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Information on EC 2.7.11.10 - IkappaB kinase
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2.7.11.10 IkappaB kinaseIUBMB Comments
The enzyme phosphorylates IkappaB proteins at specific serine residues, which marks them for destruction via the ubiquitination pathway. Subsequent degradation of the IkB complex (IKK) activates NF-kappaB, a translation factor that plays an important role in inflammation, immunity, cell proliferation and apoptosis. If the serine residues are replaced by threonine residues, the activity of the enzyme is decreased considerably.
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Word Map
- 2.7.11.10
- nf-kappab
- necrosis
- factor-kappab
- tnf-alpha
- lps
- lipopolysaccharide
-
lps-induced
- il-1beta
- jnk
- monocyte
- endothelial
- parkinson
- factor-alpha
-
nf-kappab-dependent
- mapks
- proteasome
-
signal-regulated
- c-jun
- cox-2
-
transactivation
-
receptor-associated
-
antiapoptotic
- cyclooxygenase-2
- adaptor
-
dominant-negative
-
tnf-alpha-induced
-
toll-like
- chemokine
- nemo
-
leucine-rich
-
ikappab-alpha
- parthenolide
-
tnf-induced
- rig-i
- relb
- drug development
- analysis
-
factor-alpha-induced
- dithiocarbamate
- traf2
- molecular biology
- tak1
- medicine
- bcl-xl
-
il-1beta-induced
-
cytokine-induced
-
nf-kappab-mediated
-
k63-linked
- irf-3
-
polyubiquitination
- interleukin-1beta
-
tnf-alpha-mediated
-
lps-stimulated
- pharmacology
- icam-1
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
ikappabalpha, ikkbeta, ikappab kinase, ikkalpha, ikk complex, lrrk2 kinase, tank-binding kinase 1, ikk-beta, ikkepsilon, ikk-2, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CHUK
EC 2.7.1.37
-
-
formerly, part transferred
-
I kappa B kinase alpha
IkappaB kinase
IkappaB kinase alpha
IkappaB kinase beta
IkappaB kinase-2
IkappaB kinase-beta
IKK
IKK complex
IKK-2
IKK-beta
IKK2
IKKalpha
IKKbeta
IKKepsilon
inhibitor of nuclear factor kappa B kinase beta subunit
inhibitor of nuclear factor kappa B kinase beta subunit inhibitor of nuclear factor kappa-B kinase alpha subunit
inhibitor of nuclear factor kappa-B kinase alpha subunit
-
inhibitor of nuclear factor kappa-B kinase epsilon subunit
TANK-binding kinase 1
TBK1
IkappaB kinase
-
-
IKK
-
-
IKK
-
-
IKKbeta
-
-
IKKbeta
-
inhibitor of nuclear factor kappa B kinase beta subunit
-
inhibitor of nuclear factor kappa B kinase beta subunit inhibitor of nuclear factor kappa-B kinase alpha subunit
-
inhibitor of nuclear factor kappa B kinase beta subunit inhibitor of nuclear factor kappa-B kinase alpha subunit
-
inhibitor of nuclear factor kappa-B kinase epsilon subunit
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + [IkB protein] = ADP + [IkB phosphoprotein]
-
-
-
-
ATP + [IkappaB protein] = ADP + [IkappaB phosphoprotein]
activation and reaction mechanism
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ATP + [IkappaB protein] = ADP + [IkappaB phosphoprotein]
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
phospho group transfer
-
-
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SYSTEMATIC NAME
IUBMB Comments
ATP:[IkappaB protein] phosphotransferase
The enzyme phosphorylates IkappaB proteins at specific serine residues, which marks them for destruction via the ubiquitination pathway. Subsequent degradation of the IkB complex (IKK) activates NF-kappaB, a translation factor that plays an important role in inflammation, immunity, cell proliferation and apoptosis. If the serine residues are replaced by threonine residues, the activity of the enzyme is decreased considerably.
