General Information of the Protein
Protein ID
PT03681
Protein Name
Ribosomal protein S6 kinase alpha-3
Secondarily
Protein Name
90 kDa ribosomal protein S6 kinase 3
MAP kinase-activated protein kinase 1b
Ribosomal S6 kinase 2
pp90RSK2
Gene Name
RPS6KA3
Secondarily
Gene Name
Mapkapk1b
Rps6ka-rs1
Rsk2
Sequence
MPLAQLADPWQKMAVESPSDSAENGQQIMDEPMGEEEINPQTEEGSIKEIAITHHVKEGHEKADPSQFELLKVLGQGSFGKVFLVKKISGSDARQLYAMKVLKKATLKVRDRVRTKMERDILVEVNHPFIVKLHYAFQTEGKLYLILDFLRGGDLFTRLSKEVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGLSKESIDHEKKAYSFCGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGTLPFQGKDRKETMTMILKAKLGMPQFLSPEAQSLLRMLFKRNPANRLGAGPDGVEEIKRHSFFSTIDWNKLYRREIHPPFKPATGRPEDTFYFDPEFTAKTPKDSPGIPPSANAHQLFRGFSFVAITSDDESQAMQTVGVHSIVQQLHRNSIQFTDGYEVKEDIGVGSYSVCKRCIHKATNMEFAVKIIDKSKRDPTEEIEILLRYGQHPNIITLKDVYDDGKYVYVVTELMKGGELLDKILRQKFFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYVDESGNPESIRICDFGFAKQLRAENGLLMTPCYTANFVAPEVLKRQGYDAACDIWSLGVLLYTMLTGYTPFANGPDDTPEEILARIGSGKFSLSGGYWNSVSDTAKDLVSKMLHVDPHQRLTAALVLRHPWIVHWDQLPQYQLNRQDAPHLVKGAMAATYSALNRNQSPVLEPVGRSTLAQRRGIKKITSTAL
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Organism
Mus musculus, Mouse
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
AGC protein kinase group
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:10856237, PubMed:15109498). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (By similarity). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (By similarity). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (By similarity). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (By similarity). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (By similarity). 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 (By similarity). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (By similarity). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (By similarity). 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:14504289). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (PubMed:17785202, PubMed:17906627). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (PubMed:22827337). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (PubMed:22827337). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (By similarity). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (PubMed:15109498).
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Uniprot ID
Primary ID:
P18654

Secondarily ID:
B1AXN4
Q03140
Q8K3J8
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Ensembl ID
ENSG00000177189
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: CL000077 , Ba/F3
Compound ID Compound Name Compound Formula
CP0199157
2,6-difluoro-4-[4-(4-piperazin-1-ylphenyl)pyridin-3-yl]phenol
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C21H19F2N3O
 1
1
EC50 = 140 nM
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CP0078774
2,6-difluoro-4-[4-(4-morpholin-4-ylphenyl)pyridin-3-yl]phenol
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C21H18F2N2O2
 1
1
EC50 = 210 nM
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CP0072849
2,6-difluoro-4-[4-[4-(4-methylpiperazin-1-yl)phenyl]pyridin-3-yl]phenol
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C22H21F2N3O
 1
1
EC50 = 340 nM
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CP0574333
4-[2-amino-4-(4-methylphenyl)pyrimidin-5-yl]-2,6-difluorophenol
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C17H13F2N3O
 1
1
EC50 = 360 nM
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CP0199156
4-[6-amino-4-[4-(4-methylpiperazin-1-yl)phenyl]pyridin-3-yl]-2,6-difluorophenol
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C22H22F2N4O
 1
1
EC50 = 440 nM
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CP0327292
4-[4-[3-(2-aminoethoxy)phenyl]pyridin-3-yl]-2,6-difluorophenol
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C19H16F2N2O2
 1
1
EC50 = 490 nM
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CP0126245
(7R)-2-(3,5-difluoro-4-hydroxyanilino)-5,7-dimethyl-8-(3-methylbutyl)-7H-pteridin-6-one
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C19H23F2N5O2
 1
1
EC50 = 500 nM
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CP0357163
2,6-difluoro-4-[6-(methylamino)-4-[4-(4-methylpiperazin-1-yl)phenyl]pyridin-3-yl]phenol
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C23H24F2N4O
 1
1
EC50 = 580 nM
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CP0176720
2,6-difluoro-4-[4-[4-(4-methylpiperazin-1-yl)phenyl]-2-(propan-2-ylamino)pyrimidin-5-yl]phenol
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C24H27F2N5O
 1
1
EC50 = 610 nM
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CP0126246
2,6-difluoro-4-[6-(4-methylanilino)-4-[4-(4-methylpiperazin-1-yl)phenyl]pyridin-3-yl]phenol
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C29H28F2N4O
 1
1
EC50 = 690 nM
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CP0199155
2,6-difluoro-4-[2-(methylamino)-4-(4-methylphenyl)pyrimidin-5-yl]phenol
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C18H15F2N3O
 1
1
EC50 = 690 nM
