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Protein

Ribosomal protein S6 kinase beta-1

Gene

Rps6kb1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 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 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).By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei123 – 1231ATPPROSITE-ProRule annotation
Active sitei218 – 2181Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi97 – 1059ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: RGD
  • identical protein binding Source: IntAct
  • PDZ domain binding Source: RGD
  • peptide binding Source: RGD
  • protein kinase activity Source: RGD
  • protein phosphatase 2A binding Source: RGD
  • protein serine/threonine/tyrosine kinase activity Source: Ensembl
  • ribosomal protein S6 kinase activity Source: RGD

GO - Biological processi

  • aging Source: RGD
  • apoptotic process Source: UniProtKB-KW
  • behavioral fear response Source: Ensembl
  • cell migration Source: RGD
  • cellular response to growth factor stimulus Source: UniProtKB
  • cellular response to hormone stimulus Source: RGD
  • cellular response to organic cyclic compound Source: Ensembl
  • G1/S transition of mitotic cell cycle Source: Ensembl
  • germ cell development Source: Ensembl
  • intracellular signal transduction Source: GO_Central
  • long-term memory Source: RGD
  • negative regulation of extrinsic apoptotic signaling pathway Source: Ensembl
  • negative regulation of insulin receptor signaling pathway Source: UniProtKB
  • positive regulation of mitotic cell cycle Source: Ensembl
  • positive regulation of skeletal muscle tissue growth Source: RGD
  • positive regulation of smooth muscle cell migration Source: RGD
  • positive regulation of smooth muscle cell proliferation Source: RGD
  • positive regulation of translational initiation Source: Ensembl
  • protein kinase B signaling Source: Ensembl
  • protein phosphorylation Source: RGD
  • regulation of glucose import Source: UniProtKB
  • response to amino acid Source: RGD
  • response to drug Source: RGD
  • response to electrical stimulus involved in regulation of muscle adaptation Source: RGD
  • response to ethanol Source: RGD
  • response to glucagon Source: RGD
  • response to glucocorticoid Source: RGD
  • response to glucose Source: RGD
  • response to heat Source: RGD
  • response to insulin Source: UniProtKB
  • response to leucine Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to mechanical stimulus Source: RGD
  • response to nutrient Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to organic substance Source: RGD
  • response to organonitrogen compound Source: RGD
  • response to peptide hormone Source: RGD
  • response to testosterone Source: RGD
  • response to toxic substance Source: RGD
  • response to tumor necrosis factor Source: UniProtKB
  • response to wounding Source: RGD
  • skeletal muscle atrophy Source: RGD
  • skeletal muscle contraction Source: RGD
  • TOR signaling Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle, Translation regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 5301.
ReactomeiR-RNO-166208. mTORC1-mediated signalling.
SABIO-RKP67999.

Names & Taxonomyi

Protein namesi
Recommended name:
Ribosomal protein S6 kinase beta-1 (EC:2.7.11.1)
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
p70 ribosomal S6 kinase alpha
Short name:
p70 S6 kinase alpha
Short name:
p70 S6K-alpha
Short name:
p70 S6KA
Gene namesi
Name:Rps6kb1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi620683. Rps6kb1.

Subcellular locationi

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • cell surface Source: RGD
  • cytosol Source: RGD
  • mitochondrial outer membrane Source: UniProtKB-SubCell
  • mitochondrion Source: UniProtKB
  • neuron projection Source: UniProtKB-SubCell
  • nucleoplasm Source: Ensembl
  • nucleus Source: RGD
  • perinuclear region of cytoplasm Source: RGD
  • synapse Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi28 – 325Missing : Almost complete loss of activity.
Mutagenesisi28 – 281F → A: Complete loss of activity. Abolishes interaction with RPTOR. Reduces phosphorylation. Loss of phosphorylation at T-412 and T-444. 2 Publications
Mutagenesisi29 – 291D → A: Almost complete loss of activity; when associated with A-31. 1 Publication
Mutagenesisi30 – 301I → A: Almost complete loss of activity; when associated with A-32. 1 Publication
Mutagenesisi31 – 311D → A: Almost complete loss of activity; when associated with A-29. 1 Publication
Mutagenesisi32 – 321L → A: Almost complete loss of activity; when associated with A-30. 1 Publication
Mutagenesisi123 – 1231K → M: Loss of activity towards ribosomal protein S6. 2 Publications
Mutagenesisi123 – 1231K → R: Loss of activity. 2 Publications
Mutagenesisi252 – 2521T → A: Loss of activity towards ribosomal protein S6 and reduced phosphorylation at Thr-412. 1 Publication
Mutagenesisi256 – 2561T → A: Loss of activity towards ribosomal protein S6 without effect on phosphorylation status. 1 Publication
Mutagenesisi394 – 3941S → A or D: Loss of activity towards ribosomal protein S6 and reduces phosphorylation at Thr-252. 1 Publication
Mutagenesisi412 – 4121T → A: Loss of activity towards ribosomal protein S6 and loss of phosphorylation at Thr-252. 1 Publication
Mutagenesisi412 – 4121T → E: Mimics phosphorylation. Constitutive active. No effect on activity towards ribosomal protein S6. 1 Publication
Mutagenesisi434 – 4341S → D: No effect on sensitivity to wortmannin and rapamycin; when associated with D-441, D-444 and D-447. 1 Publication
Mutagenesisi441 – 4411S → D: No effect on sensitivity to wortmannin and rapamycin; when associated with D-434, D-D-444 and D-447. 1 Publication
Mutagenesisi444 – 4441T → D: No effect on sensitivity to wortmannin and rapamycin; when associated with D-434, D-441, and D-447. 1 Publication
Mutagenesisi447 – 4471S → D: No effect on sensitivity to wortmannin and rapamycin; when associated with D-434, D-441 and D-444. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 525525Ribosomal protein S6 kinase beta-1PRO_0000024348Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei252 – 2521Phosphothreonine; by PDPK11 Publication
Modified residuei394 – 3941Phosphoserine1 Publication
Modified residuei412 – 4121Phosphothreonine; by MTOR, NEK6 and NEK73 Publications
Modified residuei434 – 4341Phosphoserine1 Publication
Modified residuei441 – 4411PhosphoserineBy similarity
Modified residuei444 – 4441Phosphothreonine1 Publication
Modified residuei447 – 4471PhosphoserineCombined sources1 Publication
Modified residuei452 – 4521PhosphoserineCombined sources
Modified residuei516 – 5161N6-acetyllysine1 Publication

