Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

IKBKB (O14920) - Overview - Molecular Target Synopsis

Protein


IKBKB, Inhibitor of nuclear factor kappa-B kinase subunit beta
Enzyme Classification 2.7.11.10
UniProt O14920

Also Known as IKKB_HUMAN, IKBKB, IKKB

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. 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. Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK-beta/IKBKB dimers are associated with four gamma/IKBKG subunits. The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex (PubMed:12612076). The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65 (By similarity). Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP (PubMed:11971985). Part of a 70-90 kDa complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA, RELA, ELP1 and MAP3K14 (PubMed:9751059). Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB (PubMed:17287217). Interacts with SQSTM1 through PRKCZ or PRKCI (PubMed:10356400). Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6 (By similarity). May interact with MAVS/IPS1 (PubMed:16177806). Interacts with NALP2 (PubMed:15456791). Interacts with TICAM1 (PubMed:14739303). Interacts with FAF1; the interaction disrupts the IKK complex formation (PubMed:17684021). Interacts with ATM (PubMed:16497931). Part of a ternary complex consisting of TANK, IKBKB and IKBKG (PubMed:12133833). Interacts with NIBP; the interaction is direct (PubMed:15951441). Interacts with ARRB1 and ARRB2 (PubMed:15173580). Interacts with TRIM21 (PubMed:19675099). Interacts with NLRC5; prevents IKBKB phosphorylation and kinase activity (PubMed:20434986). Interacts with PDPK1 (PubMed:16207722). Interacts with EIF2AK2/PKR (PubMed:10848580). The phosphorylated form interacts with PPM1A and PPM1B (PubMed:18930133). Interacts with ZNF268 isoform 2; the interaction is further increased in a TNF-alpha-dependent manner (PubMed:23091055). Interacts with IKBKE (PubMed:23453969). Interacts with NAA10, leading to NAA10 degradation (PubMed:19716809). Interacts with FOXO3 (PubMed:15084260). Interacts with AKAP13 (PubMed:23090968). Interacts with IFIT5; the interaction synergizes the recruitment of IKK to MAP3K7 and enhances IKK phosphorylation (PubMed:26334375). Interacts with LRRC14; disrupts IKBKB-IKBKG interaction preventing I-kappa-B-kinase (IKK) core complex formation and leading to a decrease of IKBKB phosphorylation and NF-kappaB activation (PubMed:27426725).

4KIK
HUMAN IKB KINASE BETA
RCSB/PDB
Inspect Structure
See all 3D Structures for IKBKB

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: IKBKB is active in the following subcellular-locations: cytoplasm, membrane raft, nucleus.
GO terms: IKBKB is active in the following subcellular-locations: CD40 receptor complex, cytoplasmic side of plasma membrane, cytosol, IkappaB kinase complex, membrane raft, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project IKBKB has gain in 5 cell-lines, loss in 3 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HOP_62, SR, HS578T

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HCC366, NCI-H1734, KG-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, K562, IMR-90

(see details)

RNA Interference


IKBKB was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: H1838, SCC90. (see details)

3D Structures


For IKBKB there are:
4 structures (12 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


IKBKB has been screened with 2184 compounds (4246 bioactivities), 502 compounds have bioactivities that show binding affinity of <= 500nM (799 bioactivities). (see details)