Summary of NFKB1
This gene encodes a protein that is a transcription regulator. It is activated by various stimuli like cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products Inappropriate activation of NFKB has been associated with a number of inflammatory diseases (R).
The Function of NFKB1
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.
Protein names
Recommended name:
Nuclear factor NF-kappa-B p105 subunitShort name:
EBP-1Alternative name(s):
DNA-binding factor KBF1Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1
- RS1585215 (NFKB1) ??
- RS230529 (NFKB1) ??
- RS230530 (NFKB1) ??
- RS3774932 (NFKB1) ??
- RS3774937 (NFKB1) ??
- RS3774959 (NFKB1) ??
- RS7665090 (NFKB1) ??
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Top Gene-Substance Interactions
NFKB1 Interacts with These Diseases
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Substances That Increase NFKB1
| Substances | Interaction | Organism | Category |
Substances That Decrease NFKB1
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Advanced Summary
Covered on Genetics Home Reference: common variable immune deficiencyFrom NCBI Gene: Immunodeficiency, common variable, 12From UniProt: Immunodeficiency, common variable, 12 (CVID12): A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. [MIM:616576]
From NCBI Gene: 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] From UniProt: 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.
Conditions with Increased Gene Activity
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Conditions with Decreased Gene Activity
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Technical
The following transcription factors affect gene expression:
Gene Pathways:
- Toll-like receptor signaling pathway
- Prostate cancer
- B cell receptor signaling pathway
- TRAF6 Mediated Induction of proinflammatory cytokines
- Apoptosis
- Epithelial cell signaling in Helicobacter pylori infection
- Cytosolic DNA-sensing pathway
- Innate Immune System
- Shigellosis
- T cell receptor signaling pathway
- Tuberculosis
- Leishmaniasis
- Adipocytokine signaling pathway
- Toxoplasmosis
- MAPK signaling pathway
- Cellular responses to stress
- Measles
- Immune System
- Acute myeloid leukemia
- Pancreatic cancer
- Small cell lung cancer
- Neurotrophin signaling pathway
- RIG-I-like receptor signaling pathway
- Chemokine signaling pathway
- NOD-like receptor signaling pathway
- Hepatitis C
- Osteoclast differentiation
- Chagas disease (American trypanosomiasis)
- Pathways in cancer
- Amoebiasis
- Chronic myeloid leukemia
- Signal Transduction
Induction:
By phorbol ester and TNF.
Molecular Function:
- Regulatory Region Dna Binding
- Transcription Regulatory Region Sequence-Specific Dna Binding
- Rna Polymerase Ii Regulatory Region Sequence-Specific Dna Binding
- Rna Polymerase Ii Distal Enhancer Sequence-Specific Dna Binding
- Transcriptional Activator Activity, Rna Polymerase Ii Distal Enhancer Sequence-Specific Binding
- Transcriptional Repressor Activity, Rna Polymerase Ii Transcription Regulatory Region Sequence-Specific Binding
- Chromatin Binding
- Transcription Factor Activity, Sequence-Specific Dna Binding
- Transcription Factor Binding
- Identical Protein Binding
- Actinin Binding
- Transcription Regulatory Region Dna Binding
- Protein Heterodimerization Activity
Biological Processes:
- Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
- Stimulatory C-Type Lectin Receptor Signaling Pathway
- Transcription From Rna Polymerase Ii Promoter
- Apoptotic Process
- Inflammatory Response
- Response To Oxidative Stress
- I-Kappab Kinase/Nf-Kappab Signaling
- Negative Regulation Of Gene Expression
- Positive Regulation Of Macrophage Derived Foam Cell Differentiation
- Positive Regulation Of Lipid Storage
- Negative Regulation Of Calcidiol 1-Monooxygenase Activity
- Negative Regulation Of Vitamin D Biosynthetic Process
- Membrane Protein Intracellular Domain Proteolysis
- Negative Regulation Of Cellular Protein Metabolic Process
- Negative Regulation Of Cholesterol Transport
- Positive Regulation Of Type I Interferon Production
- Response To Muscle Stretch
- Nik/Nf-Kappab Signaling
- Fc-Epsilon Receptor Signaling Pathway
- Negative Regulation Of Apoptotic Process
- Negative Regulation Of Interleukin-12 Biosynthetic Process
- Innate Immune Response
- Positive Regulation Of Transcription, Dna-Templated
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Response To Copper Ion
- Negative Regulation Of Inflammatory Response
- T Cell Receptor Signaling Pathway
- Positive Regulation Of Nf-Kappab Transcription Factor Activity
- Stress-Activated Mapk Cascade
- Cellular Response To Lipopolysaccharide
- Cellular Response To Mechanical Stimulus
- Cellular Response To Nicotine
- Cellular Response To Carbohydrate Stimulus
- Cellular Response To Interleukin-1
- Cellular Response To Interleukin-6
- Cellular Response To Tumor Necrosis Factor
- Cellular Response To Dsrna
- Cellular Response To Peptide Hormone Stimulus
- Positive Regulation Of Canonical Wnt Signaling Pathway
- Positive Regulation Of Hyaluronan Biosynthetic Process
- Cellular Response To Diterpene
- Cellular Response To Glucoside
- Cellular Response To Brain-Derived Neurotrophic Factor Stimulus
- Positive Regulation Of Mirna Metabolic Process
Drug Bank:
- Acetylsalicylic Acid
- Triflusal
- Pranlukast
- Thalidomide