General Information of the Protein
Protein ID
PT00959
Protein Name
Ribosomal protein S6 kinase alpha-1
Secondarily
Protein Name
90 kDa ribosomal protein S6 kinase 1
MAP kinase-activated protein kinase 1a
Ribosomal S6 kinase 1
Gene Name
RPS6KA1
Secondarily
Gene Name
MAPKAPK1A
RSK1
Sequence
MPLAQLKEPWPLMELVPLDPENGQTSGEEAGLQPSKDEGVLKEISITHHVKAGSEKADPSHFELLKVLGQGSFGKVFLVRKVTRPDSGHLYAMKVLKKATLKVRDRVRTKMERDILADVNHPFVVKLHYAFQTEGKLYLILDFLRGGDLFTRLSKEVMFTEEDVKFYLAELALGLDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGLSKEAIDHEKKAYSFCGTVEYMAPEVVNRQGHSHSADWWSYGVLMFEMLTGSLPFQGKDRKETMTLILKAKLGMPQFLSTEAQSLLRALFKRNPANRLGSGPDGAEEIKRHVFYSTIDWNKLYRREIKPPFKPAVAQPDDTFYFDTEFTSRTPKDSPGIPPSAGAHQLFRGFSFVATGLMEDDGKPRAPQAPLHSVVQQLHGKNLVFSDGYVVKETIGVGSYSECKRCVHKATNMEYAVKVIDKSKRDPSEEIEILLRYGQHPNIITLKDVYDDGKHVYLVTELMRGGELLDKILRQKFFSEREASFVLHTIGKTVEYLHSQGVVHRDLKPSNILYVDESGNPECLRICDFGFAKQLRAENGLLMTPCYTANFVAPEVLKRQGYDEGCDIWSLGILLYTMLAGYTPFANGPSDTPEEILTRIGSGKFTLSGGNWNTVSETAKDLVSKMLHVDPHQRLTAKQVLQHPWVTQKDKLPQSQLSHQDLQLVKGAMAATYSALNSSKPTPQLKPIESSILAQRRVRKLPSTTL
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
CAMK protein kinase group
>
CAMK protein kinase RSKb family
>
CAMK protein kinase RSKb subfamily
Function
Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:16223362, PubMed:15117958, PubMed:12213813, PubMed:9430688, PubMed:17360704, PubMed:26158630, PubMed:18722121, PubMed:35772404). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404).
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Uniprot ID
Primary ID:
Q15418

Secondarily ID:
A6NGG4
A8K9K7
B2RDY8
B7Z5J0
E9PRI4
Q5SVM5
Q5SVM8
Q5SVM9
Q96C05
Q9BQK2
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Ensembl ID
ENSG00000117676
HGNC ID
HGNC:10430
Subcellular Location
Nucleus
Cytoplasm
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000063 , Hep-G2
Compound ID Compound Name Compound Formula
CP0500919
US9388171, II-64
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C27H30N6O2
 1
1
IC50 = 5.47 nM
   TI
   LI
   LO
   TS
CP0564085
US9388171, I-6
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C24H27FN4O3
 1
1
IC50 = 5.96 nM
   TI
   LI
   LO
   TS
CP0515120
US9388171, II-2
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C24H25ClFN3O2
 1
1
IC50 = 8.5 nM
   TI
   LI
   LO
   TS
CP0324959
US9388171, I-8
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C21H18ClFN6O2
 1
1
IC50 = 9.84 nM
   TI
   LI
   LO
   TS
CP0324711
US9388171, II-15
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C25H21ClFN7O
 1
1
IC50 = 9.97 nM
   TI
   LI
   LO
   TS
CP0324712
US9388171, II-12
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C23H23ClFN3O3
 1
1
IC50 = 14.8 nM
   TI
   LI
   LO
   TS
CP0274071
US9388171, II-46
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C24H23ClFN5O
 1
1
IC50 = 15.7 nM
   TI
   LI
   LO
   TS
CP0483378
US9388171, I-5
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C22H22ClFN4O3
 1
1
IC50 = 16.3 nM
   TI
   LI
   LO
   TS
CP0340458
US9388171, I-21
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C26H27FN6O3
 1
1
IC50 = 18.7 nM
   TI
   LI
   LO
   TS
CP0269483
US9388171, II-37
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C27H26FN7O2
 1
1
IC50 = 30.4 nM
   TI
   LI
   LO
   TS
CP0241393
US9388171, I-24
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C24H25FN6O3
 1
1
IC50 = 37.8 nM
   TI
   LI
   LO
   TS
CP0823713
US9388171, II-23
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C22H21FN4O2
 1
1
IC50 = 65.1 nM
   TI
   LI
   LO
   TS
CP0273971
US9388171, I-11
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C21H20ClFN4O2
 1
1
IC50 = 98.9 nM
   TI
   LI
   LO
   TS
CP0324960
US9388171, I-30
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C22H22ClFN4O2
 1
1
IC50 = 476 nM
   TI
   LI
   LO
   TS
Clinical Information about the Protein
Target 1 ( Ribosomal protein S6 kinase alpha-1 (RSK1) )
Target Type Patented-recorded Target
Disease 1 Target-related Disease  1
1 Chronic lymphocytic leukaemia [ICD-11: 2A82.0]
Preclinical Drug(s) 1 Preclinical Drug  1
1 BI-D1870 Preclinical
Chronic lymphocytic leukaemia