Inhibitor of nuclear factor kappa-B kinase subunit alpha

Details

Name
Inhibitor of nuclear factor kappa-B kinase subunit alpha
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
Not Available
GO Classification
Functions
protein heterodimerization activity / ATP binding / protein kinase activity / IkappaB kinase activity / scaffold protein binding / protein homodimerization activity
Processes
toll-like receptor TLR1 / cell surface receptor signaling pathway / T cell receptor signaling pathway / TRIF-dependent toll-like receptor signaling pathway / innate immune response / MyD88-dependent toll-like receptor signaling pathway / response to acetate / toll-like receptor TLR6 / I-kappaB kinase/NF-kappaB signaling / positive regulation of type I interferon production / Fc-epsilon receptor signaling pathway / MyD88-independent toll-like receptor signaling pathway / striated muscle cell differentiation / Rho protein signal transduction / response to virus / cellular response to tumor necrosis factor / stress-activated MAPK cascade / response to lipopolysaccharide / response to drug / NIK/NF-kappaB signaling / toll-like receptor 10 signaling pathway / response to toxic substance / immune response / tumor necrosis factor-mediated signaling pathway / fibroblast growth factor receptor signaling pathway / toll-like receptor 2 signaling pathway / mammary gland alveolus development / inflammatory response / response to hydroperoxide / I-kappaB phosphorylation / neurotrophin TRK receptor signaling pathway / toll-like receptor 3 signaling pathway / lactation / positive regulation of I-kappaB kinase/NF-kappaB signaling / nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / positive regulation of transcription from RNA polymerase II promoter / toll-like receptor 4 signaling pathway / odontogenesis of dentin-containing tooth / nucleotide-binding oligomerization domain containing signaling pathway / protein phosphorylation / toll-like receptor 5 signaling pathway / anatomical structure morphogenesis / positive regulation of NF-kappaB transcription factor activity / regulation of tumor necrosis factor-mediated signaling pathway / response to muscle stretch / toll-like receptor 9 signaling pathway / phosphatidylinositol-mediated signaling / osteoclast differentiation / skeletal muscle contraction / toll-like receptor signaling pathway / stimulatory C-type lectin receptor signaling pathway / response to amino acid / epidermal growth factor receptor signaling pathway / mammary gland epithelial cell proliferation / morphogenesis of an epithelial sheet
Components
cytoplasm / CD40 receptor complex / IkappaB kinase complex / intracellular membrane-bounded organelle / cytosol / cytoplasmic side of plasma membrane / nucleoplasm
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
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
Chromosome Location
10
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDO15111
UniProtKB Entry NameIKKA_HUMAN
HGNC IDHGNC:1974
General References
Not Available

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00795SulfasalazineapprovedunknowninhibitorDetails
DB00244MesalazineapprovedunknowninhibitorDetails
DB00233Aminosalicylic AcidapprovedunknowninhibitorDetails
DB06151Acetylcysteineapproved, investigationalunknowninhibitorDetails