Scientific Background: NFKB2 is a part of the NFKB complex that is present in various cell types that express cytokines, chemokines, growth factors, cell adhesion molecules, and some acute phase proteins in health and disease states. NFKB protein is activated by a wide variety of stimuli such as cytokines, oxidant-free radicals, inhaled particles, ultraviolet irradiation, and bacterial or viral products (1). Inappropriate activation of NFKB has been linked to inflammatory events associated with autoimmune arthritis, asthma, septic shock, lung fibrosis, glomerulonephritis, atherosclerosis, and AIDS (2). Overexpression of NFKB2 protects androgen sensitive LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation.
2. Tucker, E. et al: A novel mutation in the Nfkb2 gene generates an NF-kappa-B2 'super repressor' J. Immun. 179: 7514-7522, 2007.
NCBI and Uniprot Product Information
NCBI Description
This gene encodes one of the subunits of the transcription factor complex nuclear factor-kappa-B (NFkB). The NFkB transcription factor complex is expressed in numerous cell types and functions as a central activator of genes involved in inflammation and immune function. The NFkB complex can consist of different subunits that form both homo- or heterodimers which bind specific kappa-B elements in target genes. This gene encodes the p100 subunit that is processed into the active p52 subunit. This protein can function as both a transcriptional activator and repressor, depending on its dimer partner. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, May 2012]
Uniprot Description
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. Ref.14
Subunit structure: 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. Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.23 Ref.25
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.The glycine-rich region (GRR) appears to be a critical element in the generation of p52.
Post-translational modification: 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.Subsequent to MAP3K14-dependent serine phosphorylation, p100 polyubiquitination occurs then triggering its proteasome-dependent processing.Constitutive processing is tightly suppressed by its C-terminal processing inhibitory domain, named PID, which contains the death domain.
Involvement in disease: 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.A chromosomal aberration involving NFKB2 is found in a cutaneous T-cell leukemia (C-TCL) cell line. This rearrangement produces the p80HT gene which codes for a truncated 80 kDa protein (p80HT).In B-cell leukemia (B-CLL) cell line, LB40 and EB308, can be found after heterogeneous chromosomal aberrations, such as internal deletions.
Sequence similarities: Contains 7 ANK repeats.Contains 1 death domain.Contains 1 RHD (Rel-like) domain.
Sequence caution: The sequence CAA43715.1 differs from that shown. Reason: Frameshift at positions 456, 458, 470 and 900.
Research Articles on NFKB2
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Product Notes
The NFKB2 nfkb2 (Catalog #AAA515151) is a Recombinant Protein produced from Sf9 insect cells and is intended for research purposes only. The product is available for immediate purchase. The immunogen sequence is 1-454 with tag GST tag!!Expression System||Sf9 insect cells using baculovirus!!Source Note||Recombinant human NFKB2 (1-454) was expressed in Sf9 insect cells. AAA Biotech's NFKB2 can be used in a range of immunoassay formats including, but not limited to, Western Blot (WB). Researchers should empirically determine the suitability of the NFKB2 nfkb2 for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "NFKB2, Recombinant Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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