NFKB1
entrez
4790
canonical
uniprot
P19838
canonical
ensembl
ENSG00000109320
resolver
ensp
ENSP00000226574
resolver
ensp
ENSP00000378297
resolver
ensp
ENSP00000423877
resolver
ensp
ENSP00000424790
resolver
ensp
ENSP00000548399
resolver
ensp
ENSP00000548402
resolver
ensp
ENSP00000636720
resolver
ensp
ENSP00000636725
resolver
genesymbol
NFKB1
resolver
hgnc
HGNC:7794
resolver
uniprot
A8K5Y5
resolver
uniprot
B3KVE8
resolver
uniprot
Q68D84
resolver
uniprot
Q86V43
resolver
uniprot
Q8N4X7
resolver
uniprot
Q9NZC0
resolver
uniprot_entry
NFKB1_HUMAN
resolver
uniprot_sec
A8K5Y5
resolver
uniprot_sec
B3KVE8
resolver
uniprot_sec
Q68D84
resolver
uniprot_sec
Q86V43
resolver
uniprot_sec
Q8N4X7
resolver
uniprot_sec
Q9NZC0
resolver
amino_acid_sequence
MAEDDPYLGRPEQMFHLDPSLTHTIFNPEVFQPQMALPTDGPYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDGICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGLLVHPDLAYLQAEGGGDRQLGDREKELIRQAALQQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAIYDSKAPNASNLKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIRFYEEEENGGVWEGFGDFSPTDVHRQFAIVFKTPKYKDINITKPASVFVQLRRKSDLETSEPKPFLYYPEIKDKEEVQRKRQKLMPNFSDSFGGGSGAGAGGGGMFGSGGGGGGTGSTGPGYSFPHYGFPTYGGITFHPGTTKSNAGMKHGTMDTESKKDPEGCDKSDDKNTVNLFGKVIETTEQDQEPSEATVGNGEVTLTYATGTKEESAGVQDNLFLEKAMQLAKRHANALFDYAVTGDVKMLLAVQRHLTAVQDENGDSVLHLAIIHLHSQLVRDLLEVTSGLISDDIINMRNDLYQTPLHLAVITKQEDVVEDLLRAGADLSLLDRLGNSVLHLAAKEGHDKVLSILLKHKKAALLLDHPNGDGLNAIHLAMMSNSLPCLLLLVAAGADVNAQEQKSGRTALHLAVEHDNISLAGCLLLEGDAHVDSTTYDGTTPLHIAAGRGSTRLAALLKAAGADPLVENFEPLYDLDDSWENAGEDEGVVPGTTPLDMATSWQVFDILNGKPYEPEFTSDDLLAQGDMKQLAEDVKLQLYKLLEIPDPDKNWATLAQKLGLGILNNAFRLSPAPSKTLMDNYEVSGGTVRELVEALRQMGYTEAIEVIQAASSPVKTTSQAHSLPLSPASTRQQIDELRDSDSVCDSGVETSFRKLSFTESLTSGASLLTLNKMPHDYGQEGPLEGKI
uniprot
proteins
disease_involvement
DISEASE: Immunodeficiency, common variable, 12, with autoimmunity (CVID12) [MIM:616576]: A primary immunodeficiency characterized by hypogammaglobulinemia and recurrent bacterial infections. About half of patients develop autoimmune features, including cytopenia, as well as generalized inflammation and lymphoproliferation manifest as lymphadenopathy or hepatosplenomegaly. {ECO:0000269|PubMed:26279205}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
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. {ECO:0000269|PubMed:15485931, ECO:0000269|PubMed:1740106, ECO:0000269|PubMed:2203531, ECO:0000269|PubMed:2234062, ECO:0000269|PubMed:7830764}.; FUNCTION: [Nuclear factor NF-kappa-B p105 subunit]: P105 is the precursor of the active p50 subunit (Nuclear factor NF-kappa-B p50 subunit) of the nuclear factor NF-kappa-B (PubMed:1423592). Acts as a cytoplasmic retention of attached NF-kappa-B proteins by p105 (PubMed:1423592). {ECO:0000269|PubMed:1423592}.; FUNCTION: [Nuclear factor NF-kappa-B p50 subunit]: Constitutes the active form, which associates with RELA/p65 to form the NF-kappa-B p65-p50 complex to form a transcription factor (PubMed:1740106, PubMed:7830764). Together with RELA/p65, 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 (PubMed:1740106, PubMed:7830764). {ECO:0000269|PubMed:1740106, ECO:0000269|PubMed:7830764}.
