Information on EC 2.7.11.25 - mitogen-activated protein kinase kinase kinase

Word Map on EC 2.7.11.25
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)

The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.11.25
-
RECOMMENDED NAME
GeneOntology No.
mitogen-activated protein kinase kinase kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (MAPKKKK-activated)
This enzyme phosphorylates and activates its downstream protein kinase, EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) but requires MAPKKKK for activation. Some members of this family can be activated by p21-activated kinases (PAK/STE20) or Ras. While c-Raf and c-Mos activate the classical MAPK/ERK pathway, MEKK1 and MEKK2 preferentially activate the c-Jun N-terminal protein kinase(JNK)/stress-activated protein kinase (SAPK) pathway [2]. 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
146702-84-3
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
dogfish
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
Mus musculus C57BL/6
C57BL/6 mice
-
-
Manually annotated by BRENDA team
-
1133931 A+, 1136235 A+, 1138172 A+, 1142697 A+, 1225080 A+, 1225140 A+, 1225145 A+, 1225159 A+, 1225162 A+, 1225191 A+, 1225249 A+, 1225258 A+, 1225294 A+, 1225298 A+, 1225310 A+, 1225315 A+, 1225321 A+, 1225325 A+, 1225332 A+, 1225360 A+, 1225361 A+, 1225364 A+, 1225382 A+, 1225385 A+, 1225387 A+, 1225397 A+, 1290846 A+, 1417877 A+, 1800608 A+, 1917518 A+, 1933285 A+, 1936970 A+, 1940581 A+, 1941744 A+, 2075783 A+, 2075836 A+, 2075847 A+, 2075848 A+, 2075852 A+, 2075867 A+, 2075915 A+, 2075922 A+, 2075943 A+, 2075947 A+, 2076025 A+, 2076026 A+, 2076050 A+, 2313513 A+, 2322541 A+, 2323031 A+, 2328809 A+, 2329038 A+, 2329368 A+, 2330626 A+, 2331378 A+, 2332362 A+, 2361821 A+, 2362716 A+, 2388547 A+, 2389686 A+, 2389691 A+, 2389701 A+, 2389730 A+, 2389750 A+, 2389777 A+, 2389795 A+, 2389799 A+, 2389831 A+, 2389834 A+, 2389848 A+, 2389852 A+, 2389857 A+, 2389858 A+, 2389864 A+, 2389869 A+, 2389887 A+, 2389896 A+, 2389912 A+, 2389913 A+, 2389943 A+, 2389944 A+, 2389967 A+, 2389979 A+, 2390052 A+, 2390063 A+, 2390066 A+, 2390074 A+, 2390077 A+, 2390078 A+, 2428757 A+, 2645035 A+, 2729831 A+, 2943055 A+, 2961185 A+, 2961507 A+, 2967692 A+, 2968930 A+, 2972792 A+, 2972953 A+, 2974292 A+, 2976071 A+, 2977320 A+, 2977508 A+, 3007875 A+, 3102799 A+, 3103043 A+, 3103051 A+, 3103072 A+, 3103073 A+, 3103111 A+, 3103149 A+, 3103160 A+, 3103207 A+, 3103252 A+, 681764 A+, 695197 A+, 850948 A+, 1138058 A++, 1150863 A++, 1225368 A++, 1870806 A++, 1942356 A++, 1944471 A++, 2076028 A++, 2076031 A++, 2325603 A++, 2389933 A++, 2389937 A++, 2389953 A++, 2389960 A++, 2390035 A++, 2390050 A++, 2872157 A++, 2873212 A++, 2894738 A++, 2963534 A++, 2976370 A++, 2976434 A++, 2390530 A++, 2429387 A++, 2950680 A++, 2965173 A++, 2972181 A++, 3103131 A++, 3103240 A++, 3103248 A++, 1138414 A+++, 1225101 A+++, 1225122 A+++, 1225222 A+++, 1225251 A+++, 1225278 A+++, 1225285 A+++, 1225288 A+++, 1225322 A+++, 1225378 A+++, 1225388 A+++, 1225324 A++++
