ID:NFKB2_HUMAN DESCRIPTION: RecName: Full=Nuclear factor NF-kappa-B p100 subunit; AltName: Full=DNA-binding factor KBF2; AltName: Full=H2TF1; AltName: Full=Lymphocyte translocation chromosome 10 protein; AltName: Full=Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2; AltName: Full=Oncogene Lyt-10; Short=Lyt10; Contains: RecName: Full=Nuclear factor NF-kappa-B p52 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. 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. In a non-canonical activation pathway, the MAP3K14- activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 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. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. SUBUNIT: Component of the NF-kappa-B RelB-p52 complex. Homodimer; component of the NF-kappa-B p52-p52 complex. Component of the NF- kappa-B p65-p52 complex. Component of the NF-kappa-B p52-c-Rel complex. NFKB2/p52 interacts with NFKBIE. Component of a complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3. Directly interacts with MEN1. SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B). DOMAIN: The C-terminus of p100 might be involved in cytoplasmic retention, inhibition of DNA-binding by p52 homodimers, and/or transcription activation (By similarity). DOMAIN: The glycine-rich region (GRR) appears to be a critical element in the generation of p52. PTM: While translation occurs, the particular unfolded structure after the GRR repeat promotes the generation of p52 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: Subsequent to MAP3K14-dependent serine phosphorylation, p100 polyubiquitination occurs then triggering its proteasome-dependent processing. PTM: Constitutive processing is tightly suppressed by its C- terminal processing inhibitory domain, named PID, which contains the death domain. DISEASE: Note=A chromosomal aberration involving NFKB2 is found in a case of B-cell non Hodgkin lymphoma (B-NHL). Translocation t(10;14)(q24;q32) with IGHA1. The resulting oncogene is also called Lyt-10C alpha variant. DISEASE: Note=A chromosomal aberration involving NFKB2 is found in a cutaneous T-cell leukemia (C-TCL) cell line. This rearrangement produces the p80HT gene which encodes for a truncated 80 kDa protein (p80HT). DISEASE: Note=In B-cell leukemia (B-CLL) cell line, LB40 and EB308, can be found after heterogeneous chromosomal aberrations, such as internal deletions. SIMILARITY: Contains 7 ANK repeats. SIMILARITY: Contains 1 death domain. SIMILARITY: Contains 1 RHD (Rel-like) domain. SEQUENCE CAUTION: Sequence=CAA43715.1; Type=Frameshift; Positions=456, 458, 470, 900; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/NFKB2ID362.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/nfkb2/";
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 Q00653
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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:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0003677 DNA binding GO:0003682 chromatin binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0003713 transcription coactivator activity GO:0005515 protein binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0002268 follicular dendritic cell differentiation GO:0002467 germinal center formation GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006366 transcription from RNA polymerase II promoter GO:0006954 inflammatory response GO:0007165 signal transduction GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0007568 aging GO:0030198 extracellular matrix organization GO:0032481 positive regulation of type I interferon production GO:0032496 response to lipopolysaccharide GO:0034097 response to cytokine GO:0038061 NIK/NF-kappaB signaling GO:0045087 innate immune response GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048511 rhythmic process GO:0048536 spleen development GO:0051092 positive regulation of NF-kappaB transcription factor activity
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
