ID NFKB1_HUMAN Reviewed; 968 AA. AC P19838; A8K5Y5; B3KVE8; Q68D84; Q86V43; Q8N4X7; Q9NZC0; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 20-JUN-2002, sequence version 2. DT 25-OCT-2017, entry version 226. DE RecName: Full=Nuclear factor NF-kappa-B p105 subunit; DE AltName: Full=DNA-binding factor KBF1; DE AltName: Full=EBP-1; DE AltName: Full=Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1; DE Contains: DE RecName: Full=Nuclear factor NF-kappa-B p50 subunit; GN Name=NFKB1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND PARTIAL PROTEIN SEQUENCE. RX PubMed=2203531; DOI=10.1016/0092-8674(90)90275-J; RA Kieran M., Blank V., Logeat F., Vandekerckhove J., Lottspeich F., RA le Bail O., Urban M.B., Kourilsky P., Baeuerle P.A., Israel A.; RT "The DNA binding subunit of NF-kappa B is identical to factor KBF1 and RT homologous to the rel oncogene product."; RL Cell 62:1007-1018(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2234062; DOI=10.1038/348076a0; RA Bours V., Villalobos J., Burd P.R., Kelly K., Siebenlist U.; RT "Cloning of a mitogen-inducible gene encoding a kappa B DNA-binding RT protein with homology to the rel oncogene and to cell-cycle motifs."; RL Nature 348:76-80(1990). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE. RX PubMed=1992489; DOI=10.1073/pnas.88.3.966; RA Meyer R., Hatada E.N., Hohmann H.-P., Haiker M., Bartsch C., RA Roethlisberger U., Lahm H.-W., Schlaeger E.J., van Loon A.P.G.M., RA Scheidereit C.; RT "Cloning of the DNA-binding subunit of human nuclear factor kappa B: RT the level of its mRNA is strongly regulated by phorbol ester or tumor RT necrosis factor alpha."; RL Proc. Natl. Acad. Sci. U.S.A. 88:966-970(1991). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8825636; DOI=10.1006/geno.1995.1270; RA Heron E., Deloukas P., van Loon A.P.G.M.; RT "The complete exon-intron structure of the 156-kb human gene NFKB1, RT which encodes the p105 and p50 proteins of transcription factors NF- RT kappa B and I kappa B-gamma: implications for NF-kappa B-mediated RT signal transduction."; RL Genomics 30:493-505(1995). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Chang H.-M., Tsai S.-F.; RT "Genome sequencing of the chromosome 4q region implicated in human RT hepatocellular carcinoma pathogenesis."; RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Brain, and Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Rectum tumor; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-489; VAL-506; RP ILE-566; LYS-578; GLN-711 AND THR-901. RG NIEHS SNPs program; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Muscle, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP IDENTIFICATION IN THE NF-KAPPA-B P65-P50 COMPLEX. RX PubMed=1740106; RA Hansen S.K., Nerlov C., Zabel U., Verde P., Johnsen M., Baeuerle P.A., RA Blasi F.; RT "A novel complex between the p65 subunit of NF-kappa B and c-Rel binds RT to a DNA element involved in the phorbol ester induction of the human RT urokinase gene."; RL EMBO J. 11:205-213(1992). RN [11] RP UBIQUITINATION. RX PubMed=8087845; DOI=10.1016/S0092-8674(94)90482-0; RA Palombella V.J., Rando O.J., Goldberg A.L., Maniatis T.; RT "The ubiquitin-proteasome pathway is required for processing the NF- RT kappa B1 precursor protein and the activation of NF-kappa B."; RL Cell 78:773-785(1994). RN [12] RP IDENTIFICATION IN THE NF-KAPPA-B P50-C-REL COMPLEX. RX PubMed=8152812; RA Beg A.A., Baldwin A.S. Jr.; RT "Activation of multiple NF-kappa B/Rel DNA-binding complexes by tumor RT necrosis factor."; RL Oncogene 9:1487-1492(1994). RN [13] RP PROTEOLYTIC PROCESSING OF P105, AND GENERATION OF P50 AND P105. RX PubMed=8628291; DOI=10.1128/MCB.16.5.2248; RA Lin L., Ghosh S.; RT "A glycine-rich region in NF-kappaB p105 functions as a processing RT signal for the generation of the p50 subunit."; RL Mol. Cell. Biol. 16:2248-2254(1996). RN [14] RP S-NITROSYLATION AT CYS-61, MUTAGENESIS OF CYS-61, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RX PubMed=8710491; DOI=10.1093/nar/24.12.2236; RA Matthews J.R., Botting C.H., Panico M., Morris H.R., Hay R.T.; RT "Inhibition of NF-kappaB DNA binding by nitric oxide."; RL Nucleic Acids Res. 24:2236-2242(1996). RN [15] RP INTERACTION WITH NFKBIE. RX PubMed=9315679; DOI=10.1128/MCB.17.10.6184; RA Li Z., Nabel G.J.; RT "A new member of the IkappaB protein family, IkappaB epsilon, inhibits RT RelA (p65)-mediated NF-kappaB transcription."; RL Mol. Cell. Biol. 17:6184-6190(1997). RN [16] RP COTRANSLATIONAL FOLDING/PROCESSING OF P105, AND GENERATION OF RP P50/P105. RX PubMed=9529257; DOI=10.1016/S0092-8674(00)81409-9; RA Lin L., DeMartino G.N., Greene W.C.; RT "Cotranslational biogenesis of NF-kappaB p50 by the 26S proteasome."; RL Cell 92:819-828(1998). RN [17] RP IDENTIFICATION IN A COMPLEX WITH BCL3, AND MUTAGENESIS OF SER-921; RP SER-923 AND SER-932. RX PubMed=10469655; DOI=10.1093/emboj/18.17.4766; RA Heissmeyer V., Krappmann D., Wulczyn F.G., Scheidereit C.; RT "NF-kappaB p105 is a target of IkappaB kinases and controls signal RT induction of Bcl-3-p50 complexes."; RL