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Information on EC 2.7.12.2 - mitogen-activated protein kinase kinase and Organism(s) Rattus norvegicus and UniProt Accession Q01986

for references in articles please use BRENDA:EC2.7.12.2
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IUBMB Comments
This enzyme is a dual-specific protein kinase and requires mitogen-activated protein kinase kinase kinase (MAPKKK) for activation. It is required for activation of EC 2.7.11.24, mitogen-activated protein kinase. Phosphorylation of MEK1 by Raf involves phosphorylation of two serine residues . 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.
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This record set is specific for:
Rattus norvegicus
UNIPROT: Q01986
Word Map
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
apoptosis signal-regulating kinase 1, ASK1, At3g21220, BcOs4, BOS5, CaSTE7, cdc7 protein kinase, Cdc7p kinase, cell division control protein 7, cpkk1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dual specificity mitogen-activated protein kinase kinase 1
266337
-
dual specificity mitogen-activated protein kinase kinase 2
266323
-
dual specificity mitogen-activated protein kinase kinase 5
266355
-
extracellular-signal-regulated kinase
248
-
extracellular-signal-regulated kinase 1
248
-
extracellular-signal-regulated kinase 2
248
-
MAP kinase kinase 4
248
-
MAPK/Erk kinase
248
-
MEK kinase 1
266356
-
MEK1/2
248
-
MEK5
266355
-
mitogen-activated protein kinase kinase
248
-
mitogen-activated protein kinase kinase 1
248
-
mitogen-activated protein kinase kinase 2
248
-
mitogen-activated protein kinase kinase 4
248
-
mitogen-activated protein kinase kinase kinase 1
266356
-
p21cdc42/rac1 binding protein
266359
-
serine/threonine-protein kinase PAK 2
266359
-
additional information
248
the enzyme belongs to the MKK familly
SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (MAPKKK-activated)
This enzyme is a dual-specific protein kinase and requires mitogen-activated protein kinase kinase kinase (MAPKKK) for activation. It is required for activation of EC 2.7.11.24, mitogen-activated protein kinase. Phosphorylation of MEK1 by Raf involves phosphorylation of two serine residues [5]. 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
142805-58-1
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + p42 MAP kinase
ADP + ?
show the reaction diagram
-
-
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
-
tyrosine/threonine kinase
-
-
-
ATP + Janus kinase 2
ADP + phospho-Janus kinase 2
show the reaction diagram
-
activation
-
-
?
ATP + JNK
ADP + phospho-JNK
show the reaction diagram
ATP + MAPK
ADP + phosphorylated MAPK
show the reaction diagram
-
-
-
-
?
ATP + p38
ADP + phospho-p38
show the reaction diagram
ATP + protein
ADP + phosphoprotein
show the reaction diagram
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + Janus kinase 2
ADP + phospho-Janus kinase 2
show the reaction diagram
-
activation
-
-
?
ATP + JNK
ADP + phospho-JNK
show the reaction diagram
-
the enzyme is involved in stress-activated MAP kinase pathways and tumorigenesis, overview
-
-
?
ATP + MAPK
ADP + phosphorylated MAPK
show the reaction diagram
-
-
-
-
?
ATP + p38
ADP + phospho-p38
show the reaction diagram
-
the enzyme is involved in stress-activated MAP kinase pathways and tumorigenesis, overview
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
Q64303
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Berberine
-
suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after mechanical injury in vitro
PD98059
phencyclidine
-
a N-methyl-D-aspartate receptor antagonist, it is neurotoxic to developing brains and results in schizophrenia-like behaviors later in development, it elicites time-dependent inhibition of the MEK/ERK and PI-3K/Akt pathways, overview
U0126
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
in vivo assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
from superior cervical ganglia
Manually annotated by BRENDA team
-
superior cervical
Manually annotated by BRENDA team
-
components of Porphyromonas gingivalis spent culture medium not only result in increased total MEK-1 and ERK-1 protein products, but also cause increased cellular size, DNA fragmentation, and nuclear condensation
Manually annotated by BRENDA team
enzyme MEK5 alpha
Manually annotated by BRENDA team
-
cultured cortical neurons from fetal brain
Manually annotated by BRENDA team
-
aortic, cell culture
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
MKK4, mainly
Manually annotated by BRENDA team
isoform MEK5 beta is primarily cytosolic
Manually annotated by BRENDA team
associated with
Manually annotated by BRENDA team
isoform MEK5 alpha
-
Manually annotated by BRENDA team
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
MP2K1_RAT
393
0
43465
Swiss-Prot
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
44000
-
x * 44000, calculation from nucleotide sequence
45000
-
x * 45000, calculation from nucleotide sequence
62000
x * 62000
195000
x * 195000, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
alternative splicing results in a 50000 Da alpha and a 40000 Da beta isoform of MEK5
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
isolation of cDNA
-
expression in COS cells
-
isolation of cDNA
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
Porphyromonas gingivalis-secreted factors may initiate MEK/ERK signal pathways and lead to myocardial cell hypertrophy and apoptosis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Otsu, M.; Terada, Y.; Okayama, H.
Isolation of two members of the rat MAP kinase kinase gene family
FEBS Lett.
