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Names & Taxonomy

Uniprot ID:: P19838
Entry Name:: NFKB1_HUMAN
Status:: reviewed
Protein Names:: Nuclear factor NF-kappa-B p105 subunit (DNA-binding factor KBF1) (EBP-1) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) [Cleaved into: Nuclear factor NF-kappa-B p50 subunit]
Gene Names:: NFKB1
Gene Names Primary:: NFKB1
Organism:: Homo sapiens (Human)

Structure

Length:: 968
Sequence:: MAEDDPYLGRPEQMFHLDPSLTHTIFNPEVFQPQMALPTDGPYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDGICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGLLVHPDLAYLQAEGGGDRQLGDREKELIRQAALQQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAIYDSKAPNASNLKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIRFYEEEENGGVWEGFGDFSPTDVHRQFAIVFKTPKYKDINITKPASVFVQLRRKSDLETSEPKPFLYYPEIKDKEEVQRKRQKLMPNFSDSFGGGSGAGAGGGGMFGSGGGGGGTGSTGPGYSFPHYGFPTYGGITFHPGTTKSNAGMKHGTMDTESKKDPEGCDKSDDKNTVNLFGKVIETTEQDQEPSEATVGNGEVTLTYATGTKEESAGVQDNLFLEKAMQLAKRHANALFDYAVTGDVKMLLAVQRHLTAVQDENGDSVLHLAIIHLHSQLVRDLLEVTSGLISDDIINMRNDLYQTPLHLAVITKQEDVVEDLLRAGADLSLLDRLGNSVLHLAAKEGHDKVLSILLKHKKAALLLDHPNGDGLNAIHLAMMSNSLPCLLLLVAAGADVNAQEQKSGRTALHLAVEHDNISLAGCLLLEGDAHVDSTTYDGTTPLHIAAGRGSTRLAALLKAAGADPLVENFEPLYDLDDSWENAGEDEGVVPGTTPLDMATSWQVFDILNGKPYEPEFTSDDLLAQGDMKQLAEDVKLQLYKLLEIPDPDKNWATLAQKLGLGILNNAFRLSPAPSKTLMDNYEVSGGTVRELVEALRQMGYTEAIEVIQAASSPVKTTSQAHSLPLSPASTRQQIDELRDSDSVCDSGVETSFRKLSFTESLTSGASLLTLNKMPHDYGQEGPLEGKI
Proteomes:: UP000005640