EMBO J. 18:4766-4778(1999). RN [18] RP INTERACTION WITH MAP3K8. RX PubMed=9950430; DOI=10.1038/16946; RA Belich M.P., Salmeron A., Johnston L.H., Ley S.C.; RT "TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory RT protein NF-kappaB1 p105."; RL Nature 397:363-368(1999). RN [19] RP COTRANSLATIONAL FOLDING/PROCESSING OF P105, GENERATION OF P50/P105, RP AND P50-P105 TRANSIENT HETERODIMER FORMATION. RX PubMed=10970863; DOI=10.1093/emboj/19.17.4712; RA Lin L., DeMartino G.N., Greene W.C.; RT "Cotranslational dimerization of the Rel homology domain of NF-kappaB1 RT generates p50-p105 heterodimers and is required for effective p50 RT production."; RL EMBO J. 19:4712-4722(2000). RN [20] RP INTERACTION WITH NCOA3. RX PubMed=11094166; DOI=10.1016/S0014-5793(00)02223-7; RA Werbajh S., Nojek I., Lanz R., Costas M.A.; RT "RAC-3 is a NF-kappa B coactivator."; RL FEBS Lett. 485:195-199(2000). RN [21] RP S-NITROSYLATION. RX PubMed=11327828; DOI=10.1021/bi002239y; RA Marshall H.E., Stamler J.S.; RT "Inhibition of NF-kappaB by S-nitrosylation."; RL Biochemistry 40:1688-1693(2001). RN [22] RP INTERACTION WITH DSIPI. RX PubMed=11468175; DOI=10.1182/blood.V98.3.743; RA Ayroldi E., Migliorati G., Bruscoli S., Marchetti C., Zollo O., RA Cannarile L., D'Adamio F., Riccardi C.; RT "Modulation of T-cell activation by the glucocorticoid-induced leucine RT zipper factor via inhibition of nuclear factor kappa B."; RL Blood 98:743-753(2001). RN [23] RP LIPIDATION AT CYS-61, AND MUTAGENESIS OF CYS-61. RX PubMed=11466314; DOI=10.1074/jbc.M104518200; RA Cernuda-Morollon E., Pineda-Molina E., Canada F.J., Perez-Sala D.; RT "15-Deoxy-Delta 12,14-prostaglandin J2 inhibition of NF-kappaB-DNA RT binding through covalent modification of the p50 subunit."; RL J. Biol. Chem. 276:35530-35536(2001). RN [24] RP PHOSPHORYLATION AT SER-927. RX PubMed=11297557; DOI=10.1074/jbc.M101754200; RA Salmeron A., Janzen J., Soneji Y., Bump N., Kamens J., Allen H., RA Ley S.C.; RT "Direct phosphorylation of NF-kappa B1 p105 by the Ikappa B kinase RT complex on serine 927 is essential for signal-induced p105 RT proteolysis."; RL J. Biol. Chem. 276:22215-22222(2001). RN [25] RP INTERACTION WITH MEN1. RX PubMed=11526476; DOI=10.1038/sj.onc.1204529; RA Heppner C., Bilimoria K.Y., Agarwal S.K., Kester M., Whitty L.J., RA Guru S.C., Chandrasekharappa S.C., Collins F.S., Spiegel A.M., RA Marx S.J., Burns A.L.; RT "The tumor suppressor protein menin interacts with NF-kappaB proteins RT and inhibits NF-kappaB-mediated transactivation."; RL Oncogene 20:4917-4925(2001). RN [26] RP INTERACTION WITH CFLAR. RX PubMed=13679070; DOI=10.1016/j.bbrc.2003.08.104; RA Li Z., Zhang J., Chen D., Shu H.B.; RT "Casper/c-FLIP is physically and functionally associated with NF- RT kappaB1 p105."; RL Biochem. Biophys. Res. Commun. 309:980-985(2003). RN [27] RP ACETYLATION AT LYS-431; LYS-440 AND LYS-441. RX PubMed=11739381; DOI=10.1074/jbc.M107848200; RA Furia B., Deng L., Wu K., Baylor S., Kehn K., Li H., Donnelly R., RA Coleman T., Kashanchi F.; RT "Enhancement of nuclear factor-kappa B acetylation by coactivator p300 RT and HIV-1 Tat proteins."; RL J. Biol. Chem. 277:4973-4980(2002). RN [28] RP INTERACTION WITH DSIPI. RX PubMed=12393603; DOI=10.1182/blood-2002-02-0538; RA Berrebi D., Bruscoli S., Cohen N., Foussat A., Migliorati G., RA Bouchet-Delbos L., Maillot M.-C., Portier A., Couderc J., Galanaud P., RA Peuchmaur M., Riccardi C., Emilie D.; RT "Synthesis of glucocorticoid-induced leucine zipper (GILZ) by RT macrophages: an anti-inflammatory and immunosuppressive mechanism RT shared by glucocorticoids and IL-10."; RL Blood 101:729-738(2003). RN [29] RP ACETYLATION. RX PubMed=12471036; DOI=10.1074/jbc.M209286200; RA Deng W.G., Zhu Y., Wu K.K.; RT "Up-regulation of p300 binding and p50 acetylation in tumor necrosis RT factor-alpha-induced cyclooxygenase-2 promoter activation."; RL J. Biol. Chem. 278:4770-4777(2003). RN [30] RP INTERACTION WITH GSK3B, PHOSPHORYLATION AT SER-903 AND SER-907, AND RP MUTAGENESIS OF SER-903 AND SER-907. RX PubMed=12871932; DOI=10.1074/jbc.M305676200; RA Demarchi F., Bertoli C., Sandy P., Schneider C.; RT "Glycogen synthase kinase-3 beta regulates NF-kappa B1/p105 RT stability."; RL J. Biol. Chem. 278:39583-39590(2003). RN [31] RP PHOSPHORYLATION AT SER-927 AND SER-932. RX PubMed=12482991; DOI=10.1128/MCB.23.1.402-413.2003; RA Lang V., Janzen J., Fischer G.Z., Soneji Y., Beinke S., Salmeron A., RA Allen H., Hay R.T., Ben-Neriah Y., Ley S.C.; RT "betaTrCP-mediated proteolysis of NF-kappaB1 p105 requires RT phosphorylation of p105 serines 927 and 932."; RL Mol. Cell. Biol. 23:402-413(2003). RN [32] RP INTERACTION WITH UNC5CL. RX PubMed=14769797; DOI=10.1074/jbc.M310737200; RA Zhang J., Xu L.-G., Han K.-J., Shu H.