Information on EC 2.7.11.24 - mitogen-activated protein kinase and Organism(s) Mus musculus and UniProt Accession Q61831

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Mus musculus
UNIPROT: Q61831


The taxonomic range for the selected organisms is: Mus musculus

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.11.24
-
RECOMMENDED NAME
GeneOntology No.
mitogen-activated protein kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
the kinetics of p38 MAPK follow a rapid-equilibrium random-order ternary-complex mechanism, the enzyme is highly specific for Ser-Pro or Thr-Pro motifs
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (MAPKK-activated)
Phosphorylation of specific tyrosine and threonine residues in the activation loop of this enzyme by EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) is necessary for enzyme activation. Once activated, the enzyme phosphorylates target substrates on serine or threonine residues followed by a proline [6]. A distinguishing feature of all MAPKs is the conserved sequence Thr-Xaa-Tyr (TXY). Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
CAS REGISTRY NUMBER
COMMENTARY hide
142243-02-5
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
-
p38 alpha mitogen-activated protein kinase is a key component of the cascade leading to pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1beta
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
ATP + activating transcription factor 2
ADP + phosphorylated activating transcription factor 2
show the reaction diagram
ATP + ATF-2
ADP + phosphorylated ATF-2
show the reaction diagram
-
substrate in kinase assay
-
-
?
ATP + ATF2
ADP + phosphorylated ATF2
show the reaction diagram
phosphorylation by p38 MAPK at threonine residues
-
-
?
ATP + ATF2DELTA109
ADP + phosphorylated ATF2DELTA109
show the reaction diagram
-
-
-
-
?
ATP + c-Jun
ADP + phosphorylated c-Jun
show the reaction diagram
-
-
-
-
?
ATP + EGF receptor peptide
ADP + phosphorylated EGF receptor peptide
show the reaction diagram
-
-
-
-
?
ATP + Elk-1
ADP + phosphorylated Elk-1
show the reaction diagram
-
an ETS family transcription factor
-
-
?
ATP + Elk1
ADP + phosphorylated Elk1
show the reaction diagram
-
recombinant GST-tagged Elk1, substrate of ERK2
-
-
?
ATP + MAPKAP-K2
ADP + phosphorylated MAPKAP-K2
show the reaction diagram
-
-
-
-
?
ATP + MAPKAP-K3
ADP + phosphorylated MAPKAP-K3
show the reaction diagram
-
-
-
-
?
ATP + MEF2
ADP + phosphorylated MEF2
show the reaction diagram
-
-
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
show the reaction diagram
-
substrate of ERK2
-
-
?
ATP + Net
ADP + phosphorylated Net
show the reaction diagram
-
an ETS family transcription factor
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
-
Ser/Thr kinase
-
-
-
ATP + protein ATF2
ADP + phosphorylated protein ATF2
show the reaction diagram
-
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
ATP + activating transcription factor 2
ADP + phosphorylated activating transcription factor 2
show the reaction diagram
-
ATF2
-
-
?
ATP + Elk-1
ADP + phosphorylated Elk-1
show the reaction diagram
-
an ETS family transcription factor
-
-
?
ATP + MAPKAP-K2
ADP + phosphorylated MAPKAP-K2
show the reaction diagram
-
-
-
-
?
ATP + MAPKAP-K3
ADP + phosphorylated MAPKAP-K3
show the reaction diagram
-
-
-
-
?
ATP + MEF2
ADP + phosphorylated MEF2
show the reaction diagram
-
-
-
-
?
