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: 306.28   (req: < 5)

Gene RIFs: 127   (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: 306.28   (req: >= 5)

Gene RIFs: 127   (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