-B.; RT "Identification of a ZU5 and death domain-containing inhibitor of NF- RT kappaB."; RL J. Biol. Chem. 279:17819-17825(2004). RN [33] RP INTERACTION WITH MAP3K8 AND TNIP2. RX PubMed=15169888; DOI=10.1128/MCB.24.12.5235-5248.2004; RA Lang V., Symons A., Watton S.J., Janzen J., Soneji Y., Beinke S., RA Howell S., Ley S.C.; RT "ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is RT essential for TPL-2 protein stability."; RL Mol. Cell. Biol. 24:5235-5248(2004). RN [34] RP IDENTIFICATION IN THE NF-KAPPA-B P50-C-REL COMPLEX. RX PubMed=15102766; DOI=10.1128/IAI.72.5.2582-2589.2004; RA Guizani-Tabbane L., Ben-Aissa K., Belghith M., Sassi A., Dellagi K.; RT "Leishmania major amastigotes induce p50/c-Rel NF-kappa B RT transcription factor in human macrophages: involvement in cytokine RT synthesis."; RL Infect. Immun. 72:2582-2589(2004). RN [35] RP FUNCTION, AND INTERACTION WITH MAP3K8. RX PubMed=15485931; DOI=10.1128/MCB.24.21.9658-9667.2004; RA Beinke S., Robinson M.J., Hugunin M., Ley S.C.; RT "Lipopolysaccharide activation of the TPL-2/MEK/extracellular signal- RT regulated kinase mitogen-activated protein kinase cascade is regulated RT by IkappaB kinase-induced proteolysis of NF-kappaB1 p105."; RL Mol. Cell. Biol. 24:9658-9667(2004). RN [36] RP INTERACTION WITH SPAG9. RX PubMed=14743216; DOI=10.1038/ncb1086; RA Bouwmeester T., Bauch A., Ruffner H., Angrand P.-O., Bergamini G., RA Croughton K., Cruciat C., Eberhard D., Gagneur J., Ghidelli S., RA Hopf C., Huhse B., Mangano R., Michon A.-M., Schirle M., Schlegl J., RA Schwab M., Stein M.A., Bauer A., Casari G., Drewes G., Gavin A.-C., RA Jackson D.B., Joberty G., Neubauer G., Rick J., Kuster B., RA Superti-Furga G.; RT "A physical and functional map of the human TNF-alpha/NF-kappa B RT signal transduction pathway."; RL Nat. Cell Biol. 6:97-105(2004). RN [37] RP INTERACTION WITH HIF1AN, HYDROXYLATION AT ASN-678, AND MUTAGENESIS OF RP ASN-678. RX PubMed=17003112; DOI=10.1073/pnas.0606877103; RA Cockman M.E., Lancaster D.E., Stolze I.P., Hewitson K.S., RA McDonough M.A., Coleman M.L., Coles C.H., Yu X., Hay R.T., Ley S.C., RA Pugh C.W., Oldham N.J., Masson N., Schofield C.J., Ratcliffe P.J.; RT "Posttranslational hydroxylation of ankyrin repeats in IkappaB RT proteins by the hypoxia-inducible factor (HIF) asparaginyl RT hydroxylase, factor inhibiting HIF (FIH)."; RL Proc. Natl. Acad. Sci. U.S.A. 103:14767-14772(2006). RN [38] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [39] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-937, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [40] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [41] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-903 AND SER-907, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [42] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-892, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [43] RP INVOLVEMENT IN CVID12. RX PubMed=26279205; DOI=10.1016/j.ajhg.2015.07.008; RA Fliegauf M., Bryant V.L., Frede N., Slade C., Woon S.T., Lehnert K., RA Winzer S., Bulashevska A., Scerri T., Leung E., Jordan A., Keller B., RA de Vries E., Cao H., Yang F., Schaeffer A.A., Warnatz K., Browett P., RA Douglass J., Ameratunga R.V., van der Meer J.W., Grimbacher B.; RT "Haploinsufficiency of the NF-kappaB1 Subunit p50 in Common Variable RT Immunodeficiency."; RL Am. J. Hum. Genet. 97:389-403(2015). RN [44] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-325, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co- RT modification with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [45] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-365. RX PubMed=7830764; DOI=10.1038/373311a0; RA Mueller C.W., Rey F.A., Sodeoka M., Verdine G.L., Harrison S.C.; RT "Structure of the NF-kappa B p50 homodimer bound to DNA."; RL Nature 373:311-317(1995). RN [46] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 248-354. RX PubMed=9865693; DOI=10.1016/S0092-8674(00)81698-0; RA Jacobs M.D., Harrison S.C.; RT "Structure of an IkappaBalpha/NF-kappaB complex."; RL Cell 95:749-758(1998). RN [47] RP STRUCTURE BY NMR OF 804-893. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the death domain in human nuclear factor NF- RT kappa-B p105 subunit."; RL Submitted (DEC-2006) to the PDB data bank. CC -!- FUNCTION: NF-kappa-B is a pleiotropic transcription factor present CC in almost all cell types and is the endpoint of a series of signal CC transduction events that are initiated by a vast array of stimuli CC related to many biological processes such as inflammation, CC immunity, differentiation, cell growth, tumorigenesis and CC apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed CC by the Rel-like domain-containing proteins RELA/p65, RELB, CC NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric CC p65-p50 complex appears to be most abundant one. The dimers bind CC at kappa-B sites in the DNA of their target genes and the CC individual dimers have distinct preferences for different kappa-B CC sites that they can bind with distinguishable affinity and CC specificity. Different dimer combinations act as transcriptional CC activators or repressors, respectively. NF-kappa-B is controlled CC by various mechanisms of post-translational modification and CC subcellular compartmentalization as well as by interactions with CC other cofactors or