NFKB2_HUMAN
ID NFKB2_HUMAN Reviewed; 900 AA.
AC Q00653; A8K9D9; D3DR83; Q04860; Q9BU75; Q9H471; Q9H472;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 4.
DT 03-AUG-2022, entry version 250.
DE RecName: Full=Nuclear factor NF-kappa-B p100 subunit;
DE AltName: Full=DNA-binding factor KBF2;
DE AltName: Full=H2TF1;
DE AltName: Full=Lymphocyte translocation chromosome 10 protein;
DE AltName: Full=Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2;
DE AltName: Full=Oncogene Lyt-10;
DE Short=Lyt10;
DE Contains:
DE RecName: Full=Nuclear factor NF-kappa-B p52 subunit;
GN Name=NFKB2; Synonyms=LYT10;
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] (ISOFORMS 3 AND 4).
RC TISSUE=Leukemia;
RX PubMed=1876189; DOI=10.1038/352733a0;
RA Schmid R.M., Perkins N.D., Duckett C.S., Andrews P.C., Nabel G.J.;
RT "Cloning of an NF-kappa B subunit which stimulates HIV transcription in
RT synergy with p65.";
RL Nature 352:733-736(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1531086; DOI=10.1128/mcb.12.2.685-695.1992;
RA Bours V., Burd P.R., Brown K., Villalobos J., Park S., Ryseck R.P.,
RA Bravo R., Kelly K., Siebenlist U.;
RT "A novel mitogen-inducible gene product related to p50/p105-NF-kappa B
RT participates in transactivation through a kappa B site.";
RL Mol. Cell. Biol. 12:685-695(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION, AND P80HT
RP GENERATION.
RX PubMed=8036016;
RA Thakur S., Lin H.C., Tseng W.T., Kumar S., Bravo R., Foss F., Gelinas C.,
RA Rabson A.B.;
RT "Rearrangement and altered expression of the NFKB-2 gene in human cutaneous
RT T-lymphoma cells.";
RL Oncogene 9:2335-2344(1994).
RN [4]
RP SEQUENCE REVISION.
RA Rabson A.B.;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Thymus;
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 [GENOMIC DNA], AND VARIANTS LYS-14; ARG-351 AND
RP ARG-452.
RG NIEHS SNPs program;
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Lymph;
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 [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-220.
RX PubMed=7969113; DOI=10.1128/mcb.14.12.7695-7703.1994;
RA Liptay S., Schmid R.M., Nabel E.G., Nabel G.J.;
RT "Transcriptional regulation of NF-kappa B2: evidence for kappa B-mediated
RT positive and negative autoregulation.";
RL Mol. Cell. Biol. 14:7695-7703(1994).
RN [12]
RP PROTEIN SEQUENCE OF 459-470; 580-597 AND 636-647 (ISOFORM 1).
RX PubMed=8360178; DOI=10.1016/s0021-9258(17)46709-3;
RA Potter D.A., Larson C.J., Eckes P., Schmid R.M., Nabel G.J., Verdine G.L.,
RA Sharp P.A.;
RT "Purification of the major histocompatibility complex class I transcription
RT factor H2TF1. The full-length product of the nfkb2 gene.";
RL J. Biol. Chem. 268:18882-18890(1993).
RN [13]
RP IDENTIFICATION IN A COMPLEX WITH BCL3.
RX PubMed=8453667; DOI=10.1016/0092-8674(93)90401-b;
RA Bours V., Franzoso G., Azarenko V., Park S., Kanno T., Brown K.,
RA Siebenlist U.;
RT "The oncoprotein Bcl-3 directly transactivates through kappa B motifs via
RT association with DNA-binding p50B homodimers.";
RL Cell 72:729-739(1993).
RN [14]
RP FUNCTION, AND IDENTIFICATION IN THE NF-KAPPA-B RELB-P52 COMPLEX.