ATP + Net
ADP + phosphorylated Net
show the reaction diagram
-
an ETS family transcription factor
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
show the reaction diagram
-
substrate of MAPKs, e.g. ERK2
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
II/SP600125
inhibits SAPK/JNK
(E)-3-(2,4-dimethoxyphenyl)-N-(4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]pyridin-2-yl)acrylamide
-
(E)-3-(2,4-dimethoxyphenyl)-N-(4-[5-(4-fluorophenyl)-2-methanesulfinyl-3H-imidazol-4-yl]pyridin-2-yl)acrylamide
-
(E)-3-(2,4-dimethoxyphenyl)-N-(4-[5-(4-fluorophenyl)-2-methylsulfanyl-3H-imidazol-4-yl]pyridin-2-yl)acrylamide
-
1-(2,6-dichloro-phenyl)-5-(2,4-difluoro-phenyl)-7-piperazin-1-yl-3,4-dihydro-1H-quinazolin-2-one
highly selective for p38 isozyme alpha wild-type with IC50 of 3.2 nM, the IC50 for mutants G110A and G110D are 37 nM and 56 nM, respectively, no inhibition of JNK3, JNK2, and ERK
1-(2,6-dichloro-phenyl)-5-(2,4-difluoro-phenyl)-7-piperidin-4-yl-3,4-dihydro-1H-quinolin-2-one
highly selective for p38 isozyme alpha wild-type with IC50 of 0.74 nM, the IC50 for mutants G110A and G110D are 26 nM and 67 nM, respectively, no inhibition of JNK3, JNK2, and ERK
1-(2,6-dichloro-phenyl)-6-(2,4-difluoro-phenylsulfanyl)-7-(1,2,3,6-tetrahydro-pyridin-4-yl)-3,4-dihydro-1H-pyrido[3,2-d]pyrimidin-2-one
highly selective for p38 isozyme alpha wild-type with IC50 of 4.3 nM, the IC50 for mutants G110A and G110D are 61 nM and 160 nM, respectively, no inhibition of JNK3, JNK2, and ERK
2-(4-fluorophenyl)-3-(2-isopropylaminopyridin-4-yl)pyrido[2,3-b]pyrazine
-
-
2-(4-fluorophenyl)-3-(pyridin-4-yl)pyrido[2,3-b]pyrazine
-
-
2-(4-fluorophenyl)-3-(pyridin-4-yl)quinoxaline
-
-
2-(4-fluorophenyl)-3-pyridin-4-ylpyrido[3,4-b]pyrazine
-
-
2-(4-fluorophenyl)-6,7-dimethyl-3-pyridin-4-ylquinoxaline
-
-
2-(4-fluorophenyl)-6-methoxy-3-(pyridin-4-yl)quinoxaline
-
-
2-(4-fluorophenyl)-N-[4-(3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl)pyridin-2-yl]acetamide
-
3-(4-fluorophenyl)-2-(2-isopropylaminopyridin-4-yl)pyrido[2,3-b]pyrazine
-
-
3-(4-fluorophenyl)-2-(pyridin-4-yl)pyrido[2,3-b]pyrazine
-
-
3-(4-fluorophenyl)-2-pyridin-4-ylpyrido[3,4-b]pyrazine
-
-
3-(4-fluorophenyl)-6-methoxy-2-(pyridin-4-yl)quinoxaline
-
-
4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]-N-(1(R)-phenylethyl)pyridin-2-amine
-
4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]-N-(1(S)-phenylethyl)pyridin-2-amine
-
4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]-N-(tetrahydro-2H-pyran-4-yl)pyridin-2-amine
-
4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]-N-(1-methylethyl)pyridin-2-amine
-
-
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-(1-phenylethyl)pyridin-2-amine
-
-
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-(3-methylbutan-2-yl)pyridin-2-amine
-
-
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-isobutylpyridin-2-amine
-
-
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-isopropylpyridin-2-amine
-
-
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-[(1R)-1-phenylethyl]pyridin-2-amine
-
-
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-[(1S)-1-phenylethyl]pyridin-2-amine
-
-
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-[(R)-3-methylbutan-2-yl]pyridin-2-amine
-
-
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-[(S)-3-methylbutan-2-yl]pyridin-2-amine
-
-
4-[4-[3-(4-fluorophenyl)quinoxalin-2-yl]pyridin-2-ylamine]-cyclohexanol
-
-
4-[6,7-dichloro-3-(4-fluorophenyl)quinoxalin-2-yl]-N-(1,2-dimethylpropyl)pyridin-2-amine
-
-
4-[6,7-dichloro-3-(4-fluorophenyl)quinoxalin-2-yl]-N-(1-methylethyl)pyridin-2-amine
-
-
6,7-dichloro-2-(4-fluorophenyl)-3-pyridin-4-ylquinoxaline
