NFKB1 — Nuclear factor kappa B subunit 1
NFKB1 belongs to a gene co-expression module in 9 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
NFKB1's module in each cell type
About the gene
| Synonyms | KBF1, NF-kappaB, NF-kB1, NFkappaB, NFKB-p50, p105, p50 |
|---|---|
| Chromosome | 4: 102501330-102617302 |
| Predicted location | Intracellular |
| Essential gene | No |
| Protein class | Cancer-related genes, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, RAS pathway related proteins, Transcription factors |
| Molecular function | Activator, DNA-binding |
| Biological process | Apoptosis, Transcription, Transcription regulation |
Function
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. P105 is the precursor of the active p50 subunit (Nuclear factor NF-kappa-B p50 subunit) of the nuclear factor NF-kappa-B. Acts as a cytoplasmic retention of attached NF-kappa-B proteins by p105. Constitutes the active form, which associates with RELA/p65 to form the NF-kappa-B p65- p50 complex to form a transcription factor. Together with RELA/p65, 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.
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.