RX PubMed=7925301; DOI=10.1002/j.1460-2075.1994.tb06782.x;
RA Dobrzanski P., Ryseck R.P., Bravo R.;
RT "Differential interactions of Rel-NF-kappa B complexes with I kappa B alpha
RT determine pools of constitutive and inducible NF-kappa B activity.";
RL EMBO J. 13:4608-4616(1994).
RN [15]
RP IDENTIFICATION IN THE NF-KAPPA-B P52-C-REL COMPLEX, AND IDENTIFICATION IN
RP THE NF-KAPPA-B P65-P52 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 [16]
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 [17]
RP COTRANSLATIONAL FOLDING/PROCESSING OF P100, AND GENERATION OF P52/P100.
RX PubMed=10597218; DOI=10.1038/sj.onc.1203022;
RA Heusch M., Lin L., Geleziunas R., Greene W.C.;
RT "The generation of nfkb2 p52: mechanism and efficiency.";
RL Oncogene 18:6201-6208(1999).
RN [18]
RP PHOSPHORYLATION AT SER-713; SER-715 AND SER-717, MUTAGENESIS, DIMERIZATION,
RP AND PROTEOLYTIC PROCESSING OF P100.
RX PubMed=8887665; DOI=10.1128/mcb.16.11.6363;
RA Betts J.C., Nabel G.J.;
RT "Differential regulation of NF-kappaB2(p100) processing and control by
RT amino-terminal sequences.";
RL Mol. Cell. Biol. 16:6363-6371(1996).
RN [19]
RP PHOSPHORYLATION AT SER-866 AND SER-870, MUTAGENESIS OF SER-866 AND SER-870,
RP AND PROTEOLYTIC PROCESSING OF P100.
RX PubMed=11239468; DOI=10.1016/s1097-2765(01)00187-3;
RA Xiao G., Harhaj E.W., Sun S.-C.;
RT "NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100.";
RL Mol. Cell 7:401-409(2001).
RN [20]
RP CHROMOSOMAL TRANSLOCATION WITH IGHA1.
RX PubMed=1760839; DOI=10.1016/0092-8674(91)90285-7;
RA Neri A., Chang C.C., Lombardi L., Salina M., Corradini P., Maiolo A.T.,
RA Chaganti R.S., Dalla-Favera R.;
RT "B cell lymphoma-associated chromosomal translocation involves candidate
RT oncogene lyt-10, homologous to NF-kappa B p50.";
RL Cell 67:1075-1087(1991).
RN [21]
RP CHROMOSOMAL ABERRATIONS, AND GENERATION OF LB40 AND EB308.
RX PubMed=7949142;
RA Migliazza A., Lombardi L., Rocchi M., Trecca D., Chang C.-C., Antonacci R.,
RA Fracchiolla N.S., Ciana P., Maiolo A.T., Neri A.;
RT "Heterogeneous chromosomal aberrations generate 3' truncations of the
RT NFKB2/lyt-10 gene in lymphoid malignancies.";
RL Blood 84:3850-3860(1994).
RN [22]
RP CHARACTERIZATION OF THE TWO PROMOTER REGIONS.
RX PubMed=7541912; DOI=10.1093/nar/23.12.2328;
RA Lombardi L., Ciana P., Cappellini C., Trecca D., Guerrini L., Migliazza A.,
RA Maiolo A.T., Neri A.;
RT "Structural and functional characterization of the promoter regions of the
RT NFKB2 gene.";
RL Nucleic Acids Res. 23:2328-2336(1995).
RN [23]
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 [24]
RP UBIQUITINATION AT LYS-855.
RX PubMed=14676825; DOI=10.1038/sj.onc.1207366;
RA Amir R.E., Haecker H., Karin M., Ciechanover A.;
RT "Mechanism of processing of the NF-kappa B2 p100 precursor: identification
RT of the specific polyubiquitin chain-anchoring lysine residue and analysis
RT of the role of NEDD8-modification on the SCF(beta-TrCP) ubiquitin ligase.";
RL Oncogene 23:2540-2547(2004).
