NFKB1_HUMAN
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 03-AUG-2022, entry version 260.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 protein
RT 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: the
RT level of its mRNA is strongly regulated by phorbol ester or tumor necrosis
RT 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, which
RT encodes the p105 and p50 proteins of transcription factors NF-kappa B and I
RT kappa B-gamma: implications for NF-kappa B-mediated 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA 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; ILE-566;
RP 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 project:
RT 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; DOI=10.1002/j.1460-2075.1992.tb05043.x;
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 to a
RT DNA element involved in the phorbol ester induction of the human urokinase
RT 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-kappa
RT 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 signal
RT 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 BY
RP 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 RelA
RT (p65)-mediated NF-kappaB transcription.";
RL Mol. Cell. Biol. 17:6184-6190(1997).
RN [16]
RP COTRANSLATIONAL FOLDING/PROCESSING OF P105, AND GENERATION OF 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; SER-923
RP 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 protein
RT NF-kappaB1 p105.";
RL Nature 397:363-368(1999).
RN [19]
RP COTRANSLATIONAL FOLDING/PROCESSING OF P105, GENERATION OF P50/P105, AND
RP 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 binding
RT 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., Ley S.C.;
RT "Direct phosphorylation of NF-kappa B1 p105 by the Ikappa B kinase complex
RT on serine 927 is essential for signal-induced p105 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., Marx S.J.,
RA Burns A.L.;
RT "The tumor suppressor protein menin interacts with NF-kappaB proteins and
RT 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-kappaB1
RT 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 and
RT 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 macrophages:
RT an anti-inflammatory and immunosuppressive mechanism shared by
RT 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 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 phosphorylation
RT 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 transcription
RT factor in human macrophages: involvement in cytokine 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 by
RT 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., Hopf C.,
RA Huhse B., Mangano R., Michon A.-M., Schirle M., Schlegl J., Schwab M.,
RA Stein M.A., Bauer A., Casari G., Drewes G., Gavin A.-C., Jackson D.B.,
RA Joberty G., Neubauer G., Rick J., Kuster B., Superti-Furga G.;
RT "A physical and functional map of the human TNF-alpha/NF-kappa B signal
RT 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., McDonough M.A.,
RA Coleman M.L., Coles C.H., Yu X., Hay R.T., Ley S.C., Pugh C.W.,
RA Oldham N.J., Masson N., Schofield C.J., Ratcliffe P.J.;
RT "Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by
RT the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor
RT 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 BY
RP 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., Buerckstuemmer T.,
RA 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 BY
RP 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., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT 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 MASS
RP 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-modification
RT 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-kappa-B
RT p105 subunit.";
RL Submitted (DEC-2006) to the PDB data bank.
CC -!- FUNCTION: NF-kappa-B is a pleiotropic transcription factor present in
CC 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, immunity,
CC differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B
CC is a homo- or heterodimeric complex formed by the Rel-like domain-
CC containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and
CC NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most
CC abundant one. The dimers bind at kappa-B sites in the DNA of their
CC target genes and the individual dimers have distinct preferences for
CC different kappa-B sites that they can bind with distinguishable
CC affinity and specificity. Different dimer combinations act as
CC transcriptional activators or repressors, respectively. NF-kappa-B is
CC controlled by various mechanisms of post-translational modification and
CC subcellular compartmentalization as well as by interactions with other
CC cofactors or corepressors. NF-kappa-B complexes are held in the
CC cytoplasm in an inactive state complexed with members of the NF-kappa-B
CC inhibitor (I-kappa-B) family. In a conventional activation pathway, I-
CC kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to
CC different activators, subsequently degraded thus liberating the active
CC NF-kappa-B complex which translocates to the nucleus. NF-kappa-B
CC heterodimeric p65-p50 and RelB-p50 complexes are transcriptional
CC activators. The NF-kappa-B p50-p50 homodimer is a transcriptional
CC repressor, but can act as a transcriptional activator when associated
CC with BCL3. NFKB1 appears to have dual functions such as cytoplasmic
CC retention of attached NF-kappa-B proteins by p105 and generation of p50
CC by a 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 appears to
CC occur post-translationally. p50 binds to the kappa-B consensus sequence
CC 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in
CC immune response and acute phase reactions. In a complex with MAP3K8,
CC NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is
CC released by proteasome-dependent degradation of NFKB1/p105.