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CAS REGISTRY NUMBER
COMMENTARY
159606-08-3
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + Bcl
ADP + phosphorylated Bcl10
-
Bcl10 is phosphorylated by the NEMO/IKK complex, recombinant substrate GST-Bcl10 expressed in HEK-293T cells, degradation of Bcl
-
-
?
ATP + Bcl10
ADP + phosphorylated Bcl10
-
negative regulatory activity of the IKK complex in Bcl10 degradation, which is part of the regulatory mechanisms that precisely control the response to antigens, overview
-
-
?
ATP + GST-IkappaBalpha
ADP + GST-IkappaBalpha phosphoprotein
-
activity assay
-
-
?
ATP + IkappaB protein
ADP + phosphorylated IkappaB
-
the enzyme targets the inhibitory IkappaB protein tightly bound to the transcription factor NF-kappaB for proteasomal degradation and allows the freed NF-kappaB to enter the nucleus where it can be transactivate its target gene, IKKalpha is involved in inflammation in macrophages
-
-
?
ATP + IkappaBbeta
ADP + phosphorylated IkappaBbeta
-
phosphorylation of IkappaBalpha at Ser19 and Ser23
-
-
?
ATP + interferon regulatory factor 3
ADP + phosphorylated interferon regulatory factor 3
-
-
-
?
ATP + KKKKERLLDDRHDSGLDSMKDEE
ADP + phosphorylated-KKKKERLLDDRHDSGLDSMKDEE
-
IKK substrate peptide derived from IkappaBalpha sequence
-
-
?
ATP + NF-kappaB p65 subunit
ADP + phosphorylated NF-kappaB p65 subunit
-
IKKalpha and IKKbeta phosphorylate NF-kappaB p65 subunit at Ser536
-
-
?
ATP + STAT1 transcription factor
ADP + phosphorylated STAT1 transcription factor
-
-
-
?
ATP + [biotinylated IkappaBa peptide]
ADP + [biotinylated IkappaBa phosphopeptide]
i.e. biotin-Gly-Leu-Lys-Lys-Glu-Arg-Leu-Leu-Asp-Asp-Arg-His-Asp-Ser32-Gly-Leu-Asp-Ser36-Met-Lys-Asp-Glu-Glu
-
-
?
ATP + [DELTANp73alpha protein]
ADP + [DELTANp73alpha phosphoprotein]
-
phosphorylation at Ser422 by IKKbeta, IKKbeta is inactive with S422A mutant substrate. DELTANp73alpha i a dominant negative inhibitor of p53 and p73
-
-
?
ATP + [GST-IkappaBalpha protein]
ADP + [GST-IkappaBalpha phosphoprotein]
-
-
-
-
?
ATP + [GST-IkappaBbeta protein]
ADP + [GST-IkappaBbeta phosphoprotein]
-
-
-
-
?
ATP + [IFN regulatory factor 3 protein (380-427)]
ADP + [IFN regulatory factor 3 phosphoprotein (380-427)]
-
the truncated mutant is a good substrate
-
-
?
ATP + [IRF3 protein]
ADP + [IRF3 phosphoprotein]
-
phosphorylation at Ser396 by IKK-related IKKepsilon and TBK1 kinase
-
-
?
ATP + [leucine-rich repeat kinase 2 protein]
ADP + [leucine-rich repeat kinase 2 phosphoprotein]
ATP + [MYPT1]
ADP + [MYPT1 phosphoprotein]
the enzyme phosphorylates MYPT1 at Thr853
-
-
?
ATP + [optineurin protein]
ADP + [optineurin phosphoprotein]
-
phosphorylation at Ser177 by IKK-related IKKepsilon and TBK1 kinase
-
-
?
ATP + [S386A IFN regulatory factor 3 protein]
ADP + [S386A IFN regulatory factor 3 phosphoprotein]
-
the mutant substrate is equally phosphorylated as the wild-type IRF3
-
-
?
ATP + [S396A IFN regulatory factor 3 protein]
ADP + [S396A IFN regulatory factor 3 phosphoprotein]
-
the mutant substrate is equally phosphorylated as the wild-type IRF3
-
-
?
