Kinase Atlas

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 2 critical 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. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation.

Site	Maximum Consensus Site Population	Minimum Consensus Site Population	Median Consensus Site Population
MPP	10	10	10.0
DRS	2	2	2.0
MT3	21	5	10.5
AAS	6	6	6.0
CMP	14	2	3.0
PDIG	18	2	13.0
ATP	19	5	9.5

PDB ID	Maximum Consensus Site Population
PDB ID	MPP site	DFG site	PIF site	DRS site	DEF site	EDI site	MT3 site	AAS site	LBP site	CMP site	PDIG site	ATP site	PMP site
Total Druggable Structures per Site	0	0	0	0	0	0	2	0	0	0	1	1	0
4KIK	10	0	0	2	0	0	18	0	0	14	2	19	0
4E3C	0	0	0	0	0	0	21	6	0	3	18	6	0

O14920