Showing Protein Inhibitor of nuclear factor kappa-B kinase subunit alpha (BMDBP01206)
| Identification | |||
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| BMDB Protein ID | BMDBP01206 | ||
| Secondary Accession Numbers |
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| Name | Inhibitor of nuclear factor kappa-B kinase subunit alpha | ||
| Synonyms | Not Available | ||
| Gene Name | CHUK | ||
| Protein Type | Enzyme | ||
| Biological Properties | |||
| General Function | Involved in ATP binding | ||
| Specific 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. Interacts with SASH1 (By similarity). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). | ||
| Pathways | Not Available | ||
| Reactions |
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| GO Classification | Not Available | ||
| Cellular Location | Not Available | ||
| Gene Properties | |||
| Chromosome Location | 26 | ||
| Locus | Not Available | ||
| SNPs | CHUK | ||
| Gene Sequence |
>2223 bp ATGGAGCGGCCCCCGGGGCTGCGGCCGGGCGCGGGCGGGCCCTGGGAGATGCGGGAGCGG CTGGGCACCGGCGGCTTCGGGAACGTCTGCCTGTATCAACATCGGGAACTTGATCTCAAA ATAGCAATTAAGTCTTGTCGCCTAGAGCTAAGTACCAAAAACAGAGAACGGTGGTGCCAT GAAATCCAGATCATGAAGAAGTTGAACCACGCCAATGTTGTAAAGGCCTGTGACGTTCCT GAGGAATTGAATTTTTTGATTAACGATGTGCCTCTGCTAGCAATGGAATATTGTTCTGGA GGAGATCTCCGGAAGCTACTCAACAAACCAGAAAATTGCTGTGGACTTAAAGAAAGCCAG ATACTTTCTTTACTGAGTGATATAGGATCTGGGATCCGATATTTGCATGAAAACAAAATT ATACATCGTGATCTAAAACCTGAAAACATAGTTCTTCAGGATGTTGGTGGAAAGATTATG CATAAAATAATTGATTTGGGATATGCCAAAGATGTTGATCAAGGAAGTCTTTGTACATCT TTTGTGGGAACTTTGCAGTATCTGGCCCCAGAGCTCTTTGAGAATAAGCCTTATACAGCC ACTGTTGATTATTGGAGCTTTGGGACCATGGTGTTTGAGTGTATTGCTGGATATAGGCCT TTTTTGCATCATCTGCAGCCATTTACCTGGCATGAGAAGATTAAGAAGAAGGATCCAAAG TGTATATTTGCATGTGAAGAAATGACAGGAGAAGTTCGGTTTAGTAGCCATTTACCTCAA CCAAATAGCCTTTGTAGTTTAATAGTAGAACCCATGGAAAACTGGCTGCAGTTGATGCTA AACTGGGATCCTCAGCAGAGAGGAGGACCTGTTGATCTTACTTTGAAGCAGCCAAGATGT TTTGTATTAATGGATCACATTCTGAATTTGAAGATAGTACATATCCTAAATATGACTTCT GCAAAGATAATTTCTTTTCTGTTACCACCTGATGAAAGTCTTCATTCACTACAGTCTCGT ATTGAGCGGGAAACTGGAATAAATACTGGTTCTCAAGAGCTTCTTTCAGAGATGGGAATT TCCCTGGATCCTCGGAAACCAGCCTCTCAGTGTGTTCTGGATGGAGTTAGGGGCTGTGAT AGCTATATGGTTTATTTGTTTGATAAAAGTAAGACTGTATATGAAGGACCATTTGCTTCC AGAAGTTTATCTGACTGTGTAAATTATATTGTACAGGACAGCAAAATACAGCTTCCAATT ATCCAGCTGCGTAAAGTATGGGCGGAAGCAGTACACTATGTGTCTGGGCTGAAGGAAGAC TACAGCAGGCTCTTTCAGGGGCAGAGAGCAGCCATGTTAAGTCTTCTTAGATATAATACT