CC {ECO:0000269|PubMed:15485931}.
CC -!- SUBUNIT: Component of the NF-kappa-B p65-p50 complex (PubMed:1740106).
CC Homodimer; component of the NF-kappa-B p50-p50 complex. Component of
CC the NF-kappa-B p105-p50 complex. Component of the NF-kappa-B p50-c-Rel
CC complex (PubMed:15102766, PubMed:8152812). Component of a complex
CC consisting of the NF-kappa-B p50-p50 homodimer and BCL3
CC (PubMed:10469655). Also interacts with MAP3K8 (PubMed:9950430,
CC PubMed:15485931). NF-kappa-B p50 subunit interacts with NCOA3
CC coactivator, which may coactivate NF-kappa-B dependent expression via
CC its histone acetyltransferase activity (PubMed:11094166). Interacts
CC with DSIPI; this interaction prevents nuclear translocation and DNA-
CC binding (PubMed:11468175, PubMed:12393603). Interacts with SPAG9 and
CC UNC5CL (PubMed:14769797, PubMed:14743216). NFKB1/p105 interacts with
CC CFLAR; the interaction inhibits p105 processing into p50
CC (PubMed:13679070). NFKB1/p105 forms a ternary complex with MAP3K8 and
CC TNIP2 (PubMed:15169888). Interacts with GSK3B; the interaction prevents
CC processing of p105 to p50 (PubMed:12871932). NFKB1/p50 interacts with
CC NFKBIE (PubMed:9315679). NFKB1/p50 interacts with NFKBIZ (By
CC similarity). Nuclear factor NF-kappa-B p50 subunit interacts with
CC NFKBID (By similarity). Directly interacts with MEN1 (PubMed:11526476).
CC Interacts with HIF1AN (PubMed:17003112). Interacts with FEM1A;
CC interaction is direct (By similarity). {ECO:0000250|UniProtKB:P25799,
CC ECO:0000269|PubMed:10469655, ECO:0000269|PubMed:11094166,
CC ECO:0000269|PubMed:11468175, ECO:0000269|PubMed:11526476,
CC ECO:0000269|PubMed:12393603, ECO:0000269|PubMed:12871932,
CC ECO:0000269|PubMed:13679070, ECO:0000269|PubMed:14743216,
CC ECO:0000269|PubMed:14769797, ECO:0000269|PubMed:15102766,
CC ECO:0000269|PubMed:15169888, ECO:0000269|PubMed:15485931,
CC ECO:0000269|PubMed:17003112, ECO:0000269|PubMed:1740106,
CC ECO:0000269|PubMed:8152812, ECO:0000269|PubMed:9315679,
CC ECO:0000269|PubMed:9950430}.