RN [25]
RP IDENTIFICATION IN THE NF-KAPPA-B P65-P52 COMPLEX.
RX PubMed=16477006; DOI=10.1073/pnas.0511096103;
RA Song Y.J., Jen K.Y., Soni V., Kieff E., Cahir-McFarland E.;
RT "IL-1 receptor-associated kinase 1 is critical for latent membrane protein
RT 1-induced p65/RelA serine 536 phosphorylation and NF-kappaB activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:2689-2694(2006).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-429, AND IDENTIFICATION BY
RP 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 [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [28]
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 [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; SER-161 AND SER-812, 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 [30]
RP IDENTIFICATION 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., 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 [31]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 37-327.
RX PubMed=9384586; DOI=10.1093/emboj/16.23.7078;
RA Cramer P., Larson C.J., Verdine G.L., Mueller C.W.;
RT "Structure of the human NF-kappaB p52 homodimer-DNA complex at 2.1-A
RT resolution.";
RL EMBO J. 16:7078-7090(1997).
RN [32]
RP STRUCTURE BY NMR OF 764-859.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the death domain of nuclear factor NF-kappa-B
RT p100.";
RL Submitted (DEC-2006) to the PDB data bank.
RN [33]
RP INVOLVEMENT IN CVID10.
RX PubMed=24140114; DOI=10.1016/j.ajhg.2013.09.009;
RA Chen K., Coonrod E.M., Kumanovics A., Franks Z.F., Durtschi J.D.,
RA Margraf R.L., Wu W., Heikal N.M., Augustine N.H., Ridge P.G., Hill H.R.,
RA Jorde L.B., Weyrich A.S., Zimmerman G.A., Gundlapalli A.V., Bohnsack J.F.,
RA Voelkerding K.V.;
RT "Germline mutations in NFKB2 implicate the noncanonical NF-kappaB pathway
RT in the pathogenesis of common variable immunodeficiency.";
RL Am. J. Hum. Genet. 93:812-824(2013).
RN [34]
RP VARIANTS CVID10 GLY-865 AND VAL-867.
RX PubMed=25524009; DOI=10.1186/s12881-014-0139-9;
RA Brue T., Quentien M.H., Khetchoumian K., Bensa M., Capo-Chichi J.M.,
RA Delemer B., Balsalobre A., Nassif C., Papadimitriou D.T., Pagnier A.,
RA Hasselmann C., Patry L., Schwartzentruber J., Souchon P.F., Takayasu S.,
RA Enjalbert A., Van Vliet G., Majewski J., Drouin J., Samuels M.E.;
RT "Mutations in NFKB2 and potential genetic heterogeneity in patients with
RT DAVID syndrome, having variable endocrine and immune deficiencies.";
RL BMC Med. Genet. 15:139-139(2014).
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. The dimers bind at kappa-B sites in the DNA of their target
CC genes and the individual dimers have distinct preferences for different
CC kappa-B 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 by
CC various mechanisms of post-translational modification and subcellular
CC compartmentalization as well as by interactions with other cofactors or
CC corepressors. NF-kappa-B complexes are held in the cytoplasm in an
CC inactive state complexed with members of the NF-kappa-B inhibitor (I-
CC kappa-B) family. In a conventional activation pathway, I-kappa-B is
CC phosphorylated by I-kappa-B kinases (IKKs) in response to different
CC activators, subsequently degraded thus liberating the active NF-kappa-B
CC complex which translocates to the nucleus. In a non-canonical
CC activation pathway, the MAP3K14-activated CHUK/IKKA homodimer
CC phosphorylates NFKB2/p100 associated with RelB, inducing its
CC proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B
CC RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a
CC transcriptional activator. The NF-kappa-B p52-p52 homodimer is a
CC transcriptional repressor. NFKB2 appears to have dual functions such as
CC cytoplasmic retention of attached NF-kappa-B proteins by p100 and
CC generation of p52 by a cotranslational processing. The proteasome-
CC mediated process ensures the production of both p52 and p100 and
CC preserves their independent function. p52 binds to the kappa-B
CC consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of
CC genes involved in immune response and acute phase reactions. p52 and
CC p100 are respectively the minor and major form; the processing of p100
CC being relatively poor. Isoform p49 is a subunit of the NF-kappa-B
CC protein complex, which stimulates the HIV enhancer in synergy with p65.