320
246-250
1993
Rattus norvegicus (P36506), Rattus norvegicus (Q01986)
Manually annotated by BRENDA team
Wu, J.; Harrison, J.K.; Dent, P.; Lynch, K.R.; Weber, M.J.; Sturgill, T.W.
Identification and characterization of a new mammalian mitogen-activated protein kinase kinase, MKK2
Mol. Cell. Biol.
13
4539-4548
1993
Rattus norvegicus (P36506)
Manually annotated by BRENDA team
Doring, F.; Drewes, G.; Berling, B.; Mandelkow, E.M.
Cloning and sequencing of a cDNA encoding rat brain mitogen-activated protein (MAP) kinase activator
Gene
131
303-304
1993
Rattus norvegicus (Q01986)
Manually annotated by BRENDA team
Wu, J.; Harrison, J.K.; Vincent, L.A.; Haystead, C.; Haystead, T.A.; Michel, H.; Hunt, D.F.; Lynch, K.R.; Sturgill, T.W.
Molecular structure of a protein-tyrosine/threonine kinase activating p42 mitogen-activated protein (MAP) kinase: MAP kinase kinase
Proc. Natl. Acad. Sci. USA
90
173-177
1993
Rattus norvegicus (Q01986)
Manually annotated by BRENDA team
English, J.M.; Vanderbilt, C.A.; Xu, S.; Marcus, S.; Cobb, M.H.
Isolation of MEK5 and differential expression of alternatively spliced forms
J. Biol. Chem.
270
28897-28902
1995
Rattus norvegicus (Q62862)
Manually annotated by BRENDA team
Xu, S.; Robbins, D.J.; Christerson, L.B.; English, J.M.; Vanderbilt, C.A.; Cobb, M.H.
Cloning of rat MEK kinase 1 cDNA reveals an endogenous membrane-associated 195-kDa protein with a large regulatory domain
Proc. Natl. Acad. Sci. USA
93
5291-5295
1996
Rattus norvegicus (Q62925)
Manually annotated by BRENDA team
Teo, M.; Manser, E.; Lim, L.
Identification and molecular cloning of a p21cdc42/rac1-activated serine/threonine kinase that is rapidly activated by thrombin in platelets
J. Biol. Chem.
270
26690-26697
1995
Rattus norvegicus (Q64303)
Manually annotated by BRENDA team
Gil, C.; Chaib-Oukadour, I.; Aguilera, J.
C-terminal fragment of tetanus toxin heavy chain activates Akt and MEK/ERK signalling pathways in a Trk receptor-dependent manner in cultured cortical neurons
Biochem. J.
373
613-620
2003
Rattus norvegicus
Manually annotated by BRENDA team
Liang, K.W.; Ting, C.T.; Yin, S.C.; Chen, Y.T.; Lin, S.J.; Liao, J.K.; Hsu, S.L.
Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury
Biochem. Pharmacol.
71
806-817
2006
Rattus norvegicus
Manually annotated by BRENDA team
Atwal, J.K.; Singh, K.K.; Tessier-Lavigne, M.; Miller, F.D.; Kaplan, D.R.
Semaphorin 3F antagonizes neurotrophin-induced phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase signaling: a mechanism for growth cone collapse
J. Neurosci.
23
7602-7609
2003
Rattus norvegicus
Manually annotated by BRENDA team
Lee, S.D.; Chang, S.H.; Kuo, W.H.; Ying, T.H.; Kuo, W.W.; Li, P.C.; Hsu, H.H.; Lu, M.C.; Ting, H.; Huang, C.Y.
Role of mitogen-activated protein kinase kinase in Porphyromonas gingivalis-induced myocardial cell hypertrophy and apoptosis
Eur. J. Oral Sci.
114
154-159
2006
Rattus norvegicus
Manually annotated by BRENDA team
Whitmarsh, A.J.; Davis, R.J.
Role of mitogen-activated protein kinase kinase 4 in cancer
Oncogene
26
3172-3184
2007
Drosophila melanogaster, Homo sapiens, Homo sapiens (O14733), Homo sapiens (P45985), Mus musculus, Mus musculus (P47809), Mus musculus (Q8CE90), Rattus norvegicus, Xenopus laevis
Manually annotated by BRENDA team
Chen, Y.C.; Huang, S.H.; Wang, S.M.
Adenosine-stimulated adrenal steroidogenesis involves the adenosine A2A and A2B receptors and the Janus kinase 2-mitogen-activated protein kinase kinase-extracellular signal-regulated kinase signaling pathway
Int. J. Biochem. Cell Biol.
40
2815-2825
2008
Rattus norvegicus
Manually annotated by BRENDA team
Xia, Y.; Wang, C.Z.; Liu, J.; Anastasio, N.C.; Johnson, K.M.
Lithium protection of phencyclidine-induced neurotoxicity in developing brain: the role of phosphatidylinositol-3 kinase/Akt and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathways
J. Pharmacol. Exp. Ther.
326
838-848
2008
Rattus norvegicus
Manually annotated by BRENDA team
Maharjan, S.; Serova, L.I.; Sabban, E.L.
Membrane-initiated estradiol signaling increases tyrosine hydroxylase promoter activity with ERalpha in PC12 cells
J. Neurochem.
112
42-55
2010
Rattus norvegicus
Manually annotated by BRENDA team
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