Inhibitor of nuclear factor kappa-B kinase subunit alpha
| Name | Inhibitor of nuclear factor kappa-B kinase subunit alpha |
|---|---|
| Synonyms |
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| Gene Name | CHUK |
| Organism | Human |
| Amino acid sequence | >lcl|BSEQ0013242|Inhibitor of nuclear factor kappa-B kinase subunit alpha MERPPGLRPGAGGPWEMRERLGTGGFGNVCLYQHRELDLKIAIKSCRLELSTKNRERWCH EIQIMKKLNHANVVKACDVPEELNILIHDVPLLAMEYCSGGDLRKLLNKPENCCGLKESQ ILSLLSDIGSGIRYLHENKIIHRDLKPENIVLQDVGGKIIHKIIDLGYAKDVDQGSLCTS FVGTLQYLAPELFENKPYTATVDYWSFGTMVFECIAGYRPFLHHLQPFTWHEKIKKKDPK CIFACEEMSGEVRFSSHLPQPNSLCSLVVEPMENWLQLMLNWDPQQRGGPVDLTLKQPRC FVLMDHILNLKIVHILNMTSAKIISFLLPPDESLHSLQSRIERETGINTGSQELLSETGI SLDPRKPASQCVLDGVRGCDSYMVYLFDKSKTVYEGPFASRSLSDCVNYIVQDSKIQLPI IQLRKVWAEAVHYVSGLKEDYSRLFQGQRAAMLSLLRYNANLTKMKNTLISASQQLKAKL EFFHKSIQLDLERYSEQMTYGISSEKMLKAWKEMEEKAIHYAEVGVIGYLEDQIMSLHAE IMELQKSPYGRRQGDLMESLEQRAIDLYKQLKHRPSDHSYSDSTEMVKIIVHTVQSQDRV LKELFGHLSKLLGCKQKIIDLLPKVEVALSNIKEADNTVMFMQGKRQKEIWHLLKIACTQ SSARSLVGSSLEGAVTPQTSAWLPPTSAEHDHSLSCVVTPQDGETSAQMIEENLNCLGHL STIIHEANEEQGNSMMNLDWSWLTE |
| Number of residues | 745 |
| Molecular Weight | 84638.88 |
| Theoretical pI | Not Available |
| GO Classification | Functions
Processes
Components
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| General Function | Scaffold protein 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 (PubMed:15084260). |
| Pfam Domain Function | |
| Transmembrane Regions | Not Available |
| GenBank Protein ID | Not Available |
| UniProtKB ID | O15111 |
| UniProtKB Entry Name | IKKA_HUMAN |
| Cellular Location | Cytoplasm |
| Gene sequence | >lcl|BSEQ0013243|Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK) ATGGAGCGGCCCCCGGGGCTGCGGCCGGGCGCGGGCGGGCCCTGGGAGATGCGGGAGCGG CTGGGCACCGGCGGCTTCGGGAACGTCTGTCTGTACCAGCATCGGGAACTTGATCTCAAA ATAGCAATTAAGTCTTGTCGCCTAGAGCTAAGTACCAAAAACAGAGAACGATGGTGCCAT GAAATCCAGATTATGAAGAAGTTGAACCATGCCAATGTTGTAAAGGCCTGTGATGTTCCT GAAGAATTGAATATTTTGATTCATGATGTGCCTCTTCTAGCAATGGAATACTGTTCTGGA GGAGATCTCCGAAAGCTGCTCAACAAACCAGAAAATTGTTGTGGACTTAAAGAAAGCCAG ATACTTTCTTTACTAAGTGATATAGGGTCTGGGATTCGATATTTGCATGAAAACAAAATT