Protein: Transcription factor p65 (Nuclear factor NF-kappa-B p65 subunit) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3) (Q04207)
Organism: Mus musculus (Mouse)
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. The heterodimeric RELA-NFKB1 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. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. 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. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Beside its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (By similarity). The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression (By similarity).
Subcellular location: Nucleus {ECO:0000269|PubMed:21131967, ECO:0000269|PubMed:28378844}. Cytoplasm {ECO:0000269|PubMed:21131967}. Note=Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B) (PubMed:21131967). Colocalized with DDX1 in the nucleus upon TNF-alpha induction (By similarity). Colocalizes with GFI1 in the nucleus after lipopolysaccharide (LPS) stimulation. {ECO:0000250|UniProtKB:Q04206, ECO:0000269|PubMed:21131967}.
Interaction partners:
- Nuclear factor NF-kappa-B p105 subunit
- Nuclear factor NF-kappa-B p100 subunit
- NF-kappa-B inhibitor beta
- Histone lysine acetyltransferase CREBBP
- NF-kappa-B inhibitor alpha
- Transcription factor RelB
- NF-kappa-B inhibitor epsilon
- Proto-oncogene c-Rel
- Inhibitor of nuclear factor kappa-B kinase subunit beta
- Inhibitor of nuclear factor kappa-B kinase subunit alpha
Sequence:
MDDLFPLIFPSEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGYYEADLCPDRSIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFHVPIEEQRGDYDLNAVRLCFQVTVRDPAGRPLLLTPVLSHPIFDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGPGWEARGSFSQADVHRQVAIVFRTPPYADPSLQAPVRVSMQLRRPSDRELSEPMEFQYLPDTDDRHRIEEKRKRTYETFKSIMKKSPFNGPTEPRPPTRRIAVPTRNSTSVPKPAPQPYTFPASLSTINFDEFSPMLLPSGQISNQALALAPSSAPVLAQTMVPSSAMVPLAQPPAPAPVLTPGPPQSLSAPVPKSTQAGEGTLSEALLHLQFDADEDLGALLGNSTDPGVFTDLASVDNSEFQQLLNQGVSMSHSTAEPMLMEYPEAITRLVTGSQRPPDPAPTPLGTSGLPNGLSGDEDFSSIADMDFSALLSQISS