NF-kappa B p52 subunit; NF-kappa p100; DNA-binding factor KBF2; H2TF1; lymphocyte translocation chromosome 10; oncogene Lyt-10; Lyt10 (NFKB2, LYT10)

Function

• p100 cleaved to form p52 & p49
• 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 & formation of NF-kappa-B RelB-p52 complexes
• NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator
• 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 & generation of p52 by cotranslational processing
• proteasome-mediated process ensures production of both p52 & p100 & 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 & acute phase reactions
• p52 & p100 are respectively the minor & 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
• component of the NF-kappa-B RelB-p52 complex
• 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 & BCL3
• while translation occurs, the particular unfolded structure after the GRR repeat promotes the generation of p52 making it an acceptable substrate for the proteasome (cotranslational processing; the processed form is active & 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

Structure

• homodimer
• heterodimer with other NF kappa B protein
• C-terminus of p100 might be involved in cytoplasmic retention, inhibition of DNA-binding by p52 homodimers, &/or transcription activation (putative)
• glycine-rich region (GRR) appears to be a critical element in the generation of p52
• contains 7 ANK repeats
• contains 1 death domain
• contains 1 RHD (Rel-like) domain

Compartment

• nucleus, cytoplasm
• nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B)

Alternative splicing

named isoforms=2

Pathology

• chromosomal translocation t(10;14)(q24;q32) involving NFKB2 with IGHA1 is found in a case of B-cell non Hodgkin lymphoma, the resulting oncogene is also called Lyt-10C alpha variant
• 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 kD protein (p80HT)
• heterogeneous chromosomal aberrations founs in B-cell leukemia (B-CLL) cell lines, LB40 & EB308

More general terms

• oligomerizing protein
• rel protein family
• phosphoprotein

Database

• UniProt: http://www.uniprot.org/uniprot/Q00653.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4791
• OMIM: https://mirror.omim.org/entry/164012
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4791