nuclear factor kappa B subunit 1
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Diagnostic Grade (Green)
COVID-19 research
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownPrimary immunodeficiency or monogenic inflammatory bowel disease
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownRespiratory ciliopathies including non-CF bronchiectasis
MONOALLELIC, autosomal or pseudoautosomal, NOT imprintedFamilial Meniere Disease
common variable immunodeficiency
primary biliary cholangitis
immunodeficiency disease
allergic rhinitis
Graves disease
systemic sclerosis
Eczematoid dermatitis
ulcerative colitis
hypothyroidism
upper respiratory tract disorder
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Nuclear factor NF-kappa-B p105 subunit
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
NFKB1 · P19838
Mean pLDDT
73.2/ 100
Confident
968 residues
Confidence breakdown
AlphaFold (Jumper et al., 2021) · CC BY 4.0