corepressors. NF-kappa-B complexes are held in CC the cytoplasm in an inactive state complexed with members of the CC NF-kappa-B inhibitor (I-kappa-B) family. In a conventional CC activation pathway, I-kappa-B is phosphorylated by I-kappa-B CC kinases (IKKs) in response to different activators, subsequently CC degraded thus liberating the active NF-kappa-B complex which CC translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and CC RelB-p50 complexes are transcriptional activators. The NF-kappa-B CC p50-p50 homodimer is a transcriptional repressor, but can act as a CC transcriptional activator when associated with BCL3. NFKB1 appears CC to have dual functions such as cytoplasmic retention of attached CC NF-kappa-B proteins by p105 and generation of p50 by a CC cotranslational processing. The proteasome-mediated process CC ensures the production of both p50 and p105 and preserves their CC independent function, although processing of NFKB1/p105 also CC appears to occur post-translationally. p50 binds to the kappa-B CC consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region CC of genes involved in immune response and acute phase reactions. In CC a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK CC signaling; active MAP3K8 is released by proteasome-dependent CC degradation of NFKB1/p105. {ECO:0000269|PubMed:15485931}. CC -!- SUBUNIT: Component of the NF-kappa-B p65-p50 complex. Component of CC the NF-kappa-B p65-p50 complex. Homodimer; component of the NF- CC kappa-B p50-p50 complex. Component of the NF-kappa-B p105-p50 CC complex. Component of the NF-kappa-B p50-c-Rel complex. Component CC of a complex consisting of the NF-kappa-B p50-p50 homodimer and CC BCL3. Also interacts with MAP3K8. NF-kappa-B p50 subunit interacts CC with NCOA3 coactivator, which may coactivate NF-kappa-B dependent CC expression via its histone acetyltransferase activity. Interacts CC with DSIPI; this interaction prevents nuclear translocation and CC DNA-binding. Interacts with SPAG9 and UNC5CL. NFKB1/p105 interacts CC with CFLAR; the interaction inhibits p105 processing into p50. CC NFKB1/p105 forms a ternary complex with MAP3K8 and TNIP2. CC Interacts with GSK3B; the interaction prevents processing of p105 CC to p50. NFKB1/p50 interacts with NFKBIE. NFKB1/p50 interacts with CC NFKBIZ. Nuclear factor NF-kappa-B p50 subunit interacts with CC NFKBID (By similarity). Directly interacts with MEN1. Interacts CC with HIF1AN. {ECO:0000250, ECO:0000269|PubMed:10469655, CC ECO:0000269|PubMed:11094166, ECO:0000269|PubMed:11468175, CC ECO:0000269|PubMed:11526476, ECO:0000269|PubMed:12393603, CC ECO:0000269|PubMed:12871932, ECO:0000269|PubMed:13679070, CC ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:14769797, CC ECO:0000269|PubMed:15102766, ECO:0000269|PubMed:15169888, CC ECO:0000269|PubMed:15485931, ECO:0000269|PubMed:17003112, CC ECO:0000269|PubMed:1740106, ECO:0000269|PubMed:8152812, CC ECO:0000269|PubMed:9315679, ECO:0000269|PubMed:9950430}. CC -!- INTERACTION: CC Self; NbExp=7; IntAct=EBI-300010, EBI-300010; CC Q92887:ABCC2; NbExp=3; IntAct=EBI-300010, EBI-3916193; CC O15111:CHUK; NbExp=3; IntAct=EBI-300010, EBI-81249; CC P35606:COPB2; NbExp=3; IntAct=EBI-300010, EBI-1056534; CC P35222:CTNNB1; NbExp=3; IntAct=EBI-300010, EBI-491549; CC P03372:ESR1; NbExp=3; IntAct=EBI-697771, EBI-78473; CC Q13547:HDAC1; NbExp=5; IntAct=EBI-300010, EBI-301834; CC Q9NWT6:HIF1AN; NbExp=7; IntAct=EBI-300010, EBI-745632; CC P08238:HSP90AB1; NbExp=3; IntAct=EBI-300010, EBI-352572; CC P34931:HSPA1L; NbExp=3; IntAct=EBI-300010, EBI-354912; CC O14920:IKBKB; NbExp=3; IntAct=EBI-300010, EBI-81266; CC P41279:MAP3K8; NbExp=13; IntAct=EBI-300010, EBI-354900; CC O00255:MEN1; NbExp=2; IntAct=EBI-697771, EBI-592789; CC O00255-2:MEN1; NbExp=4; IntAct=EBI-697771, EBI-9869387; CC Q00653:NFKB2; NbExp=8; IntAct=EBI-300010, EBI-307326; CC P25963:NFKBIA; NbExp=6; IntAct=EBI-300010, EBI-307386; CC P46531:NOTCH1; NbExp=2; IntAct=EBI-300010, EBI-636374; CC Q14690:PDCD11; NbExp=2; IntAct=EBI-300010, EBI-300028; CC Q8IZL8:PELP1; NbExp=2; IntAct=EBI-300010, EBI-716449; CC Q8IV08:PLD3; NbExp=2; IntAct=EBI-300010, EBI-2689908; CC Q04206:RELA; NbExp=13; IntAct=EBI-300010, EBI-73886; CC Q01201:RELB; NbExp=5; IntAct=EBI-300010, EBI-357837; CC P23396:RPS3; NbExp=4; IntAct=EBI-300010, EBI-351193; CC Q15025:TNIP1; NbExp=4; IntAct=EBI-300010, EBI-357849; CC Q8NFZ5:TNIP2; NbExp=8; IntAct=EBI-1452239, EBI-359372; CC P10226:UL42 (xeno); NbExp=4; IntAct=EBI-300010, EBI-1029310; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nuclear, but also CC found in the cytoplasm in an inactive form complexed to an CC inhibitor (I-kappa-B). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P19838-1; Sequence=Displayed; CC Name=2; CC IsoId=P19838-2; Sequence=VSP_021025; CC Name=3; CC IsoId=P19838-3; Sequence=VSP_042869, VSP_042870; CC Note=No experimental confirmation available.; CC -!- INDUCTION: By phorbol ester and TNF. CC -!- DOMAIN: The C-terminus of p105 might be involved in cytoplasmic CC retention, inhibition of DNA-binding, and transcription CC activation. CC -!