CC -!- INTERACTION:
CC P19838; Q92887: ABCC2; NbExp=3; IntAct=EBI-300010, EBI-3916193;
CC P19838; O15111: CHUK; NbExp=3; IntAct=EBI-300010, EBI-81249;
CC P19838; P35606: COPB2; NbExp=5; IntAct=EBI-300010, EBI-1056534;
CC P19838; P35222: CTNNB1; NbExp=3; IntAct=EBI-300010, EBI-491549;
CC P19838; Q13547: HDAC1; NbExp=5; IntAct=EBI-300010, EBI-301834;
CC P19838; Q9NWT6: HIF1AN; NbExp=7; IntAct=EBI-300010, EBI-745632;
CC P19838; O14920: IKBKB; NbExp=3; IntAct=EBI-300010, EBI-81266;
CC P19838; P41279: MAP3K8; NbExp=14; IntAct=EBI-300010, EBI-354900;
CC P19838; P19838: NFKB1; NbExp=7; IntAct=EBI-300010, EBI-300010;
CC P19838; Q00653: NFKB2; NbExp=8; IntAct=EBI-300010, EBI-307326;
CC P19838; P25963: NFKBIA; NbExp=8; IntAct=EBI-300010, EBI-307386;
CC P19838; Q15653: NFKBIB; NbExp=3; IntAct=EBI-300010, EBI-352889;
CC P19838; P46531: NOTCH1; NbExp=2; IntAct=EBI-300010, EBI-636374;
CC P19838; Q14690: PDCD11; NbExp=2; IntAct=EBI-300010, EBI-300028;
CC P19838; Q8IZL8: PELP1; NbExp=2; IntAct=EBI-300010, EBI-716449;
CC P19838; Q8IV08: PLD3; NbExp=2; IntAct=EBI-300010, EBI-2689908;
CC P19838; Q04206: RELA; NbExp=14; IntAct=EBI-300010, EBI-73886;
CC P19838; Q01201: RELB; NbExp=5; IntAct=EBI-300010, EBI-357837;
CC P19838; P23396: RPS3; NbExp=4; IntAct=EBI-300010, EBI-351193;
CC P19838; Q15025: TNIP1; NbExp=5; IntAct=EBI-300010, EBI-357849;
CC P19838; Q8NFZ5: TNIP2; NbExp=7; IntAct=EBI-300010, EBI-359372;
CC P19838; P10226: UL42; Xeno; NbExp=4; IntAct=EBI-300010, EBI-1029310;
CC P19838-1; Q8NFZ5: TNIP2; NbExp=8; IntAct=EBI-1452239, EBI-359372;
CC P19838-2; P42858: HTT; NbExp=3; IntAct=EBI-1452242, EBI-466029;
CC PRO_0000030311; P03372: ESR1; NbExp=3; IntAct=EBI-697771, EBI-78473;
CC PRO_0000030311; O00255: MEN1; NbExp=2; IntAct=EBI-697771, EBI-592789;
CC PRO_0000030311; O00255-2: MEN1; NbExp=4; IntAct=EBI-697771, EBI-9869387;
CC PRO_0000030311; Q04206: RELA; NbExp=7; IntAct=EBI-697771, EBI-73886;
CC PRO_0000030311; P10226: UL42; Xeno; NbExp=2; IntAct=EBI-697771, EBI-1029310;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nuclear, but also found
CC in the cytoplasm in an inactive form complexed to an inhibitor (I-
CC 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 -!- 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 activation.
CC -!- DOMAIN: Glycine-rich region (GRR) appears to be a critical element in
CC the generation of p50.
CC -!- PTM: While translation occurs, the particular unfolded structure after
CC the GRR repeat promotes the generation of p50 making it an acceptable
CC substrate for the proteasome. This process is known as cotranslational
CC processing. The processed form is active and the unprocessed form acts
CC as an inhibitor (I kappa B-like), being able to form cytosolic
CC complexes with NF-kappa B, trapping it in the cytoplasm. Complete
CC folding of the region downstream of the GRR repeat precludes
CC 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 BTRC/BTRCP-
CC 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 an
CC alternative to other cysteine modifications, such as S-nitrosylation
CC and S-palmitoylation.
CC -!- DISEASE: Immunodeficiency, common variable, 12, with autoimmunity
CC (CVID12) [MIM:616576]: A primary immunodeficiency characterized by
CC hypogammaglobulinemia and recurrent bacterial infections. About half of
CC patients develop autoimmune features, including cytopenia, as well as
CC generalized inflammation and lymphoproliferation manifest as
CC lymphadenopathy or hepatosplenomegaly. {ECO:0000269|PubMed:26279205}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC 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 ---------------------------------------------------------------------------
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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 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 PDB; 7LEQ; X-ray; 2.24 A; B=355-368.
DR PDB; 7LET; X-ray; 2.40 A; B=355-368.
DR PDB; 7LF4; X-ray; 2.85 A; B/F=355-368.
DR PDB; 7LFC; X-ray; 2.10 A; B=355-368.