-
-
7-(6-N-phenylaminohexyl)amino-2H-anthra[1,9-cd]pyrazol-6-one
-
AV-7
adenylyl-beta,gamma-methylene diphosphonic acid
-
i.e. AMP-PCP, MgAMP-PCP shows a mixed inhibition pattern in the kinase reaction, and a competitive pattern in the ATPase reaction
ADP
-
MgADP- shows an uncompetitive inhibition pattern
alsterpaullone
-
36% inhibition of MAPK2/ERK2 at 0.01 mM
AMP-PCP
-
-
BIRB796
binding structure with isozyme p38alpha
II/SP600125
inhibits SAPK/JNK
kenpaullone
-
30% inhibition of MAPK2/ERK2 at 0.01 mM
lignocaine
-
the enzyme inhibition by lignocine may involve voltage-sensitive sodium channels, the enzyme attenuates the induction of MAPK activation by lipopolysaccharides, overview
N-(1,2-dimethylpropyl)-4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-amine
-
-
N-(4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]pyridin-2-yl)2-phenoxypropanamide
-
N-benzyl-4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-amine
-
-
N-benzyl-4-[3-(4-fluorophenyl)quinoxalin-2-yl]pyridin-2-amine
-
-
N-benzyl-4-[6,7-dichloro-3-(4-fluorophenyl)quinoxalin-2-yl]pyridin-2-amine
-
-
N-sec-butyl-4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]pyridin-2-amine
-
N-sec-butyl-4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-amine
-
-
N-sec-butyl-4-[3-(4-fluorophenyl)quinoxalin-2-yl]pyridin-2-amine
-
-
N-tert-butyl-4-[2-(4-fluorophenyl)pyrido[3,4-b]pyrazin-3-yl]pyridin-2-amine
-
-
N-tert-butyl-4-[3-(4-fluorophenyl)pyrido[3,4-b]pyrazin-2-yl]pyridin-2-amine
-
-
N-[4-(3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl)pyridin-2-yl]acetamide
-
purvalanol
-
74% inhibition of MAPK2/ERK2 at 0.01 mM
pyridinyl imidazole-type inhibitors
IC50 of 15-48 nM
-
roscovitine
-
19% inhibition of MAPK2/ERK2 at 0.01 mM
SB202190
SB203580
siRNA
-
-
-
skepinone-L
-
the specificity by which SCD-1 modulates the phospholipid composition and inhibits p38 MAPK signaling (among survival/stress pathways), thereby preventing endoplasmic reticulum stress (but not other SCD-1-dependent responses), suggests selective protein-lipid interactions
-
SP600125
trans-4-([4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-yl]amino)cyclohexanol
-
-
trans-4-([4-[6,7-dichloro-3-(4-fluorophenyl)quinoxalin-2-yl]pyridin-2-yl]amino)cyclohexanol
-
-
U0126
-
specific inhibitor of ERK
[4-[3-methyl-2-piperidin-4-yl-5-(3-trifluoromethyl-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-((S)-1-phenyl-ethyl)-amine
highly selective for p38 isozyme alpha wild-type and mutants with IC50 of 0.10-0.14 nM, IC50 for JNK2 is 680 nM, for JNK3 970 nM and for ERK 660 nM
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
EGF
-
induces phosphorylation of Smad3
-
palmitate
-
activates p38 MAPK phosphorylation and activates it
Ras
-
Ras induces phosphorylation of c-Jun by JNKs
-
TNF-alpha
-
activates p38 MAPK mediated by protein kinases MKK3, MKK4, and MKK6, overview
-
UV radiation
-
activates p38 MAPK mediated by protein kinases, overview
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.002 - 0.02
ATF2DELTA109
-
0.048 - 0.096
ATP
0.656 - 2.8
EGF receptor peptide
additional information
additional information
-
steady-state kinetics, kinetic mechanism for p38 MAP kinase alpha kinase and ATPase activities, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.8 - 4.7
ATF2DELTA109
-
6.99 - 31.6
EGF receptor peptide
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2
ADP
-
above, pH 7.6, 27°C, recombinant p38 MAPK
0.187 - 0.242
AMP-PCP
0.000021
SB203580
-
ATPase reaction versus ATP, pH 7.6, 27°C, recombinant p38 MAPK
additional information
additional information
-
inhibition kinetics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00009
