Summary

Name NFKB2
Full Name Nuclear factor NF-kappa-B p100 subunit
Synonyms DNA-binding factor KBF2, H2TF1, Lymphocyte translocation chromosome 10 protein, Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2, Oncogene Lyt-10, Lyt10 | LYT10
Primary ID Q00653
Links - -
Type protein
Relations 15
Pathways NF-KB Non Canonical
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 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. 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 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The 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 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and 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 and acute phase reactions. p52 and p100 are respectively the minor and 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. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer.

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▶Modifications Tables

Relations

Regulator Mechanism target score ℹ
+ CHUKup-regulates activity img/direct-activation.png phosphorylation NFKB2 0.784
Publications: 2 Organism: Mus Musculus
Pathways:NF-KB Non Canonical
+ MAP3K14up-regulates activity img/direct-activation.png phosphorylation NFKB2 0.664
Publications: 2 Organism: Homo Sapiens
Pathways:NF-KB Non Canonical
+ SCF-betaTRCPup-regulates activity img/direct-activation.png ubiquitination NFKB2 0.534
Publications: 1 Organism: Homo Sapiens
Pathways:NF-KB Non Canonical
+ TSC22D3down-regulates activity img/direct_inhibition.png binding NFKB2 0.332
Publications: 1 Organism: Homo Sapiens
+ NOTCH1up-regulates quantity by expression img/indirect-activation.png transcriptional regulation NFKB2 0.292
Publications: 1 Organism: Homo Sapiens
+ BCL3up-regulates img/direct-activation.png binding NFKB2 0.554
Publications: 1 Organism: Homo Sapiens
+ RBPJdown-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation NFKB2 0.27
Publications: 1 Organism: Homo Sapiens
+ Cullin 1-RBX1-Skp1down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination NFKB2 0.431
Publications: 1 Organism: Mus Musculus
+ TP53up-regulates img/direct-activation.png binding NFKB2 0.436
Publications: 1 Organism: Homo Sapiens
+ RBX1up-regulates img/direct-activation.png ubiquitination NFKB2 0.285
Publications: 1 Organism: Homo Sapiens
+ NFKB2up-regulates activity img/direct-activation.png binding RELB 0.75
Publications: 1 Organism: Homo Sapiens
Pathways:NF-KB Non Canonical
+ BCL3up-regulates img/indirect-activation.png NFKB2 0.554
Publications: 1 Organism: Homo Sapiens
+ FBXW7down-regulates quantity by destabilization img/direct_inhibition.png binding NFKB2 0.405
Publications: 1 Organism: Mus Musculus