ATACATCGAGATCTAAAACCTGAAAACATAGTTCTTCAGGATGTTGGTGGAAAGATAATA CATAAAATAATTGATCTGGGATATGCCAAAGATGTTGATCAAGGAAGTCTGTGTACATCT TTTGTGGGAACACTGCAGTATCTGGCCCCAGAGCTCTTTGAGAATAAGCCTTACACAGCC ACTGTTGATTATTGGAGCTTTGGGACCATGGTATTTGAATGTATTGCTGGATATAGGCCT TTTTTGCATCATCTGCAGCCATTTACCTGGCATGAGAAGATTAAGAAGAAGGATCCAAAG TGTATATTTGCATGTGAAGAGATGTCAGGAGAAGTTCGGTTTAGTAGCCATTTACCTCAA CCAAATAGCCTTTGTAGTTTAGTAGTAGAACCCATGGAAAACTGGCTACAGTTGATGTTG AATTGGGACCCTCAGCAGAGAGGAGGACCTGTTGACCTTACTTTGAAGCAGCCAAGATGT TTTGTATTAATGGATCACATTTTGAATTTGAAGATAGTACACATCCTAAATATGACTTCT GCAAAGATAATTTCTTTTCTGTTACCACCTGATGAAAGTCTTCATTCACTACAGTCTCGT ATTGAGCGTGAAACTGGAATAAATACTGGTTCTCAAGAACTTCTTTCAGAGACAGGAATT TCTCTGGATCCTCGGAAACCAGCCTCTCAATGTGTTCTAGATGGAGTTAGAGGCTGTGAT AGCTATATGGTTTATTTGTTTGATAAAAGTAAAACTGTATATGAAGGGCCATTTGCTTCC AGAAGTTTATCTGATTGTGTAAATTATATTGTACAGGACAGCAAAATACAGCTTCCAATT ATACAGCTGCGTAAAGTGTGGGCTGAAGCAGTGCACTATGTGTCTGGACTAAAAGAAGAC TATAGCAGGCTCTTTCAGGGACAAAGGGCAGCAATGTTAAGTCTTCTTAGATATAATGCT AACTTAACAAAAATGAAGAACACTTTGATCTCAGCATCACAACAACTGAAAGCTAAATTG GAGTTTTTTCACAAAAGCATTCAGCTTGACTTGGAGAGATACAGCGAGCAGATGACGTAT GGGATATCTTCAGAAAAAATGCTAAAAGCATGGAAAGAAATGGAAGAAAAGGCCATCCAC TATGCTGAGGTTGGTGTCATTGGATACCTGGAGGATCAGATTATGTCTTTGCATGCTGAA ATCATGGAGCTACAGAAGAGCCCCTATGGAAGACGTCAGGGAGACTTGATGGAATCTCTG GAACAGCGTGCCATTGATCTATATAAGCAGTTAAAACACAGACCTTCAGATCACTCCTAC AGTGACAGCACAGAGATGGTGAAAATCATTGTGCACACTGTGCAGAGTCAGGACCGTGTG CTCAAGGAGCTGTTTGGTCATTTGAGCAAGTTGTTGGGCTGTAAGCAGAAGATTATTGAT CTACTCCCTAAGGTGGAAGTGGCCCTCAGTAATATCAAAGAAGCTGACAATACTGTCATG TTCATGCAGGGAAAAAGGCAGAAAGAAATATGGCATCTCCTTAAAATTGCCTGTACACAG AGTTCTGCCCGGTCCCTTGTAGGATCCAGTCTAGAAGGTGCAGTAACCCCTCAGACATCA GCATGGCTGCCCCCGACTTCAGCAGAACATGATCATTCTCTGTCATGTGTGGTAACTCCT CAAGATGGGGAGACTTCAGCACAAATGATAGAAGAAAATTTGAACTGCCTTGGCCATTTA AGCACTATTATTCATGAGGCAAATGAGGAACAGGGCAATAGTATGATGAATCTTGATTGG AGTTGGTTAACAGAATGA |
| GenBank Gene ID | Not Available |
| GeneCard ID | Not Available |
| GenAtlas ID | Not Available |
| HGNC ID | HGNC:1974 |
| Chromosome Location | 10 |
| Locus | Not Available |
| References |
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