II/SP600125
Mus musculus;
Q61831, Q91Y86, Q9WTU6
inhibition of JNK3
0.00252
(E)-3-(2,4-dimethoxyphenyl)-N-(4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]pyridin-2-yl)acrylamide
Mus musculus;
P47811
-
0.000041
(E)-3-(2,4-dimethoxyphenyl)-N-(4-[5-(4-fluorophenyl)-2-methanesulfinyl-3H-imidazol-4-yl]pyridin-2-yl)acrylamide
Mus musculus;
P47811
-
0.000019
(E)-3-(2,4-dimethoxyphenyl)-N-(4-[5-(4-fluorophenyl)-2-methylsulfanyl-3H-imidazol-4-yl]pyridin-2-yl)acrylamide
Mus musculus;
P47811
-
0.0000043 - 0.00016
1-(2,6-dichloro-phenyl)-6-(2,4-difluoro-phenylsulfanyl)-7-(1,2,3,6-tetrahydro-pyridin-4-yl)-3,4-dihydro-1H-pyrido[3,2-d]pyrimidin-2-one
0.000333
2-(4-fluorophenyl)-3-(2-isopropylaminopyridin-4-yl)pyrido[2,3-b]pyrazine
Mus musculus;
-
-
0.00315
2-(4-fluorophenyl)-3-(pyridin-4-yl)quinoxaline
Mus musculus;
-
-
0.0037
2-(4-fluorophenyl)-6,7-dimethyl-3-pyridin-4-ylquinoxaline
Mus musculus;
-
-
0.00156
2-(4-fluorophenyl)-N-[4-(3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl)pyridin-2-yl]acetamide
Mus musculus;
P47811
-
0.000038
3-(4-fluorophenyl)-2-(2-isopropylaminopyridin-4-yl)pyrido[2,3-b]pyrazine
Mus musculus;
-
-
0.00319
3-(4-fluorophenyl)-2-(pyridin-4-yl)pyrido[2,3-b]pyrazine
Mus musculus;
-
-
0.00614
3-(4-fluorophenyl)-6-methoxy-2-(pyridin-4-yl)quinoxaline
Mus musculus;
-
-
0.00045
4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]-N-(1(R)-phenylethyl)pyridin-2-amine
Mus musculus;
P47811
-
0.000006
4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]-N-(1(S)-phenylethyl)pyridin-2-amine
Mus musculus;
P47811
-
0.00006
4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]-N-(tetrahydro-2H-pyran-4-yl)pyridin-2-amine
Mus musculus;
P47811
-
0.000238
4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]-N-(1-methylethyl)pyridin-2-amine
Mus musculus;
-
-
0.00072
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-(1-phenylethyl)pyridin-2-amine
Mus musculus;
-
-
0.000794
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-(3-methylbutan-2-yl)pyridin-2-amine
Mus musculus;
-
-
0.000642
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-isobutylpyridin-2-amine
Mus musculus;
-
-
0.000081
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-isopropylpyridin-2-amine
Mus musculus;
-
-
0.00479
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-[(1R)-1-phenylethyl]pyridin-2-amine
Mus musculus;
-
-
0.000431
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-[(1S)-1-phenylethyl]pyridin-2-amine
Mus musculus;
-
-
0.00159
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-[(R)-3-methylbutan-2-yl]pyridin-2-amine
Mus musculus;
-
-
0.00576
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-[(S)-3-methylbutan-2-yl]pyridin-2-amine
Mus musculus;
-
-
0.000211
4-[4-[3-(4-fluorophenyl)quinoxalin-2-yl]pyridin-2-ylamine]-cyclohexanol
Mus musculus;
-
-
0.00946
4-[6,7-dichloro-3-(4-fluorophenyl)quinoxalin-2-yl]-N-(1,2-dimethylpropyl)pyridin-2-amine
Mus musculus;
-
-
0.000412
4-[6,7-dichloro-3-(4-fluorophenyl)quinoxalin-2-yl]-N-(1-methylethyl)pyridin-2-amine
Mus musculus;
-
-
0.00004
II/SP600125
0.00138
N-(1,2-dimethylpropyl)-4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-amine
Mus musculus;
-
-
0.00089
N-(4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]pyridin-2-yl)2-phenoxypropanamide
Mus musculus;
P47811
-
0.00153
N-benzyl-4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-amine
Mus musculus;
-
-
0.00003
N-sec-butyl-4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]pyridin-2-amine
Mus musculus;
P47811
-
0.000595
N-sec-butyl-4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-amine
Mus musculus;
-
-
0.000114
