Inhibitor of nuclear factor kappa-B kinase subunit alpha
Name | Inhibitor of nuclear factor kappa-B kinase subunit alpha |
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Synonyms | 2.7.11.10 Conserved helix-loop-helix ubiquitous kinase I-kappa-B kinase 1 I-kappa-B kinase alpha IKK1 IKKA NFKBIKA Nuclear factor NF-kappa-B inhibitor kinase alpha TCF-16 TCF16 Transcription factor 16 |
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 | None |
GO Classification |
Functions
protein homodimerization activity IkappaB kinase activity protein heterodimerization activity ATP binding protein kinase activity scaffold protein binding Processes
odontogenesis of dentin-containing tooth positive regulation of type I interferon production striated muscle cell differentiation protein phosphorylation toll-like receptor 5 signaling pathway anatomical structure morphogenesis positive regulation of NF-kappaB transcription factor activity response to muscle stretch toll-like receptor 9 signaling pathway phosphatidylinositol-mediated signaling osteoclast differentiation stimulatory C-type lectin receptor signaling pathway toll-like receptor signaling pathway response to amino acid epidermal growth factor receptor signaling pathway mammary gland epithelial cell proliferation cell surface receptor signaling pathway toll-like receptor TLR1 T cell receptor signaling pathway I-kappaB phosphorylation innate immune response MyD88-dependent toll-like receptor signaling pathway toll-like receptor TLR6 I-kappaB kinase/NF-kappaB signaling nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Fc-epsilon receptor signaling pathway MyD88-independent toll-like receptor signaling pathway Rho protein signal transduction response to virus nucleotide-binding oligomerization domain containing signaling pathway cellular response to tumor necrosis factor stress-activated MAPK cascade response to lipopolysaccharide NIK/NF-kappaB signaling response to drug regulation of tumor necrosis factor-mediated signaling pathway toll-like receptor 10 signaling pathway response to toxic substance tumor necrosis factor-mediated signaling pathway immune response skeletal muscle contraction fibroblast growth factor receptor signaling pathway toll-like receptor 2 signaling pathway mammary gland alveolus development inflammatory response response to hydroperoxide morphogenesis of an epithelial sheet neurotrophin TRK receptor signaling pathway toll-like receptor 3 signaling pathway lactation positive regulation of I-kappaB kinase/NF-kappaB signaling TRIF-dependent toll-like receptor signaling pathway response to acetate positive regulation of transcription from RNA polymerase II promoter toll-like receptor 4 signaling pathway Components
cytosol cytoplasmic side of plasma membrane CD40 receptor complex nucleoplasm IkappaB kinase complex cytoplasm intracellular membrane-bounded organelle |
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). |
Transmembrane Regions | |
GenBank Protein ID | |
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 | |
GeneCard ID | None |
GenAtlas ID | |
HGNC ID | HGNC:1974 |
Chromosome Location | 10 |
Locus | None |
References |
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Related FRC
FRCD ID | Name | Exact Mass | Structure |
---|---|---|---|
Acrolein |
56.064 |