Molecule Information
General Information of the Molecule (ID: Mol00098)
Name |
Nuclear factor kappa-B kinase subunit alpha inhibitor (IKKalpha)
,Homo sapiens
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Synonyms |
I-kappa-B kinase alpha; IKK-A; IKK-alpha; IkBKA; IkappaB kinase; Conserved helix-loop-helix ubiquitous kinase; I-kappa-B kinase 1; IKK1; Nuclear factor NF-kappa-B inhibitor kinase alpha; NFKBIKA; Transcription factor 16; TCF-16; IKKA; TCF16
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Molecule Type |
Protein
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Gene Name |
CHUK
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Gene ID | |||||
Location |
chr10:100188300-100229596[-]
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Sequence |
MERPPGLRPGAGGPWEMRERLGTGGFGNVCLYQHRELDLKIAIKSCRLELSTKNRERWCH
EIQIMKKLNHANVVKACDVPEELNILIHDVPLLAMEYCSGGDLRKLLNKPENCCGLKESQ ILSLLSDIGSGIRYLHENKIIHRDLKPENIVLQDVGGKIIHKIIDLGYAKDVDQGSLCTS FVGTLQYLAPELFENKPYTATVDYWSFGTMVFECIAGYRPFLHHLQPFTWHEKIKKKDPK CIFACEEMSGEVRFSSHLPQPNSLCSLVVEPMENWLQLMLNWDPQQRGGPVDLTLKQPRC FVLMDHILNLKIVHILNMTSAKIISFLLPPDESLHSLQSRIERETGINTGSQELLSETGI SLDPRKPASQCVLDGVRGCDSYMVYLFDKSKTVYEGPFASRSLSDCVNYIVQDSKIQLPI IQLRKVWAEAVHYVSGLKEDYSRLFQGQRAAMLSLLRYNANLTKMKNTLISASQQLKAKL EFFHKSIQLDLERYSEQMTYGISSEKMLKAWKEMEEKAIHYAEVGVIGYLEDQIMSLHAE IMELQKSPYGRRQGDLMESLEQRAIDLYKQLKHRPSDHSYSDSTEMVKIIVHTVQSQDRV LKELFGHLSKLLGCKQKIIDLLPKVEVALSNIKEADNTVMFMQGKRQKEIWHLLKIACTQ SSARSLVGSSLEGAVTPQTSAWLPPTSAEHDHSLSCVVTPQDGETSAQMIEENLNCLGHL STIIHEANEEQGNSMMNLDWSWLTE Click to Show/Hide
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Function |
Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Participates also in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities. Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP. Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor. Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death. Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity.
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Uniprot ID | |||||
Ensembl ID | |||||
HGNC ID | |||||
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Type(s) of Resistant Mechanism of This Molecule
UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
1 drug(s) in total
Fluorouracil
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Disease Class: Colon cancer | [1] | |||
Resistant Disease | Colon cancer [ICD-11: 2B90.1] | |||
Resistant Drug | Fluorouracil | |||
Molecule Alteration | Expression | Down-regulation |
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Experimental Note | Revealed Based on the Cell Line Data | |||
Cell Pathway Regulation | Cell apoptosis | Activation | hsa04210 | |
NF-kappaB signaling pathway | Inhibition | hsa04064 | ||
In Vitro Model | DLD1 cells | Colon | Homo sapiens (Human) | CVCL_0248 |
SW620 cells | Colon | Homo sapiens (Human) | CVCL_0547 | |
HCT116 cells | Colon | Homo sapiens (Human) | CVCL_0291 | |
NCM460 cells | Colon | Homo sapiens (Human) | CVCL_0460 | |
SW1116 cells | Colon | Homo sapiens (Human) | CVCL_0544 | |
In Vivo Model | Nude mouse xenograft model | Mus musculus | ||
Experiment for Molecule Alteration |
Western blot analysis; Dual-Luciferase Reporter Assay | |||
Experiment for Drug Resistance |
CellTiter-Glo Luminescent Cell Viability Assay; CCK8 assay; Flow cytometric analysis | |||
Mechanism Description | miR15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-kB/XIAP axis. miR15b-5p results in significant reductions in the levels of NF-kB1 and Ikk-alpha, two key modulators in inflammation and cell apoptosis. |
Disease- and Tissue-specific Abundances of This Molecule
ICD Disease Classification 02
Colon cancer [ICD-11: 2B90]
Differential expression of molecule in resistant diseases | ||
The Studied Tissue | Colon | |
The Specified Disease | Colon cancer | |
The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 2.61E-04; Fold-change: 1.34E-01; Z-score: 3.38E-01 | |
The Expression Level of Disease Section Compare with the Adjacent Tissue | p-value: 4.15E-09; Fold-change: -4.37E-01; Z-score: -5.60E-01 | |
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
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Disease-specific Molecule Abundances | Click to View the Clearer Original Diagram | |
Tissue-specific Molecule Abundances in Healthy Individuals
References
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