{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P19838","secondaryAccessions":["A8K5Y5","B3KVE8","Q68D84","Q86V43","Q8N4X7","Q9NZC0"],"uniProtkbId":"NFKB1_HUMAN","entryAudit":{"firstPublicDate":"1991-02-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2002-06-20","entryVersion":279,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Nuclear factor NF-kappa-B p105 subunit"}},"alternativeNames":[{"fullName":{"value":"DNA-binding factor KBF1"}},{"fullName":{"value":"EBP-1"}},{"fullName":{"value":"Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1"}}],"contains":[{"recommendedName":{"fullName":{"value":"Nuclear factor NF-kappa-B p50 subunit"}}}]},"genes":[{"geneName":{"value":"NFKB1"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15485931"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1740106"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2203531"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2234062"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7830764"}],"value":"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"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1423592"}],"value":"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)"}],"commentType":"FUNCTION","molecule":"Nuclear factor NF-kappa-B p105 subunit"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1740106"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7830764"}],"value":"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)"}],"commentType":"FUNCTION","molecule":"Nuclear factor NF-kappa-B p50 subunit"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P25799"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10469655"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11094166"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11468175"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11526476"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12393603"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12871932"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"13679070"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1423592"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14743216"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14769797"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15102766"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15169888"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15485931"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17003112"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1740106"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33314660"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7830764"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8152812"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9315679"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9950430"}],"value":"Component of the NF-kappa-B p65-p50 complex (PubMed:1740106, PubMed:7830764). Homodimer; component of the NF-kappa-B p50-p50 complex. Component of the NF-kappa-B p105-p50 complex (PubMed:1423592). Component of the NF-kappa-B p50-c-Rel complex (PubMed:15102766, PubMed:8152812). Component of a complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3 (PubMed:10469655). Also interacts with MAP3K8 (PubMed:15485931, PubMed:9950430). NF-kappa-B p50 subunit interacts with NCOA3 coactivator, which may coactivate NF-kappa-B dependent expression via its histone acetyltransferase activity (PubMed:11094166). Interacts with TSC22D3; this interaction prevents nuclear translocation and DNA-binding (PubMed:11468175, PubMed:12393603). Interacts with SPAG9 and UNC5CL (PubMed:14743216, PubMed:14769797). NFKB1/p105 interacts with CFLAR; the interaction inhibits p105 processing into p50 (PubMed:13679070). NFKB1/p105 forms a ternary complex with MAP3K8 and TNIP2 (PubMed:15169888). Interacts with GSK3B; the interaction prevents processing of p105 to p50 (PubMed:12871932). NFKB1/p50 interacts with NFKBIE (PubMed:9315679). NFKB1/p50 interacts with NFKBIZ (By similarity). Nuclear factor NF-kappa-B p50 subunit interacts with NFKBID (By similarity). Directly interacts with MEN1 (PubMed:11526476). Interacts with HIF1AN (PubMed:17003112). Interacts with FEM1A; interaction is direct (By similarity). NFKB1/p50 interacts with FOXM1 isoform 5 (FOXM1D); this promotes its nuclear translocation along with the RELA/p65 subunit, leading to increased VEGFA transcription (PubMed:33314660)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"Q92887","geneName":"ABCC2","intActId":"EBI-3916193"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"O15111","geneName":"CHUK","intActId":"EBI-81249"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"P35606","geneName":"COPB2","intActId":"EBI-1056534"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"P35222","geneName":"CTNNB1","intActId":"EBI-491549"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"Q13547","geneName":"HDAC1","intActId":"EBI-301834"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"Q9NWT6","geneName":"HIF1AN","intActId":"EBI-745632"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"O14920","geneName":"IKBKB","intActId":"EBI-81266"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"P41279","geneName":"MAP3K8","intActId":"EBI-354900"},"numberOfExperiments":14,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"P19838","geneName":"NFKB1","intActId":"EBI-300010"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"Q00653","geneName":"NFKB2","intActId":"EBI-307326"},"numberOfExperiments":10,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"P25963","geneName":"NFKBIA","intActId":"EBI-307386"},"numberOfExperiments":10,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"Q15653","