DR PDB; 7RG4; X-ray; 2.60 A; B=331-370.
DR PDB; 7RG5; X-ray; 2.15 A; B=331-370.
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 PDBsum; 7LEQ; -.
DR PDBsum; 7LET; -.
DR PDBsum; 7LF4; -.
DR PDBsum; 7LFC; -.
DR PDBsum; 7RG4; -.
DR PDBsum; 7RG5; -.
DR AlphaFoldDB; P19838; -.
DR SMR; P19838; -.
DR BioGRID; 110857; 248.
DR ComplexPortal; CPX-5828; NF-kappaB DNA-binding transcription factor complex, p50/p65.
DR ComplexPortal; CPX-5832; NF-kappaB DNA-binding transcription factor complex, p50/c-Rel.
DR ComplexPortal; CPX-5833; NF-kappaB DNA-binding transcription factor complex, p50/RelB.
DR ComplexPortal; CPX-5837; NF-kappaB transcription regulation complex, p50/p52.
DR ComplexPortal; CPX-5838; NF-kappaB transcription regulation complex, p50/p50.
DR CORUM; P19838; -.
DR DIP; DIP-106N; -.
DR ELM; P19838; -.
DR IntAct; P19838; 497.
DR MINT; P19838; -.
DR STRING; 9606.ENSP00000226574; -.
DR BindingDB; P19838; -.
DR ChEMBL; CHEMBL3251; -.
DR DrugBank; DB05767; Andrographolide.
DR DrugBank; DB05487; Custirsen.
DR DrugBank; DB00843; Donepezil.
DR DrugBank; DB13961; Fish oil.
DR DrugBank; DB13751; Glycyrrhizic acid.
DR DrugBank; DB05212; HE3286.
DR DrugBank; DB05559; NF-kappaB Decoy.
DR DrugBank; DB05464; NOX-700.
DR DrugBank; DB05451; P54.
DR DrugBank; DB01411; Pranlukast.
DR DrugBank; DB00852; Pseudoephedrine.
DR DrugBank; DB14059; SC-236.
DR DrugBank; DB05471; SGN-30.
DR DrugBank; DB01041; Thalidomide.
DR DrugBank; DB08814; Triflusal.
DR DrugCentral; P19838; -.
DR GlyGen; P19838; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P19838; -.
DR MetOSite; P19838; -.
DR PhosphoSitePlus; P19838; -.
DR BioMuta; NFKB1; -.
DR DMDM; 21542418; -.
DR CPTAC; CPTAC-1260; -.
DR CPTAC; CPTAC-1330; -.
DR EPD; P19838; -.
DR jPOST; P19838; -.
DR MassIVE; P19838; -.
DR MaxQB; P19838; -.
DR PaxDb; P19838; -.
DR PeptideAtlas; P19838; -.
DR PRIDE; P19838; -.
DR ProteomicsDB; 53694; -. [P19838-1]
DR ProteomicsDB; 53695; -. [P19838-2]
DR ProteomicsDB; 53696; -. [P19838-3]
DR Antibodypedia; 3415; 2446 antibodies from 51 providers.
DR DNASU; 4790; -.
DR Ensembl; ENST00000226574.9; ENSP00000226574.4; ENSG00000109320.13. [P19838-2]
DR Ensembl; ENST00000394820.8; ENSP00000378297.4; ENSG00000109320.13. [P19838-1]
DR Ensembl; ENST00000505458.5; ENSP00000424790.1; ENSG00000109320.13. [P19838-1]
DR Ensembl; ENST00000600343.5; ENSP00000469340.1; ENSG00000109320.13. [P19838-3]
DR GeneID; 4790; -.
DR KEGG; hsa:4790; -.
DR MANE-Select; ENST00000226574.9; ENSP00000226574.4; NM_003998.4; NP_003989.2. [P19838-2]
DR UCSC; uc011cep.2; human. [P19838-1]
DR CTD; 4790; -.
DR DisGeNET; 4790; -.