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
1105035 A+, 1130284 A+, 1130428 A+, 1135535 A+, 1188033 A+, 1225090 A+, 1225157 A+, 1225170 A+, 1225203 A+, 1225225 A+, 1225226 A+, 1225242 A+, 1225264 A+, 1225342 A+, 1225347 A+, 1225389 A+, 1310132 A+, 1416138 A+, 1482526 A+, 1536823 A+, 1544832 A+, 1547472 A+, 1703260 A+, 1823170 A+, 1907091 A+, 1919660 A+, 1924176 A+, 1925577 A+, 1926565 A+, 1929638 A+, 1933238 A+, 1936657 A+, 1938918 A+, 1939862 A+, 1941800 A+, 1944630 A+, 2016049 A+, 2016089 A+, 2016174 A+, 2075788 A+, 2075809 A+, 2075850 A+, 2248430 A+, 2278495 A+, 2318946 A+, 2321513 A+, 2324717 A+, 2326415 A+, 2326518 A+, 2328045 A+, 2328161 A+, 2328550 A+, 2329674 A+, 2331621 A+, 2340863 A+, 2361481 A+, 2386368 A+, 2389675 A+, 2389677 A+, 2389683 A+, 2389684 A+, 2389689 A+, 2389690 A+, 2389699 A+, 2389701 A+, 2389702 A+, 2389704 A+, 2389714 A+, 2389721 A+, 2389730 A+, 2389734 A+, 2389742 A+, 2389752 A+, 2389775 A+, 2389892 A+, 2389921 A+, 2390057 A+, 2390408 A+, 2413266 A+, 2642810 A+, 2726572 A+, 2737902 A+, 2792817 A+, 2800986 A+, 2948923 A+, 2952365 A+, 2952757 A+, 2952818 A+, 2958178 A+, 2963490 A+, 2964659 A+, 2965369 A+, 2965556 A+, 2969829 A+, 3103084 A+, 969723 A+, 1150863 A++, 1939373 A++, 2328954 A++, 1935711 A++, 1945199 A++, 2389974 A++, 2973296 A++, 1128011 A+++, 1130404 A+++, 1225087 A+++, 1225104 A+++, 1225106 A+++, 1225115 A+++, 1225136 A+++, 1225142 A+++, 1225146 A+++, 1225166 A+++, 1225169 A+++, 1225197 A+++, 1225201 A+++, 1225217 A+++, 1225219 A+++, 1225223 A+++, 1225286 A+++, 1225336 A+++, 491921 A+++, 492001 A+++, 492052 A+++, 492057 A+++
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
synthetic construct
-
-
-
Manually annotated by BRENDA team
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Manually annotated by BRENDA team
yeasts
-
-
-
Automatic Mining of ENzyme DAta
-
-
-
Automatic Mining of ENzyme DAta
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
MEKK3 is a central intermediate signaling component in lysophosphatidic acid-induced activation of the nuclear factor-kappa B
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 + ASK1
ADP + phosphorylated ASK1
show the reaction diagram
ATP + cdc42
ADP + phosphorylated cdc42
show the reaction diagram
-
-
-
-
?
ATP + ERK
ADP + phosphorylated ERK
show the reaction diagram
ATP + ERK5
ADP + phosphorylated ERK5
show the reaction diagram
ATP + F-kappaB luciferase
ADP + phosphorylated F-kappaB luciferase
show the reaction diagram
synthetic construct
-
Ser526 and Thr530 are required for MEKK3-dependent activity
-
-
-
ATP + GSK3beta
ADP + phosphorylated GSK3beta
show the reaction diagram
ATP + histone H1
ADP + phosphorylated histone H1
show the reaction diagram
-
-
-
-
?
ATP + JNK
ADP + phosphorylated JNK
show the reaction diagram
ATP + MAPKK
ADP + phosphorylated MAPKK
show the reaction diagram
-
MAPKK activation
-
-
?
