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

More general terms

• oligomerizing protein
• rel protein family
• human longevity protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4790
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4790
• Kegg: http://www.genome.jp/dbget-bin/www_bget?
• OMIM: https://mirror.omim.org/entry/164011
• UniProt: http://www.uniprot.org/uniprot/P19838.html