DR GeneCards; NFKB1; -.
DR HGNC; HGNC:7794; NFKB1.
DR HPA; ENSG00000109320; Low tissue specificity.
DR MalaCards; NFKB1; -.
DR MIM; 164011; gene.
DR MIM; 616576; phenotype.
DR neXtProt; NX_P19838; -.
DR OpenTargets; ENSG00000109320; -.
DR Orphanet; 1572; Common variable immunodeficiency.
DR PharmGKB; PA248; -.
DR VEuPathDB; HostDB:ENSG00000109320; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000158625; -.
DR HOGENOM; CLU_004343_1_0_1; -.
DR InParanoid; P19838; -.
DR OMA; MTWIPRK; -.
DR OrthoDB; 916931at2759; -.
DR PhylomeDB; P19838; -.
DR TreeFam; TF325632; -.
DR PathwayCommons; P19838; -.
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-dependent IKK and NF-kappa-B activation.
DR Reactome; R-HSA-448706; Interleukin-1 processing.
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-844456; The NLRP3 inflammasome.
DR Reactome; R-HSA-8853884; Transcriptional Regulation by VENTX.
DR Reactome; R-HSA-9020702; Interleukin-1 signaling.
DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
DR Reactome; R-HSA-9609690; HCMV Early Events.
DR Reactome; R-HSA-9660826; Purinergic signaling in leishmaniasis infection.
DR SignaLink; P19838; -.
DR SIGNOR; P19838; -.
DR BioGRID-ORCS; 4790; 23 hits in 1105 CRISPR screens.
DR ChiTaRS; NFKB1; human.
DR EvolutionaryTrace; P19838; -.
DR GeneWiki; NFKB1; -.
DR GenomeRNAi; 4790; -.
DR Pharos; P19838; Tclin.
DR PRO; PR:P19838; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P19838; protein.
DR Bgee; ENSG00000109320; Expressed in endometrium epithelium and 160 other tissues.
DR ExpressionAtlas; P19838; baseline and differential.
DR Genevisible; P19838; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
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:0071159; C:NF-kappaB complex; IPI:ComplexPortal.
DR GO; GO:0035525; C:NF-kappaB p50/p65 complex; IC:ComplexPortal.
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; IEA:Ensembl.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:ARUK-UCL.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IMP:BHF-UCL.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0019899; F:enzyme binding; IPI:ARUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0001223; F:transcription coactivator binding; IPI:ARUK-UCL.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:1904385; P:cellular response to angiotensin; IMP:BHF-UCL.
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:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0098586; P:cellular response to virus; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB.
DR GO; GO:0007254; P:JNK cascade; IEA:Ensembl.
DR GO; GO:0060056; P:mammary gland involution; IEA:Ensembl.
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: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:0032695; P:negative regulation of interleukin-12 production; IEA:Ensembl.
DR GO; GO:0051248; P:negative regulation of protein metabolic process; IC:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0010957; P:negative regulation of vitamin D biosynthetic process; IC:BHF-UCL.
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:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ARUK-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0035994; P:response to muscle stretch; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:UniProtKB.
DR CDD; cd01177; IPT_NFkappaB; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 2.60.40.340; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR002909; IPT_dom.
