DegronMD - O14920(IKBKB)

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 (PubMed:30337470). Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation. 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 (PubMed:11297557, PubMed:20410276). 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 (PubMed:15084260). Also phosphorylates other substrates including NCOA3, BCL10 and IRS1 (PubMed:17213322). Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation (PubMed:11297557). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus (PubMed:25326418). {ECO:0000250|UniProtKB:O88351, ECO:0000269|PubMed:11297557, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17213322, ECO:0000269|PubMed:19716809, ECO:0000269|PubMed:20410276, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20797629, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:25326418, ECO:0000269|PubMed:30337470}. View more >>

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GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.N28I	TCGA-21-1080	LUSC	TCGA	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation rewiring degron network	0.1667
p.N28I	DO26502	LUSC	ICGC	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation rewiring degron network	0.1667
p.N34K	TCGA-A5-A0G2	UCEC	TCGA	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation altering degron motif	0.6918
p.N34S	TCGA-AX-A06F	UCEC	TCGA	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation altering degron motif	0.5958
p.Q35E	TCGA-DK-A1AC	BLCA	TCGA	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation altering degron motif	0.5633
p.I30M	TCGA-XF-A9SK	BLCA	TCGA	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation rewiring degron network	0.2222
p.M24I	DO52646	BOCA	ICGC	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation rewiring degron network	0.0556
p.R46G	DO15535	HNSC	ICGC	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation rewiring degron network	0.1389
p.A36S	DO228938	LICA	ICGC	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation altering degron motif	0.7588
p.C48F	DO228974	LICA	ICGC	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation rewiring degron network	0.0833
p.C48F	DO228976	LICA	ICGC	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation rewiring degron network	0.0833
p.A38V	DO218900	SKCA	ICGC	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation altering degron motif	0.6936
p.A36V	DO37707	SKCM	ICGC	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation altering degron motif	0.6936
p.R46W	DO48766	SKCM	ICGC	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation rewiring degron network	0.1389
p.P24Q	DO229163	THCA	ICGC	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation rewiring degron network	0.0556
p.C31R	DO229181	THCA	ICGC	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation rewiring degron network	0.25
p.P29S	DO43418	UCEC	ICGC	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation rewiring degron network	0.1944
p.R44Q	DO42504	UCEC	ICGC	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation blocking ubiquitination signal	0.6389
p.D31N	HCC-78	lung	COSMIC	NQETGE	DEG_Kelch_Keap1_1	34:39	Mutation rewiring degron network	0.25

DegronMD: protein-targeted degradation, mutation and drug response to degrons

IKBKB

UniProt ID: O14920

Entrez ID: 3551

Protein name: Inhibitor of nuclear factor kappa-B kinase subunit beta (I-kappa-B-kinase beta) (IKK-B) (IKK-beta) (IkBKB) (EC 2.7.11.10) (I-kappa-B kinase 2) (IKK2) (Nuclear factor NF-kappa-B inhibitor kinase beta) (NFKBIKB) (Serine/threonine protein kinase IKBKB) (EC 2.7.11.1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for IKBKB in