======= NFKB1 =======
== Gene Information ==
* **Official Symbol**: NFKB1
* **Official Name**: nuclear factor kappa B subunit 1
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=4790|4790]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P19838|P19838]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=NFKB1&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20NFKB1|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/164011|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: 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 Summary**: 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. {ECO:0000269|PubMed:15485931}.
|Death|
|RHD|
|Ank 2|
|Ank|
|negative regulation of interleukin-12 biosynthetic process|
|I-kappaB/NF-kappaB complex|
|negative regulation of calcidiol 1-monooxygenase activity|
|positive regulation of hyaluronan biosynthetic process|
|positive regulation of miRNA metabolic process|
|negative regulation of vitamin D biosynthetic process|
|negative regulation of vitamin metabolic process|
|regulation of calcidiol 1-monooxygenase activity|
|regulation of hyaluronan biosynthetic process|
|regulation of vitamin D biosynthetic process|
|regulation of interleukin-12 biosynthetic process|
|cellular response to nicotine|
|regulation of miRNA metabolic process|
|negative regulation of hormone biosynthetic process|
|negative regulation of hormone metabolic process|
|negative regulation of monooxygenase activity|
|negative regulation of sterol transport|
|actinin binding|
|negative regulation of cholesterol transport|
|negative regulation of alcohol biosynthetic process|
|regulation of vitamin metabolic process|
|negative regulation of interleukin-12 production|
|positive regulation of macrophage derived foam cell differentiation|
|response to muscle stretch|
|membrane protein intracellular domain proteolysis|
|positive regulation of lipid storage|
|cellular response to angiotensin|
|cellular response to dsRNA|
|negative regulation of steroid biosynthetic process|
|negative regulation of oxidoreductase activity|
|negative regulation of steroid metabolic process|
|response to angiotensin|
|negative regulation of lipid transport|
|regulation of hormone biosynthetic process|
|regulation of macrophage derived foam cell differentiation|
|negative regulation of cytokine biosynthetic process|
|cellular response to interleukin-6|
|response to interleukin-6|
|membrane protein proteolysis|
|regulation of polysaccharide biosynthetic process|
|regulation of hormone metabolic process|
|negative regulation of lipid localization|
|regulation of polysaccharide metabolic process|
|regulation of cholesterol transport|
|regulation of lipid storage|
|regulation of sterol transport|
|response to nicotine|
|negative regulation of lipid biosynthetic process|
|response to dsRNA|
|regulation of interleukin-12 production|
|regulation of monooxygenase activity|
|specific granule lumen|
|regulation of alcohol biosynthetic process|
|transcription regulatory region sequence-specific DNA binding|
|positive regulation of type I interferon production|
|positive regulation of carbohydrate metabolic process|
|cellular response to mechanical stimulus|
|positive regulation of lipid localization|
|negative regulation of lipid metabolic process|
|regulation of steroid biosynthetic process|
|negative regulation of small molecule metabolic process|
|regulation of carbohydrate biosynthetic process|
|regulation of oxidoreductase activity|
|interleukin-1-mediated signaling pathway|
|RNA polymerase II distal enhancer sequence-specific DNA binding|
|regulation of cytokine biosynthetic process|
|stress-activated MAPK cascade|
|regulation of lipid transport|
|stimulatory C-type lectin receptor signaling pathway|
|regulation of steroid metabolic process|
|secretory granule lumen|
|innate immune response activating cell surface receptor signaling pathway|
|regulation of type I interferon production|
|negative regulation of inflammatory response|
|regulation of lipid localization|
|positive regulation of small molecule metabolic process|
|stress-activated protein kinase signaling cascade|
|positive regulation of canonical Wnt signaling pathway|
|positive regulation of NF-kappaB transcription factor activity|
|Fc-epsilon receptor signaling pathway|
|cellular response to interleukin-1|
|T cell receptor signaling pathway|
|positive regulation of Wnt signaling pathway|
|cellular response to lipopolysaccharide|
|regulation of lipid biosynthetic process|
|cellular response to molecule of bacterial origin|
|response to interleukin-1|
|regulation of carbohydrate metabolic process|
|negative regulation of defense response|
|response to mechanical stimulus|
|cellular response to toxic substance|
|cellular response to biotic stimulus|
|transcription regulatory region DNA binding|
|innate immune response-activating signal transduction|
|cellular response to tumor necrosis factor|
|Fc receptor signaling pathway|
|DNA-binding transcription repressor activity, RNA polymerase II-specific|
|activation of innate immune response|
|positive regulation of DNA-binding transcription factor activity|
|response to tumor necrosis factor|
|cellular response to peptide hormone stimulus|
|negative regulation of cytokine production|
|regulation of canonical Wnt signaling pathway|
|antigen receptor-mediated signaling pathway|
|RNA polymerase II regulatory region sequence-specific DNA binding|
|response to lipopolysaccharide|
|cellular response to abiotic stimulus|
|cellular response to environmental stimulus|
|cellular response to peptide|
|response to molecule of bacterial origin|
|transcription factor binding|
