Tchem NFKB2 Nuclear factor NF-kappa-B p100 subunit

Protein Summary

Description

NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, 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. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer. This gene encodes a subunit of the transcription factor complex nuclear factor-kappa-B (NFkB). The NFkB complex is expressed in numerous cell types and functions as a central activator of genes involved in inflammation and immune function. The protein encoded by this gene can function as both a transcriptional activator or repressor depending on its dimerization partner. The p100 full-length protein is co-translationally processed into a p52 active form. Chromosomal rearrangements and translocations of this locus have been observed in B cell lymphomas, some of which may result in the formation of fusion proteins. There is a pseudogene for this gene on chromosome 18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

Uniprot Accession IDs

• Q00653
• A8K9D9
• D3DR83
• Q04860
• Q9BU75
• Q9H471
• Q9H472

Gene Name

• NFKB2

Ensembl ID

• ENST00000189444
• ENSP00000189444
• ENSG00000077150
• ENST00000369966
• ENSP00000358983
• ENST00000428099
• ENSP00000410256

Symbol

• LYT10
• p52
• p100
• H2TF1
• LYT10
• CVID10
• LYT-10
• NF-kB2
• p49/p100

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	1
protein domain	1
biological process	0.93
virus perturbation	0.92
molecular function	0.91

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Nuclear Factor Nf-kappa-b P100 Subunit

Protein / ... / P53-like Transcription Factor / Nuclear Factor Nf-kappa-b P100 Subunit

Protein / ... / Rel Homology Transcription Factor / Nuclear Factor Nf-kappa-b P100 Subunit

DTO Classes

Protein / Transcription Factor / Immunoglobulin Fold Transcription Factor / Rel Homology Transcription Factor / Nuclear Factor Nf-kappa-b P100 Subunit

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: 266.1   (req: < 5)

Gene RIFs: 114   (req: <= 3)

Antibodies: 903   (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: 266.1   (req: >= 5)

Gene RIFs: 114   (req: > 3)

Antibodies: 903   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

Tchem

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

Active Ligand: 0

Tclin

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

Active Drug: 1

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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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 (1)

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1 – 1 of 1

bortezomib

NFKB2Tchem TF

INHIBITOR pKi : 9.26

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (257)

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1 – 10 of 257

• See Interactions on String-DB

RELB

Tbio

Family:  TF

Novelty:  0.00216805

p_int:  1

Score:  0.998

Data Source:  BioPlex,Reactome,STRINGDB

REL

Tbio

Family:  TF

Novelty:  0.00038265

p_int:  0.999999979

p_ni:  2.1e-8

Score:  0.971

Data Source:  BioPlex,STRINGDB

NFKBIA

Tchem

Novelty:  0.00022873

p_int:  0.999999966

p_ni:  3.4e-8

Score:  0.994

Data Source:  BioPlex,Reactome,STRINGDB

NFKBIB

Tbio

Novelty:  0.00517222

p_int:  0.999996888

p_ni:  0.000003112

Score:  0.989

Data Source:  BioPlex,Reactome,STRINGDB

PIP

Tbio

Novelty:  0.00208509

p_int:  0.999513731

p_ni:  0.000486237

p_wrong:  3.3e-8

Data Source:  BioPlex

NFKBID

Tbio

Novelty:  0.04272718

p_int:  0.99873111

p_ni:  0.00126889

Score:  0.828

Data Source:  BioPlex,STRINGDB

DEF6

Tbio

Novelty:  0.0378487

p_int:  0.998590833

p_ni:  0.001409167

Score:  0.215

Data Source:  BioPlex,STRINGDB

PADI3

Tchem

Family:  Enzyme

Novelty:  0.01110139

p_int:  0.987863184

p_ni:  0.012136815

Score:  0.173

Data Source:  BioPlex,STRINGDB

ASB2

Tbio

Novelty:  0.02852942

p_int:  0.979411089

p_ni:  0.020588905

p_wrong:  6e-9

Score:  0.345

Data Source:  BioPlex,STRINGDB

HIF1AN

Tbio

Novelty:  0.00861018

p_int:  0.978263576

p_ni:  0.021736424

p_wrong:  1e-9

Score:  0.61

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (4)

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Upstream (2)