CC In concert with RELB, regulates the circadian clock by repressing the
CC transcriptional activator activity of the CLOCK-ARNTL/BMAL1
CC heterodimer. {ECO:0000269|PubMed:7925301}.
CC -!- SUBUNIT: Component of the NF-kappa-B RelB-p52 complex. Homodimer;
CC component of the NF-kappa-B p52-p52 complex. Component of the NF-kappa-
CC B p65-p52 complex. Component of the NF-kappa-B p52-c-Rel complex.
CC NFKB2/p52 interacts with NFKBIE. Component of a complex consisting of
CC the NF-kappa-B p50-p50 homodimer and BCL3. Directly interacts with
CC MEN1. {ECO:0000269|PubMed:11526476, ECO:0000269|PubMed:16477006,
CC ECO:0000269|PubMed:7925301, ECO:0000269|PubMed:8152812,
CC ECO:0000269|PubMed:8453667, ECO:0000269|PubMed:9315679}.
CC -!- INTERACTION:
CC Q00653; P41279: MAP3K8; NbExp=2; IntAct=EBI-307326, EBI-354900;
CC Q00653; P19838: NFKB1; NbExp=8; IntAct=EBI-307326, EBI-300010;
CC Q00653; P25963: NFKBIA; NbExp=2; IntAct=EBI-307326, EBI-307386;
CC Q00653; Q04864: REL; NbExp=2; IntAct=EBI-307326, EBI-307352;
CC Q00653; Q01201: RELB; NbExp=2; IntAct=EBI-307326, EBI-357837;
CC Q00653; P63165: SUMO1; NbExp=2; IntAct=EBI-307326, EBI-80140;
CC PRO_0000030322; O00255-2: MEN1; NbExp=3; IntAct=EBI-9869360, EBI-9869387;
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; Synonyms=p100;
CC IsoId=Q00653-1; Sequence=Displayed;
CC Name=3; Synonyms=p49;
CC IsoId=Q00653-3; Sequence=VSP_040082, VSP_040083;
CC Name=4;
CC IsoId=Q00653-4; Sequence=VSP_040084;
CC -!- DOMAIN: The C-terminus of p100 might be involved in cytoplasmic
CC retention, inhibition of DNA-binding by p52 homodimers, and/or
CC transcription activation. {ECO:0000250}.
CC -!- DOMAIN: The glycine-rich region (GRR) appears to be a critical element
CC in the generation of p52.
CC -!- PTM: While translation occurs, the particular unfolded structure after
CC the GRR repeat promotes the generation of p52 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.
CC -!- PTM: Subsequent to MAP3K14-dependent serine phosphorylation, p100
CC polyubiquitination occurs then triggering its proteasome-dependent
CC processing. {ECO:0000269|PubMed:11239468, ECO:0000269|PubMed:14676825,
CC ECO:0000269|PubMed:8887665}.
CC -!- PTM: Constitutive processing is tightly suppressed by its C-terminal
CC processing inhibitory domain, named PID, which contains the death
CC domain.
CC -!- DISEASE: Note=A chromosomal aberration involving NFKB2 is found in a
CC case of B-cell non Hodgkin lymphoma (B-NHL). Translocation
CC t(10;14)(q24;q32) with IGHA1. The resulting oncogene is also called
CC Lyt-10C alpha variant.