AACTTGACAAAAATGAAAAACACTTTGATCTCAGCATCTCAGCAACTGAAAGCTAAATTG GAGTTTTTTCACAAAAGCATTCAGCTTGACTTGGAAAGATATAGTGAGCAGATGACTTAC GGGATATCCTCAGAAAAAATGTTAAAAGCATGGAAAGAAATGGAAGAAAAGGCTATCCAC TATGCTGAGGTGGGTGTCATTGGATACCTGGAGGATCAAATCATGTCCCTGCACACTGAA ATCATGGAGCTACAGAAGAGCCCCTACGGACGACGTCAGGGAGACTTGATGGAATCTCTG GAACAGCGCGCAATTGATCTATATAAGCAGTTAAAGCACAGACCTTCAGATCACTCCTAC AGCGACAGCACGGAGATGGTGAAGATCATTGTGCATACTGTGCAGAGTCAGGACCGGGTT CTCAAGGAGCTGTTTGGTCATCTGAGCAAGTTGTTGGGCTGTAAGCAGAAGATTATTGAT CTACTGCCCAAGGTGGAAATGGCCCTCAGTAACATCAAAGAAGCTGACAGTACTGTCATG TTTATGCAGGGGAAGAGGCAGAAAGAAATATGGCATCTCCTTAAAATTGCCTGTACTCAG AGTTCTGCTCGGTCCCTTGTAGGATCCAGTCTAGAAGGTGTAACCCCTCAGCTGCCCCCA ACTTCAGCAGAACGTGAACATCCTCTGTCATGCGTGGTAACTCCTCAAGATGGGGAGACT TTAGCACAAATGATAGAAGAAAATTTGAACTGTCTTGGCCATTTAAGCACTATTATTCAT GAAGCAAATGAAAAACAGGGCAACAATATGATGAGTCTTGATTGGAGTTGGTTAACAGAA TGA |
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| Protein Properties | |||
| Number of Residues | 740 | ||
| Molecular Weight | 84344.0 | ||
| Theoretical pI | 6.88 | ||
| Pfam Domain Function | Not Available | ||
| Signals |
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| Transmembrane Regions | Not Available | ||
| Protein Sequence |
>Inhibitor of nuclear factor kappa-B kinase subunit alpha MERPPGLRPGAGGPWEMRERLGTGGFGNVCLYQHRELDLKIAIKSCRLELSTKNRERWCH EIQIMKKLNHANVVKACDVPEELNFLINDVPLLAMEYCSGGDLRKLLNKPENCCGLKESQ ILSLLSDIGSGIRYLHENKIIHRDLKPENIVLQDVGGKIMHKIIDLGYAKDVDQGSLCTS FVGTLQYLAPELFENKPYTATVDYWSFGTMVFECIAGYRPFLHHLQPFTWHEKIKKKDPK CIFACEEMTGEVRFSSHLPQPNSLCSLIVEPMENWLQLMLNWDPQQRGGPVDLTLKQPRC FVLMDHILNLKIVHILNMTSAKIISFLLPPDESLHSLQSRIERETGINTGSQELLSEMGI SLDPRKPASQCVLDGVRGCDSYMVYLFDKSKTVYEGPFASRSLSDCVNYIVQDSKIQLPI IQLRKVWAEAVHYVSGLKEDYSRLFQGQRAAMLSLLRYNTNLTKMKNTLISASQQLKAKL EFFHKSIQLDLERYSEQMTYGISSEKMLKAWKEMEEKAIHYAEVGVIGYLEDQIMSLHTE IMELQKSPYGRRQGDLMESLEQRAIDLYKQLKHRPSDHSYSDSTEMVKIIVHTVQSQDRV LKELFGHLSKLLGCKQKIIDLLPKVEMALSNIKEADSTVMFMQGKRQKEIWHLLKIACTQ SSARSLVGSSLEGVTPQLPPTSAEREHPLSCVVTPQDGETLAQMIEENLNCLGHLSTIIH EANEKQGNNMMSLDWSWLTE |
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| External Links | |||
| GenBank ID Protein | CAC93686.1 | ||
| UniProtKB/Swiss-Prot ID | Q95KV1 | ||
| UniProtKB/Swiss-Prot Entry Name | IKKA_BOVIN | ||
| PDB IDs | Not Available | ||
| GenBank Gene ID | AJ414555 | ||
| GeneCard ID | CHUK | ||
| GenAtlas ID | Not Available | ||
| HGNC ID | Not Available | ||
| References | |||
| General References | Not Available | ||