geneName":"NFKBIB","intActId":"EBI-352889"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"P46531","geneName":"NOTCH1","intActId":"EBI-636374"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"Q14690","geneName":"PDCD11","intActId":"EBI-300028"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"Q8IZL8","geneName":"PELP1","intActId":"EBI-716449"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"Q8IV08","geneName":"PLD3","intActId":"EBI-2689908"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"Q04206","geneName":"RELA","intActId":"EBI-73886"},"numberOfExperiments":16,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"Q01201","geneName":"RELB","intActId":"EBI-357837"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"P23396","geneName":"RPS3","intActId":"EBI-351193"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"Q15025","geneName":"TNIP1","intActId":"EBI-357849"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"Q8NFZ5","geneName":"TNIP2","intActId":"EBI-359372"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838","intActId":"EBI-300010"},"interactantTwo":{"uniProtKBAccession":"P10226","geneName":"UL42","intActId":"EBI-1029310"},"numberOfExperiments":4,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P19838-1","intActId":"EBI-1452239"},"interactantTwo":{"uniProtKBAccession":"Q8NFZ5","geneName":"TNIP2","intActId":"EBI-359372"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P19838-2","intActId":"EBI-1452242"},"interactantTwo":{"uniProtKBAccession":"P42858","geneName":"HTT","intActId":"EBI-466029"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"chainId":"PRO_0000030311","intActId":"EBI-697771"},"interactantTwo":{"uniProtKBAccession":"P03372","geneName":"ESR1","intActId":"EBI-78473"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"chainId":"PRO_0000030311","intActId":"EBI-697771"},"interactantTwo":{"uniProtKBAccession":"O00255","geneName":"MEN1","intActId":"EBI-592789"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"chainId":"PRO_0000030311","intActId":"EBI-697771"},"interactantTwo":{"uniProtKBAccession":"O00255-2","geneName":"MEN1","intActId":"EBI-9869387"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"chainId":"PRO_0000030311","intActId":"EBI-697771"},"interactantTwo":{"uniProtKBAccession":"Q04206","geneName":"RELA","intActId":"EBI-73886"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"chainId":"PRO_0000030311","intActId":"EBI-697771"},"interactantTwo":{"uniProtKBAccession":"P10226","geneName":"UL42","intActId":"EBI-1029310"},"numberOfExperiments":2,"organismDiffer":true}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Nuclear factor NF-kappa-B p105 subunit","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1423592"}],"value":"Cytoplasm","id":"SL-0086"}}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Nuclear factor NF-kappa-B p50 subunit","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9865693"}],"value":"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)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9865693"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9865693"}],"value":"Cytoplasm","id":"SL-0086"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["P19838-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["P19838-2"],"sequenceIds":["VSP_021025"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["P19838-3"],"sequenceIds":["VSP_042869","VSP_042870"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1992489"}],"value":"By phorbol ester and TNF"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1423592"}],"value":"The C-terminus of p105 might be involved in cytoplasmic retention, inhibition of DNA-binding, and transcription activation"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8628291"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9529257"}],"value":"Glycine-rich region (GRR) is a critical element in the generation of p50 (Nuclear factor NF-kappa-B p50 subunit) by acting as a proteasomal 'stop signal', which leads to limited proteasomal degradation of the C-terminus, while generating p50"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10970863"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25860612"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8628291"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9529257"}],"value":"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)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10835356"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11158290"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11297557"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12482991"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12871932"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14673179"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25860612"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8626394"}],"value":"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)"}],"commentType":"PTM","molecule":"Nuclear factor NF-kappa-B p105 subunit"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11158290"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14673179"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25860612"}],"value":"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)"}],"commentType":"PTM","molecule":"Nuclear factor NF-kappa-B p105 subunit"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11327828"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8710491"}],"value":"S-nitrosylation of Cys-61 affects DNA binding"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11466314"}],"value":"The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. 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