CC -!- DISEASE: Note=A chromosomal aberration involving NFKB2 is found in a
CC cutaneous T-cell leukemia (C-TCL) cell line. This rearrangement
CC produces the p80HT gene which codes for a truncated 80 kDa protein
CC (p80HT).
CC -!- DISEASE: Note=In B-cell leukemia (B-CLL) cell line, LB40 and EB308, can
CC be found after heterogeneous chromosomal aberrations, such as internal
CC deletions.
CC -!- DISEASE: Immunodeficiency, common variable, 10 (CVID10) [MIM:615577]: A
CC primary immunodeficiency characterized by childhood-onset of recurrent
CC infections, hypogammaglobulinemia, and decreased numbers of memory and
CC marginal zone B-cells. Some patients may develop autoimmune features
CC and have circulating autoantibodies. An unusual feature is central
CC adrenal insufficiency. {ECO:0000269|PubMed:24140114,
CC ECO:0000269|PubMed:25524009}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA43715.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- SEQUENCE CAUTION: [Isoform 3]:
CC Sequence=CAA43716.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NFKB2ID362.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/nfkb2/";
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DR EMBL; X61498; CAA43715.1; ALT_FRAME; mRNA.
DR EMBL; X61499; CAA43716.1; ALT_FRAME; mRNA.
DR EMBL; S76638; AAB21124.1; -; mRNA.
DR EMBL; U09609; AAA21462.2; -; mRNA.
DR EMBL; BT009769; AAP88771.1; -; mRNA.
DR EMBL; AK292654; BAF85343.1; -; mRNA.
DR EMBL; AY865619; AAW56071.1; -; Genomic_DNA.
DR EMBL; AL121928; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49700.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49701.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49702.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49704.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49706.1; -; Genomic_DNA.
DR EMBL; BC002844; AAH02844.1; -; mRNA.
DR EMBL; U20816; AAA68171.1; -; Genomic_DNA.
DR CCDS; CCDS41564.1; -. [Q00653-1]
DR CCDS; CCDS41565.1; -. [Q00653-4]
DR PIR; A42024; A42024.
DR PIR; A57034; A57034.
DR PIR; I38609; I38609.
DR PIR; S17233; S17233.
DR RefSeq; NP_001070962.1; NM_001077494.3. [Q00653-1]
DR RefSeq; NP_001248332.1; NM_001261403.2. [Q00653-4]
DR RefSeq; NP_001275653.1; NM_001288724.1. [Q00653-4]
DR RefSeq; NP_001309863.1; NM_001322934.1. [Q00653-1]
DR RefSeq; NP_001309864.1; NM_001322935.1.
DR RefSeq; NP_002493.3; NM_002502.5. [Q00653-4]
DR PDB; 1A3Q; X-ray; 2.10 A; A/B=37-327.
DR PDB; 2D96; NMR; -; A=766-859.
DR PDB; 3DO7; X-ray; 3.05 A; B=37-329.
DR PDB; 4OT9; X-ray; 3.35 A; A=407-765.
DR PDB; 5ZMC; X-ray; 2.99 A; A=35-329.
DR PDB; 7CLI; X-ray; 3.00 A; A/B=1-398.
DR PDB; 7VUP; X-ray; 3.40 A; A/B=1-398.
DR PDB; 7VUQ; X-ray; 3.10 A; A/B=1-398.
DR PDB; 7W7L; X-ray; 3.00 A; A/B=1-327.
DR PDBsum; 1A3Q; -.
DR PDBsum; 2D96; -.
DR PDBsum; 3DO7; -.
DR PDBsum; 4OT9; -.
DR PDBsum; 5ZMC; -.
DR PDBsum; 7CLI; -.
DR PDBsum; 7VUP; -.
DR PDBsum; 7VUQ; -.
DR PDBsum; 7W7L; -.
DR AlphaFoldDB; Q00653; -.