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CP0126247
2,6-difluoro-4-[4-[3-(4-methylpiperazin-1-yl)phenyl]pyridin-3-yl]phenol
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C22H21F2N3O
 1
1
EC50 = 1100 nM
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CP0158460
2,6-difluoro-4-[4-[3-(1H-pyrazol-4-yl)phenyl]pyridin-3-yl]phenol
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C20H13F2N3O
 1
1
EC50 = 1100 nM
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CP0545519
2,6-difluoro-4-[4-(4-methoxyphenyl)pyridin-3-yl]phenol
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C18H13F2NO2
 1
1
EC50 = 1100 nM
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CP0126250
2,6-difluoro-4-[4-(4-hydroxyphenyl)-1H-pyrazol-5-yl]phenol
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C15H10F2N2O2
 1
1
EC50 = 1400 nM
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CP0178739
2,6-difluoro-4-[4-(4-methylphenyl)-2-(propan-2-ylamino)pyrimidin-5-yl]phenol
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C20H19F2N3O
 1
1
EC50 = 1500 nM
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CP0314064
2,6-difluoro-4-[4-(4-methylphenyl)pyridin-3-yl]phenol
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C18H13F2NO
 1
1
EC50 = 1600 nM
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CP0206696
4-[3-(3,5-difluoro-4-hydroxyphenyl)pyridin-4-yl]-N-methylbenzamide
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C19H14F2N2O2
 1
1
EC50 = 2100 nM
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CP0416884
2,6-difluoro-4-[4-(oxan-4-yl)pyridin-3-yl]phenol
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C16H15F2NO2
 1
1
EC50 = 2200 nM
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CP0206697
2,6-difluoro-4-[4-(3-morpholin-4-ylphenyl)pyridin-3-yl]phenol
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C21H18F2N2O2
 1
1
EC50 = 2300 nM
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CP0546766
2,6-difluoro-4-[4-[4-(4-methylpiperazin-1-yl)phenyl]-6-(2-methylpropylamino)pyridin-3-yl]phenol
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C26H30F2N4O
 1
1
EC50 = 2500 nM
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CP0266393
4-[5-(4-hydroxyphenyl)-1H-pyrazol-4-yl]phenol
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C15H12N2O2
 1
1
EC50 = 2800 nM
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CP0367664
4-(3-amino-4-phenyl-1H-pyrazol-5-yl)phenol
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C15H13N3O
 1
1
EC50 = 3200 nM
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CP0460252
2,6-difluoro-4-[4-(3-methylphenyl)pyridin-3-yl]phenol
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C18H13F2NO
 1
1
EC50 = 4100 nM
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CP0539591
2,6-difluoro-4-(4-phenylpyridin-3-yl)phenol
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C17H11F2NO
 1
1
EC50 = 4200 nM
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CP0137028
2,6-difluoro-4-[4-(6-methoxypyridin-3-yl)pyridin-3-yl]phenol
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C17H12F2N2O2
 1
1
EC50 = 5300 nM
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CP0314067
2,6-difluoro-4-[4-(3-methoxyphenyl)pyridin-3-yl]phenol
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C18H13F2NO2
 1
1
EC50 = 5600 nM
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CP0206698
2,6-difluoro-4-[4-(4-hydroxyphenyl)pyridin-3-yl]phenol
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C17H11F2NO2
 1
1
EC50 = 6400 nM
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CP0206700
4-[3-(4-hydroxyphenyl)pyridin-4-yl]phenol
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C17H13NO2
 1
1
EC50 = 9300 nM
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CP0099119
2,6-difluoro-4-[4-(4-fluorophenyl)pyridin-3-yl]phenol
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C17H10F3NO
 1
1
EC50 = 10400 nM
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CP0176722
2,6-difluoro-4-(4-piperidin-4-ylpyridin-3-yl)phenol
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C16H16F2N2O
 1
1
EC50 > 20000 nM
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CP0361284
2,6-difluoro-4-(4-propan-2-ylpyridin-3-yl)phenol
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C14H13F2NO
 1
1
EC50 > 20000 nM
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CP0369096
4-(5-phenyl-1H-pyrazol-4-yl)phenol
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C15H12N2O
 1
1
EC50 > 20000 nM
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CP0539472
2,6-dichloro-4-[4-(4-fluorophenyl)pyridin-3-yl]phenol
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C17H10Cl2FNO
 1
1
EC50 > 20000 nM
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CP0545502
4-(4-phenyl-1H-pyrazol-5-yl)phenol
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C15H12N2O
 1
1
EC50 > 20000 nM
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Similar Protein(s) and Bioactivity Statistics
50% Identity
Protein ID Protein Name Protein Organism
PT00856 Ribosomal protein S6 kinase alpha-3 Homo sapiens, Human