RPS6KB1
entrez
6198
canonical
uniprot
P23443
canonical
ensembl
ENSG00000108443
resolver
ensp
ENSP00000225577
resolver
ensp
ENSP00000376744
resolver
ensp
ENSP00000384335
resolver
ensp
ENSP00000441993
resolver
ensp
ENSP00000550533
resolver
ensp
ENSP00000598833
resolver
ensp
ENSP00000657150
resolver
ensp
ENSP00000657151
resolver
ensp
ENSP00000657154
resolver
ensp
ENSP00000657157
resolver
ensp
ENSP00000686175
resolver
ensp
ENSP00000764947
resolver
genesymbol
RPS6KB1
resolver
genesymbol_syn
STK14A
resolver
hgnc
HGNC:10436
resolver
uniprot
B2R779
resolver
uniprot
B4DLT4
resolver
uniprot
B4DTG1
resolver
uniprot
E7ESB8
resolver
uniprot
F6UYM1
resolver
uniprot
Q7Z721
resolver
uniprot_entry
KS6B1_HUMAN
resolver
uniprot_sec
B2R779
resolver
uniprot_sec
B4DLT4
resolver
uniprot_sec
B4DTG1
resolver
uniprot_sec
E7ESB8
resolver
uniprot_sec
F6UYM1
resolver
uniprot_sec
Q7Z721
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. {ECO:0000269|PubMed:17446865, ECO:0000269|PubMed:19570988, ECO:0000269|PubMed:28178239, ECO:0000269|PubMed:9445476}.
uniprot
proteins
amino_acid_sequence
MRRRRRRDGFYPAPDFRDREAEDMAGVFDIDLDQPEDAGSEDELEEGGQLNESMDHGGVGPYELGMEHCEKFEISETSVNRGPEKIRPECFELLRVLGKGGYGKVFQVRKVTGANTGKIFAMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYLSGGELFMQLEREGIFMEDTACFYLAEISMALGHLHQKGIIYRDLKPENIMLNHQGHVKLTDFGLCKESIHDGTVTHTFCGTIEYMAPEILMRSGHNRAVDWWSLGALMYDMLTGAPPFTGENRKKTIDKILKCKLNLPPYLTQEARDLLKKLLKRNAASRLGAGPGDAGEVQAHPFFRHINWEELLARKVEPPFKPLLQSEEDVSQFDSKFTRQTPVDSPDDSTLSESANQVFLGFTYVAPSVLESVKEKFSFEPKIRSPRRFIGSPRTPVSPVKFSPGDFWGRGASASTANPQTPVEYPMETSGIEQMDVTMSGEASAPLPIRQPNSGPYKKQAFPMISKRPEHLRMNL
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:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:22017876, PubMed:23429703, 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:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:22017876, PubMed:23429703, PubMed:28178239). Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex (PubMed:16286006). Upon mitogenic stimulation, phosphorylation by the mechanistic target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation (PubMed:16286006). 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 (PubMed:16286006). Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis (PubMed:17053147). Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR (PubMed:15341740). 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 MAPKAP1/SIN1, MTOR and RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling (PubMed:15899889, PubMed:19720745, PubMed:19935711, PubMed:19995915). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). 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 (PubMed:17936702). 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 (PubMed:17936702). Mediates TNF-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 (PubMed:17052453). May be involved in cytoskeletal rearrangement through binding to neurabin (By similarity). Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (PubMed:23429703). 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:P67999, ECO:0000250|UniProtKB:Q8BSK8, ECO:0000269|PubMed:11500364, ECO:0000269|PubMed:12801526, ECO:0000269|PubMed:14673156, ECO:0000269|PubMed:15071500, ECO:0000269|PubMed:15341740, ECO:0000269|PubMed:15899889, ECO:0000269|PubMed:16286006, ECO:0000269|PubMed:17052453, ECO:0000269|PubMed:17053147, ECO:0000269|PubMed:17936702, ECO:0000269|PubMed:18952604, ECO:0000269|PubMed:19085255, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:28178239}.