DR SMR; Q00653; -.
DR BioGRID; 110858; 114.
DR ComplexPortal; CPX-5829; NF-kappaB DNA-binding transcription factor complex, p52/p65.
DR ComplexPortal; CPX-5830; NF-kappaB DNA-binding transcription factor complex, p52/c-Rel.
DR ComplexPortal; CPX-5831; NF-kappaB DNA-binding transcription factor complex, p52/RelB.
DR ComplexPortal; CPX-5837; NF-kappaB transcription regulation complex, p50/p52.
DR ComplexPortal; CPX-5839; NF-kappaB transcription regulation complex, p52/p52.
DR CORUM; Q00653; -.
DR DIP; DIP-24239N; -.
DR DIP; DIP-27535N; -.
DR IntAct; Q00653; 48.
DR MINT; Q00653; -.
DR STRING; 9606.ENSP00000358983; -.
DR ChEMBL; CHEMBL3003; -.
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; DB14059; SC-236.
DR DrugBank; DB05471; SGN-30.
DR DrugCentral; Q00653; -.
DR CarbonylDB; Q00653; -.
DR GlyGen; Q00653; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q00653; -.
DR PhosphoSitePlus; Q00653; -.
DR SwissPalm; Q00653; -.
DR BioMuta; NFKB2; -.
DR DMDM; 116242678; -.
DR CPTAC; CPTAC-721; -.
DR EPD; Q00653; -.
DR jPOST; Q00653; -.
DR MassIVE; Q00653; -.
DR MaxQB; Q00653; -.
DR PaxDb; Q00653; -.
DR PeptideAtlas; Q00653; -.
DR PRIDE; Q00653; -.
DR ProteomicsDB; 57866; -. [Q00653-1]
DR ProteomicsDB; 57867; -. [Q00653-3]
DR ProteomicsDB; 57868; -. [Q00653-4]
DR ABCD; Q00653; 1 sequenced antibody.
DR Antibodypedia; 1322; 1027 antibodies from 47 providers.
DR CPTC; Q00653; 1 antibody.
DR DNASU; 4791; -.
DR Ensembl; ENST00000189444.11; ENSP00000189444.6; ENSG00000077150.20. [Q00653-4]
DR Ensembl; ENST00000369966.8; ENSP00000358983.3; ENSG00000077150.20. [Q00653-1]
DR Ensembl; ENST00000428099.6; ENSP00000410256.1; ENSG00000077150.20. [Q00653-4]
DR Ensembl; ENST00000652277.1; ENSP00000498308.1; ENSG00000077150.20. [Q00653-4]
DR Ensembl; ENST00000661543.1; ENSP00000499294.1; ENSG00000077150.20. [Q00653-1]
DR GeneID; 4791; -.
DR KEGG; hsa:4791; -.
DR MANE-Select; ENST00000661543.1; ENSP00000499294.1; NM_001322934.2; NP_001309863.1.
DR UCSC; uc001kva.4; human. [Q00653-1]
DR CTD; 4791; -.
DR DisGeNET; 4791; -.
DR GeneCards; NFKB2; -.
DR HGNC; HGNC:7795; NFKB2.
DR HPA; ENSG00000077150; Low tissue specificity.
DR MalaCards; NFKB2; -.
DR MIM; 164012; gene.
DR MIM; 615577; phenotype.
DR neXtProt; NX_Q00653; -.
DR OpenTargets; ENSG00000077150; -.
DR Orphanet; 1572; Common variable immunodeficiency.
DR Orphanet; 293978; Deficiency in anterior pituitary function-variable immunodeficiency syndrome.
DR PharmGKB; PA31600; -.
DR VEuPathDB; HostDB:ENSG00000077150; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000160968; -.
DR HOGENOM; CLU_004343_1_1_1; -.
DR InParanoid; Q00653; -.
DR OMA; EQMAHII; -.
DR OrthoDB; 916931at2759; -.