ATP + [S402A/S404A/S405A IFN regulatory factor 3 protein]
ADP + [S402A/S404A/S405A IFN regulatory factor 3 phosphoprotein]
-
low activity with the IRF3 mutant
-
-
?
ATP + a protein
ADP + a phosphoprotein
CHUK associates with the NF-kappaB inhibitory protein, IkappaB-alpha, in mammalian cells. CHUK specifically phosphorylates IkappaB-alpha on both Ser32 and Ser36, modifications that are required for targeted degradation of IkappaB-alpha via the ubiquitin-proteasome pathway
-
-
?
ATP + a protein
ADP + a phosphoprotein
the I kappa B/NF-kappa B system is a key determinant of mucosal inflammation and protection
-
-
?
ATP + a protein
ADP + a phosphoprotein
phosphorylation of IkappaBs marks them out for destruction, thereby relieving their inhibitory effect on NF-kappaB
-
-
?
ATP + a protein
ADP + a phosphoprotein
phosphorylates IkappaB inhibitory proteins, causing their degradation and activation of transcription factor NF-kappaB, a master activator of inflammatory responses
-
-
?
ATP + a protein
ADP + a phosphoprotein
the I kappa B/NF-kappa B system is a key determinant of mucosal inflammation and protection
-
-
?
ATP + a protein
ADP + a phosphoprotein
phosphorylates IkappaB inhibitory proteins, causing their degradation and activation of transcription factor NF-kappaB, a master activator of inflammatory responses
-
-
?
ATP + a protein
ADP + a phosphoprotein
autophosphorylation at both Ser and Thr
-
-
?
ATP + a protein
ADP + a phosphoprotein
the expression of pkn1 is developmentally regulated to start immediately before spore formation. The enzyme plays an important role in the onset of proper differentiation
-
-
?
ATP + Bcl
ADP + phosphorylated Bcl
-
phosphorylation at the C-terminus of Bcl by IKKbeta disrupts Bcl10/Malt1 association and Bcl10-mediated signaling
-
-
?
ATP + Bcl
ADP + phosphorylated Bcl
-
phosphorylation at the C-terminus of Bcl by IKKbeta, inactive with a C-terminal 93 amino acid-deletion mutant of Bcl
-
-
?
ATP + Bcl
ADP + phosphorylated Bcl
-
phosphorylation at the C-terminus of Bcl by IKKbeta disrupts Bcl10/Malt1 association and Bcl10-mediated signaling
-
-
?
ATP + Bcl
ADP + phosphorylated Bcl
-
phosphorylation at the C-terminus of Bcl by IKKbeta, inactive with a C-terminal 93 amino acid-deletion mutant of Bcl
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
-
a step in NF-kappaB activation, the IKK complex, composed of IKKalpha, IKKbeta, and NEMO/IKKgamma, is the convergence point for many diverse NFkappaB-activating stimuli including TNFalpha, LPS, and IL-1, overview, IKKbeta is the primary positive regulator of NFkappaB activity in inflammatory processes, is the molecular link between inflammation and cancer
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
-
degradation of IkappaBalpha
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
-
recombinant GST-fusion substrate
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
phosphorylation at Ser-32 and Ser-36
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
-
phosphorylation of IkappaBalpha at Ser32 and Ser36
-
-
?
ATP + protein p100
ADP + phosphorylated protein p100
-
interaction with the NF-kappaB complex
-
-
?
ATP + protein p100
ADP + phosphorylated protein p100
-
required for the interaction with the NF-kappaB complex
-
-
?
ATP + protein p165
ADP + phosphorylated protein p165
-
p65 is part of the IKKepsilon complex with p25, interaction with the NF-kappaB complex
-
-
?
ATP + protein p165
ADP + phosphorylated protein p165
-
required for the interaction with the NF-kappaB complex
-
-
?
ATP + [acetylated histone H3 protein]
ADP + [acetylated histone H3 phosphoprotein]
-
IKKalpha is required for histone function regulation in the nucleus
-
-
?
