Any feedback?
Information on EC 2.7.11.10 - IkappaB kinase and Organism(s) Rattus norvegicus and UniProt Accession Q9QY78
for references in articles please use BRENDA:EC2.7.11.10Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
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.
Specify your search results
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 taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
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, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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.
CAS REGISTRY NUMBER
COMMENTARY
159606-08-3
-
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 + [MYPT1]
ADP + [MYPT1 phosphoprotein]
the enzyme phosphorylates MYPT1 at Thr853
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
-
-
-
?
additional information
?
-
-
the IkappaB kinase regulates chromatin structure during reconsolidation of conditioned fear memories, IKKalpha is involved in the regulation of histone H3 phosphorylation and acetylation at specific gene promoters in hippocampus in the NF-kappaB pathway, inhibition of IKKalpha regulation results in impairments in fear memory reconsolidation, mechanism, overview
-
-
?
NATURAL SUBSTRATE
NATURAL 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 + [MYPT1]
ADP + [MYPT1 phosphoprotein]
the enzyme phosphorylates MYPT1 at Thr853
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
-
-
-
?
additional information
?
-
-
the IkappaB kinase regulates chromatin structure during reconsolidation of conditioned fear memories, IKKalpha is involved in the regulation of histone H3 phosphorylation and acetylation at specific gene promoters in hippocampus in the NF-kappaB pathway, inhibition of IKKalpha regulation results in impairments in fear memory reconsolidation, mechanism, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
S1627
preferentially inhibits the beta-subunit of the IKK complex. Specific inhibition of I-kappaB kinase by S1627 modulates the nociceptive response in various nociceptive models in rats. S1627 inhibits the activation of NF-kappaB in the spinal cord and thereby thermal and mechanical hyperalgesia in the zymosan-induced paw inflammation model and the inflammatory edema. It also reduces tactile and cold allodynia in a model of neuropathic pain
-
2-methoxy-N-((6-(1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7yl)pyridin-2-yl)methyl)acetamide
-
BMS-066, inhibitor of IKKbeta
4-(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline
-
BMS-345541, inhibitor of IKKbeta
8-(5-chloro-2-(4-methylpiperazin-1-yl)isonicotinamido)-1-(4-fluorophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide
-
PHA-408, ATP-competitive, selective IKK-2 inhibitor
tetrandrine
-
a bis-benzylisoquinoline alkaloid isolated from the roots of Han-Fang-Ji (Stephania Tetrandra S Moore) effectively inhibits IKKs phosphorylation
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
inhibitor kappa B kinase 2 plays an essential role in the activation of nuclear factor kappa B
physiological function
inhibitor kappa B kinase 2 is involved in the vascular contraction through regulation of myosin light chain phosphatase activity by phosphorylating MYPT1 at Thr853 in rat mesenteric arteries
physiological function
physiological function
-
IkappaB kinase activates NF-kappaB which plays a pivotal role in pro-inflammatory response in the lung
physiological function
-
IKK-2 plays a role in regulating NF-kappaB signaling
physiological function
-
the IkappaB kinase complex is essential in transducing the signal-inducible activation of the transcription factor NF-kappaB in response to proinflammatory stimuli
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). IKKB_RAT
757
0
86866
Swiss-Prot
other Location (Reliability: 2)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oligomer
-
the multisubunit IkappaB kinase complex is composed of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit termed NEMO or IKKgamma
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K44M
S177E/S181E
overexpression of a constitutively active IKKbeta-EGFP show a marked increase in NF-kappaB activity and a decrease in fiber size of weight-bearing soleus muscles, while muscles overexpressing wild-type IKKbeta-HA have no effect
K44M
S176E/S180E
overexpression of a constitutively active IKKalpha-EGFP fusion protein shows that IKKalpha is sufficient to activate NF-kappaB activity and induce fiber atrophy in muscle
K44M
gene transfer of a dominant negative (kinase-dead form) IKKbeta into rat soleus muscles show complete inhibition of 7-day disuse-induced activation of a kappaB reporter gene, while overexpression of wild-type IKKbeta does not. Overexpression of a dominant-negative mutant IKKbeta-EGFP fusion protein show that atrophy is inhibited by 50%, indicating that IKKbeta is required for the atrophy process
K44M
overexpression of a dominant negative (kinase-dead form) IKKbeta plus dominant-negative IKKalpha show an additive effect on the inhibition of disuse atrophy (70%), suggesting that both kinases of the IKK complex are required for muscle atrophy
K44M
overexpression of a dominant negative (kinase-dead form) IKKbeta plus dominant-negative IKKalpha show an additive effect on the inhibition of disuse atrophy (70%), suggesting that both kinases of the IKK complex are required for muscle atrophy
K44M
overexpression of a dominat-negative (kinase-dead form) of the IKKalpha protein decreases unloading-induced NF-kappaB activation and inhibits atrophy by 50%, while overexpression of the wild-type protein has no effect
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
the IkappaB kinases IKKalpha and IKKbeta are necessary and sufficient for skeletal muscle atrophy
medicine
molecular biology
-
tetrandrine suppresses LPS-induced astrocyte activation via modulating IKKs-IkappaBalpha-NF-kappaB signaling pathway
medicine
the IkappaB kinases IKKalpha and IKKbeta are necessary and sufficient for skeletal muscle atrophy
medicine
-
PHA-408 is efficacious in a chronic model of arthritis with no adverse effects
medicine
-
the IKKbeta/IKK2 inhibitor PHA-408 is a powerful anti-inflammatory agent against LPS- and cigarette smoke-mediated lung inflammation
medicine
-
the role of IKK-2 in regulating NF-kappaB signaling in resonse to proinflammatory stimuli has made IKK-2 a primary anti-inflammation therapeutic target
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Jobin, C.; Sartor, R.B.
