NFKB1 - Nuclear factor NF-kappa-B p105 subunit - human protein (Function)
 
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NFKB1 »  Nuclear factor NF-kappa-B p105 subunit
 
Protein also known as:  Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1. Cleaved into:  Nuclear factor NF-kappa-B p50 subunit.
Gene name:  NFKB1
Entry whose protein(s) existence is based on evidence at protein level
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1 1708 3
GENE REF ISO

Function

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Overview 
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. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105.  
1
  • CuratedUniProtKB
GO molecular function 
Double-stranded DNA bindingdefinition[GO:0003690] silver  
  • IEAOrtholog Compara
Heat shock protein bindingdefinition[GO:0031072] silver  
  • IEAOrtholog Compara
Nucleic acid binding transcription factor activitydefinition[GO:0001071]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
27
  • IPIIntAct
  • IPIUniProtKB
Protein homodimerization activitydefinition[GO:0042803] silver  
  • IEAOrtholog Compara
Regulatory region DNA bindingdefinition[GO:0000975]  
1
  • IDAUniProtKB
Sequence-specific DNA binding transcription factor activitydefinition[GO:0003700] silver  
  • IEAInterPro 2 GO
Transcription factor bindingdefinition[GO:0008134]  
1
  • IDAMGI
Transcription regulatory region DNA bindingdefinition[GO:0044212]  
1
  • IDABHF-UCL
Transcription regulatory region sequence-specific DNA bindingdefinition[GO:0000976]  
1
  • IDAUniProtKB
GO biological process 
Apoptotic processdefinition[GO:0006915]  
  • IEAUniProtKB KW
Cellular response to interleukin-1definition[GO:0071347]  
1
  • IEPBHF-UCL
Cellular response to lipopolysaccharidedefinition[GO:0071222]  
1
  • IMPMGI
Cellular response to mechanical stimulusdefinition[GO:0071260]  
1
  • IEPUniProtKB
Inflammatory responsedefinition[GO:0006954]  
1
  • TASUniProtKB
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • TASUniProtKB
Negative regulation of calcidiol 1-monooxygenase activitydefinition[GO:0010956]  
1
  • IDABHF-UCL
Negative regulation of cellular protein metabolic processdefinition[GO:0032269]  
1
  • ICBHF-UCL
Negative regulation of cholesterol transportdefinition[GO:0032375]  
1
  • ICBHF-UCL
Negative regulation of cytokine productiondefinition[GO:0001818] silver  
  • IEAOrtholog Compara
Negative regulation of inflammatory responsedefinition[GO:0050728] silver  
  • IEAOrtholog Compara
Negative regulation of interleukin-12 biosynthetic processdefinition[GO:0045083] silver  
  • IEAOrtholog Compara
Negative regulation of transcription from RNA polymerase II promoterdefinition[GO:0000122]  
2
  • IMPUniProtKB
  • ICBHF-UCL
Negative regulation of vitamin D biosynthetic processdefinition[GO:0010957]  
1
  • ICBHF-UCL
Positive regulation of canonical Wnt signaling pathwaydefinition[GO:0090263]  
1
  • IMPUniProtKB
Positive regulation of hyaluronan biosynthetic processdefinition[GO:1900127]  
1
  • IDAUniProtKB
Positive regulation of lipid storagedefinition[GO:0010884]  
1
  • ICBHF-UCL
Positive regulation of macrophage derived foam cell differentiationdefinition[GO:0010744]  
1
  • ICBHF-UCL
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944] silver  
  • IEAOrtholog Compara
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
3
  • IMPUniProtKB
Response to copper iondefinition[GO:0046688] silver  
  • IEAOrtholog Compara
Response to oxidative stressdefinition[GO:0006979] silver  
  • IEAOrtholog Compara
Transcription from RNA polymerase II promoterdefinition[GO:0006366]  
1
  • TASUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Acute myeloid leukemia  hsa05221+4790  
Adipocytokine signaling pathway  hsa04920+4790  
Amoebiasis  hsa05146+4790  
Apoptosis  hsa04210+4790  
B cell receptor signaling pathway  hsa04662+4790  
Chagas disease (American trypanosomiasis)  hsa05142+4790  
Chemokine signaling pathway  hsa04062+4790  
Chronic myeloid leukemia  hsa05220+4790  
Cytosolic DNA-sensing pathway  hsa04623+4790  
Epithelial cell signaling in Helicobacter pylori infection  hsa05120+4790  
Hepatitis C  hsa05160+4790  
Herpes simplex infection  hsa05168+4790  
HTLV-I infection  hsa05166+4790  
Influenza A  hsa05164+4790  
Legionellosis  hsa05134+4790  
Leishmaniasis  hsa05140+4790  
MAPK signaling pathway  hsa04010+4790  
Measles  hsa05162+4790  
Neurotrophin signaling pathway  hsa04722+4790  
NOD-like receptor signaling pathway  hsa04621+4790  
Osteoclast differentiation  hsa04380+4790  
Pancreatic cancer  hsa05212+4790  
Pathways in cancer  hsa05200+4790  
Pertussis  hsa05133+4790  
Prostate cancer  hsa05215+4790  
RIG-I-like receptor signaling pathway  hsa04622+4790  
Salmonella infection  hsa05132+4790  
Shigellosis  hsa05131+4790  
Small cell lung cancer  hsa05222+4790  
T cell receptor signaling pathway  hsa04660+4790  
Toll-like receptor signaling pathway  hsa04620+4790  
Toxoplasmosis  hsa05145+4790  
Tuberculosis  hsa05152+4790  
According to Reactome, this protein belongs to the following pathways:
Cellular responses to stress  REACT_120956  
Immune System  REACT_6900  
Signal Transduction  REACT_111102  
TRAF6 Mediated Induction of proinflammatory cytokines  REACT_6782  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Activator  definition   [KW-0010]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: NFKB1
GenomeRNAi: 4790
PRO: PR:P19838