Downstream (2)

1 – 2 of 2

PIK3CD

Tclin

Family:  Kinase

KEGG Distance:  3

Common Pathways:  7

1: Human T-cell leukemia virus 1 infection

2: Breast cancer

3: C-type lectin receptor signaling pathway

4: Viral carcinogenesis

more:  3 more common pathways

PIK3CA

Tclin

Family:  Kinase

KEGG Distance:  3

Common Pathways:  7

1: Human T-cell leukemia virus 1 infection

2: Breast cancer

3: C-type lectin receptor signaling pathway

4: Viral carcinogenesis

more:  3 more common pathways

Pathways (91)

Reactome (50)

KEGG (10)

PathwayCommons (8)

WikiPathways (23)

C-type lectin receptors (CLRs) (R-HSA-5621481)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	C-type lectin receptors (CLRs)	144 targets	R-HSA-5621481
Reactome	CLEC7A (Dectin-1) signaling	101 targets	R-HSA-5607764
Reactome	Chromatin modifying enzymes	238 targets	R-HSA-3247509
Reactome	Chromatin organization	238 targets	R-HSA-4839726
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215

Name	Explore in Pharos	Explore in Source
C-type lectin receptors (CLRs)	144 targets	R-HSA-5621481
CLEC7A (Dectin-1) signaling	101 targets	R-HSA-5607764
Chromatin modifying enzymes	238 targets	R-HSA-3247509
Chromatin organization	238 targets	R-HSA-4839726
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (23)

Functions (5)

Components (5)

Processes (13)

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GO Term	Evidence	Assigned by
proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific	Inferred from Direct Assay (IDA)	NTNU_SB
RNA polymerase II proximal promoter sequence-specific DNA binding	Inferred from Direct Assay (IDA)	NTNU_SB
DNA-binding transcription factor activity, RNA polymerase II-specific	Inferred from Sequence Alignment (ISA)	NTNU_SB
DNA-binding transcription factor activity	Traceable Author Statement (TAS)	ProtInc
transcription coactivator activity	Traceable Author Statement (TAS)	ProtInc

Disease Associations ()

No disease associations found

GWAS Traits (25)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
allergic rhinitis	EFO_0005854	2	2	0	1	81.4
intelligence	EFO_0004337	3	4	3	6.4	75.6
household income	EFO_0009695	1	2	2		67.5
cognitive function measurement	EFO_0008354	2	1	2		65.6
platelet crit	EFO_0007985	1	1	1		64.4

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
allergic rhinitis	EFO_0005854	0	1	81.4
intelligence	EFO_0004337	3	6.4	75.6
household income	EFO_0009695	2		67.5
cognitive function measurement	EFO_0008354	2		65.6
platelet crit	EFO_0007985	1		64.4

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Activator
Alternative splicing
ANK repeat
Biological rhythms
Chromosomal rearrangement
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation

GWAS Trait Find Similar Targets

No Header	No Header
allergic rhinitis
allergy
apolipoprotein B measurement
asthma
birth weight
BMI-adjusted hip circumference
BMI-adjusted waist circumference
cognitive function measurement
Eczema
grip strength measurement

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cellular phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
immune system phenotype
integument phenotype
liver/biliary system phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	nuclear factor kappa B subunit 2	VGNC:10454	450697
Macaque	nuclear factor kappa B subunit 2		714689
Mouse	nuclear factor of kappa light polypeptide gene enhancer in B cells 2, p49/p100	MGI:1099800	18034
Rat	nuclear factor kappa B subunit 2	RGD:1307189	309452
Dog	nuclear factor kappa B subunit 2	VGNC:43781	486858

Species	Name	OMA	EggNOG	Inparanoid
Chimp	nuclear factor kappa B subunit 2
Macaque	nuclear factor kappa B subunit 2
Mouse	nuclear factor of kappa light polypeptide gene enhancer in B cells 2, p49/p100
Rat	nuclear factor kappa B subunit 2
Dog	nuclear factor kappa B subunit 2

Publication Statistics

PubMed Score 266.10

PubMed score by year

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PubTator Score 367.99

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Related Publications

Text Mined References (240)

GeneRif Annotations (114)

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PMID	Year	Title