The I kappa B/NF-kappa B system: a key determinant of mucosalinflammation and protection
Am. J. Physiol.
278
C451-462
2000
Homo sapiens (O14920), Homo sapiens (O15111), Mus musculus (O88351), Mus musculus (Q60680), Rattus norvegicus (Q9QY78)
Nemoto, S.; DiDonato, J.A.; Lin, A.
Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase
Mol. Cell. Biol.
18
7336-7343
1998
Homo sapiens (O14920), Homo sapiens (O15111), Mus musculus (O88351), Mus musculus (Q60680), Rattus norvegicus (Q9QY78)
Lubin, F.D.; Sweatt, J.D.
The IkappaB kinase regulates chromatin structure during reconsolidation of conditioned fear memories
Neuron
55
942-957
2007
Rattus norvegicus
Niederberger, E.; Geisslinger, G.
The IKK-NF-kB pathway: a source for novel molecular drug targets in pain therapy?
FASEB J.
22
3432-3442
2008
Mus musculus (O88351), Rattus norvegicus (Q9QY78)
Van Gammeren, D.; Damrauer, J.S.; Jackman, R.W.; Kandarian, S.C.
The IkappaB kinases IKKalpha and IKKbeta are necessary and sufficient for skeletal muscle atrophy
FASEB J.
23
362-370
2008
Rattus norvegicus, Rattus norvegicus (Q9QY78)
Lin, S.T.; Wang, Y.; Xue, Y.; Feng, D.C.; Xu, Y.; Xu, L.Y.
Tetrandrine suppresses LPS-induced astrocyte activation via modulating IKKs-IkappaBalpha-NF-kappaB signaling pathway
Mol. Cell. Biochem.
315
41-49
2008
Rattus norvegicus
Chiang, P.C.; Kishore, N.N.; Thompson, D.C.
Combined use of pharmacokinetic modeling and a steady-state delivery approach allows early assessment of IkappaB kinase-2 (IKK-2) target safety and efficacy
J. Pharm. Sci.
99
1278-1287
2010
Rattus norvegicus
Mbalaviele, G.; Sommers, C.D.; Bonar, S.L.; Mathialagan, S.; Schindler, J.F.; Guzova, J.A.; Shaffer, A.F.; Melton, M.A.; Christine, L.J.; Tripp, C.S.; Chiang, P.C.; Thompson, D.C.; Hu, Y.; Kishore, N.
A novel, highly selective, tight binding IkappaB kinase-2 (IKK-2) inhibitor: a tool to correlate IKK-2 activity to the fate and functions of the components of the nuclear factor-kappaB pathway in arthritis-relevant cells and animal models
J. Pharmacol. Exp. Ther.
329
14-25
2009
Rattus norvegicus, Homo sapiens (O14920), Homo sapiens (Q15111)
Gillooly, K.M.; Pattoli, M.A.; Taylor, T.L.; Chen, L.; Cheng, L.; Gregor, K.R.; Whitney, G.S.; Susulic, V.; Watterson, S.H.; Kempson, J.; Pitts, W.J.; Booth-Lute, H.; Yang, G.; Davies, P.; Kukral, D.W.; Strnad, J.; McIntyre, K.W.; Darienzo, C.J.; Salter-Cid, L.; Yang, Z.; Wang-Iverson, D.B.; Burke, J.R.
Periodic, partial inhibition of IkappaB kinase beta-mediated signaling yields therapeutic benefit in preclinical models of rheumatoid arthritis
J. Pharmacol. Exp. Ther.
331
349-360
2009
Canis lupus familiaris, Homo sapiens, Mus musculus, Rattus norvegicus
Rajendrasozhan, S.; Hwang, J.W.; Yao, H.; Kishore, N.; Rahman, I.
Anti-inflammatory effect of a selective IkappaB kinase-beta inhibitor in rat lung in response to LPS and cigarette smoke
Pulm. Pharmacol. Ther.
23
172-181
2010
Rattus norvegicus
EXTERNAL LINKS (specific for EC-Number 2.7.11.10)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