ATP + MEK
ADP + phosphorylated MEK
show the reaction diagram
ATP + Mek1
ADP + phospho-Mek1
show the reaction diagram
-
-
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
show the reaction diagram
ATP + MEK2
ADP + phosphorylated MEK2
show the reaction diagram
ATP + MEK4
ADP + phosphorylated MEK4
show the reaction diagram
synthetic construct
-
-
-
-
?
ATP + MEK5
ADP + phosphorylated MEK5
show the reaction diagram
ATP + MKK
ADP + phosphorylated MKK
show the reaction diagram
ATP + MKK1
ADP + phosphorylated MKK1
show the reaction diagram
ATP + MKK3
ADP + phosphorylated MKK3
show the reaction diagram
ATP + MKK4
ADP + phosphorylated MKK4
show the reaction diagram
ATP + MKK6
ADP + phosphorylated MKK6
show the reaction diagram
ATP + MKK7
ADP + phosphorylated MKK7
show the reaction diagram
ATP + MPK4
ADP + phosphorylated MPK4
show the reaction diagram
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
show the reaction diagram
ATP + p38
ADP + phosphorylated p38
show the reaction diagram
ATP + p42 MAPK
ADP + phosphorylated p42 MAPK
show the reaction diagram
ATP + Pbs2p
ADP + phosphorylated Pbs2p
show the reaction diagram
-
-
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
ATP + Rac
ADP + phosphorylated Rac
show the reaction diagram
-
-
-
-
?
ATP + Ror2
ADP + phospho-Ror2
show the reaction diagram
ATP + SEK
ADP + phosphorylated SEK
show the reaction diagram
-
recombinant GST-tagged inactive KR-mutant SEK, i.e. SAPK/ERK or stress-activated protein kinase/extracellular-signal-regulated kinase, substrate
-
-
?
ATP + SMRT
ADP + phosphorylated SMRT
show the reaction diagram
synthetic construct
-
SMRT is regulated by MAPKKK cascades that induce its release from its receptor partners, its export from nucleus to cytoplasm, and derepression of target gene expression. SMRTalpha, SMRTtau, and SMRTsp2 splice variants are released from their nuclear receptor partners in response to MAPKKK activation, the SMRTsp18 variant, which resembles N-CoR in its overall molecular architecture, is relatively refractory to this kinase-induced release
-
-
?
ATP + Wis1
ADP + phosphorylated Wis1
show the reaction diagram
ATP + WRKY53
ADP + phosphorylated WRKY53
show the reaction diagram
-
phosphorylation increases DNA-binding activity of WRKY53
-
-
?
BAD + ATP
BAD-phosphate + ADP
show the reaction diagram
-
activation of the proapoptotic protein BAD
-
-
-
MAP2K + ATP
MAP2K-phosphate + ADP
show the reaction diagram
-
involved in reducing c-jun N-terminal kinase (JNK, MAPK8) activation and protecting the mice from nickel-induced acute lung injury
-
-
-
MEK-1 + ATP
phosphorylated MEK-1 + ADP
show the reaction diagram
-
essential step of the MAP-kinase cascade, activation of MEK-1 which is a MAPKK, essential role in vegetative hyphal growth, conidiation and protoperithecial development, as well as a more limited involvement in maintenance of cell wall integrity, not essential for the resistance to osmotic stress, negatively regulates tyrosinase expression
-
-
?
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 + ERK
ADP + phosphorylated ERK
show the reaction diagram
ATP + ERK5
ADP + phosphorylated ERK5
show the reaction diagram
-
substrate of MEKK2 and MEKK3, activation of the ERK-dependent signaling pathway
-
-
?
ATP + JNK
ADP + phosphorylated JNK
show the reaction diagram
-
i.e. Jun amino terminal kinase
-
-
?
ATP + MAPKK
ADP + phosphorylated MAPKK
show the reaction diagram
-
MAPKK activation
-
-
?
