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Protein

Ribosomal protein S6 kinase beta-1

Gene

RPS6KB1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Inactivated by binding to URI1. 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

GO - Biological processi

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

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
Gene namesi
Name:RPS6KB1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 527527Ribosomal protein S6 kinase beta-1PRO_0000248285Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei252 – 2521Phosphothreonine; by PDPK1By similarity
Modified residuei394 – 3941PhosphoserineBy similarity
Modified residuei412 – 4121Phosphothreonine; by MTOR, NEK6 and NEK7By similarity
Modified residuei434 – 4341PhosphoserineBy similarity
Modified residuei441 – 4411PhosphoserineBy similarity
Modified residuei444 – 4441PhosphothreonineBy similarity
Modified residuei447 – 4471PhosphoserineBy similarity
Modified residuei452 – 4521PhosphoserineBy similarity
Modified residuei516 – 5161N6-acetyllysineBy similarity

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

PaxDbiQ6TJY3.
PRIDEiQ6TJY3.

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

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000022415.

Structurei

3D structure databases

ProteinModelPortaliQ6TJY3.
SMRiQ6TJY3. 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 – 527104Autoinhibitory 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.By similarity
The TOS (TOR signaling) motif is essential for activation by mTORC1.By similarity

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ6TJY3.
KOiK04688.

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]

Sequencei

Sequence statusi: Complete.

Q6TJY3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRRRRRRDGF YPAPDFRDRE 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 PVDSPDDSAL
410 420 430 440 450
SESANQVFLG FTYVAPSVLE SVKEKFSFEP KIRSPRRFIG SPRTPVSPVK
460 470 480 490 500
FSPGDFWGRG ASASTANPQT PVEYPMETSG IEQMDVTMSG EASAPLPIRQ
510 520
PNSGPYKKQA FPMISKRPEH LRMNLEL
Length:527
Mass (Da):59,352
Last modified:July 5, 2004 - v1
Checksum:i094D904BA13CD1DF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY396564 mRNA. Translation: AAR01025.1.
RefSeqiNP_991385.1. NM_205816.1.
UniGeneiBt.41950.

Genome annotation databases

GeneIDi404181.
KEGGibta:404181.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY396564 mRNA. Translation: AAR01025.1.
RefSeqiNP_991385.1. NM_205816.1.
UniGeneiBt.41950.

3D structure databases

ProteinModelPortaliQ6TJY3.
SMRiQ6TJY3. Positions 79-376.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000022415.

Proteomic databases

PaxDbiQ6TJY3.
PRIDEiQ6TJY3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi404181.
KEGGibta:404181.

Organism-specific databases

CTDi6198.

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ6TJY3.
KOiK04688.

Miscellaneous databases

NextBioi20817610.

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...

Publicationsi

  1. Arvisais E.W., Davis J.S.
    Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiKS6B1_BOVIN
AccessioniPrimary (citable) accession number: Q6TJY3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: July 5, 2004
Last modified: May 11, 2016
This is version 97 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, 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.