uniprot
proteins
mass_dalton
105356
uniprot
proteins
mutagenesis
MUTAGEN 61; /note="C->S: Suppresses S-nitrosylation-induced inhibition of DNA-binding activity. Loss of S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine-induced inhibition of DNA-binding activity."; /evidence="ECO:0000269|PubMed:11466314, ECO:0000269|PubMed:8710491"; MUTAGEN 678; /note="N->A: Fails to promote HIF1AN-dependent 2-oxoglutarate decarboxylation."; /evidence="ECO:0000269|PubMed:17003112"; MUTAGEN 903; /note="S->A: Prevents p105 proteolysis in response to TNF."; /evidence="ECO:0000269|PubMed:12871932"; MUTAGEN 907; /note="S->A: Prevents p105 proteolysis in response to TNF."; /evidence="ECO:0000269|PubMed:12871932"; MUTAGEN 921; /note="S->A: Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-923 and A-932."; /evidence="ECO:0000269|PubMed:10469655"; MUTAGEN 923; /note="S->A: Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-921 and A-932."; /evidence="ECO:0000269|PubMed:10469655"; MUTAGEN 927; /note="S->A: Decreased phosphorylation by IKBKB/IKKB and decreased generation of the NF-kappa-B p50 subunit from p105."; /evidence="ECO:0000269|PubMed:25860612"; MUTAGEN 932; /note="S->A: Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-921 and A-923."; /evidence="ECO:0000269|PubMed:10469655
uniprot
proteins
post_translational_modification
PTM: Generation of the NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) transcription factor takes place both cotranslationally and post-translationally via non-mutually exclusive mechanisms (PubMed:10970863, PubMed:25860612, PubMed:8628291, PubMed:9529257). A cotranslational processing allows the production of both p50 and p105 (Nuclear factor NF-kappa-B p105 subunit) from a single NFKB1 mRNA (PubMed:10970863, PubMed:8628291, PubMed:9529257). While translation occurs, the particular unfolded structure after the GRR repeat region acts as a substrate for the proteasome, promoting degradation of the C-terminus (PubMed:10970863, PubMed:9529257). The GRR acts as a proteasomal 'stop signal', protecting the region upstream of the GRR from degradation and promoting generation of p50 (PubMed:10970863, PubMed:9529257). It is unclear if limited proteasome degradation during cotranslational processing depends on ubiquitination (PubMed:10970863, PubMed:9529257). NF-kappa-B p50 is also generated post-translationally following ubiquitination by the KPC complex, leading to limited processing by the proteasome downstream of the GRR region, thereby generating p50 (PubMed:25860612). {ECO:0000269|PubMed:10970863, ECO:0000269|PubMed:25860612, ECO:0000269|PubMed:8628291, ECO:0000269|PubMed:9529257}.; PTM: [Nuclear factor NF-kappa-B p105 subunit]: Phosphorylation at the C-terminus by IKBKB/IKKB acts as a signal for ubiquitination and promotes either complete degradation or processing to generate the NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) (PubMed:10835356, PubMed:11158290, PubMed:11297557, PubMed:12482991, PubMed:14673179, PubMed:25860612, PubMed:8626394). Phosphorylation at Ser-903 and Ser-907 primes p105 for proteolytic processing in response to TNF stimulation (PubMed:12871932). Phosphorylation at Ser-923, Ser-927 and Ser-932 are required for BTRC/BTRCP-mediated ubiquitination and proteolysis (PubMed:10835356, PubMed:11158290, PubMed:11297557, PubMed:12482991, PubMed:14673179). Phosphorylation at Ser-927 