Subcellular location

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

Function

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. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105.
Cross Reference Drug Bank:: DB00945 DB01411 DB01041 DB08814
Gene Ontology Go:: cytoplasm
cytosol
I-kappaB/NF-kappaB complex
mitochondrion
neuron projection
nucleoplasm
nucleus
actinin binding
chromatin binding
identical protein binding
protein heterodimerization activity
regulatory region DNA binding
RNA polymerase II distal enhancer sequence-specific DNA binding
RNA polymerase II regulatory region sequence-specific DNA binding
transcription factor activity, sequence-specific DNA binding
transcription factor binding
transcription regulatory region DNA binding
transcription regulatory region sequence-specific DNA binding
transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding
transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding
apoptotic process
cellular response to brain-derived neurotrophic factor stimulus
cellular response to carbohydrate stimulus
cellular response to diterpene
cellular response to dsRNA
cellular response to glucoside
cellular response to interleukin-1
cellular response to interleukin-6
cellular response to lipopolysaccharide
cellular response to mechanical stimulus
cellular response to nicotine
cellular response to peptide hormone stimulus
cellular response to tumor necrosis factor
Fc-epsilon receptor signaling pathway
I-kappaB kinase/NF-kappaB signaling
inflammatory response
innate immune response
membrane protein intracellular domain proteolysis
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of apoptotic process
negative regulation of calcidiol 1-monooxygenase activity
negative regulation of cellular protein metabolic process
negative regulation of cholesterol transport
negative regulation of inflammatory response
negative regulation of interleukin-12 biosynthetic process
negative regulation of transcription from RNA polymerase II promoter
negative regulation of vitamin D biosynthetic process
neurotrophin TRK receptor signaling pathway
NIK/NF-kappaB signaling
positive regulation of canonical Wnt signaling pathway
positive regulation of hyaluronan biosynthetic process
positive regulation of lipid storage
positive regulation of macrophage derived foam cell differentiation
positive regulation of miRNA metabolic process
positive regulation of NF-kappaB transcription factor activity
positive regulation of transcription from RNA polymerase II promoter
positive regulation of transcription, DNA-templated
positive regulation of type I interferon production
response to copper ion
response to muscle stretch
response to oxidative stress
stimulatory C-type lectin receptor signaling pathway
stress-activated MAPK cascade
T cell receptor signaling pathway
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
transcription from RNA polymerase II promoter
TRIF-dependent toll-like receptor signaling pathway
Gene Ontology Biological Process:: apoptotic process
cellular response to brain-derived neurotrophic factor stimulus
cellular response to carbohydrate stimulus
cellular response to diterpene
cellular response to dsRNA
cellular response to glucoside
cellular response to interleukin-1
cellular response to interleukin-6
cellular response to lipopolysaccharide
cellular response to mechanical stimulus
cellular response to nicotine
cellular response to peptide hormone stimulus
cellular response to tumor necrosis factor
Fc-epsilon receptor signaling pathway
I-kappaB kinase/NF-kappaB signaling
inflammatory response
innate immune response
membrane protein intracellular domain proteolysis
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of apoptotic process
negative regulation of calcidiol 1-monooxygenase activity
negative regulation of cellular protein metabolic process
negative regulation of cholesterol transport
negative regulation of inflammatory response
negative regulation of interleukin-12 biosynthetic process
negative regulation of transcription from RNA polymerase II promoter
negative regulation of vitamin D biosynthetic process
neurotrophin TRK receptor signaling pathway
NIK/NF-kappaB signaling
positive regulation of canonical Wnt signaling pathway
positive regulation of hyaluronan biosynthetic process
positive regulation of lipid storage
positive regulation of macrophage derived foam cell differentiation
positive regulation of miRNA metabolic process
positive regulation of NF-kappaB transcription factor activity
positive regulation of transcription, DNA-templated
positive regulation of transcription from RNA polymerase II promoter
positive regulation of type I interferon production
response to copper ion
response to muscle stretch
response to oxidative stress
stimulatory C-type lectin receptor signaling pathway
stress-activated MAPK cascade
T cell receptor signaling pathway
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
transcription from RNA polymerase II promoter
TRIF-dependent toll-like receptor signaling pathway
Gene Ontology Molecular Function:: actinin binding
chromatin binding
identical protein binding
protein heterodimerization activity
regulatory region DNA binding
RNA polymerase II distal enhancer sequence-specific DNA binding
RNA polymerase II regulatory region sequence-specific DNA binding
transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding
transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding
transcription factor activity, sequence-specific DNA binding
transcription factor binding
transcription regulatory region DNA binding
transcription regulatory region sequence-specific DNA binding
Gene Ontology Cellular Component:: cytoplasm
cytosol
I-kappaB/NF-kappaB complex
mitochondrion
neuron projection
nucleoplasm
nucleus
Keywords:: 3D-structure
ANK repeat
Acetylation
Activator
Alternative splicing
Apoptosis
Complete proteome
Cytoplasm
DNA-binding
Direct protein sequencing
Hydroxylation
Lipoprotein
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Repeat
S-nitrosylation
Transcription
Transcription regulation
Ubl conjugation
Interacts With:: Itself; Q92887; P35606; P35222; P03372; Q13547; P08238; P34931; P41279; O00255; O00255-2; Q00653; P25963; P46531; Q14690; Q8IZL8; Q8IV08; Q04206; Q01201; P23396; Q15025; Q8NFZ5; P10226

Names & Taxonomy

Structure

Subcellular location

Function

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