Human Gene NFKB1 (ENST00000394820.8) Description and Page Index
Description: Homo sapiens nuclear factor kappa B subunit 1 (NFKB1), transcript variant 2, mRNA. (from RefSeq NM_001165412) RefSeq Summary (NM_001165412): 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]. Gencode Transcript: ENST00000394820.8 Gencode Gene: ENSG00000109320.13 Transcript (Including UTRs) Position: hg38 chr4:102,501,331-102,616,915 Size: 115,585 Total Exon Count: 24 Strand: + Coding Region Position: hg38 chr4:102,525,519-102,616,594 Size: 91,076 Coding Exon Count: 23
ID:NFKB1_HUMAN DESCRIPTION: RecName: Full=Nuclear factor NF-kappa-B p105 subunit; AltName: Full=DNA-binding factor KBF1; AltName: Full=EBP-1; AltName: Full=Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1; Contains: RecName: Full=Nuclear factor NF-kappa-B p50 subunit; 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. SUBUNIT: Component of the NF-kappa-B p65-p50 complex. Component of the NF-kappa-B p65-p50 complex. Homodimer; component of the NF- kappa-B p50-p50 complex. Component of the NF-kappa-B p105-p50 complex. Component of the NF-kappa-B p50-c-Rel complex. Component of a complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3. Also interacts with MAP3K8. NF-kappa-B p50 subunit interacts with NCOA3 coactivator, which may coactivate NF-kappa-B dependent expression via its histone acetyltransferase activity. Interacts with DSIPI; this interaction prevents nuclear translocation and DNA-binding. Interacts with SPAG9 and UNC5CL. NFKB1/p105 interacts with CFLAR; the interaction inhibits p105 processing into p50. NFKB1/p105 forms a ternary complex with MAP3K8 and TNIP2. Interacts with GSK3B; the interaction prevents processing of p105 to p50. NFKB1/p50 interacts with NFKBIE. NFKB1/p50 interacts with NFKBIZ. Nuclear factor NF-kappa-B p50 subunit interacts with NFKBID (By similarity). Directly interacts with MEN1. Interacts with HIF1AN. INTERACTION: Q92887:ABCC2; NbExp=3; IntAct=EBI-300010, EBI-3916193; P03372:ESR1; NbExp=3; IntAct=EBI-697771, EBI-78473; Q13547:HDAC1; NbExp=4; IntAct=EBI-300010, EBI-301834; P25963:NFKBIA; NbExp=2; IntAct=EBI-300010, EBI-307386; Q14690:PDCD11; NbExp=2; IntAct=EBI-300010, EBI-300028; Q8IZL8:PELP1; NbExp=2; IntAct=EBI-300010, EBI-716449; Q8IV08:PLD3; NbExp=2; IntAct=EBI-300010, EBI-2689908; Q04206:RELA; NbExp=9; IntAct=EBI-300010, EBI-73886; P23396:RPS3; NbExp=2; IntAct=EBI-300010, EBI-351193; Q8NFZ5:TNIP2; NbExp=8; IntAct=EBI-1452239, EBI-359372; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B). INDUCTION: By phorbol ester and TNF. DOMAIN: The C-terminus of p105 might be involved in cytoplasmic retention, inhibition of DNA-binding, and transcription activation. DOMAIN: Glycine-rich region (GRR) appears to be a critical element in the generation of p50. PTM: While translation occurs, the particular unfolded structure after the GRR repeat promotes the generation of p50 making it an acceptable substrate for the proteasome. This process is known as cotranslational processing. The processed form is active and the unprocessed form acts as an inhibitor (I kappa B-like), being able to form cytosolic complexes with NF-kappa B, trapping it in the cytoplasm. Complete folding of the region downstream of the GRR repeat precludes processing. PTM: Phosphorylation at 'Ser-903' and 'Ser-907' primes p105 for proteolytic processing in response to TNF-alpha stimulation. Phosphorylation at 'Ser-927' and 'Ser-932' are required for BTRC/BTRCP-mediated proteolysis. PTM: Polyubiquitination seems to allow p105 processing. PTM: S-nitrosylation of Cys-61 affects DNA binding. PTM: The covalent modification of cysteine by 15-deoxy-Delta12,14- prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S- nitrosylation and S-palmitoylation. SIMILARITY: Contains 7 ANK repeats. SIMILARITY: Contains 1 death domain. SIMILARITY: Contains 1 RHD (Rel-like) domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/NFKB1ID323.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/nfkb1/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P19838
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000976 transcription regulatory region sequence-specific DNA binding GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000980 RNA polymerase II distal enhancer sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001205 transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding GO:0001227 transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003677 DNA binding GO:0003682 chromatin binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0008134 transcription factor binding GO:0042802 identical protein binding GO:0042803 protein homodimerization activity GO:0042805 actinin binding GO:0043565 sequence-specific DNA binding GO:0044212 transcription regulatory region DNA binding GO:0046982 protein heterodimerization activity
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0001818 negative regulation of cytokine production GO:0002223 stimulatory C-type lectin receptor signaling pathway GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006366 transcription from RNA polymerase II promoter GO:0006915 apoptotic process GO:0006954 inflammatory response GO:0007165 signal transduction GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0010629 negative regulation of gene expression GO:0010744 positive regulation of macrophage derived foam cell differentiation GO:0010884 positive regulation of lipid storage GO:0010956 negative regulation of calcidiol 1-monooxygenase activity GO:0010957 negative regulation of vitamin D biosynthetic process GO:0031293 membrane protein intracellular domain proteolysis GO:0032269 negative regulation of cellular protein metabolic process GO:0032375 negative regulation of cholesterol transport GO:0032481 positive regulation of type I interferon production GO:0035994 response to muscle stretch GO:0038061 NIK/NF-kappaB signaling GO:0038095 Fc-epsilon receptor signaling pathway GO:0043066 negative regulation of apoptotic process GO:0043312 neutrophil degranulation GO:0045083 negative regulation of interleukin-12 biosynthetic process GO:0045087 innate immune response GO:0045892 negative regulation of transcription, DNA-templated GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0050728 negative regulation of inflammatory response GO:0050852 T cell receptor signaling pathway GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0051403 stress-activated MAPK cascade GO:0070498 interleukin-1-mediated signaling pathway GO:0071222 cellular response to lipopolysaccharide GO:0071260 cellular response to mechanical stimulus GO:0071316 cellular response to nicotine GO:0071347 cellular response to interleukin-1 GO:0071354 cellular response to interleukin-6 GO:0071356 cellular response to tumor necrosis factor GO:0071359 cellular response to dsRNA GO:0090263 positive regulation of canonical Wnt signaling pathway GO:1900127 positive regulation of hyaluronan biosynthetic process GO:1904385 cellular response to angiotensin GO:2000630 positive regulation of miRNA metabolic process