- DOMAIN: Glycine-rich region (GRR) appears to be a critical element CC in the generation of p50. CC -!- PTM: While translation occurs, the particular unfolded structure CC after the GRR repeat promotes the generation of p50 making it an CC acceptable substrate for the proteasome. This process is known as CC cotranslational processing. The processed form is active and the CC unprocessed form acts as an inhibitor (I kappa B-like), being able CC to form cytosolic complexes with NF-kappa B, trapping it in the CC cytoplasm. Complete folding of the region downstream of the GRR CC repeat precludes processing. {ECO:0000269|PubMed:8628291}. CC -!- PTM: Phosphorylation at 'Ser-903' and 'Ser-907' primes p105 for CC proteolytic processing in response to TNF-alpha stimulation. CC Phosphorylation at 'Ser-927' and 'Ser-932' are required for CC BTRC/BTRCP-mediated proteolysis. {ECO:0000269|PubMed:11297557, CC ECO:0000269|PubMed:12482991, ECO:0000269|PubMed:12871932, CC ECO:0000269|PubMed:8628291}. CC -!- PTM: Polyubiquitination seems to allow p105 processing. CC {ECO:0000269|PubMed:8087845, ECO:0000269|PubMed:8628291}. CC -!- PTM: S-nitrosylation of Cys-61 affects DNA binding. CC {ECO:0000269|PubMed:11327828, ECO:0000269|PubMed:8710491}. CC -!- PTM: The covalent modification of cysteine by 15-deoxy-Delta12,14- CC prostaglandin-J2 is autocatalytic and reversible. It may occur as CC an alternative to other cysteine modifications, such as S- CC nitrosylation and S-palmitoylation. CC -!- DISEASE: Immunodeficiency, common variable, 12 (CVID12) CC [MIM:616576]: A primary immunodeficiency characterized by antibody CC deficiency, hypogammaglobulinemia, recurrent bacterial infections CC and an inability to mount an antibody response to antigen. CC {ECO:0000269|PubMed:26279205}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/NFKB1ID323.html"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/nfkb1/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M55643; AAA36361.1; -; mRNA. DR EMBL; M58603; AAA36360.1; -; mRNA. DR EMBL; Z47748; CAB94757.1; -; Genomic_DNA. DR EMBL; Z47749; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47750; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47751; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47752; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47753; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47754; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47755; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47734; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47735; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47736; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47737; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47738; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47739; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47740; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47741; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47742; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47743; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; Z47744; CAB94757.1; JOINED; Genomic_DNA. DR EMBL; AF213884; AAF35232.1; -; Genomic_DNA. DR EMBL; AK122850; BAG53760.1; -; mRNA. DR EMBL; AK291450; BAF84139.1; -; mRNA. DR EMBL; CR749522; CAH18336.1; -; mRNA. DR EMBL; AY223820; AAO30127.1; -; Genomic_DNA. DR EMBL; BC033210; AAH33210.1; -; mRNA. DR EMBL; BC051765; AAH51765.1; -; mRNA. DR CCDS; CCDS3657.1; -. [P19838-2] DR CCDS; CCDS54783.1; -. [P19838-1] DR PIR; A37867; A37867. DR RefSeq; NP_001158884.1; NM_001165412.1. [P19838-1] DR RefSeq; NP_001306155.1; NM_001319226.1. [P19838-1] DR RefSeq; NP_003989.2; NM_003998.3. [P19838-2] DR UniGene; Hs.618430; -. DR PDB; 1MDI; NMR; -; B=55-67. DR PDB; 1MDJ; NMR; -; B=55-67. DR PDB; 1MDK; NMR; -; B=55-67. DR PDB; 1NFI; X-ray; 2.70 A; B/D=248-354. DR PDB; 1SVC; X-ray; 2.60 A; P=2-365. DR PDB; 2DBF; NMR; -; A=806-893. DR PDB; 2O61; X-ray; 2.80 A; B=40-352. DR PDB; 3GUT; X-ray; 3.59 A; B/D/F/H=41-352. DR PDBsum; 1MDI; -. DR PDBsum; 1MDJ; -. DR PDBsum; 1MDK; -. DR PDBsum; 1NFI; -. DR PDBsum; 1SVC; -. DR PDBsum; 2DBF; -. DR PDBsum; 2O61; -. DR PDBsum; 3GUT; -. DR ProteinModelPortal; P19838; -. DR SMR; P19838; -. DR BioGrid; 110857; 156. DR CORUM; P19838; -. DR DIP; DIP-106N; -. DR ELM; P19838; -. DR IntAct; P19838; 475. DR MINT; MINT-85658; -. DR STRING; 9606.ENSP00000226574; -. DR BindingDB; P19838; -. DR ChEMBL; CHEMBL3251; -. DR DrugBank; DB00945; Acetylsalicylic acid. DR DrugBank; DB05487; CC-8490. DR DrugBank; DB05212; HE3286. DR DrugBank; DB05767; HMPL-004. DR DrugBank; DB05464; NOX-700. DR DrugBank; DB05451; P54. DR DrugBank; DB01411; Pranlukast. DR DrugBank; DB05471; SGN-30. DR DrugBank; DB01041; Thalidomide. DR DrugBank; DB08814; Triflusal. DR iPTMnet; P19838; -. DR PhosphoSitePlus; P19838; -. DR BioMuta; NFKB1; -. DR DMDM; 21542418; -. DR EPD; P19838; -. DR MaxQB; P19838; -. DR PaxDb; P19838; -. DR PeptideAtlas; P19838; -. DR PRIDE; P19838; -. DR DNASU; 4790; -. DR Ensembl; ENST00000226574; ENSP00000226574; ENSG00000109320. [P19838-2] DR