DR PhylomeDB; Q00653; -.
DR TreeFam; TF325632; -.
DR PathwayCommons; Q00653; -.
DR Reactome; R-HSA-1810476; RIP-mediated NFkB activation via ZBP1.
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-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-HSA-448706; Interleukin-1 processing.
DR Reactome; R-HSA-4755510; SUMOylation of immune response proteins.
DR Reactome; R-HSA-5603029; IkBA variant leads to EDA-ID.
DR Reactome; R-HSA-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
DR Reactome; R-HSA-5676590; NIK-->noncanonical NF-kB signaling.
DR Reactome; R-HSA-844456; The NLRP3 inflammasome.
DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
DR Reactome; R-HSA-9660826; Purinergic signaling in leishmaniasis infection.
DR SignaLink; Q00653; -.
DR SIGNOR; Q00653; -.
DR BioGRID-ORCS; 4791; 39 hits in 1106 CRISPR screens.
DR ChiTaRS; NFKB2; human.
DR EvolutionaryTrace; Q00653; -.
DR GeneWiki; NFKB2; -.
DR GenomeRNAi; 4791; -.
DR Pharos; Q00653; Tchem.
DR PRO; PR:Q00653; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q00653; protein.
DR Bgee; ENSG00000077150; Expressed in granulocyte and 141 other tissues.
DR ExpressionAtlas; Q00653; baseline and differential.
DR Genevisible; Q00653; HS.
DR GO; GO:0033257; C:Bcl3/NF-kappaB2 complex; IDA:UniProtKB.
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:0071159; C:NF-kappaB complex; IPI:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0002268; P:follicular dendritic cell differentiation; IEA:Ensembl.
DR GO; GO:0002467; P:germinal center formation; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IC:ComplexPortal.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0048536; P:spleen development; IEA:Ensembl.
DR CDD; cd01177; IPT_NFkappaB; 1.
DR DisProt; DP03039; -.
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; IPR000451; NFkB/Dor.
DR InterPro; IPR030497; NFkB_p100.
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:SF21; PTHR24169:SF21; 1.
DR Pfam; PF12796; Ank_2; 2.
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; Activator; Alternative splicing; ANK repeat;
KW Biological rhythms; Chromosomal rearrangement; Cytoplasm;
KW Direct protein sequencing; Disease variant; DNA-binding; Isopeptide bond;
KW Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome; Repeat;
KW Repressor; Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..900
FT /note="Nuclear factor NF-kappa-B p100 subunit"
FT /id="PRO_0000030321"
FT CHAIN 1..454
FT /note="Nuclear factor NF-kappa-B p52 subunit"
FT /id="PRO_0000030322"
FT DOMAIN 38..343
FT /note="RHD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00265"
FT REPEAT 487..519
FT /note="ANK 1"
FT REPEAT 526..555
FT /note="ANK 2"
FT REPEAT 559..591
FT /note="ANK 3"
FT REPEAT 599..628
FT /note="ANK 4"
FT REPEAT 633..663
FT /note="ANK 5"
FT REPEAT 667..696
FT /note="ANK 6"
FT REPEAT 729..758
FT /note="ANK 7"
FT DOMAIN 764..851
FT /note="Death"
FT REGION 346..377
FT /note="GRR"
FT REGION 404..435
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 698..734
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 849..900
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 337..341
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 715..729
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 454..455
FT /note="Cleavage (when cotranslationally processed)"
FT SITE 490..491
FT /note="Breakpoint for translocation to form NFKB2-IGHA1
FT oncogene"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 429
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 713
