General Information of the Protein
Protein ID
PT02266
Protein Name
Dual specificity mitogen-activated protein kinase kinase 4
Secondarily
Protein Name
JNK-activating kinase 1
MAPK/ERK kinase 4
SAPK/ERK kinase 1
Stress-activated protein kinase kinase 1
c-Jun N-terminal kinase kinase 1
Gene Name
MAP2K4
Secondarily
Gene Name
JNKK1
MEK4
MKK4
PRKMK4
SEK1
SERK1
SKK1
Sequence
MAAPSPSGGGGSGGGSGSGTPGPVGSPAPGHPAVSSMQGKRKALKLNFANPPFKSTARFTLNPNPTGVQNPHIERLRTHSIESSGKLKISPEQHWDFTAEDLKDLGEIGRGAYGSVNKMVHKPSGQIMAVKRIRSTVDEKEQKQLLMDLDVVMRSSDCPYIVQFYGALFREGDCWICMELMSTSFDKFYKYVYSVLDDVIPEEILGKITLATVKALNHLKENLKIIHRDIKPSNILLDRSGNIKLCDFGISGQLVDSIAKTRDAGCRPYMAPERIDPSASRQGYDVRSDVWSLGITLYELATGRFPYPKWNSVFDQLTQVVKGDPPQLSNSEEREFSPSFINFVNLCLTKDESKRPKYKELLKHPFILMYEERAVEVACYVCKILDQMPATPSSPMYVD
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
STE protein kinase group
>
STE protein kinase STE7 family
Function
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.
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Uniprot ID
Primary ID:
P45985

Secondarily ID:
B2R7N7
B3KYB2
D3DTS5
Q5U0B8
Q6FHX4
Q6P9H2
Q6PIE6
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Ensembl ID
ENSG00000065559
HGNC ID
HGNC:6844
Subcellular Location
Cytoplasm
Nucleus
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: CL000012 , Sf21
Compound ID Compound Name Compound Formula
CP0129670
4-(6-fluoro-1H-indazol-3-yl)benzenesulfonamide
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C13H10FN3O2S
 1
1
IC50 = 61 nM
   TI
   LI
   LO
   TS
CP0137371
4-[[3-(6-fluoro-1H-indazol-3-yl)phenyl]sulfonylamino]benzamide
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C20H15FN4O3S
 1
1
IC50 = 83 nM
   TI
   LI
   LO
   TS
CP0562320
3-(6-fluoro-1H-indazol-3-yl)benzoic acid
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C14H9FN2O2
 1
1
IC50 = 96 nM
   TI
   LI
   LO
   TS
CP0533766
3-(6-fluoro-1H-indazol-3-yl)-N-(4-methylsulfonylphenyl)benzenesulfonamide
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C20H16FN3O4S2
 1
1
IC50 = 290 nM
   TI
   LI
   LO
   TS
CP0534383
3-(6-fluoro-1H-indazol-3-yl)-N-phenylbenzenesulfonamide
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C19H14FN3O2S
 1
1
IC50 = 310 nM
   TI
   LI
   LO
   TS
CP0573422
6-fluoro-3-phenyl-1H-indazole
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C13H9FN2
 1
1
IC50 = 310 nM
   TI
   LI
   LO
   TS
CP0548607
N-cyclopropyl-3-(6-fluoro-1H-indazol-3-yl)benzenesulfonamide
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C16H14FN3O2S
 1
1
IC50 = 380 nM
   TI
   LI
   LO
   TS
CP0575119
3-(6-fluoro-1H-indazol-3-yl)-N-(4-methoxyphenyl)benzenesulfonamide
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C20H16FN3O3S
 1
1
IC50 = 390 nM
   TI
   LI
   LO
   TS
CP0565349
3-(6-fluoro-1H-indazol-3-yl)-N-(2-methoxyphenyl)benzenesulfonamide
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C20H16FN3O3S
 1
1
IC50 = 420 nM
   TI
   LI
   LO
   TS
CP0546431
3-(6-fluoro-1H-indazol-3-yl)-N-pyridin-3-ylbenzenesulfonamide
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C18H13FN4O2S
 1
1
IC50 = 450 nM
