Target Information
Target General Infomation | |||||
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Target ID |
T91173
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Former ID |
TTDR01344
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Target Name |
mRNA of Inhibitor-kappa B Kinase-alpha
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Gene Name |
CHUK
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Synonyms |
CHUK (mRNA); Conserved helixloophelix ubiquitous kinase (mRNA); IKK1 (mRNA); IKKA (mRNA); IKKalpha (mRNA); IkBKA (mRNA); IkappaB kinase (mRNA); IkappaB kinase 1 (mRNA); IkappaB kinase alpha (mRNA); Inhibitor of nuclear factor kappaB kinase subunit alpha (mRNA); NFKBIKA (mRNA); Nuclear factor NFkappaB inhibitor kinase alpha (mRNA); TCF16 (mRNA); Transcription factor 16 (mRNA); CHUK
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Target Type |
Research
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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 damagesor 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 ofthe 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.
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BioChemical Class |
Kinase
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Target Validation |
T91173
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UniProt ID | |||||
EC Number |
EC 2.7.11.10
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Sequence |
MERPPGLRPGAGGPWEMRERLGTGGFGNVCLYQHRELDLKIAIKSCRLELSTKNRERWCH
EIQIMKKLNHANVVKACDVPEELNILIHDVPLLAMEYCSGGDLRKLLNKPENCCGLKESQ ILSLLSDIGSGIRYLHENKIIHRDLKPENIVLQDVGGKIIHKIIDLGYAKDVDQGSLCTS FVGTLQYLAPELFENKPYTATVDYWSFGTMVFECIAGYRPFLHHLQPFTWHEKIKKKDPK CIFACEEMSGEVRFSSHLPQPNSLCSLVVEPMENWLQLMLNWDPQQRGGPVDLTLKQPRC FVLMDHILNLKIVHILNMTSAKIISFLLPPDESLHSLQSRIERETGINTGSQELLSETGI SLDPRKPASQCVLDGVRGCDSYMVYLFDKSKTVYEGPFASRSLSDCVNYIVQDSKIQLPI IQLRKVWAEAVHYVSGLKEDYSRLFQGQRAAMLSLLRYNANLTKMKNTLISASQQLKAKL EFFHKSIQLDLERYSEQMTYGISSEKMLKAWKEMEEKAIHYAEVGVIGYLEDQIMSLHAE IMELQKSPYGRRQGDLMESLEQRAIDLYKQLKHRPSDHSYSDSTEMVKIIVHTVQSQDRV LKELFGHLSKLLGCKQKIIDLLPKVEVALSNIKEADNTVMFMQGKRQKEIWHLLKIACTQ SSARSLVGSSLEGAVTPQTSAWLPPTSAEHDHSLSCVVTPQDGETSAQMIEENLNCLGHL STIIHEANEEQGNSMMNLDWSWLTE |
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Pathways | |||||
KEGG Pathway | MAPK signaling pathway | ||||
Ras signaling pathway | |||||
Chemokine signaling pathway | |||||
NF-kappa B signaling pathway | |||||
FoxO signaling pathway | |||||
PI3K-Akt signaling pathway | |||||
Apoptosis | |||||
Osteoclast differentiation | |||||
Toll-like receptor signaling pathway | |||||
NOD-like receptor signaling pathway | |||||
RIG-I-like receptor signaling pathway | |||||
Cytosolic DNA-sensing pathway | |||||
T cell receptor signaling pathway | |||||
B cell receptor signaling pathway | |||||
TNF signaling pathway | |||||
Adipocytokine signaling pathway | |||||
Epithelial cell signaling in Helicobacter pylori infection | |||||
Shigellosis | |||||
Chagas disease (American trypanosomiasis) | |||||
Toxoplasmosis | |||||
Hepatitis C | |||||
Hepatitis B | |||||
Measles | |||||
HTLV-I infection | |||||
Herpes simplex infection | |||||
Epstein-Barr virus infection | |||||
Pathways in cancer | |||||
Pancreatic cancer | |||||
Prostate cancer | |||||
Chronic myeloid leukemia | |||||
Acute myeloid leukemia | |||||
Small cell lung cancer | |||||
NetPath Pathway | IL5 Signaling Pathway | ||||
FSH Signaling Pathway | |||||
PANTHER Pathway | Apoptosis signaling pathway | ||||
B cell activation | |||||
Inflammation mediated by chemokine and cytokine signaling pathway | |||||
Interleukin signaling pathway | |||||
PDGF signaling pathway | |||||
T cell activation | |||||
Toll receptor signaling pathway | |||||
Pathway Interaction Database | Fc-epsilon receptor I signaling in mast cells | ||||
BCR signaling pathway | |||||
TCR signaling in na& | |||||
#xef | |||||
ve CD4+ T cells | |||||
Canonical NF-kappaB pathway | |||||
Alternative NF-kappaB pathway | |||||
Osteopontin-mediated events | |||||
TRAIL signaling pathway | |||||
TCR signaling in na& | |||||
ve CD8+ T cells | |||||
FAS (CD95) signaling pathway | |||||
IL1-mediated signaling events | |||||
TNF receptor signaling pathway | |||||
FoxO family signaling | |||||
p75(NTR)-mediated signaling | |||||
Negative effector of Fas and TNF-alpha | |||||
Validated nuclear estrogen receptor alpha network | |||||
Class I PI3K signaling events mediated by Akt | |||||
Validated transcriptional targets of TAp63 isoforms | |||||
Endogenous TLR signaling | |||||
PathWhiz Pathway | Intracellular Signalling Through Adenosine Receptor A2a and Adenosine | ||||
Intracellular Signalling Through Adenosine Receptor A2b and Adenosine | |||||
Reactome | Activation of NF-kappaB in B cells | ||||
NOD1/2 Signaling Pathway | |||||
RIP-mediated NFkB activation via ZBP1 | |||||
AKT phosphorylates targets in the cytosol | |||||
FCERI mediated NF-kB activation | |||||
TAK1 activates NFkB by phosphorylation and activation of IKKs complex | |||||
Interleukin-1 signaling | |||||
Regulation of TNFR1 signaling | |||||
TNFR1-induced NFkappaB signaling pathway | |||||
IKBKB deficiency causes SCID | |||||
IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR) | |||||
IkBA variant leads to EDA-ID | |||||
Dectin-1 mediated noncanonical NF-kB signaling | |||||
CLEC7A (Dectin-1) signaling | |||||
Constitutive Signaling by AKT1 E17K in Cancer | |||||
NIK--> | |||||
noncanonical NF-kB signaling | |||||
MAP3K8 (TPL2)-dependent MAPK1/3 activation | |||||
TRAF6 mediated NF-kB activation | |||||
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 | |||||
IRAK1 recruits IKK complex | |||||
IKK complex recruitment mediated by RIP1 | |||||
IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation | |||||
WikiPathways | PDGF Pathway | ||||
References |
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