is also required for ubiquitination by the KPC complex and limited processing to generate NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) (PubMed:25860612). {ECO:0000269|PubMed:10835356, ECO:0000269|PubMed:11158290, ECO:0000269|PubMed:11297557, ECO:0000269|PubMed:12482991, ECO:0000269|PubMed:12871932, ECO:0000269|PubMed:14673179, ECO:0000269|PubMed:25860612, ECO:0000269|PubMed:8626394}.; PTM: [Nuclear factor NF-kappa-B p105 subunit]: Polyubiquitinated at multiple Lys residues in the C-terminus (PubMed:11158290, PubMed:14673179, PubMed:25860612). Polyubiquitinated by the SCF(FBXW11) and SCF(BTRC) complexes following phosphorylation at Ser-923, Ser-927 and Ser-932, leading to its complete degradation (PubMed:11158290). In contrast, polyubiquitination by the KPC complex following phosphorylation at Ser-927 leads to limited proteosomal processing and generation of the active NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) (PubMed:25860612). {ECO:0000269|PubMed:11158290, ECO:0000269|PubMed:14673179, ECO:0000269|PubMed:25860612}.; PTM: S-nitrosylation of Cys-61 affects DNA binding. {ECO:0000269|PubMed:11327828, ECO:0000269|PubMed:8710491}.; PTM: The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation. {ECO:0000269|PubMed:11466314}.
uniprot
proteins
pubmed
10469655
uniprot
proteins
pubmed
10835356
uniprot
proteins
pubmed
10970863
uniprot
proteins
pubmed
11094166
uniprot
proteins
pubmed
11158290
uniprot
proteins
pubmed
11297557
uniprot
proteins
pubmed
11327828
uniprot
proteins
pubmed
11466314
uniprot
proteins
pubmed
11468175
uniprot
proteins
pubmed
11526476
uniprot
proteins
pubmed
11739381
uniprot
proteins
pubmed
12393603
uniprot
proteins
pubmed
12471036
uniprot
proteins
pubmed
12482991
uniprot
proteins
pubmed
12871932
uniprot
proteins
pubmed
13679070
uniprot
proteins
pubmed
1423592
uniprot
proteins
pubmed
14673179
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14743216
uniprot
proteins
pubmed
14769797
uniprot
proteins
pubmed
15102766
uniprot
proteins
pubmed
15169888
uniprot
proteins
pubmed
15485931
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17003112
uniprot
proteins
pubmed
1740106
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
1992489
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
2203531
uniprot
proteins
pubmed
2234062
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25860612
uniprot
proteins
pubmed
26279205
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
33314660
uniprot
proteins
pubmed
7830764
uniprot
proteins
pubmed
8087845
uniprot
proteins
pubmed
8152812
uniprot
proteins
pubmed
8626394
uniprot
proteins
pubmed
8628291
uniprot
proteins
pubmed
8710491
uniprot
proteins
pubmed
8825636
uniprot
proteins
pubmed
9315679
uniprot
proteins
pubmed
9529257
uniprot
proteins
pubmed
9865693
uniprot
proteins
pubmed
9950430
uniprot
proteins
sequence_length
968
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Nuclear factor NF-kappa-B p105 subunit]: Cytoplasm {ECO:0000269|PubMed:1423592}.; SUBCELLULAR LOCATION: [Nuclear factor NF-kappa-B p50 subunit]: Nucleus {ECO:0000269|PubMed:9865693}. Cytoplasm {ECO:0000269|PubMed:9865693}. Note=Association with NFKBIA inhibitor (I-kappa-B), promotes its retention in the cytoplasm in an inactive form (PubMed:9865693). Translocates into the nucleus following NFKBIA degradation (PubMed:9865693). {ECO:0000269|PubMed:9865693}.
uniprot
proteins