ATP + MEK
ADP + phosphorylated MEK
show the reaction diagram
ATP + MEK1
ADP + phosphorylated MEK1
show the reaction diagram
ATP + MEK2
ADP + phosphorylated MEK2
show the reaction diagram
Q6VAB6
activation by MEKK3 of MAPK signaling pathways
-
-
?
ATP + MEK5
ADP + phosphorylated MEK5
show the reaction diagram
-
activated MEK5 activates ERK5
-
-
?
ATP + MKK
ADP + phosphorylated MKK
show the reaction diagram
-
induction of the JNK pathway activation
-
-
?
ATP + MKK1
ADP + phosphorylated MKK1
show the reaction diagram
-
MKK1 activates the ERK2 signaling pathway
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
show the reaction diagram
ATP + MKK4
ADP + phosphorylated MKK4
show the reaction diagram
ATP + MKK6
ADP + phosphorylated MKK6
show the reaction diagram
ATP + MKK7
ADP + phosphorylated MKK7
show the reaction diagram
ATP + p42 MAPK
ADP + phosphorylated p42 MAPK
show the reaction diagram
-
Ras-induced activation of the MAPK signaling cascade
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
ATP + Ror2
ADP + phospho-Ror2
show the reaction diagram
Q62073
TGF-beta activated kinase 1, a MAPKKK, interacts with Ror2 and phosphorylates its intracellular carboxyterminal serine/thronine/proline-rich, STP, domain, Wnt-ligand binding differentially controls the Ror2/TAK1 interaction, Ror2 seems to act as a Wnt co-receptor enhancing Wnt-dependent canonical pathways while Tyr- and Ser/Thr-phosphorylation of Ror2 negatively controls the efficiency of these pathways, overview
-
-
?
BAD + ATP
BAD-phosphate + ADP
show the reaction diagram
-
activation of the proapoptotic protein BAD
-
-
-
MAP2K + ATP
MAP2K-phosphate + ADP
show the reaction diagram
-
involved in reducing c-jun N-terminal kinase (JNK, MAPK8) activation and protecting the mice from nickel-induced acute lung injury
-
-
-
MEK-1 + ATP
phosphorylated MEK-1 + ADP
show the reaction diagram
-
essential step of the MAP-kinase cascade, activation of MEK-1 which is a MAPKK, essential role in vegetative hyphal growth, conidiation and protoperithecial development, as well as a more limited involvement in maintenance of cell wall integrity, not essential for the resistance to osmotic stress, negatively regulates tyrosinase expression
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
-
preferred divalent cation as ATP metal cofactor
additional information
-
no or nearly no activity with Ni2+, Zn2+, Co2+, and Cu2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
BAY 43-9006
-
c-Raf inhibitor, shows promising response rate in patients with primary renal cell carcinomas
CEP-1347
-
inhibits MLKs and is well tolerated in human trials, does not perform in trials for neurodegenerative disorders such as Parkinson“s disease
EGTA
-
negative regulation of COT
farnesylthiosalicylic acid
-
a Ras antagonist, inhibits the wild-type and V599E mutant enzyme in vivo and in vitro
glutathione
-
binding to glutathione inhibits MEKK1 in vitro
hKSR-2
i.e. human kinase suppressor of ras 2, selectively inhibits MEKK3-activated MAP kinase and NF-kappaB pathways in inflammation, selectively inhibits Cot, no inhibition of MEKK4, TAK1, and Ras-Raf
-
menadione
-
i.e. 2-methyl-1,4-naphthoquinone, oxidative stress caused by menadione inhibits MEKK1, which can be reversed by DTT and glutathione, inhibition is thus caused by a reversible Cys1238 oxidation mechanism followed by binding to glutathione, no inhibition of MEKK1 mutant C1238V
N-ethylmaleimide
-
MEKK1 inhibition through Cys1238 alkylation, Cys1238 is located in the ATP binding domain, no inhibition of MEKK1 mutant C1238V
p105
-
p38
-
negatively regulates tAK1 activation
-
PD98059
Protein phosphatase 2A
PP2A, dephosphorylates and inactivates MEKK3
-