Search
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
General
oligomerizing protein
phosphoprotein
rel protein family
Properties
SIZE: entity length = 900 aa
MW = 97 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: RHD {38-343}
MOTIF: nuclear translocation signal {337-341}
GRR {346-377}
glycine-rich region {350-400}
Cleavage {454-455}
ankyrin repeat
NAME: ankyrin repeat
SITE: 487-519
MOTIF: Breakpoint {490-491}
ankyrin repeat
NAME: ankyrin repeat
SITE: 526-555
ankyrin repeat
NAME: ankyrin repeat
SITE: 559-591
ankyrin repeat
NAME: ankyrin repeat
SITE: 599-628
ankyrin repeat
NAME: ankyrin repeat
SITE: 633-663
ankyrin repeat
NAME: ankyrin repeat
SITE: 667-696
Ser phosphorylation site {S713}
Ser phosphorylation site {S715}
Ser phosphorylation site {S717}
ankyrin repeat
NAME: ankyrin repeat
SITE: 729-758
death domain
NAME: death domain
SITE: 764-851
Ser phosphorylation site {S866}
Ser phosphorylation site {S870}
Database Correlations
OMIM 164012
UniProt Q00653
PFAM correlations
Entrez Gene 4791
Kegg hsa:4791
References
- UniProt :accession Q00653
- Entrez Gene :accession 4791
- Atlas of genetics & cytogenetics in oncology & haematology
http://atlasgeneticsoncology.org/genes/NFKB2ID362.html