Protein: Nuclear factor NF-kappa-B p105 subunit (DNA-binding factor KBF1) (EBP-1) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) [Cleaved into: Nuclear factor NF-kappa-B p50 subunit] (Q63369)
Organism: Rattus norvegicus (Rat)
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 and the heterodimeric p65-p50 complex appears to be most abundant one. 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. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The 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 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and 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 and acute phase reactions. Plays a role in the regulation of apoptosis. Isoform 5, isoform 6 and isoform 7 act as inhibitors of transactivation of p50 NF-kappa-B subunit, probably by sequestering it in the cytoplasm. Isoform 3 (p98) (but not p84 or p105) acts as a transactivator of NF-kappa-B-regulated gene expression. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105 (By similarity).
Subcellular location: [Nuclear factor NF-kappa-B p105 subunit]: Cytoplasm {ECO:0000250|UniProtKB:P19838}.; SUBCELLULAR LOCATION: [Nuclear factor NF-kappa-B p50 subunit]: Nucleus {ECO:0000250|UniProtKB:P19838}. Cytoplasm {ECO:0000250|UniProtKB:P19838}. Note=Association with NFKBIA inhibitor (I-kappa-B), promotes its retention in the cytoplasm in an inactive form. Translocates into the nucleus following NFKBIA degradation. {ECO:0000250|UniProtKB:P19838}.
Interaction partners:
- Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2, p49/p100, isoform CRA_a.
- NF-kappa-B inhibitor alpha
- Transcription factor RelB
- Transcription factor p65
- Inhibitor of nuclear factor kappa-B kinase subunit alpha
- REL proto-oncogene, NF-kB subunit
- NF-kappa-B inhibitor beta
- BCL3, transcription coactivator
- Inhibitor of nuclear factor kappa-B kinase subunit beta
- Mitogen-activated protein kinase kinase kinase 8
Sequence:
MADDDPFGTGQMFHLNTALTHSIFNAELYSTDIPLSTADGPYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDGICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGLLVHSDLAYLQAEGGGDRQLTDREKEIIRQAALQQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAIYDSKAPNASNLKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIRFYEEEENGGVWEGFGDFSPTDVHRQFAIVFKTPKYKDVNITKPASVFVQLRRKSDLETSEPKPFLYYPEIKDKEEVQRKRQKLMPNFSDSFGGGSGAGAGGGGMFGSGGGGGGSTGSPGPGYGFPHYGFPAYGGIAFHPGATKSNTGITHGTINTKFKNEPRDCAKSDDREILNPPEKETQGEGPSLFMASTKTEAIAPASTMEDKEEDVGFQDNLFLEKALQLAKRHANALFDYAVTGDVKMLLAVQRHLTAVQDENGDSVLHLAIIHLHAQLVRDLLEVTSGSISDDIINMRNDLYQTPLHLAVITKQEDVVEDLLRVGADLSLLDRWGNSVLHLAAKEGHDKILGVLLKNSKAALLINHPNGEGLNAIHIAVMSNSLSCLQLLVAAGAEVNAQEQKSGRTALHLAVEYDNISLAGCLLLEGDALVDSTTYDGTTPLHIAAGRGSTRLAALLKAAGADPLVENFEPLYDLDDSWEKAGEDEGVVPGTTPLDMAANWQVFDILNGKPYEPVFTSDDILPQGDIKQLTEDTRLQLCKLLEIPDPDKNWATLAQKLGLGILNNAFRLSPAPSKTLMDNYEVSGGTIKELVEALRQMGYTEAIEVIQAAFRTPETTASSPVTTAQAHLLPLSSSSTRQHIDELRDNDSVCDSGVETSFRKLSFSESLTGDGPLLSLNKMPHNYGQDGPIEGKI