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NF-kappa B p50 subunit; NF-kappa B p105 subunit; NF-kappa C; DNA-binding factor KBF1; EBP-1 (NFKB1)
Function:
- p105 precursor processed to p50
- component of the NF-kappa-B p65-p50 complex
- component of NF-kappa-B p65-p50 complex
- 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 & BCL3.
- NF-kappa-B heterodimeric p65-p50 & RelB-p50 complexes are transcriptional activators.
- 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 & generation of p50 by a cotranslational processing
- proteasome-mediated process ensures the production of both p50 & p105 & 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 & 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
- 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 & DNA-binding
- interacts with SPAG9 & UNC5CL
- NFKB1/p105 interacts with CFLAR; the interaction inhibits p105 processing into p50
- NFKB1/p105 forms a ternary complex with MAP3K8 & 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 IKBNS
- while translation occurs, the particular unfolded structure after the GRR repeat promotes the generation of p50 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
- phosphorylation at Ser-903 & Ser-907 primes p105 for proteolytic processing in response to TNF-alpha stimulation
- phosphorylation at Ser-927 & Ser-932 are required for BTRC/BTRCP-mediated proteolysis
- polyubiquitination seems to allow p105 processing
Structure:
- p105 processed to p50
- homodimer (dubbed NF-kappa C)
- heterodimer with other NF kappa B proteins
- the C-terminus of p105 might be involved in cytoplasmic retention, inhibition of DNA-binding, & transcription activation
- glycine-rich region (GRR) appears to be a critical element in the generation of p50
- 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=3
Expression:
- NF-kappa B p50 homodimer found in resting T cells
- induced by phorbol ester & TNF-alpha
General
human longevity protein
oligomerizing protein
rel protein family
Properties
SIZE: entity length = 968 aa
MW = 105 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: RHD {42-367}
MOTIF: Ser phosphorylation site {S337}
nuclear translocation signal {360-365}
GRR {372-394}
glycine-rich region {375-433}
Cleavage {433-434}
CFLAR interaction {435-968}
MOTIF: ankyrin repeat
NAME: ankyrin repeat
SITE: 542-571
ankyrin repeat
NAME: ankyrin repeat
SITE: 581-610
ankyrin repeat
NAME: ankyrin repeat
SITE: 614-643
ankyrin repeat
NAME: ankyrin repeat
SITE: 650-679
ankyrin repeat
NAME: ankyrin repeat
SITE: 684-714
ankyrin repeat
NAME: ankyrin repeat
SITE: 718-747
ankyrin repeat
NAME: ankyrin repeat
SITE: 771-801
death domain
NAME: death domain
SITE: 805-892
Ser phosphorylation site {S903}
Ser phosphorylation site {S907}
Ser phosphorylation site {S927}
Ser phosphorylation site {S932}
Database Correlations
OMIM 164011
UniProt P19838
PFAM correlations
Entrez Gene 4790
KEGG correlations
References
- Ruben SM, Dillon PJ, Schreck R, Henkel T, Chen CH, Maher M,
Baeuerle PA, Rosen CA.
Isolation of a rel-related human cDNA that potentially encodes
the 65-kD subunit of NF-kappa B.
Science. 1991 Oct 4;254(5028):11.
PMID: 1925549
- Ruben SM, Dillon PJ, Schreck R, Henkel T, Chen CH, Maher M, Baeuerle PA, Rosen CA.
Isolation of a rel-related human cDNA that potentially encodes
the 65-kD subunit of NF-kappa B.
Science. 1991 Mar 22;251(5000):1490-3. Erratum in: Science.
1991 Oct 4;254(5028):11.
PMID: 2006423
- Riviere Y, Blank V, Kourilsky P, Isra'l A.
Processing of the precursor of NF-kappa B by the HIV-1
protease during acute infection.
Nature. 1991 Apr 18;350(6319):625-6.
PMID: 2017258
- Kang SM, Tran AC, Grilli M, Lenardo MJ.
NF-kappa B subunit regulation in nontransformed CD4+
T lymphocytes.
Science. 1992 Jun 5;256(5062):1452-6.
PMID: 1604322
- UniProt :accession P19838
- Atlas of genetics & cytogenetics in oncology & haematology
http://atlasgeneticsoncology.org/genes/NFKB1ID323.html
- NIEHS-SNPs
http://egp.gs.washington.edu/data/nfkb1/
Component-of
nuclear factor kappa-B (NF-kappa B)