Tchem IKBKB Inhibitor of nuclear factor kappa-B kinase subunit beta

Protein Summary

Description

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. The protein encoded by this gene phosphorylates the inhibitor in the inhibitor/NF-kappa-B complex, causing dissociation of the inhibitor and activation of NF-kappa-B. The encoded protein itself is found in a complex of proteins. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Sep 2011]

Uniprot Accession IDs

• O14920
• B4DZ30
• B4E0U4
• O75327
• I-kappa-B-kinase beta

Gene Name

• IKBKB

Ensembl ID

• ENST00000416505
• ENSP00000404920
• ENSG00000104365
• ENST00000520810
• ENSP00000430684
• ENST00000520835
• ENSP00000430868
• ENST00000649612
• ENSP00000497383

Symbol

• IKKB
• IKK2
• IKKB
• IMD15
• IMD15A
• IMD15B
• NFKBIKB
• IKK-beta

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	1
biological term	0.99
chemical	0.99
kinase	0.99
molecular function	0.99

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Inhibitor Of Nuclear Factor Kappa-b Kinase Subunit Beta

DTO Classes

Protein / Kinase / Protein Kinase / Other Group / Ikk Family / Inhibitor Of Nuclear Factor Kappa-b Kinase Subunit Beta

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1086.69   (req: < 5)

Gene RIFs: 229   (req: <= 3)

Antibodies: 2128   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1086.69   (req: >= 5)

Gene RIFs: 229   (req: > 3)

Antibodies: 2128   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 38

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 221

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (221)

Explore Active Ligands

1 – 10 of 221

staurosporine

IKBKBTchem Kinase

pKd : 7.89

lestaurtinib

IKBKBTchem Kinase

pKd : 7.57

CHEMBL129857

IKBKBTchem Kinase

pKi : 7.7

BMS-345541

IKBKBTchem Kinase

pKd : 6.89

compound 47 [PMID: 28737909]

IKBKBTchem Kinase

pKi : 5.64

PHA-408

IKBKBTchem Kinase

pIC50 : 8.8

IKK-2 inhibitor IV

IKBKBTchem Kinase

pKd : 7.66

CHEMBL2164412

IKBKBTchem Kinase

pIC50 : 8.4

CHEMBL2164410

IKBKBTchem Kinase

pIC50 : 8.3

CHEMBL2164411

IKBKBTchem Kinase

pIC50 : 8.2

Protein-Protein Interactions (267)

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1 – 10 of 267

• See Interactions on String-DB

IKBKG

Tbio

Family:  Kinase

Novelty:  0.0006149

p_int:  0.999999996

p_ni:  2e-9

p_wrong:  2e-9

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

MAP3K14

Tchem

Family:  Kinase

Novelty:  0.0350173

p_int:  0.999999019

p_ni:  9.8e-7

p_wrong:  1e-9

Score:  0.993

Data Source:  BioPlex,STRINGDB

PSG1

Tbio

Novelty:  0.0239046

p_int:  0.999997657

p_ni:  0.000002343

Score:  0.622

Data Source:  BioPlex,STRINGDB

CHUK

Tchem

Family:  Kinase

Novelty:  0.00151532

p_int:  0.996745796

p_ni:  0.000002203

p_wrong:  0.003252

Score:  0.991

Data Source:  BioPlex,Reactome,STRINGDB

TNF

Tclin

Novelty:  0.00001457

Score:  0.999

Data Source:  STRINGDB

NFKBIA

Tchem

Novelty:  0.00022873

Score:  0.999

Data Source:  Reactome,STRINGDB

RELA

Tchem

Family:  TF

Novelty:  0.0007137

Score:  0.997

Data Source:  Reactome,STRINGDB

NFKB1

Tclin

Family:  TF

Novelty:  0.00198195

Score:  0.995

Data Source:  Reactome,STRINGDB

BCL10

Tbio

Novelty:  0.00253704

Score:  0.993

Data Source:  Reactome,STRINGDB

MAP3K7

Tchem

Family:  Kinase

Novelty:  0.00540177

Score:  0.991

Data Source:  Reactome,STRINGDB

Nearest Tclin Targets (10)

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Upstream (1)

Downstream (9)

1 – 1 of 1

TNF

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  30

1: mTOR signaling pathway

2: Adipocytokine signaling pathway

3: T cell receptor signaling pathway

4: Yersinia infection

more:  26 more common pathways

Pathways (216)

Reactome (66)

KEGG (52)

PathwayCommons (46)

WikiPathways (52)

Activation of NF-kappaB in B cells (R-HSA-1169091)

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5

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of NF-kappaB in B cells	68 targets	R-HSA-1169091
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Antigen processing-Cross presentation	169 targets	R-HSA-1236975
Reactome	C-type lectin receptors (CLRs)	144 targets	R-HSA-5621481
Reactome	CLEC7A (Dectin-1) signaling	101 targets	R-HSA-5607764

Name	Explore in Pharos	Explore in Source
Activation of NF-kappaB in B cells	68 targets	R-HSA-1169091
Adaptive Immune System	894 targets	R-HSA-1280218
Antigen processing-Cross presentation	169 targets	R-HSA-1236975
C-type lectin receptors (CLRs)	144 targets	R-HSA-5621481
CLEC7A (Dectin-1) signaling	101 targets	R-HSA-5607764

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (44)

Functions (9)

Components (6)

Processes (29)

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1 – 9 of 9

GO Term	Evidence	Assigned by
protein heterodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB
protein homodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB
protein kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
scaffold protein binding	Inferred from Direct Assay (IDA)	MGI
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
protein kinase binding	Inferred from Physical Interaction (IPI)	UniProtKB
IkappaB kinase activity	Traceable Author Statement (TAS)	UniProtKB
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations ()

No disease associations found

GWAS Traits (2)

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1 – 2 of 2

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
tissue plasminogen activator measurement	EFO_0004791	1	2	2		49.2
systemic lupus erythematosus	EFO_0002690	1	1	0	1.9	17.8

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 2 of 2

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
tissue plasminogen activator measurement	EFO_0004791	2		49.2
systemic lupus erythematosus	EFO_0002690	0	1.9	17.8

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
ATP-binding
Complete proteome
Cytoplasm
Direct protein sequencing
Host-virus interaction
Hydroxylation
Isopeptide bond

GWAS Trait Find Similar Targets

No Header	No Header
systemic lupus erythematosus
tissue plasminogen activator measurement

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
cellular phenotype
digestive/alimentary phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
liver/biliary system phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (8)

1 – 5 of 8

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	inhibitor of nuclear factor kappa B kinase subunit beta		704683
Mouse	inhibitor of kappaB kinase beta	MGI:1338071	16150
Rat	inhibitor of nuclear factor kappa B kinase subunit beta	RGD:621375	84351
Dog	inhibitor of nuclear factor kappa B kinase subunit beta	VGNC:51803	482839
Cow	inhibitor of nuclear factor kappa B kinase subunit beta		281854

Species	Name	OMA	EggNOG	Inparanoid
Macaque	inhibitor of nuclear factor kappa B kinase subunit beta
Mouse	inhibitor of kappaB kinase beta
Rat	inhibitor of nuclear factor kappa B kinase subunit beta
Dog	inhibitor of nuclear factor kappa B kinase subunit beta
Cow	inhibitor of nuclear factor kappa B kinase subunit beta

Publication Statistics

PubMed Score 1086.69

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PubTator Score 622.58

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Related Publications

Text Mined References (360)

GeneRif Annotations (229)

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PMID	Year	Title