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Literature summary for 2.7.11.10 extracted from
- Beyond NF-kappaB activation: Nuclear functions of IkappaB kinase alpha (2013), J. Biomed. Sci., 20, 3.
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| K44M | a kinase-dead mutant of IKKalpha | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytoplasm | IKKalpha is located both in cytoplasm and nucleus, IKKbeta is predominantly cytoplasmic | Mus musculus | 5737 | - |
| cytoplasm | IKKalpha is located both in cytoplasm and nucleus, IKKbeta is predominantly cytoplasmic | Homo sapiens | 5737 | - |
| additional information | treatment with ATM inhibitors blocks the nuclear IKKalpha accumulation by cisplatin, suggesting that ATM plays a role in the nuclear translocation of IKKalpha | Mus musculus | - |
- |
| additional information | treatment with ATM inhibitors blocks the nuclear IKKalpha accumulation by cisplatin, suggesting that ATM plays a role in the nuclear translocation of IKKalpha | Homo sapiens | - |
- |
| nucleus | IKKalpha is located both in cytoplasm and nucleus, e.g. TNF-alpha, a critical pro-inflammatory cytokine, and Helicobacter pylori stimulate IKKalpha nuclear translocation, mechanisms of IKKalpha nuclear translocation, overview. Kinase activation is required for IKKalpha to translocate into the nucleus | Mus musculus | 5634 | - |
| nucleus | IKKalpha is located both in cytoplasm and nucleus, e.g. TNF-alpha, a critical pro-inflammatory cytokine, cisplatin, estrogen, EGF, and Helicobacter pylori stimulate IKKalpha nuclear translocation, mechanisms of IKKalpha nuclear translocation, overview. Overexpression of Kaposi's sarcoma-associated herpesvirus-encoded viral FLICE inhibitory protein K13 and hepatitis B virus-encoded X protein also induce IKKalpha nuclear translocation to regulate NF-kappaB activity. Kinase activation is required for IKKalpha to translocate into the nucleus | Homo sapiens | 5634 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + [IkappaB protein] | Mus musculus | - |
ADP + [IkappaB phosphoprotein] | - |
? |  |
| ATP + [IkappaB protein] | Homo sapiens | - |
ADP + [IkappaB phosphoprotein] | - |
? | |
| ATP + [p73 protein] | Homo sapiens | IKKalpha in the nucleus | ADP + [p73 phosphoprotein] | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Mus musculus | - |
- |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | ATM activates and phosphorylates IKKalpha at Ser473 in an in vitro kinase assay | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| HeLa cell | - |
Homo sapiens | - |
| Hep-G2 cell | - |
Homo sapiens | - |
| HL-60 cell | - |
Homo sapiens | - |
| MOLT-4 cell | - |
Homo sapiens | - |
| additional information | IKKalpha is present in the nucleus of most primary colorectal tumor tissues and CRC cell lines but not in HS27 or HEK-293 control cells | Homo sapiens | - |
| U2-OS cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + [IkappaB protein] | - |
Mus musculus | ADP + [IkappaB phosphoprotein] | - |
? | |
| ATP + [IkappaB protein] | - |
Homo sapiens | ADP + [IkappaB phosphoprotein] | - |
? | |
| ATP + [p73 protein] | IKKalpha in the nucleus | Homo sapiens | ADP + [p73 phosphoprotein] | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| dimer | the IkappaB kinase complex, IKK, contains two kinase subunits, IKKalpha and IKKbeta | Mus musculus |
| dimer | the IkappakappaB kinase complex, IKK, contains two kinase subunits, IKKalpha and IKKbeta | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| IkappaB kinase alpha | - |
Mus musculus |
| IkappaB kinase alpha | - |
Homo sapiens |
| IkappaB kinase beta | - |
Mus musculus |
| IkappaB kinase beta | - |
Homo sapiens |
| IKKalpha | - |
Mus musculus |
| IKKalpha | - |
Homo sapiens |
| IKKbeta | - |
Mus musculus |
| IKKbeta | - |
Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | different patterns of beta-catenin activation in IKKalpha- and IKKbeta-deficient mouse embryonic fibroblast cells | Mus musculus |
| metabolism | when cells receive appropriate stimuli, such as TNF-alpha, a ternary IKK complex consisting of IKKalpha, IKKbeta and NEMO (IKKgamma) induces IkappaB phosphorylation, leading to IkappaB ubiquitination and proteasomal degradation that are required for liberation of NF-kappaB in the nucleus where it binds to specific promoter elements to activate gene expression. Regulations of cell cycle progression by nuclear IKKalpha, and nuclear function of IKKalpha in tumorigenesis and metastasis, overview | Mus musculus |
| metabolism | when cells receive appropriate stimuli, such as TNF-alpha, a ternary IKK complex consisting of IKKalpha, IKKbeta and NEMO (IKKgamma) induces IkappaB phosphorylation, leading to IkappaB ubiquitination and proteasomal degradation that are required for liberation of NF-kappaB in the nucleus where it binds to specific promoter elements to activate gene expression. Regulations of cell cycle progression by nuclear IKKalpha, and nuclear function of IKKalpha in tumorigenesis and metastasis, overview | Homo sapiens |
| physiological function | the IkappaB kinase complex is the master kinase for NF-kappaB activation, in addition to mediating NF-kappaB signaling by phosphorylating IkappaB proteins during inflammatory and immune responses, the activation of the IKK complex also responds to various stimuli to regulate diverse functions independently of NF-kappaB. IKKalpha and IKKbeta have distinct physiological and pathological roles, while IKKbeta is predominantly cytoplasmic, IKKalpha shuttles between the cytoplasm and the nucleus with nuclear-specific roles of IKKalpha. Nuclear IKKalpha regulates NF-kappaB-dependent gene transcription and inflammation, regulatory functions of NF-kappaB, detailed overview. beta-Catenin-dependent transcription is decreased by IKKbeta but increased by IKKalpha. Regulation of apoptosis by nuclear IKKalpha. Nuclear IKKalpha is essential for cell cycle arrest and differentiation of keratinocyte in the epidermis and the morphogenesis of skeletal and craniofacial morphogenesis | Mus musculus |
| physiological function | the IkappaB kinase complex is the master kinase for NF-kappaB activation, in addition to mediating NF-kappaB signaling by phosphorylating IkappaB proteins during inflammatory and immune responses, the activation of the IKK complex also responds to various stimuli to regulate diverse functions independently of NF-kappaB. IKKalpha and IKKbeta have distinct physiological and pathological roles, while IKKbeta is predominantly cytoplasmic, IKKalpha shuttles between the cytoplasm and the nucleus with nuclear-specific roles of IKKalpha. Nuclear IKKalpha regulates NF-kappaB-dependent gene transcription and inflammation, regulatory functions of NF-kappaB, detailed overview. Regulation of apoptosis by nuclear IKKalpha. Nuclear IKKalpha phosphorylates p73 within its N-terminal region, which may protect p73 from ubiquitination and proteasomal degradation, indispensable role of IKKalpha in cisplatin sensitivity. Nuclear IKKalpha is essential for cell cycle arrest and differentiation of keratinocyte in the epidermis and the morphogenesis of skeletal and craniofacial morphogenesis. Function of TGFbeta-induced nuclear IKKalpha seems to counter its metastatic role in breast cancer cells | Homo sapiens |
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