InnateDB: Systems Biology of the Innate Immune Response

Bos taurus Protein: RPS6KB1

Summary

InnateDB Protein

IDBP-681217.2

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

RPS6KB1

Protein Name

Ribosomal protein S6 kinase beta-1

Synonyms

S6K1;

Species

Bos taurus

Ensembl Protein

ENSBTAP00000022415

InnateDB Gene

IDBG-629797 (RPS6KB1)

Protein Structure

UniProt Annotation

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. 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). {ECO:0000250}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Cell junction, synapse, synaptosome {ECO:0000250}. Mitochondrion outer membrane {ECO:0000250}. Mitochondrion {ECO:0000250}. Note=Colocalizes with URI1 at mitochondrion. {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.
They are also associated with 59 interaction(s) predicted by orthology.

Predicted by orthology
Total	59 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000166	nucleotide binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004712	protein serine/threonine/tyrosine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016301	kinase activity
GO:0016740	transferase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0000082	G1/S transition of mitotic cell cycle
GO:0006417	regulation of translation
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007049	cell cycle
GO:0007165	signal transduction
GO:0007281	germ cell development
GO:0016310	phosphorylation
GO:0031929	TOR signaling
GO:0043066	negative regulation of apoptotic process
GO:0043491	protein kinase B signaling
GO:0045727	positive regulation of translation
GO:0045931	positive regulation of mitotic cell cycle
GO:0045948	positive regulation of translational initiation
GO:0046627	negative regulation of insulin receptor signaling pathway
GO:0071363	cellular response to growth factor stimulus
GO:2001237	negative regulation of extrinsic apoptotic signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005741	mitochondrial outer membrane
GO:0016020	membrane
GO:0030054	cell junction
GO:0043005	neuron projection
GO:0045202	synapse

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR000961 AGC-kinase, C-terminal
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR016238 Ribosomal protein S6 kinase
IPR017892 Protein kinase, C-terminal
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF00433

PRINTS

PR00109

PIRSF

PIRSF000605

SMART

SM00133
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References