Post-translational modificationi

Dephosphorylation by PPP1CC at Thr-412 in mitochondrion (By similarity). 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.By similarity3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP67999.
PRIDEiP67999.

PTM databases

iPTMnetiP67999.
PhosphoSiteiP67999.

Expressioni

Tissue specificityi

Brain.

Gene expression databases

BgeeiENSRNOG00000003919.
GenevisibleiP67999. RN.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-2639458,EBI-2639458
Ppp1r9aO358674EBI-2639458,EBI-7092421
RPTORQ8N1222EBI-2639458,EBI-1567928From a different organism.

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • PDZ domain binding Source: RGD
  • protein phosphatase 2A binding Source: RGD

Protein-protein interaction databases

BioGridi249866. 3 interactions.
IntActiP67999. 6 interactions.
MINTiMINT-1212774.
STRINGi10116.ENSRNOP00000005226.

Structurei

3D structure databases

ProteinModelPortaliP67999.
SMRiP67999. Positions 79-376.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini91 – 352262Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini353 – 42371AGC-kinase C-terminalAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni424 – 525102Autoinhibitory domainAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi28 – 325TOS motif

Domaini

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

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00820000126961.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiP67999.
KOiK04688.
OMAiHGGVGQY.
OrthoDBiEOG091G05Z7.
PhylomeDBiP67999.
TreeFamiTF313438.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016238. Ribosomal_S6_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000605. Ribsml_S6_kin_1. 1 hit.
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform Alpha I (identifier: P67999-1) [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 YPAPDFRHRE 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 IEQMDVTTSG EASAPLPIRQ
510 520
PNSGPYKKQA FPMISKRPEH LRMNL
Length:525
Mass (Da):59,132
Last modified:October 11, 2004 - v1
Checksum:i013BA13EFB3508D7
GO
Isoform Alpha II (identifier: P67999-2) [UniParc]FASTAAdd to basket

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

Show »
Length:502
Mass (Da):56,159
Checksum:i00E6CF3FCAADDDB6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti367 – 3671P → R in AAA42104 (PubMed:2236064).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2323Missing in isoform Alpha II. CuratedVSP_018842Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M58340 mRNA. Translation: AAA42104.1.
M57428 mRNA. Translation: AAA42103.1.
PIRiA36484. TVRTK6.
RefSeqiNP_114191.1. NM_031985.1.
UniGeneiRn.4042.

Genome annotation databases

EnsembliENSRNOT00000005226; ENSRNOP00000005226; ENSRNOG00000003919. [P67999-1]
GeneIDi83840.
KEGGirno:83840.

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M58340 mRNA. Translation: AAA42104.1.
M57428 mRNA. Translation: AAA42103.1.
PIRiA36484. TVRTK6.
RefSeqiNP_114191.1. NM_031985.1.
UniGeneiRn.4042.

3D structure databases

ProteinModelPortaliP67999.
SMRiP67999. Positions 79-376.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249866. 3 interactions.
IntActiP67999. 6 interactions.
MINTiMINT-1212774.
STRINGi10116.ENSRNOP00000005226.

PTM databases

iPTMnetiP67999.
PhosphoSiteiP67999.

Proteomic databases

PaxDbiP67999.
PRIDEiP67999.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000005226; ENSRNOP00000005226; ENSRNOG00000003919. [P67999-1]
GeneIDi83840.
KEGGirno:83840.

Organism-specific databases

CTDi6198.
RGDi620683. Rps6kb1.

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00820000126961.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiP67999.
KOiK04688.
OMAiHGGVGQY.
OrthoDBiEOG091G05Z7.
PhylomeDBiP67999.
TreeFamiTF313438.

Enzyme and pathway databases

BRENDAi2.7.11.1. 5301.
ReactomeiR-RNO-166208. mTORC1-mediated signalling.
SABIO-RKP67999.

Miscellaneous databases

PROiP67999.

Gene expression databases

BgeeiENSRNOG00000003919.
GenevisibleiP67999. RN.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016238. Ribosomal_S6_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000605. Ribsml_S6_kin_1. 1 hit.
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKS6B1_RAT
AccessioniPrimary (citable) accession number: P67999
Secondary accession number(s): P21425
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: September 7, 2016
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.