InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Nfkb2

Summary

InnateDB Protein

IDBP-257180.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Nfkb2

Protein Name

nuclear factor of kappa light polypeptide gene enhancer in B-cells 2, p49/p100

Synonyms

lyt; NF-kappaB2; p49; p49/p100; p50B; p52;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000107512

InnateDB Gene

IDBG-172544 (Nfkb2)

Protein Structure

UniProt Annotation

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 (By similarity). In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer. {ECO:0000250, ECO:0000269PubMed:22894897}.

Subcellular Localization

Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Note=Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B). {ECO:0000250}.

Disease Associations

Tissue Specificity

Highly expressed in lymph nodes and thymus. {ECO:0000269PubMed:10398801}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 30 experimentally validated interaction(s) in this database.
They are also associated with 133 interaction(s) predicted by orthology.

Experimentally validated
Total	30 [view]
Protein-Protein	17 [view]
Protein-DNA	13 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	133 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0005515	protein binding

Biological Process

GO:0002268	follicular dendritic cell differentiation
GO:0002467	germinal center formation
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0007165	signal transduction
GO:0030198	extracellular matrix organization
GO:0038061	NIK/NF-kappaB signaling
GO:0048535	lymph node development
GO:0048536	spleen development

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0033257	Bcl3/NF-kappaB2 complex

Protein Structure and Domains

PDB ID

MGI:1099800

InterPro

IPR000451 NF-kappa-B/Rel/Dorsal
IPR000488 Death domain
IPR002110 Ankyrin repeat
IPR002909 IPT domain
IPR008967 p53-like transcription factor, DNA-binding
IPR011029 Death-like domain
IPR011539 Rel homology domain
IPR014756 Immunoglobulin E-set
IPR020683 Ankyrin repeat-containing domain

PFAM