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; ANK repeat;
KW Apoptosis; Cytoplasm; Direct protein sequencing; DNA-binding;
KW Hydroxylation; Isopeptide bond; Lipoprotein; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; S-nitrosylation; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..968
FT /note="Nuclear factor NF-kappa-B p105 subunit"
FT /id="PRO_0000030310"
FT CHAIN 1..433
FT /note="Nuclear factor NF-kappa-B p50 subunit"
FT /id="PRO_0000030311"
FT DOMAIN 42..367
FT /note="RHD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00265"
FT REPEAT 542..571
FT /note="ANK 1"
FT REPEAT 581..610
FT /note="ANK 2"
FT REPEAT 614..643
FT /note="ANK 3"
FT REPEAT 650..679
FT /note="ANK 4"
FT REPEAT 684..714
FT /note="ANK 5"
FT REPEAT 718..747
FT /note="ANK 6"
FT REPEAT 771..801
FT /note="ANK 7"
FT DOMAIN 805..892
FT /note="Death"
FT REGION 372..394
FT /note="GRR"
FT REGION 425..453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 435..968
FT /note="Interaction with CFLAR"
FT /evidence="ECO:0000269|PubMed:13679070"
FT REGION 650..684
FT /note="Essential for interaction with HIF1AN"
FT /evidence="ECO:0000269|PubMed:17003112"
FT MOTIF 360..365
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 434..453
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 433..434
FT /note="Cleavage (when cotranslationally processed)"
FT MOD_RES 61
FT /note="S-nitrosocysteine; alternate"
FT /evidence="ECO:0000269|PubMed:8710491"
FT MOD_RES 337
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000255"
FT MOD_RES 431
FT /note="N6-acetyllysine; by EP300"
FT /evidence="ECO:0000305|PubMed:11739381"
FT MOD_RES 440
FT /note="N6-acetyllysine; by EP300"
FT /evidence="ECO:0000305|PubMed:11739381"
FT MOD_RES 441
FT /note="N6-acetyllysine; by EP300"
FT /evidence="ECO:0000305|PubMed:11739381"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P25799"
FT MOD_RES 678
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN; partial"
FT /evidence="ECO:0000269|PubMed:17003112"
FT MOD_RES 759
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63369"
FT MOD_RES 892
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 903
FT /note="Phosphoserine; by GSK3-beta; in vitro"
FT /evidence="ECO:0000269|PubMed:12871932,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 907
FT /note="Phosphoserine; by GSK3-beta; in vitro"
FT /evidence="ECO:0000269|PubMed:12871932,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 927
FT /note="Phosphoserine; by IKKB"
FT /evidence="ECO:0000269|PubMed:11297557,
FT ECO:0000269|PubMed:12482991"
FT MOD_RES 932
FT /note="Phosphoserine; by IKKB"
FT /evidence="ECO:0000269|PubMed:12482991"
FT MOD_RES 937
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 943
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P25799"
FT LIPID 61
FT /note="S-(15-deoxy-Delta12,14-prostaglandin J2-9-
FT yl)cysteine; alternate"
FT /evidence="ECO:0000269|PubMed:11466314"
FT CROSSLNK 325
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..180
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042869"
FT VAR_SEQ 39
FT /note="T -> TA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:2203531"
FT /id="VSP_021025"
FT VAR_SEQ 181..189
FT /note="EGGGDRQLG -> MNGLCCMAL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042870"
FT VARIANT 489
FT /note="T -> I (in dbSNP:rs4648065)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_016268"
FT VARIANT 506
FT /note="M -> V (in dbSNP:rs4648072)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_016269"
FT VARIANT 566
FT /note="T -> I (in dbSNP:rs4648085)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_016270"
FT VARIANT 578
FT /note="R -> K (in dbSNP:rs4648086)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_016271"
FT VARIANT 711
FT /note="H -> Q (in dbSNP:rs4648099)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_016272"
FT VARIANT 901
FT /note="A -> T (in dbSNP:rs4648118)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_016273"
FT MUTAGEN 61
FT /note="C->S: Suppresses S-nitrosylation-induced inhibition
FT of DNA-binding activity. Loss of S-(15-deoxy-Delta12,14-
FT prostaglandin J2-9-yl)cysteine-induced inhibition of DNA-
FT binding activity."
FT /evidence="ECO:0000269|PubMed:11466314,
FT ECO:0000269|PubMed:8710491"
FT MUTAGEN 678
FT /note="N->A: Fails to promote HIF1AN-dependent 2-
FT oxoglutarate decarboxylation."
FT /evidence="ECO:0000269|PubMed:17003112"
FT MUTAGEN 903
FT /note="S->A: Prevents p105 proteolysis in response to TNF-
FT alpha."
FT /evidence="ECO:0000269|PubMed:12871932"
FT MUTAGEN 907
FT /note="S->A: Prevents p105 proteolysis in response to TNF-
FT alpha."