Ensembl; ENST00000394820; ENSP00000378297; ENSG00000109320. [P19838-1] DR Ensembl; ENST00000505458; ENSP00000424790; ENSG00000109320. [P19838-1] DR Ensembl; ENST00000600343; ENSP00000469340; ENSG00000109320. [P19838-3] DR GeneID; 4790; -. DR KEGG; hsa:4790; -. DR UCSC; uc011cep.2; human. [P19838-1] DR CTD; 4790; -. DR DisGeNET; 4790; -. DR EuPathDB; HostDB:ENSG00000109320.11; -. DR GeneCards; NFKB1; -. DR HGNC; HGNC:7794; NFKB1. DR HPA; CAB004031; -. DR HPA; HPA027305; -. DR MalaCards; NFKB1; -. DR MIM; 164011; gene. DR MIM; 616576; phenotype. DR neXtProt; NX_P19838; -. DR OpenTargets; ENSG00000109320; -. DR PharmGKB; PA248; -. DR eggNOG; KOG0504; Eukaryota. DR eggNOG; COG0666; LUCA. DR GeneTree; ENSGT00500000044765; -. DR HOGENOM; HOG000004822; -. DR HOVERGEN; HBG052613; -. DR InParanoid; P19838; -. DR KO; K02580; -. DR OMA; PFRYKPR; -. DR OrthoDB; EOG091G03PF; -. DR PhylomeDB; P19838; -. DR TreeFam; TF325632; -. DR Reactome; R-HSA-1169091; Activation of NF-kappaB in B cells. DR Reactome; R-HSA-1810476; RIP-mediated NFkB activation via ZBP1. DR Reactome; R-HSA-193692; Regulated proteolysis of p75NTR. DR Reactome; R-HSA-202424; Downstream TCR signaling. DR Reactome; R-HSA-209560; NF-kB is activated and signals survival. DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation. DR Reactome; R-HSA-3134963; DEx/H-box helicases activate type I IFN and inflammatory cytokines production. DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR Reactome; R-HSA-445989; TAK1 activates NFkB by phosphorylation and activation of IKKs complex. DR Reactome; R-HSA-446652; Interleukin-1 family signaling. DR Reactome; R-HSA-448706; Interleukin-1 processing. DR Reactome; R-HSA-5603027; IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR). DR Reactome; R-HSA-5603029; IkBA variant leads to EDA-ID. DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-HSA-5621575; CD209 (DC-SIGN) signaling. DR Reactome; R-HSA-5660668; CLEC7A/inflammasome pathway. DR Reactome; R-HSA-5684264; MAP3K8 (TPL2)-dependent MAPK1/3 activation. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation. DR SignaLink; P19838; -. DR SIGNOR; P19838; -. DR ChiTaRS; NFKB1; human. DR EvolutionaryTrace; P19838; -. DR GeneWiki; NFKB1; -. DR GenomeRNAi; 4790; -. DR PMAP-CutDB; P19838; -. DR PRO; PR:P19838; -. DR Proteomes; UP000005640; Chromosome 4. DR Bgee; ENSG00000109320; -. DR CleanEx; HS_NFKB1; -. DR ExpressionAtlas; P19838; baseline and differential. DR Genevisible; P19838; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0033256; C:I-kappaB/NF-kappaB complex; TAS:BHF-UCL. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome. DR GO; GO:0042805; F:actinin binding; IPI:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:CAFA. DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl. DR GO; GO:0000975; F:regulatory region DNA binding; IDA:UniProtKB. DR GO; GO:0000980; F:RNA polymerase II distal enhancer sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IDA:MGI. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0008134; F:transcription factor binding; IDA:MGI. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL. DR GO; GO:0000976; F:transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0001205; F:transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding; IDA:NTNU_SB. DR GO; GO:0001227; F:transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding; IDA:MGI. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0071359; P:cellular response to dsRNA; IEA:Ensembl. DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:BHF-UCL. DR GO; GO:0071354; P:cellular response to interleukin-6; IMP:BHF-UCL. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:MGI. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB. DR GO; GO:0071316; P:cellular response to nicotine; IMP:BHF-UCL. DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IMP:BHF-UCL. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central. DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB. DR GO; GO:0045087; P:innate immune response; IBA:GO_Central. DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; TAS:Reactome. DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB. DR GO; GO:0010956; P:negative regulation of calcidiol 1-monooxygenase activity; IDA:BHF-UCL. DR GO; GO:0032269; P:negative regulation of cellular protein metabolic process; IC:BHF-UCL. DR GO; GO:0032375; P:negative regulation of cholesterol transport; IC:BHF-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl. DR GO; GO:0045083; P:negative regulation of interleukin-12 biosynthetic process; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB. DR GO; GO:0010957; P:negative regulation of vitamin D biosynthetic process; IC:BHF-UCL. DR GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome. DR GO; GO:0038061; P:NIK/NF-kappaB signaling; IBA:GO_Central. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:UniProtKB. DR GO; GO:1900127; P:positive regulation of hyaluronan biosynthetic process; IDA:UniProtKB. DR GO; GO:0010884; P:positive regulation of lipid storage; IC:BHF-UCL. DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IC:BHF-UCL. DR GO; GO:2000630; P:positive regulation of miRNA metabolic process; IMP:BHF-UCL. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:Reactome. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:NTNU_SB. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0032481; P:positive regulation of type I interferon production; TAS:Reactome. DR GO; GO:0035994; P:response to muscle stretch; IEA:Ensembl. DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; TAS:Reactome. DR GO; GO:0051403; P:stress-activated MAPK cascade; TAS:Reactome. DR GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:UniProtKB. DR CDD; cd00204; ANK; 1. DR CDD; cd01177; IPT_NFkappaB; 1. DR Gene3D; 1.25.40.20; -; 3. DR Gene3D; 2.60.40.10; -; 1. DR Gene3D; 2.60.40.340; -; 1. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR020683; Ankyrin_rpt-contain_dom. DR InterPro; IPR036770; Ankyrin_rpt-contain_sf. DR InterPro; IPR011029; DEATH-like_dom. DR InterPro; IPR000488; Death_domain. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR002909; IPT. DR InterPro; IPR033926; IPT_NFkappaB. DR InterPro; IPR030503; NF-kB_p105. DR InterPro; IPR000451; NFkB/Dor. DR InterPro; IPR008967; p53-like_TF_DNA-bd. DR InterPro; IPR030492; RHD_CS. DR InterPro; IPR032397; RHD_dimer. DR InterPro; IPR011539; RHD_DNA_bind_dom. DR InterPro; IPR037059; RHD_DNA_bind_dom_sf. DR PANTHER; PTHR24169; PTHR24169; 1. DR PANTHER; PTHR24169:SF9; PTHR24169:SF9; 1. DR Pfam; PF00023; Ank; 1. DR Pfam; PF12796; Ank_2; 1. DR Pfam; PF00531; Death; 1. DR Pfam; PF16179; RHD_dimer; 1. DR Pfam; PF00554; RHD_DNA_bind; 1. DR PRINTS; PR01415; ANKYRIN. DR PRINTS; PR00057; NFKBTNSCPFCT. DR SMART; SM00248; ANK; 6. DR SMART; SM00005; DEATH; 1. DR SMART; SM00429; IPT; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR SUPFAM; SSF48403; SSF48403; 1. DR SUPFAM; SSF49417; SSF49417; 1. DR SUPFAM; SSF81296; SSF81296; 1. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 5. DR PROSITE; PS01204; REL_1; 1. DR PROSITE; PS50254; REL_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW ANK repeat; Apoptosis; Complete proteome; Cytoplasm; KW Direct protein sequencing; DNA-binding; Hydroxylation; KW Isopeptide bond; Lipoprotein; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Repeat; S-nitrosylation; Transcription; KW Transcription regulation; Ubl conjugation. FT CHAIN 1 968 Nuclear factor NF-kappa-B p105 subunit. FT /FTId=PRO_0000030310. FT CHAIN 1 433 Nuclear factor NF-kappa-B p50 subunit. FT /FTId=PRO_0000030311. FT DOMAIN 42 367 RHD. {ECO:0000255|PROSITE- FT ProRule:PRU00265}. FT REPEAT 542 571 ANK 1. FT REPEAT 581 610 ANK 2. FT REPEAT 614 643 ANK 3. FT REPEAT 650 679 ANK 4. FT REPEAT 684 714 ANK 5. FT REPEAT 718 747 ANK 6. FT REPEAT 771 801 ANK 7. FT DOMAIN 805 892 Death. FT REGION 372 394 GRR. FT REGION 435 968 Interaction with CFLAR. FT {ECO:0000269|PubMed:13679070}. FT REGION 650 684 Essential for interaction with HIF1AN. FT {ECO:0000269|PubMed:17003112}. FT MOTIF 360 365 Nuclear localization signal. FT {ECO:0000255}. FT COMPBIAS 375 433 Gly-rich. FT SITE 433 434 Cleavage (when cotranslationally FT processed). FT MOD_RES 61 61 S-nitrosocysteine; alternate. FT {ECO:0000269|PubMed:8710491}. FT MOD_RES 337 337 Phosphoserine; by PKA. {ECO:0000255}. FT MOD_RES 431 431 N6-acetyllysine; by EP300. FT {ECO:0000305|PubMed:11739381}. FT MOD_RES 440 440 N6-acetyllysine; by EP300. FT {ECO:0000305|PubMed:11739381}. FT MOD_RES 441 441 N6-acetyllysine; by EP300. FT {ECO:0000305|PubMed:11739381}. FT MOD_RES 449 449 Phosphoserine. FT {ECO:0000250|UniProtKB:P25799}. FT MOD_RES 678 678 (3S)-3-hydroxyasparagine; by HIF1AN; FT partial. {ECO:0000269|PubMed:17003112}. FT MOD_RES 759 759 Phosphoserine. FT {ECO:0000250|UniProtKB:Q63369}. FT MOD_RES 892 892 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 903 903 Phosphoserine; by GSK3-beta; in vitro. FT {ECO:0000244|PubMed:23186163, FT ECO:0000269|PubMed:12871932}. FT MOD_RES 907 907 Phosphoserine; by GSK3-beta; in vitro. FT {ECO:0000244|PubMed:23186163, FT ECO:0000269|PubMed:12871932}. FT MOD_RES 927 927 Phosphoserine; by IKKB. FT {ECO:0000269|PubMed:11297557, FT ECO:0000269|PubMed:12482991}. FT MOD_RES 932 932 Phosphoserine; by IKKB. FT {ECO:0000269|PubMed:12482991}. FT MOD_RES 937 937 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 943 943 Phosphothreonine. FT {ECO:0000250|UniProtKB:P25799}. FT LIPID 61 61 S-(15-deoxy-Delta12,14-prostaglandin J2- FT 9-yl)cysteine; alternate. FT {ECO:0000269|PubMed:11466314}. FT CROSSLNK 325 325 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:28112733}. FT VAR_SEQ 1 180 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_042869. FT VAR_SEQ 39 39 T -> TA (in isoform 2). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:2203531}. FT /FTId=VSP_021025. FT VAR_SEQ 181 189 EGGGDRQLG -> MNGLCCMAL (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_042870. FT VARIANT 489 489 T -> I (in dbSNP:rs4648065). FT {ECO:0000269|Ref.8}. FT /FTId=VAR_016268. FT VARIANT 506 506 M -> V (in dbSNP:rs4648072). FT {ECO:0000269|Ref.8}. FT /FTId=VAR_016269. FT VARIANT 566 566 T -> I (in dbSNP:rs4648085). FT {ECO:0000269|Ref.8}. FT /FTId=VAR_016270. FT VARIANT 578 578 R -> K (in dbSNP:rs4648086). FT {ECO:0000269|Ref.8}. FT /FTId=VAR_016271. FT VARIANT 711 711 H -> Q (in dbSNP:rs4648099). FT {ECO:0000269|Ref.8}. FT /FTId=VAR_016272. FT VARIANT 901 901 A -> T (in dbSNP:rs4648118). FT {ECO:0000269|Ref.8}. FT /FTId=VAR_016273. FT MUTAGEN 61 61 C->S: Suppresses S-nitrosylation-induced FT inhibition of DNA-binding activity. Loss FT of S-(15-deoxy-Delta12,14-prostaglandin FT J2-9-yl)cysteine-induced inhibition of FT DNA-binding activity. FT {ECO:0000269|PubMed:11466314, FT ECO:0000269|PubMed:8710491}. FT MUTAGEN 678 678 N->A: Fails to promote HIF1AN-dependent FT 2-oxoglutarate decarboxylation. FT {ECO:0000269|PubMed:17003112}. FT MUTAGEN 903 903 S->A: Prevents p105 proteolysis in FT response to TNF-alpha. FT {ECO:0000269|PubMed:12871932}. FT MUTAGEN 907 907 S->A: Prevents p105 proteolysis in FT response to TNF-alpha. FT {ECO:0000269|PubMed:12871932}. FT MUTAGEN 921 921 S->A: Decrease in stimuli-induced FT phosphorylation. Loss of phosphorylation; FT when associated with A-923 and A-932. FT {ECO:0000269|PubMed:10469655}. FT MUTAGEN 923 923 S->A: Decrease in stimuli-induced FT phosphorylation. Loss of phosphorylation; FT when associated with A-921 and A-932. FT {ECO:0000269|PubMed:10469655}. FT MUTAGEN 932 932 S->A: Decrease in stimuli-induced FT phosphorylation. Loss of phosphorylation; FT when associated with A-921 and A-923. FT {ECO:0000269|PubMed:10469655}. FT CONFLICT 243 243 K -> SE (in Ref. 4; CAB94757). FT {ECO:0000305}. FT CONFLICT 361 361 R -> G (in Ref. 7; CAH18336). FT {ECO:0000305}. FT CONFLICT 551 552 II -> SS (in Ref. 4; CAB94757). FT {ECO:0000305}. FT CONFLICT 573 573 D -> G (in Ref. 6; BAF84139). FT {ECO:0000305}. FT CONFLICT 726 726 A -> V (in Ref. 4; CAB94757). FT {ECO:0000305}. FT CONFLICT 825 825 I -> T (in Ref. 7; CAH18336). FT {ECO:0000305}. FT CONFLICT 869 869 V -> I (in Ref. 4; CAB94757). FT {ECO:0000305}. FT CONFLICT 927 927 S -> T (in Ref. 1; AAA36361, 3; AAA36360 FT and 4; CAB94757). {ECO:0000305}. FT STRAND 43 48 {ECO:0000244|PDB:1SVC}. FT STRAND 52 54 {ECO:0000244|PDB:1SVC}. FT HELIX 60 62 {ECO:0000244|PDB:1SVC}. FT STRAND 83 88 {ECO:0000244|PDB:1SVC}. FT STRAND 94 100 {ECO:0000244|PDB:1SVC}. FT STRAND 103 105 {ECO:0000244|PDB:1SVC}. FT STRAND 110 115 {ECO:0000244|PDB:1SVC}. FT STRAND 122 126 {ECO:0000244|PDB:1SVC}. FT STRAND 133 135 {ECO:0000244|PDB:1SVC}. FT STRAND 138 143 {ECO:0000244|PDB:1SVC}. FT HELIX 146 148 {ECO:0000244|PDB:1SVC}. FT HELIX 149 163 {ECO:0000244|PDB:1SVC}. FT HELIX 167 170 {ECO:0000244|PDB:1SVC}. FT HELIX 173 178 {ECO:0000244|PDB:1SVC}. FT STRAND 180 182 {ECO:0000244|PDB:2O61}. FT TURN 184 187 {ECO:0000244|PDB:1SVC}. FT HELIX 190 204 {ECO:0000244|PDB:1SVC}. FT STRAND 211 221 {ECO:0000244|PDB:1SVC}. FT STRAND 223 225 {ECO:0000244|PDB:1SVC}. FT STRAND 227 230 {ECO:0000244|PDB:1SVC}. FT STRAND 234 240 {ECO:0000244|PDB:1SVC}. FT HELIX 245 247 {ECO:0000244|PDB:1SVC}. FT STRAND 252 256 {ECO:0000244|PDB:1SVC}. FT STRAND 258 261 {ECO:0000244|PDB:1SVC}. FT STRAND 267 274 {ECO:0000244|PDB:1SVC}. FT HELIX 277 279 {ECO:0000244|PDB:1SVC}. FT STRAND 281 288 {ECO:0000244|PDB:1SVC}. FT TURN 289 291 {ECO:0000244|PDB:1SVC}. FT STRAND 292 297 {ECO:0000244|PDB:1SVC}. FT HELIX 302 304 {ECO:0000244|PDB:1SVC}. FT TURN 307 309 {ECO:0000244|PDB:1SVC}. FT STRAND 310 314 {ECO:0000244|PDB:1SVC}. FT STRAND 319 322 {ECO:0000244|PDB:2O61}. FT STRAND 327 334 {ECO:0000244|PDB:1SVC}. FT TURN 336 338 {ECO:0000244|PDB:1SVC}. FT STRAND 345 350 {ECO:0000244|PDB:1SVC}. FT HELIX 813 823 {ECO:0000244|PDB:2DBF}. FT HELIX 832 839 {ECO:0000244|PDB:2DBF}. FT HELIX 842 844 {ECO:0000244|PDB:2DBF}. FT HELIX 845 850 {ECO:0000244|PDB:2DBF}. FT HELIX 854 864 {ECO:0000244|PDB:2DBF}. FT HELIX 869 879 {ECO:0000244|PDB:2DBF}. FT HELIX 883 892 {ECO:0000244|PDB:2DBF}. SQ SEQUENCE 968 AA; 105356 MW; 2A7C8FF86A10D1A8 CRC64; MAEDDPYLGR PEQMFHLDPS LTHTIFNPEV FQPQMALPTD GPYLQILEQP KQRGFRFRYV CEGPSHGGLP GASSEKNKKS YPQVKICNYV GPAKVIVQLV TNGKNIHLHA HSLVGKHCED GICTVTAGPK DMVVGFANLG ILHVTKKKVF ETLEARMTEA CIRGYNPGLL VHPDLAYLQA EGGGDRQLGD REKELIRQAA LQQTKEMDLS VVRLMFTAFL PDSTGSFTRR LEPVVSDAIY DSKAPNASNL KIVRMDRTAG CVTGGEEIYL LCDKVQKDDI QIRFYEEEEN GGVWEGFGDF SPTDVHRQFA IVFKTPKYKD INITKPASVF VQLRRKSDLE TSEPKPFLYY PEIKDKEEVQ RKRQKLMPNF SDSFGGGSGA GAGGGGMFGS GGGGGGTGST GPGYSFPHYG FPTYGGITFH PGTTKSNAGM KHGTMDTESK KDPEGCDKSD DKNTVNLFGK VIETTEQDQE PSEATVGNGE VTLTYATGTK EESAGVQDNL FLEKAMQLAK RHANALFDYA VTGDVKMLLA VQRHLTAVQD ENGDSVLHLA IIHLHSQLVR DLLEVTSGLI SDDIINMRND LYQTPLHLAV ITKQEDVVED LLRAGADLSL LDRLGNSVLH LAAKEGHDKV LSILLKHKKA ALLLDHPNGD GLNAIHLAMM SNSLPCLLLL VAAGADVNAQ EQKSGRTALH LAVEHDNISL AGCLLLEGDA HVDSTTYDGT TPLHIAAGRG STRLAALLKA AGADPLVENF EPLYDLDDSW ENAGEDEGVV PGTTPLDMAT SWQVFDILNG KPYEPEFTSD DLLAQGDMKQ LAEDVKLQLY KLLEIPDPDK NWATLAQKLG LGILNNAFRL SPAPSKTLMD NYEVSGGTVR ELVEALRQMG YTEAIEVIQA ASSPVKTTSQ AHSLPLSPAS TRQQIDELRD SDSVCDSGVE TSFRKLSFTE SLTSGASLLT LNKMPHDYGQ EGPLEGKI //