ATP + [acetylated histone H3 protein]
ADP + [acetylated histone H3 phosphoprotein]
-
phosphorylation at Ser10
-
-
?
ATP + [acetylated histone H3 protein]
ADP + [acetylated histone H3 phosphoprotein]
-
IKKalpha is required for histone function regulation in the nucleus
-
-
?
ATP + [acetylated histone H3 protein]
ADP + [acetylated histone H3 phosphoprotein]
-
phosphorylation at Ser10
-
-
?
ATP + [GST-IkappaBalpha1-54 protein]
ADP + [GST-IkappaBalpha1-54 phosphoprotein]
-
-
-
-
?
ATP + [GST-IkappaBalpha1-54 protein]
ADP + [GST-IkappaBalpha1-54 phosphoprotein]
-
-
-
-
?
ATP + [GST-IkappaBalpha1-54 protein]
ADP + [GST-IkappaBalpha1-54 phosphoprotein]
-
recombinant substrate derived from mouse IkappaBalpha
-
-
?
ATP + [histone H3 protein]
ADP + [histone H3 phosphoprotein]
-
histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression
-
-
?
ATP + [histone H3 protein]
ADP + [histone H3 phosphoprotein]
-
histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression
-
-
?
ATP + [histone H3 protein]
ADP + [histone H3 phosphoprotein]
-
phosphorylation at Ser10 by IKK-alpha
-
-
?
ATP + [IFN regulatory factor 3 protein]
ADP + [IFN regulatory factor 3 phosphoprotein]
-
IRF3 activation is triggered by IKKepsilon/TBK1-mediated phosphorylation on Ser396
-
-
?
ATP + [IFN regulatory factor 3 protein]
ADP + [IFN regulatory factor 3 phosphoprotein]
-
phosphorylation on Ser396, and phosphorylation of Ser402/404/405 cluster in the C-terminal regulatory domain of IRF3 in vitro
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
-
661346, 661547, 662155, 662516, 662684, 662847, 662942, 663441, 702333, 702590, 703253, 703737, 704348, 704783, 705026, 705033, 705074, 705320, 722119, 722826, 723174, 738780, 739047, 739219
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
signalling step of IKK bound to NFkappaB for subsequent ubiquitination of IkappaB and proteolytic degradation
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
the enzyme is also active with a peptide derived from IkappaB protein spanning Ser32 and Ser36 which are phosphorylated
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
the IkappaBalpha subunit of NF-kappaB is phosphorylated at serine residues 32 and 36
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
phosphorylation at Ser32 and Ser36 catalyzed by IkappaBalpha kinase
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
-
661559, 662500, 662516, 662570, 662731, 662931, 662942, 663395, 663441, 703140, 704912, 705074, 705320, 705662, 722119, 722826
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
inhibition and degradation of IkappaB, an inhibitor of NF-kappaB retaining it in the cytoplasm, phosphorylation of IkappaB marks the protein for ubiquitination followed by degradation, activated NF-kappaB is translocated to the nucleus initiating signalling pathways, regulation mechanism, overview
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
inhibitor substrate is bound to NF-kappaB
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
phosphorylation of IkappaB results in its proteolytic degradation
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
required for activation of NF-kappaB resulting in activation of signalling pathways
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
parasite IKKalpha, localized in parasitophorous vacuole membrane, activates mouse' intracellular NF-kappaB in early infection stage resulting in NF-kappaB nuclear translocation and subsequent gene expression independently from the host IKK complex
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
-
enzyme is involved in activation of pro-inflammation signalling
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
-
phosphorylation at Ser32 and Ser36
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
-
IKKbeta-dependent phosphorylation and subsequent ubiquitin-dependent proteolytic degradation of IKKalpha, the 2 subunits have opposing function in NF-kappaB metabolism, overview
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
-
phosphorylation at Ser32 and Ser36
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
-
phosphorylation on Ser32 and Ser36