|cellular response to external stimulus|
|regulation of inflammatory response|
|positive regulation of innate immune response|
|regulation of Wnt signaling pathway|
|positive regulation of response to biotic stimulus|
|negative regulation of response to external stimulus|
|MAPK cascade|
|response to peptide hormone|
|signal transduction by protein phosphorylation|
|chromatin binding|
|regulation of lipid metabolic process|
|cellular response to drug|
|regulation of small molecule metabolic process|
|regulation of DNA-binding transcription factor activity|
|DNA-binding transcription activator activity, RNA polymerase II-specific|
|positive regulation of cytokine production|
|immune response-activating cell surface receptor signaling pathway|
|regulation of innate immune response|
|response to peptide|
|positive regulation of defense response|
|transcription by RNA polymerase II|
|immune response-regulating cell surface receptor signaling pathway|
|negative regulation of transport|
|neutrophil degranulation|
|protein heterodimerization activity|
|neutrophil activation involved in immune response|
|inflammatory response|
|neutrophil mediated immunity|
|neutrophil activation|
|granulocyte activation|
|response to toxic substance|
|positive regulation of multi-organism process|
|leukocyte degranulation|
|myeloid leukocyte mediated immunity|
|cellular response to lipid|
|regulation of response to biotic stimulus|
|myeloid cell activation involved in immune response|
|regulation of hormone levels|
|cellular response to organic cyclic compound|
|immune response-activating signal transduction|
|myeloid leukocyte activation|
|immune response-regulating signaling pathway|
|cellular response to organonitrogen compound|
|positive regulation of response to external stimulus|
|cellular response to hormone stimulus|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|activation of immune response|
|transcription, DNA-templated|
|nucleic acid-templated transcription|
|RNA biosynthetic process|
|cellular response to nitrogen compound|
|cytokine-mediated signaling pathway|
|DNA-binding transcription factor activity|
|response to bacterium|
|regulation of cytokine production|
|regulated exocytosis|
|regulation of defense response|
|leukocyte mediated immunity|
|regulation of multi-organism process|
|negative regulation of catalytic activity|
|exocytosis|
|response to lipid|
|negative regulation of transcription by RNA polymerase II|
|positive regulation of immune response|
|protein homodimerization activity|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|response to hormone|
|response to organic cyclic compound|
|apoptotic process|
|leukocyte activation|
|positive regulation of cell differentiation|
|protein phosphorylation|
|negative regulation of cell death|
|response to organonitrogen compound|
|secretion by cell|
|cellular response to cytokine stimulus|
|response to drug|
|negative regulation of cellular protein metabolic process|
|export from cell|
|programmed cell death|
|cellular response to oxygen-containing compound|
|identical protein binding|
|cell activation|
|response to nitrogen compound|
|cell death|
|immune effector process|
|regulation of response to external stimulus|
|nucleobase-containing compound biosynthetic process|
|response to cytokine|
|negative regulation of protein metabolic process|
|secretion|
|negative regulation of molecular function|
|regulation of immune response|
|positive regulation of immune system process|
|response to abiotic stimulus|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|negative regulation of transcription, DNA-templated|
|negative regulation of multicellular organismal process|
|positive regulation of transcription by RNA polymerase II|
|cellular response to endogenous stimulus|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|mitochondrion|
|proteolysis|
|phosphorylation|
|response to other organism|
|organic cyclic compound biosynthetic process|
|response to external biotic stimulus|
|response to biotic stimulus|
|negative regulation of RNA metabolic process|
|defense response|
|positive regulation of developmental process|
|negative regulation of cellular macromolecule biosynthetic process|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|regulation of apoptotic process|
|positive regulation of transcription, DNA-templated|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|DNA-binding transcription factor activity, RNA polymerase II-specific|
|regulation of programmed cell death|
|negative regulation of response to stimulus|
|cellular nitrogen compound biosynthetic process|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|positive regulation of signal transduction|
|regulation of immune system process|
|RNA metabolic process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|cellular macromolecule biosynthetic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|macromolecule biosynthetic process|
|positive regulation of molecular function|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of transport|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|extracellular region|
|vesicle-mediated transport|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|gene expression|
|positive regulation of biosynthetic process|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp189|Temozolomide 200μM R04 exp189]]|-1.73|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 5/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|3/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 15159
* **Expression level (log2 read counts)**: 5.98
{{:chemogenomics:nalm6 dist.png?nolink |}}