uniprot
proteins
mass_dalton
59140
uniprot
proteins
mutagenesis
MUTAGEN 167; /note="K->N: Greatly reduces activity. Greatly reduces phosphorylation at T-412 and moderately reduces phosphorylation at T-252."; /evidence="ECO:0000269|PubMed:17446865"; MUTAGEN 394; /note="S->A: Loss of activity. Loss of phosphorylation at T-412."; /evidence="ECO:0000269|PubMed:17446865"; MUTAGEN 412; /note="T->E: Mimics phosphorylation. Facilitates phosphorylation of T-252 by PDPK1; when associated with E-434; E-441; E-444 and E-447. Mimics phosphorylation. No effect on interaction with PDPK1 and phosphorylation of T-252. Impairs association with the eIF3 complex."; /evidence="ECO:0000269|PubMed:16286006, ECO:0000269|PubMed:19570988, ECO:0000269|PubMed:9445476"; MUTAGEN 434; /note="S->E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-441; E-444 and E-447."; /evidence="ECO:0000269|PubMed:9445476"; MUTAGEN 441; /note="S->E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-444 and E-447."; /evidence="ECO:0000269|PubMed:9445476"; MUTAGEN 444; /note="T->E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-441 and E-447."; /evidence="ECO:0000269|PubMed:9445476"; MUTAGEN 447; /note="S->E: Facilitates phosphorylation of T-252 by PDPK1; when associated with E-412; E-434; E-441 and E-444."; /evidence="ECO:0000269|PubMed:9445476
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Thr-412 is regulated by mTORC1. The phosphorylation at this site is maintained by an agonist-dependent autophosphorylation mechanism (PubMed:18925875, PubMed:19085255, PubMed:22017876, PubMed:23429703, PubMed:29236692). Activated by phosphorylation at Thr-252 by PDPK1 (PubMed:19864428, PubMed:9445476). Dephosphorylation by PPP1CC at Thr-412 in mitochondrion (PubMed:17936702). {ECO:0000269|PubMed:17936702, ECO:0000269|PubMed:18925875, ECO:0000269|PubMed:19085255, ECO:0000269|PubMed:19864428, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:29236692, ECO:0000269|PubMed:9445476}.
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
11500364
uniprot
proteins
pubmed
12150926
uniprot
proteins
pubmed
12801526
uniprot
proteins
pubmed
14673156
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15071500
uniprot
proteins
pubmed
15341740
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15899889
uniprot
proteins
pubmed
16286006
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17052453
uniprot
proteins
pubmed
17053147
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17446865
uniprot
proteins
pubmed
17936702
uniprot
proteins
pubmed
18092230
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18925875
uniprot
proteins
pubmed
18952604
uniprot
proteins
pubmed
19085255
uniprot
proteins
pubmed
1922062
uniprot
proteins
pubmed
19570988
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19720745
uniprot
proteins
pubmed
19864428
uniprot
proteins
pubmed
19935711
uniprot
proteins
pubmed
19995915
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20932932
uniprot
proteins
pubmed
22017876
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23429703
uniprot
proteins
pubmed
26496226
uniprot
proteins
pubmed
28178239
uniprot
proteins
pubmed
29236692
uniprot
proteins
pubmed
29750193
uniprot
proteins
pubmed
32295907
uniprot
proteins
pubmed
9445476
uniprot
proteins
pubmed
9804755
uniprot
proteins
sequence_length
525
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Synapse, synaptosome {ECO:0000250}. Mitochondrion outer membrane. Mitochondrion. Note=Colocalizes with URI1 at mitochondrion.; SUBCELLULAR LOCATION: [Isoform Alpha I]: Nucleus. Cytoplasm.; SUBCELLULAR LOCATION: [Isoform Alpha II]: Cytoplasm.
uniprot
proteins