FT /evidence="ECO:0000269|PubMed:12871932"
FT MUTAGEN 921
FT /note="S->A: Decrease in stimuli-induced phosphorylation.
FT Loss of phosphorylation; when associated with A-923 and A-
FT 932."
FT /evidence="ECO:0000269|PubMed:10469655"
FT MUTAGEN 923
FT /note="S->A: Decrease in stimuli-induced phosphorylation.
FT Loss of phosphorylation; when associated with A-921 and A-
FT 932."
FT /evidence="ECO:0000269|PubMed:10469655"
FT MUTAGEN 932
FT /note="S->A: Decrease in stimuli-induced phosphorylation.
FT Loss of phosphorylation; when associated with A-921 and A-
FT 923."
FT /evidence="ECO:0000269|PubMed:10469655"
FT CONFLICT 243
FT /note="K -> SE (in Ref. 4; CAB94757)"
FT /evidence="ECO:0000305"
FT CONFLICT 361
FT /note="R -> G (in Ref. 7; CAH18336)"
FT /evidence="ECO:0000305"
FT CONFLICT 551..552
FT /note="II -> SS (in Ref. 4; CAB94757)"
FT /evidence="ECO:0000305"
FT CONFLICT 573
FT /note="D -> G (in Ref. 6; BAF84139)"
FT /evidence="ECO:0000305"
FT CONFLICT 726
FT /note="A -> V (in Ref. 4; CAB94757)"
FT /evidence="ECO:0000305"
FT CONFLICT 825
FT /note="I -> T (in Ref. 7; CAH18336)"
FT /evidence="ECO:0000305"
FT CONFLICT 869
FT /note="V -> I (in Ref. 4; CAB94757)"
FT /evidence="ECO:0000305"
FT CONFLICT 927
FT /note="S -> T (in Ref. 1; AAA36361, 3; AAA36360 and 4;
FT CAB94757)"
FT /evidence="ECO:0000305"
FT STRAND 43..48
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:1SVC"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 94..100
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 110..115
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 122..126
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 138..143
FT /evidence="ECO:0007829|PDB:1SVC"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:1SVC"
FT HELIX 149..163
FT /evidence="ECO:0007829|PDB:1SVC"
FT HELIX 167..170
FT /evidence="ECO:0007829|PDB:1SVC"
FT HELIX 173..178
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:2O61"
FT TURN 184..187
FT /evidence="ECO:0007829|PDB:1SVC"
FT HELIX 190..204
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 211..221
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 234..240
FT /evidence="ECO:0007829|PDB:1SVC"
FT HELIX 245..247
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 252..256
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 258..261
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 267..274
FT /evidence="ECO:0007829|PDB:1SVC"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 281..288
FT /evidence="ECO:0007829|PDB:1SVC"
FT TURN 289..291
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 292..297
FT /evidence="ECO:0007829|PDB:1SVC"
FT HELIX 302..304
FT /evidence="ECO:0007829|PDB:1SVC"
FT TURN 307..309
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 310..314
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 319..322
FT /evidence="ECO:0007829|PDB:2O61"
FT STRAND 327..334
FT /evidence="ECO:0007829|PDB:1SVC"
FT TURN 336..338
FT /evidence="ECO:0007829|PDB:1SVC"
FT STRAND 345..350
FT /evidence="ECO:0007829|PDB:1SVC"
FT HELIX 813..823
FT /evidence="ECO:0007829|PDB:2DBF"
FT HELIX 832..839
FT /evidence="ECO:0007829|PDB:2DBF"
FT HELIX 842..844
FT /evidence="ECO:0007829|PDB:2DBF"
FT HELIX 845..850
FT /evidence="ECO:0007829|PDB:2DBF"
FT HELIX 854..864
FT /evidence="ECO:0007829|PDB:2DBF"
FT HELIX 869..879
FT /evidence="ECO:0007829|PDB:2DBF"
FT HELIX 883..892
FT /evidence="ECO:0007829|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
