein interaction databases

BioGridi215408, 11 interactors
IntActiQ8BSK8, 6 interactors
MINTiQ8BSK8
STRINGi10090.ENSMUSP00000119715

Structurei

3D structure databases

ProteinModelPortaliQ8BSK8
SMRiQ8BSK8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini91 – 352Protein kinasePROSITE-ProRule annotationAdd BLAST262
Domaini353 – 423AGC-kinase C-terminalAdd BLAST71

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni424 – 525Autoinhibitory domainAdd BLAST102

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi28 – 32TOS motif5

Domaini

The autoinhibitory domain is believed to block phosphorylation within the AGC-kinase C-terminal domain and the activation loop.By similarity
The TOS (TOR signaling) motif is essential for activation by mTORC1.By similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0598 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00930000150811
HOGENOMiHOG000233033
HOVERGENiHBG108317
InParanoidiQ8BSK8
KOiK04688
OMAiRSPRKFP
OrthoDBiEOG091G05Z7
TreeFamiTF313438

Family and domain databases

InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR011009 Kinase-like_dom_sf
IPR017892 Pkinase_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR016238 Ribosomal_S6_kinase
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF00433 Pkinase_C, 1 hit
PIRSFiPIRSF000605 Ribsml_S6_kin_1, 1 hit
SMARTiView protein in SMART
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform Alpha I (identifier: Q8BSK8-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MRRRRRRDGF YLAPDFRHRE AEDMAGVFDI DLDQPEDAGS EDELEEGGQL
60 70 80 90 100
NESMDHGGVG PYELGMEHCE KFEISETSVN RGPEKIRPEC FELLRVLGKG
110 120 130 140 150
GYGKVFQVRK VTGANTGKIF AMKVLKKAMI VRNAKDTAHT KAERNILEEV
160 170 180 190 200
KHPFIVDLIY AFQTGGKLYL ILEYLSGGEL FMQLEREGIF MEDTACFYLA
210 220 230 240 250
EISMALGHLH QKGIIYRDLK PENIMLNHQG HVKLTDFGLC KESIHDGTVT
260 270 280 290 300
HTFCGTIEYM APEILMRSGH NRAVDWWSLG ALMYDMLTGA PPFTGENRKK
310 320 330 340 350
TIDKILKCKL NLPPYLTQEA RDLLKKLLKR NAASRLGAGP GDAGEVQAHP
360 370 380 390 400
FFRHINWEEL LARKVEPPFK PLLQSEEDVS QFDSKFTRQT PVDSPDDSTL
410 420 430 440 450
SESANQVFLG FTYVAPSVLE SVKEKFSFEP KIRSPRRFIG SPRTPVSPVK
460 470 480 490 500
FSPGDFWGRG ASASTANPQT PVEYPMETSG IEQMDVTVSG EASAPLPIRQ
510 520
PNSGPYKKQA FPMISKRPEH LRMNL
Length:525
Mass (Da):59,146
Last modified:July 27, 2011 - v2
Checksum:i5B3C09F6BB365EE2
GO
Isoform Alpha II (identifier: Q8BSK8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: Missing.

Show »
Length:502
Mass (Da):56,157
Checksum:i5AE6CF3FCAAE8B83
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q8C3J7Q8C3J7_MOUSE
Ribosomal protein S6 kinase beta-1
Rps6kb1
316Annotation score:
Q5SWG2Q5SWG2_MOUSE
Ribosomal protein S6 kinase beta-1
Rps6kb1
74Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti60G → E in BAC28000 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0188401 – 23Missing in isoform Alpha II. CuratedAdd BLAST23

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK032724 mRNA Translation: BAC28000.1
AL604063 Genomic DNA Translation: CAI25799.1
CH466556 Genomic DNA Translation: EDL15788.1
BC038491 mRNA Translation: AAH38491.1
CCDSiCCDS48875.1 [Q8BSK8-1]
RefSeqiNP_001107806.1, NM_001114334.1 [Q8BSK8-1]
UniGeneiMm.394280
Mm.446624
Mm.479484

Genome annotation databases

EnsembliENSMUST00000154617; ENSMUSP00000119715; ENSMUSG00000020516 [Q8BSK8-1]
GeneIDi72508
KEGGimmu:72508
UCSCiuc007ksn.2 mouse [Q8BSK8-1]

Keywords - Coding sequence diversityi

Alternative initiation

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK032724 mRNA Translation: BAC28000.1
AL604063 Genomic DNA Translation: CAI25799.1
CH466556 Genomic DNA Translation: EDL15788.1
BC038491 mRNA Translation: AAH38491.1
CCDSiCCDS48875.1 [Q8BSK8-1]
RefSeqiNP_001107806.1, NM_001114334.1 [Q8BSK8-1]
UniGeneiMm.394280
Mm.446624
Mm.479484

3D structure databases

ProteinModelPortaliQ8BSK8
SMRiQ8BSK8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi215408, 11 interactors
IntActiQ8BSK8, 6 interactors
MINTiQ8BSK8
STRINGi10090.ENSMUSP00000119715

Chemistry databases

ChEMBLiCHEMBL5429

PTM databases

iPTMnetiQ8BSK8
PhosphoSitePlusiQ8BSK8

Proteomic databases

PaxDbiQ8BSK8
PRIDEiQ8BSK8

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000154617; ENSMUSP00000119715; ENSMUSG00000020516 [Q8BSK8-1]
GeneIDi72508
KEGGimmu:72508
UCSCiuc007ksn.2 mouse [Q8BSK8-1]

Organism-specific databases

CTDi6198
MGIiMGI:1270849 Rps6kb1

Phylogenomic databases

eggNOGiKOG0598 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00930000150811
HOGENOMiHOG000233033
HOVERGENiHBG108317
InParanoidiQ8BSK8
KOiK04688
OMAiRSPRKFP
OrthoDBiEOG091G05Z7
TreeFamiTF313438

Enzyme and pathway databases

ReactomeiR-MMU-166208 mTORC1-mediated signalling

Miscellaneous databases

ChiTaRSiRps6kb1 mouse
PROiPR:Q8BSK8
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020516 Expressed in 297 organ(s), highest expression level in lacrimal gland
CleanExiMM_RPS6KB1
ExpressionAtlasiQ8BSK8 baseline and differential
GenevisibleiQ8BSK8 MM

Family and domain databases

InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR011009 Kinase-like_dom_sf
IPR017892 Pkinase_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR016238 Ribosomal_S6_kinase
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF00433 Pkinase_C, 1 hit
PIRSFiPIRSF000605 Ribsml_S6_kin_1, 1 hit
SMARTiView protein in SMART
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKS6B1_MOUSE
AccessioniPrimary (citable) accession number: Q8BSK8
Secondary accession number(s): Q5SWG1, Q8CHX0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 153 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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Main funding by: National Institutes of Health

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