   TI
   LI
   LO
   TS
CP0527598
N-(4-cyanophenyl)-3-(6-fluoro-1H-indazol-3-yl)benzenesulfonamide
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C20H13FN4O2S
 1
1
IC50 = 470 nM
   TI
   LI
   LO
   TS
CP0546430
N-[4-(6-fluoro-1H-indazol-3-yl)phenyl]methanesulfonamide
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C14H12FN3O2S
 1
1
IC50 = 480 nM
   TI
   LI
   LO
   TS
CP0444629
2,2,2-trifluoro-1-[4-(6-fluoro-1H-indazol-3-yl)phenyl]ethanone
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C15H8F4N2O
 1
1
IC50 = 600 nM
   TI
   LI
   LO
   TS
CP0546433
3-(6-fluoro-1H-indazol-3-yl)-N-(4-sulfamoylphenyl)benzenesulfonamide
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C19H15FN4O4S2
 1
1
IC50 = 620 nM
   TI
   LI
   LO
   TS
CP0555701
N-[4-(6-fluoro-1H-indazol-3-yl)phenyl]pyridine-3-sulfonamide
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C18H13FN4O2S
 1
1
IC50 = 750 nM
   TI
   LI
   LO
   TS
CP0418480
N-(4-acetylphenyl)-3-(6-fluoro-1H-indazol-3-yl)benzenesulfonamide
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C21H16FN3O3S
 1
1
IC50 = 860 nM
   TI
   LI
   LO
   TS
CP0533775
N-cyclohexyl-3-(6-fluoro-1H-indazol-3-yl)benzenesulfonamide
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C19H20FN3O2S
 1
1
IC50 = 860 nM
   TI
   LI
   LO
   TS
CP0555699
3-(6-fluoro-1H-indazol-3-yl)-N-(4-fluorophenyl)benzenesulfonamide
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C19H13F2N3O2S
 1
1
IC50 = 880 nM
   TI
   LI
   LO
   TS
CP0548606
N-cyclopropyl-4-(6-fluoro-1H-indazol-3-yl)benzenesulfonamide
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C16H14FN3O2S
 1
1
IC50 = 1300 nM
   TI
   LI
   LO
   TS
CP0575118
N-[3-(6-fluoro-1H-indazol-3-yl)phenyl]pyridine-3-sulfonamide
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C18H13FN4O2S
 1
1
IC50 = 1300 nM
   TI
   LI
   LO
   TS
CP0527595
N-(4-chlorophenyl)-3-(6-fluoro-1H-indazol-3-yl)benzenesulfonamide
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C19H13ClFN3O2S
 1
1
IC50 = 1400 nM
   TI
   LI
   LO
   TS
CP0565350
3-(6-fluoro-1H-indazol-3-yl)-N-(4-methylphenyl)benzenesulfonamide
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C20H16FN3O2S
 1
1
IC50 = 1500 nM
   TI
   LI
   LO
   TS
CP0546432
N-(3,4-dichlorophenyl)-3-(6-fluoro-1H-indazol-3-yl)benzenesulfonamide
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C19H12Cl2FN3O2S
 1
1
IC50 = 1600 nM
   TI
   LI
   LO
   TS
CP0451138
N-[4-(6-fluoro-1H-indazol-3-yl)phenyl]cyclohexanesulfonamide
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C19H20FN3O2S
 1
1
IC50 = 1900 nM
   TI
   LI
   LO
   TS
CP0451139
N-[3-(6-fluoro-1H-indazol-3-yl)phenyl]cyclopropanesulfonamide
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C16H14FN3O2S
 1
1
IC50 = 2500 nM
   TI
   LI
   LO
   TS
CP0527596
3-(6-fluoro-1H-indazol-3-yl)-N-[4-(trifluoromethyl)phenyl]benzenesulfonamide
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C20H13F4N3O2S
 1
1
IC50 = 3100 nM
   TI
   LI
   LO
   TS
CP0562321
3-(6-fluoro-1H-indazol-3-yl)benzenesulfonamide
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C13H10FN3O2S
