Rps6kb1
entrez
83840
canonical
uniprot
P67999
canonical
ensembl
ENSRNOG00000003919
resolver
ensembl
ENSRNOG00055030559
resolver
ensembl
ENSRNOG00060019524
resolver
ensembl
ENSRNOG00065018112
resolver
ensp
ENSRNOP00000078345
resolver
ensp
ENSRNOP00000102550
resolver
ensp
ENSRNOP00000111651
resolver
enst
ENSRNOT00000157804
resolver
genesymbol
Rps6kb1
resolver
uniprot
A0ABK0LM96
resolver
uniprot
P21425
resolver
uniprot_entry
A0ABK0LM96_RAT
resolver
uniprot_entry
KS6B1_RAT
resolver
uniprot_sec
P21425
resolver
activity_regulation
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). {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MRRRRRRDGFYPAPDFRHREAEDMAGVFDIDLDQPEDAGSEDELEEGGQLNESMDHGGVGPYELGMEHCEKFEISETSVNRGPEKIRPECFELLRVLGKGGYGKVFQVRKVTGANTGKIFAMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYLSGGELFMQLEREGIFMEDTACFYLAEISMALGHLHQKGIIYRDLKPENIMLNHQGHVKLTDFGLCKESIHDGTVTHTFCGTIEYMAPEILMRSGHNRAVDWWSLGALMYDMLTGAPPFTGENRKKTIDKILKCKLNLPPYLTQEARDLLKKLLKRNAASRLGAGPGDAGEVQAHPFFRHINWEELLARKVEPPFKPLLQSEEDVSQFDSKFTRQTPVDSPDDSTLSESANQVFLGFTYVAPSVLESVKEKFSFEPKIRSPRRFIGSPRTPVSPVKFSPGDFWGRGASASTANPQTPVEYPMETSGIEQMDVTTSGEASAPLPIRQPNSGPYKKQAFPMISKRPEHLRMNL
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
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:8524831). Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD (By similarity). 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 (By similarity). Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating MAPKAP1/SIN1, MTOR and 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 (By similarity). 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-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1 (By similarity). In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B (By similarity). May be involved in cytoskeletal rearrangement through binding to neurabin (PubMed:9653190). 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). {ECO:0000250|UniProtKB:P23443, ECO:0000250|UniProtKB:Q8BSK8, ECO:0000269|PubMed:28178239, ECO:0000269|PubMed:8524831, ECO:0000269|PubMed:9653190}.
uniprot
proteins
mass_dalton
59132
uniprot
proteins
mutagenesis
MUTAGEN 28..32; /note="Missing: Almost complete loss of activity."; /evidence="ECO:0000269|PubMed:9653190"; MUTAGEN 28; /note="F->A: Complete loss of activity. Abolishes interaction with RPTOR. Reduces phosphorylation. Loss of phosphorylation at T-412 and T-444."; /evidence="ECO:0000269|PubMed:11967149, ECO:0000269|PubMed:12604610"; MUTAGEN 29; /note="D->A: Almost complete loss of activity; when associated with A-31."; /evidence="ECO:0000269|PubMed:11967149"; MUTAGEN 30; /note="I->A: Almost complete loss of activity; when associated with A-32."; /evidence="ECO:0000269|PubMed:11967149"; MUTAGEN 31; /note="D->A: Almost complete loss of activity; when associated with A-29."; /evidence="ECO:0000269|PubMed:11967149"; MUTAGEN 32; /note="L->A: Almost complete loss of activity; when associated with A-30."; /evidence="ECO:0000269|PubMed:11967149"; MUTAGEN 123; /note="K->M: Loss of activity towards ribosomal protein S6."; /evidence="ECO:0000269|PubMed:8524831, ECO:0000269|PubMed:9632736"; MUTAGEN 123; /note="K->R: Loss of activity."; /evidence="ECO:0000269|PubMed:8524831, ECO:0000269|PubMed:9632736"; MUTAGEN 252; /note="T->A: Loss of activity towards ribosomal protein S6 and reduced phosphorylation at Thr-412."; /evidence="ECO:0000269|PubMed:9632736"; MUTAGEN 256; /note="T->A: Loss of activity towards ribosomal protein S6 without effect on phosphorylation status."; /evidence="ECO:0000269|PubMed:9632736"; MUTAGEN 394; /note="S->A,D: Loss of activity towards ribosomal protein S6 and reduces phosphorylation at Thr-252."; /evidence="ECO:0000269|PubMed:9632736"; MUTAGEN 412; /note="T->A: Loss of activity towards ribosomal protein S6 and loss of phosphorylation at Thr-252."; /evidence="ECO:0000269|PubMed:9632736"; MUTAGEN 412; /note="T->E: Mimics phosphorylation. Constitutive active. No effect on activity towards ribosomal protein S6."; /evidence="ECO:0000269|PubMed:9632736"; MUTAGEN 434; /note="S->D: No effect on sensitivity to wortmannin and rapamycin; when associated with D-441, D-444 and D-447."; /evidence="ECO:0000269|PubMed:8524831"; MUTAGEN 441; /note="S->D: No effect on sensitivity to wortmannin and rapamycin; when associated with D-434, D-D-444 and D-447."; /evidence="ECO:0000269|PubMed:8524831"; MUTAGEN 444; /note="T->D: No effect on sensitivity to wortmannin and rapamycin; when associated with D-434, D-441, and D-447."; /evidence="ECO:0000269|PubMed:8524831"; MUTAGEN 447; /note="S->D: No effect on sensitivity to wortmannin and rapamycin; when associated with D-434, D-441 and D-444."; /evidence="ECO:0000269|PubMed:8524831
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000250, ECO:0000269|PubMed:11516946, ECO:0000269|PubMed:9465032, ECO:0000269|PubMed:9632736}.
uniprot
proteins
protein_family
AGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
S6 kinase subfamily
uniprot
proteins
pubmed
11516946
uniprot
proteins
pubmed
11967149
uniprot
proteins
pubmed
12183455
uniprot
proteins
pubmed
12604610
uniprot
proteins
pubmed
1699226
uniprot
proteins
pubmed
20599721
uniprot
proteins
pubmed
2236064
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
28178239
uniprot
proteins
pubmed
8524831
uniprot
proteins
pubmed
9427642
uniprot
proteins
pubmed
9465032
uniprot
proteins
pubmed
9632736
uniprot
proteins
pubmed
9653190
uniprot
proteins
sequence_length
525
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Synapse, synaptosome. Mitochondrion outer membrane. Mitochondrion {ECO:0000250}. Note=Colocalizes with URI1 at mitochondrion. {ECO:0000250}.
uniprot
proteins