InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Nfkb1

Summary

InnateDB Protein

IDBP-195447.6

Last Modified

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

Gene Symbol

Nfkb1

Protein Name

nuclear factor of kappa light polypeptide gene enhancer in B-cells 1, p105

Synonyms

NF-kappaB; NF-kappaB1; NF-KB1; p105; p50; p50/p105;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000029812

InnateDB Gene

IDBG-195445 (Nfkb1)

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 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.

Subcellular Localization

Nucleus. Cytoplasm. Note=Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B).Isoform 5: Cytoplasm.Isoform 6: Nucleus. Cytoplasm.Isoform 7: Nucleus.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 111 experimentally validated interaction(s) in this database.
They are also associated with 209 interaction(s) predicted by orthology.

Experimentally validated
Total	111 [view]
Protein-Protein	41 [view]
Protein-DNA	65 [view]
Protein-RNA	4 [view]
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	209 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000975	regulatory region DNA binding
GO:0000976	transcription regulatory region sequence-specific DNA binding
GO:0001071	nucleic acid binding transcription factor activity
GO:0003677	DNA binding
GO:0003690	double-stranded DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0031072	heat shock protein binding
GO:0042803	protein homodimerization activity
GO:0043565	sequence-specific DNA binding
GO:0044212	transcription regulatory region DNA binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001818	negative regulation of cytokine production
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006915	apoptotic process
GO:0006979	response to oxidative stress
GO:0007165	signal transduction
GO:0009617	response to bacterium
GO:0010956	negative regulation of calcidiol 1-monooxygenase activity
GO:0043066	negative regulation of apoptotic process
GO:0045083	negative regulation of interleukin-12 biosynthetic process
GO:0045087	innate immune response (InnateDB)
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046688	response to copper ion
GO:0048535	lymph node development
GO:0050728	negative regulation of inflammatory response
GO:0071222	cellular response to lipopolysaccharide
GO:0071260	cellular response to mechanical stimulus
GO:0071316	cellular response to nicotine
GO:0071347	cellular response to interleukin-1
GO:0071354	cellular response to interleukin-6
GO:0071375	cellular response to peptide hormone stimulus
GO:0090263	positive regulation of canonical Wnt signaling pathway
GO:1900127	positive regulation of hyaluronan biosynthetic process
GO:2000630	positive regulation of miRNA metabolic process

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005829	cytosol
GO:0043234	protein complex

Protein Structure and Domains

PDB ID

MGI:97312

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