 1
1
IC50 = 3100 nM
   TI
   LI
   LO
   TS
CP0543897
N-[3,5-bis(trifluoromethyl)phenyl]-3-(6-fluoro-1H-indazol-3-yl)benzenesulfonamide
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C21H12F7N3O2S
 1
1
IC50 = 3300 nM
   TI
   LI
   LO
   TS
CP0565348
4-(6-fluoro-1H-indazol-3-yl)-N-phenylbenzenesulfonamide
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C19H14FN3O2S
 1
1
IC50 = 3500 nM
   TI
   LI
   LO
   TS
CP0548605
N-[4-(6-fluoro-1H-indazol-3-yl)phenyl]cyclopropanesulfonamide
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C16H14FN3O2S
 1
1
IC50 = 4400 nM
   TI
   LI
   LO
   TS
CP0562319
6-fluoro-N-[(4-fluorophenyl)methyl]-1H-indazol-3-amine
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C14H11F2N3
 1
1
IC50 = 4700 nM
   TI
   LI
   LO
   TS
CP0534384
3-(6-fluoro-1H-indazol-3-yl)-N-(4-propan-2-yloxyphenyl)benzenesulfonamide
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C22H20FN3O3S
 1
1
IC50 = 6100 nM
   TI
   LI
   LO
   TS
CP0565346
6-fluoro-N-[(4-methoxyphenyl)methyl]-1H-indazol-3-amine
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C15H14FN3O
 1
1
IC50 = 8700 nM
   TI
   LI
   LO
   TS
CP0578799
N-cyclohexyl-4-(6-fluoro-1H-indazol-3-yl)benzenesulfonamide
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C19H20FN3O2S
 1
1
IC50 = 10000 nM
   TI
   LI
   LO
   TS
CP0527594
5-fluoro-2-[[(6-fluoro-1H-indazol-3-yl)amino]methyl]phenol
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C14H11F2N3O
 1
1
IC50 = 11000 nM
   TI
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CP0562318
N-(1,3-benzodioxol-5-ylmethyl)-6-fluoro-1H-indazol-3-amine
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C15H12FN3O2
 1
1
IC50 = 11000 nM
   TI
   LI
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   TS
CP0565347
N-[3-(6-fluoro-1H-indazol-3-yl)phenyl]cyclohexanesulfonamide
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C19H20FN3O2S
 1
1
IC50 = 14000 nM
   TI
   LI
   LO
   TS
CP0527597
3-(6-fluoro-1H-indazol-3-yl)-N-(4-propan-2-ylphenyl)benzenesulfonamide
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C22H20FN3O2S
 1
1
IC50 = 23000 nM
   TI
   LI
   LO
   TS
CP0422725
(E)-4-chloro-N-[2-(6-fluoro-1H-indazol-3-yl)phenyl]but-2-enamide
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C17H13ClFN3O
 1
1
IC50 > 80000 nM
   TI
   LI
   LO
   TS
CP0533774
(E)-4-(dimethylamino)-N-[2-(6-fluoro-1H-indazol-3-yl)phenyl]but-2-enamide
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C19H19FN4O
 1
1
IC50 > 80000 nM
   TI
   LI
   LO
   TS
CP0555698
N-[2-(6-fluoro-1H-indazol-3-yl)phenyl]prop-2-enamide
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C16H12FN3O
 1
1
IC50 > 80000 nM
   TI
   LI
   LO
   TS
CP0573424
2-(6-fluoro-1H-indazol-3-yl)aniline
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C13H10FN3
 1
1
IC50 > 80000 nM
   TI
   LI
   LO
   TS
CP0573426
N-[2-(6-fluoro-1H-indazol-3-yl)phenyl]propanamide
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C16H14FN3O
 1
1
IC50 > 80000 nM
   TI
   LI
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   TS