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Literature summary for 2.7.11.10 extracted from
- Site-specific monoubiquitination of IkappaB kinase IKKbeta regulates its phosphorylation and persistent activation (2005), J. Biol. Chem., 280, 43272-43279.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| additional information | IKKgamma phosphorylation by IKKbeta is induced by the cytokine TNF-R1, IKKbeta is recruited to the cytoplasmic tail of TNF-R1 by adaptor proteins, such as RIP | Homo sapiens | |
| NEMO | i.e. NF-kappaB essential modifier, complexing with IkappaB kinase-gamma | Homo sapiens | |
| Tax | viral oncoprotein, activates by direct binding, involved in ubiquitination and phosphorylation | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| coexpression of FLAG-atgged wild-type and mutant IKKbeta proteins with T7-tagged IKKgamma and HA-tagged ubiquitin in 293T cells | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| K106R | site-directed mutagenesis, ubiquitination and phosphorylation of the mutant is unaltered compared to the wild-type IKKbeta | Homo sapiens |
| K147R | site-directed mutagenesis, reduced monoubiquitination of IKKbeta mutant | Homo sapiens |
| K163R | site-directed mutagenesis, monoubiquitination-defective mutant of IKKbeta retaining kinase activity in Tax-expressing cells | Homo sapiens |
| K171R | site-directed mutagenesis, ubiquitination and phosphorylation of the mutant is unaltered compared to the wild-type IKKbeta | Homo sapiens |
| K18R | site-directed mutagenesis, ubiquitination and phosphorylation of the mutant is unaltered compared to the wild-type IKKbeta | Homo sapiens |
| K198R | site-directed mutagenesis, ubiquitination and phosphorylation of the mutant is unaltered compared to the wild-type IKKbeta | Homo sapiens |
| K234R | site-directed mutagenesis, ubiquitination and phosphorylation of the mutant is unaltered compared to the wild-type IKKbeta | Homo sapiens |
| K238R | site-directed mutagenesis, monoubiquitination-defective mutant of IKKbeta | Homo sapiens |
| K254R | site-directed mutagenesis, ubiquitination and phosphorylation of the mutant is unaltered compared to the wild-type IKKbeta | Homo sapiens |
| K275R | site-directed mutagenesis, ubiquitination and phosphorylation of the mutant is unaltered compared to the wild-type IKKbeta | Homo sapiens |
| K44R | site-directed mutagenesis, monoubiquitination-defective mutant of IKKbeta | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytoplasm | - |
Homo sapiens | 5737 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + [IkappaBbeta protein] | Homo sapiens | - |
ADP + [IkappaBbeta phosphoprotein] | - |
? |  |
| additional information | Homo sapiens | IKKbeta regulates the translocation of NF-kappaB from cytoplasm to nucleus earmarking the transcription factor for polyubiquitination and proteasome-mediated degradation, the cytokine TNFalpha-induced T-loop-phosphorylated IKKbeta becomes monoubiquitinated at Lyk163 proximal to the T-loop, mechanism of post-translational crosstalk, overview | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | IKKbeta is phosphorylated at the T loop residues Ser171 and Ser181, chronic phosphorylation leads to attachment of one ubiquitin molecule at nearby Lys163, which in turn modulates the phosphorylation status at select C-terminal serines | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + [GST-IkappaBalpha1-54 protein] | - |
Homo sapiens | ADP + [GST-IkappaBalpha1-54 phosphoprotein] | - |
? | |
| ATP + [IkappaBbeta protein] | - |
Homo sapiens | ADP + [IkappaBbeta phosphoprotein] | - |
? | |
| additional information | IKKbeta regulates the translocation of NF-kappaB from cytoplasm to nucleus earmarking the transcription factor for polyubiquitination and proteasome-mediated degradation, the cytokine TNFalpha-induced T-loop-phosphorylated IKKbeta becomes monoubiquitinated at Lyk163 proximal to the T-loop, mechanism of post-translational crosstalk, overview | Homo sapiens | ? | - |
? | |
| additional information | TNF-R1-activated IKKbeta phosphorylates IKKgamma and IKKalpha, autophosphorylation patterns involving K163 of IKKbeta, regulation, overview | Homo sapiens | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| More | IKKbeta contains a leucine zipper, a T-loop, and a HLH domain important for phosphorylation and ubiquitination, the IKK complex consists of 3 subunits: catalytic IKKalpha and IKKbeta, and noncatalytic, regulatory NEMO/IKKgamma | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| IKKbeta | - |
Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Homo sapiens | |
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