InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Rps6kb1

Summary

InnateDB Protein

IDBP-541289.3

Last Modified

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

Gene Symbol

Rps6kb1

Protein Name

ribosomal protein S6 kinase, polypeptide 1

Synonyms

2610318I15Rik; 4732464A07Rik; 70kDa; AA959758; AI256796; AI314060; p70/85s6k; p70s6k; S6K1;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000119715

InnateDB Gene

IDBG-206895 (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:0000269PubMed:11493700}. 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 20 experimentally validated interaction(s) in this database.
They are also associated with 60 interaction(s) predicted by orthology.

Experimentally validated
Total	20 [view]
Protein-Protein	20 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	60 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004711	ribosomal protein S6 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:0016772	transferase activity, transferring phosphorus-containing groups
GO:0042277	peptide binding

Biological Process

GO:0000082	G1/S transition of mitotic cell cycle
GO:0003009	skeletal muscle contraction
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007165	signal transduction
GO:0007281	germ cell development
GO:0007568	aging
GO:0007584	response to nutrient
GO:0007616	long-term memory
GO:0009408	response to heat
GO:0009611	response to wounding
GO:0009612	response to mechanical stimulus
GO:0009636	response to toxic substance
GO:0009749	response to glucose
GO:0010033	response to organic substance
GO:0014070	response to organic cyclic compound
GO:0014732	skeletal muscle atrophy
GO:0014878	response to electrical stimulus involved in regulation of muscle adaptation
GO:0014911	positive regulation of smooth muscle cell migration
GO:0016477	cell migration
GO:0031929	TOR signaling
GO:0032496	response to lipopolysaccharide
GO:0032868	response to insulin
GO:0032870	cellular response to hormone stimulus
GO:0033574	response to testosterone
GO:0033762	response to glucagon
GO:0034612	response to tumor necrosis factor
GO:0042493	response to drug
GO:0043066	negative regulation of apoptotic process
GO:0043200	response to amino acid
GO:0043201	response to leucine
GO:0043434	response to peptide hormone
GO:0043491	protein kinase B signaling
GO:0045471	response to ethanol
GO:0045727	positive regulation of translation
GO:0045931	positive regulation of mitotic cell cycle
GO:0045948	positive regulation of translational initiation
GO:0046324	regulation of glucose import
GO:0046627	negative regulation of insulin receptor signaling pathway
GO:0048633	positive regulation of skeletal muscle tissue growth
GO:0048661	positive regulation of smooth muscle cell proliferation
GO:0051384	response to glucocorticoid
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:0009986	cell surface
GO:0030054	cell junction
GO:0043005	neuron projection
GO:0045202	synapse
GO:0048471	perinuclear region of cytoplasm

Protein Structure and Domains

PDB ID

MGI:1270849

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