N-sec-butyl-4-[3-(4-fluorophenyl)quinoxalin-2-yl]pyridin-2-amine
Mus musculus;
-
-
0.000522
N-tert-butyl-4-[2-(4-fluorophenyl)pyrido[3,4-b]pyrazin-3-yl]pyridin-2-amine
Mus musculus;
-
mixture of N-tert-butyl-4-[3-(4-fluorophenyl)pyrido[3,4-b]pyrazin-2-yl]pyridin-2-amine and N-tert-butyl-4-[2-(4-fluorophenyl)pyrido[3,4-b]pyrazin-3-yl]pyridin-2-amine
0.000522
N-tert-butyl-4-[3-(4-fluorophenyl)pyrido[3,4-b]pyrazin-2-yl]pyridin-2-amine
Mus musculus;
-
mixture of N-tert-butyl-4-[3-(4-fluorophenyl)pyrido[3,4-b]pyrazin-2-yl]pyridin-2-amine and N-tert-butyl-4-[2-(4-fluorophenyl)pyrido[3,4-b]pyrazin-3-yl]pyridin-2-amine
0.0003
N-[4-(3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl)pyridin-2-yl]acetamide
Mus musculus;
P47811
-
0.000015 - 0.000048
pyridinyl imidazole-type inhibitors
Mus musculus;
P47811
IC50 of 15-48 nM
-
0.000025 - 0.00005
skepinone-L
Mus musculus;
-
pH 7.4, 22°C
-
0.000259
trans-4-([4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-yl]amino)cyclohexanol
Mus musculus;
-
-
0.000608
trans-4-([4-[6,7-dichloro-3-(4-fluorophenyl)quinoxalin-2-yl]pyridin-2-yl]amino)cyclohexanol
Mus musculus;
-
-
0.0000001 - 0.00097
[4-[3-methyl-2-piperidin-4-yl-5-(3-trifluoromethyl-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-((S)-1-phenyl-ethyl)-amine
additional information
2-(4-fluorophenyl)-3-(pyridin-4-yl)pyrido[2,3-b]pyrazine
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
assay at
7.5
-
assay at
7.6
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
21
-
assay at room temperature
22
-
assay at room temperature
27
-
assay at
additional information
-
using a relatively low induction temperature (21°C in comparison to 32°C) phosphorylation is almost completely prevented. Combining a short 5 h induction with a low expression temperature (21°C) results in highly homogeneous unphosphorylated protein
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
post-mitotic
Manually annotated by BRENDA team
-
primary cultures prepared from embryonic mouse brains, i.e. cerebral hemisphere and thalamus
Manually annotated by BRENDA team
-
activated ERK2
Manually annotated by BRENDA team
-
p38 MAPK is expressed predominantly in nestin-positive cells in the cerebral cortex in embryonic day 10 brain
Manually annotated by BRENDA team
-
mixed glial cultures
Manually annotated by BRENDA team
-
the MAPK family enzymes have regulatory function in the myocardium
Manually annotated by BRENDA team
additional information
-
CD4+ T cell
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
64000
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x * 64000, recombinant p38alpha MAP kinase, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 64000, recombinant p38alpha MAP kinase, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
MAPKs are activated by phosphorylation through MAPK kinases
phosphoprotein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified recombinant p38alpha MAP kinase free or in complex with inhibitor SB203580, sitting or hanging drop vapour diffusion method at 16-20°C, 16 mg/ml protein in 25 mM Tris-HCl, pH 7.5, 100 mM NaCl, 10 mM MgCl2, 10 mM DTT, and 5% glycerol is mixed with reservoir solution containing 10-20% PEG 4000, 18% ethylene glycol, 0.1 M cacodylic acid, pH 6.0, at a volume ratio of 3:2, X-ray diffraction structure determination and analysis at 1.9-2.7 A resolution
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purified p38 isozyme alpha bound to several inhibitors pyridinyl imidazole-type inhibitors, X-ray diffraction structure determination and analysis at 2.1-2.5 A resolution
