Q8BSK8 · KS6B1_MOUSE
- ProteinRibosomal protein S6 kinase beta-1
- GeneRps6kb1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids525 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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 (PubMed:11493700, PubMed:11500364, PubMed:15060135).
Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD (PubMed:11493700, PubMed:11500364).
Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex (By similarity).
Upon mitogenic stimulation, phosphorylation by the mechanistic target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation (By similarity).
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 (By similarity).
Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis (By similarity).
Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR (By similarity).
In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2 (PubMed:11500364).
Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling (By similarity).
Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (By similarity).
Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function (PubMed:11493700).
Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex (By similarity).
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 (By similarity).
Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1 (PubMed:18952604).
In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B (By similarity).
May be involved in cytoskeletal rearrangement through binding to neurabin (By similarity).
Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (By similarity).
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).
Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD (PubMed:11493700, PubMed:11500364).
Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex (By similarity).
Upon mitogenic stimulation, phosphorylation by the mechanistic target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation (By similarity).
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 (By similarity).
Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis (By similarity).
Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR (By similarity).
In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2 (PubMed:11500364).
Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling (By similarity).
Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (By similarity).
Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function (PubMed:11493700).
Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex (By similarity).
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 (By similarity).
Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1 (PubMed:18952604).
In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B (By similarity).
May be involved in cytoskeletal rearrangement through binding to neurabin (By similarity).
Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (By similarity).
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).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Activity regulation
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).
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRibosomal protein S6 kinase beta-1
- EC number
- Short namesS6K-beta-1; S6K1
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8BSK8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Colocalizes with URI1 at mitochondrion.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Impairment of body growth. Lethal in combination with Rps6kb2 deficiency.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 35 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000024344 | 1-525 | Ribosomal protein S6 kinase beta-1 | |||
Sequence: MRRRRRRDGFYLAPDFRHREAEDMAGVFDIDLDQPEDAGSEDELEEGGQLNESMDHGGVGPYELGMEHCEKFEISETSVNRGPEKIRPECFELLRVLGKGGYGKVFQVRKVTGANTGKIFAMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYLSGGELFMQLEREGIFMEDTACFYLAEISMALGHLHQKGIIYRDLKPENIMLNHQGHVKLTDFGLCKESIHDGTVTHTFCGTIEYMAPEILMRSGHNRAVDWWSLGALMYDMLTGAPPFTGENRKKTIDKILKCKLNLPPYLTQEARDLLKKLLKRNAASRLGAGPGDAGEVQAHPFFRHINWEELLARKVEPPFKPLLQSEEDVSQFDSKFTRQTPVDSPDDSTLSESANQVFLGFTYVAPSVLESVKEKFSFEPKIRSPRRFIGSPRTPVSPVKFSPGDFWGRGASASTANPQTPVEYPMETSGIEQMDVTVSGEASAPLPIRQPNSGPYKKQAFPMISKRPEHLRMNL | ||||||
Modified residue | 252 | Phosphothreonine; by PDPK1 | ||||
Sequence: T | ||||||
Modified residue | 394 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 412 | Phosphothreonine; by MTOR, NEK6 and NEK7 | ||||
Sequence: T | ||||||
Modified residue | 434 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 441 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 444 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 447 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 452 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 516 | N6-acetyllysine | ||||
Sequence: K |
Post-translational modification
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).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
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.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8BSK8 | Mdm2 P23804 | 2 | EBI-646423, EBI-641788 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif, compositional bias, region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 28-32 | TOS motif | ||||
Sequence: FDIDL | ||||||
Compositional bias | 32-48 | Acidic residues | ||||
Sequence: LDQPEDAGSEDELEEGG | ||||||
Region | 32-54 | Disordered | ||||
Sequence: LDQPEDAGSEDELEEGGQLNESM | ||||||
Domain | 91-352 | Protein kinase | ||||
Sequence: FELLRVLGKGGYGKVFQVRKVTGANTGKIFAMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYLSGGELFMQLEREGIFMEDTACFYLAEISMALGHLHQKGIIYRDLKPENIMLNHQGHVKLTDFGLCKESIHDGTVTHTFCGTIEYMAPEILMRSGHNRAVDWWSLGALMYDMLTGAPPFTGENRKKTIDKILKCKLNLPPYLTQEARDLLKKLLKRNAASRLGAGPGDAGEVQAHPFF | ||||||
Domain | 353-423 | AGC-kinase C-terminal | ||||
Sequence: RHINWEELLARKVEPPFKPLLQSEEDVSQFDSKFTRQTPVDSPDDSTLSESANQVFLGFTYVAPSVLESVK | ||||||
Region | 380-399 | Disordered | ||||
Sequence: SQFDSKFTRQTPVDSPDDST | ||||||
Region | 424-525 | Autoinhibitory domain | ||||
Sequence: EKFSFEPKIRSPRRFIGSPRTPVSPVKFSPGDFWGRGASASTANPQTPVEYPMETSGIEQMDVTVSGEASAPLPIRQPNSGPYKKQAFPMISKRPEHLRMNL |
Domain
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 similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative initiation.
Q8BSK8-1
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.
- NameAlpha I
- Length525
- Mass (Da)59,146
- Last updated2011-07-27 v2
- Checksum5B3C09F6BB365EE2
Q8BSK8-2
- NameAlpha II
- Differences from canonical
- 1-23: Missing
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_018840 | 1-23 | in isoform Alpha II | |||
Sequence: Missing | ||||||
Compositional bias | 32-48 | Acidic residues | ||||
Sequence: LDQPEDAGSEDELEEGG | ||||||
Sequence conflict | 60 | in Ref. 1; BAC28000 | ||||
Sequence: G → E |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK032724 EMBL· GenBank· DDBJ | BAC28000.1 EMBL· GenBank· DDBJ | mRNA | ||
AL604063 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH466556 EMBL· GenBank· DDBJ | EDL15788.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC038491 EMBL· GenBank· DDBJ | AAH38491.1 EMBL· GenBank· DDBJ | mRNA |