Tclin NFKB1 Nuclear factor NF-kappa-B p105 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 and the heterodimeric p65-p50 complex appears to be most abundant one. 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. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 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. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105. This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappa-B (NFKB) protein complex. NFKB is a transcription regulator that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NFKB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions. Inappropriate activation of NFKB has been associated with a number of inflammatory diseases while persistent inhibition of NFKB leads to inappropriate immune cell development or delayed cell growth. Alternative splicing results in multiple transcript variants encoding different isoforms, at least one of which is proteolytically processed. [provided by RefSeq, Feb 2016]

Uniprot Accession IDs

• P19838
• A8K5Y5
• B3KVE8
• Q68D84
• Q86V43
• Q8N4X7
• Q9NZC0

Gene Name

• NFKB1

Ensembl ID

• ENST00000226574
• ENSP00000226574
• ENSG00000109320
• ENST00000394820
• ENSP00000378297
• ENST00000505458
• ENSP00000424790
• ENST00000600343
• ENSP00000469340

Symbol

• p50
• KBF1
• p105
• EBP-1
• CVID12
• NF-kB1
• NFKB-p50
• NFkappaB
• NF-kappaB
• NFKB-p105
• NF-kappa-B1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
chemical	1
hub protein	1
protein domain	1
molecular function	0.96

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Nuclear Factor Nf-kappa-b P105 Subunit

Protein / ... / P53-like Transcription Factor / Nuclear Factor Nf-kappa-b P105 Subunit

Protein / ... / Rel Homology Transcription Factor / Nuclear Factor Nf-kappa-b P105 Subunit

DTO Classes

Protein / Transcription Factor / Immunoglobulin Fold Transcription Factor / Rel Homology Transcription Factor / Nuclear Factor Nf-kappa-b P105 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: 529.51   (req: < 5)

Gene RIFs: 2802   (req: <= 3)

Antibodies: 2189   (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: 529.51   (req: >= 5)

Gene RIFs: 2802   (req: > 3)

Antibodies: 2189   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 51

Tchem

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

Active Ligands: 11

Tclin

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

Active Drug: 1