p38alpha active mutants crystallized by sitting-drop vapour-diffusion method, mutant D176A/F327L to 1.45 A resolution, crystals of the three p38alpha mutants belong to the orthorhombic space group P212121, with one molecule in the asymmetric unit
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, 100 mM NaCl, 50 mM Tris-HCl buffer, pH 7.4, 10 mM DTT, 10 mM MgCl2, 5% glycerol
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
p38alpha active mutants, by gel filtration, on Ni2+-column
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recombinant GST-tagged p38 isozyme alpha from Escherichia coli strain BL21(DE3) by two steps of ion exchange chromatography to homogeneity, the recombinant enzyme is detagged
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recombinant His-tagged p38alpha from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography to homogeneity
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recombinant His-tagged p38alpha MAP kinase from Escherichia coli strain BL21(DE3) by nickel chelate affinity chromatohgraphy, dialysis, and ion exchange chromatography to homogeneity, the His-tag is cleaved off by thrombin
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in COS-7 cells
expression in COS-7 cells
expression of GST-tagged p38 isozyme alpha in Escherichia coli strain BL21(DE3)
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expression of His-tagged p38alpha in Escherichia coli strain BL21(DE3)
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expression of His-tagged wild-type and mutant p38 isozyme alpha
p38alpha active mutants subcloned into vector pET-28a and expressed in Rosetta strain of Escherichia coli
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p38alpha MAP kinase expression in Escherichia coli strain BL21(DE3) as His-tagged protein with a thrombin cleavage site
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quantitative RT-PCR enzyme expression analysis
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recombinant expression of GST-tagged enzyme
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
G110A
site-directed mutagenesis of isozyme alpha, the mutant shows a slightly decreased Km value for ATP, but unaltered activity compared to the wild-type enzyme, decreased sensitivity for inhibitors compared to the wild-type enzyme
G110D
site-directed mutagenesis of isozyme alpha, the mutant shows a decreased Km value for ATP, but unaltered activity compared to the wild-type enzyme, decreased sensitivity for inhibitors compared to the wild-type enzyme
D176A
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active p38alpha mutant, crystals do not appear spontaneously, cross-seeding approaches using crystals of mutant D176A+F327L as the source of microseeds results in crystals suitable for X-ray analysis
D176A/F327L
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most active p38alpha mutant, improvement of crystallization assays, obtained with abolishing phosporylation completely by reducing both the temperature and duration of induction and by significantly shortening the N-terminal hexahistidine spacer, facilitating the growth of well diffracting crystals
D176A/F327S
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active p38alpha mutant, crystals do not appear spontaneously, cross-seeding approaches using crystals of mutant D176A+F327L as the source of microseeds results in crystals suitable for X-ray analysis
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
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MAPKs are targets for drug development
medicine
pharmacology
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MAPKs are targets for inhibitors and pharmacological drug development