| Identification |
|---|
| BMDB Protein ID
| BMDBP01206 |
| Secondary Accession Numbers
| |
| 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
|
| NF-kappa-B inhibitor alpha → NF-kappa-B inhibitor alpha + Hydrogen phosphate |
details
|
|
| 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
|
| Protein Properties |
|---|
| Number of Residues
| 740 |
| Molecular Weight
| 84344.0 |
| Theoretical pI
| 6.88 |
| Pfam Domain Function
|
Not Available |
| Signals
|
|
|
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
|
| 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 |
