Tchem NFKB2 Nuclear factor NF-kappa-B p100 subunit

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

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

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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: 261.79   (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: 261.79   (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

Approved Drugs (1)

Explore Approved Drugs

1 – 1 of 1

bortezomib

NFKB2Tchem TF

IC50 : 8.01

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

Protein Data Bank (5)

1 – 5 of 5

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (91)

Reactome (50)

KEGG (10)

PathwayCommons (8)

WikiPathways (23)

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

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Items per page:

5

1 – 5 of 50

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

Gene Ontology Terms (23)

Functions (5)

Components (5)

Processes (13)

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Items per page:

10

1 – 5 of 5

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

Protein-Protein Interactions (257)

Explore Interacting Targets

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

Publication Statistics

PubMed Score  261.79

PubMed score by year

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PubTator Score  367.99

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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3D-structure
Activator
Alternative splicing
ANK repeat
Biological rhythms
Chromosomal rearrangement
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation

MGI Phenotype Find Similar Targets

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