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:8887665"
FT MOD_RES 715
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:8887665"
FT MOD_RES 717
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:8887665"
FT MOD_RES 812
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 866
FT /note="Phosphoserine; by MAP3K14"
FT /evidence="ECO:0000269|PubMed:11239468"
FT MOD_RES 870
FT /note="Phosphoserine; by MAP3K14"
FT /evidence="ECO:0000269|PubMed:11239468"
FT CROSSLNK 855
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:14676825"
FT VAR_SEQ 374..428
FT /note="GSLGFFPSSLAYSPYQSGAGPMGCYPGGGGGAQMAATVPSRDSGEEAAEPSA
FT PSR -> EGVLMEGGVKVREAVEEKNLGEAGRGLHACNPALWEAKAGRLPEIRSSRPAW
FT PTA (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:1876189"
FT /id="VSP_040082"
FT VAR_SEQ 429..900
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:1876189"
FT /id="VSP_040083"
FT VAR_SEQ 860
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:1876189,
FT ECO:0000303|Ref.5"
FT /id="VSP_040084"
FT VARIANT 14
FT /note="E -> K (in dbSNP:rs45581936)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_022223"
FT VARIANT 351
FT /note="G -> R (in dbSNP:rs45580031)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_022224"
FT VARIANT 392
FT /note="A -> G (in dbSNP:rs11574848)"
FT /id="VAR_051781"
FT VARIANT 452
FT /note="G -> R (in dbSNP:rs45471103)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_022225"
FT VARIANT 618..900
FT /note="Missing (in truncated form EB308)"
FT /id="VAR_018452"
FT VARIANT 667..669
FT /note="AGN -> SAS (in truncated form p80HT)"
FT /id="VAR_006909"
FT VARIANT 670..900
FT /note="Missing (in truncated form p80HT)"
FT /id="VAR_006910"
FT VARIANT 703..900
FT /note="Missing (in truncated form LB40)"
FT /id="VAR_018453"
FT VARIANT 865
FT /note="D -> G (in CVID10; unknown pathological
FT significance; de novo mutation; dbSNP:rs727502787)"
FT /evidence="ECO:0000269|PubMed:25524009"
FT /id="VAR_074035"
FT VARIANT 867
FT /note="A -> V (in CVID10; unknown pathological
FT significance; de novo mutation; dbSNP:rs727502788)"
FT /evidence="ECO:0000269|PubMed:25524009"
FT /id="VAR_074036"
FT MUTAGEN 247..249
FT /note="YLL->AAA: Two-fold reduction in heterodimerization
FT with RelA."
FT /evidence="ECO:0000269|PubMed:8887665"
FT MUTAGEN 399
FT /note="P->A: No change in cleavage rate or products."
FT /evidence="ECO:0000269|PubMed:8887665"
FT MUTAGEN 404
FT /note="G->A: No change in cleavage rate or products."
FT /evidence="ECO:0000269|PubMed:8887665"
FT MUTAGEN 405
FT /note="A->P: No change in cleavage rate or products."
FT /evidence="ECO:0000269|PubMed:8887665"
FT MUTAGEN 406
FT /note="Q->N: No change in cleavage rate or products."
FT /evidence="ECO:0000269|PubMed:8887665"
FT MUTAGEN 713
FT /note="S->G: Loss of phosphorylation; when associated with
FT A-715 and A-717."
FT /evidence="ECO:0000269|PubMed:8887665"
FT MUTAGEN 715
FT /note="S->A: Loss of phosphorylation; when associated with
FT G-713 and A-717."
FT /evidence="ECO:0000269|PubMed:8887665"
FT MUTAGEN 717
FT /note="S->A: Loss of phosphorylation; when associated with
FT G-713 and A-715."
FT /evidence="ECO:0000269|PubMed:8887665"
FT MUTAGEN 866
FT /note="S->A: Decrease in MAP3K14-induced phosphorylation;
FT no inducible processing occurs; when associated with A-
FT 869."
FT /evidence="ECO:0000269|PubMed:11239468"
FT MUTAGEN 870
FT /note="S->A: Decrease in MAP3K14-induced phosphorylation;
FT no inducible processing occurs; when associated with A-
FT 865."
FT /evidence="ECO:0000269|PubMed:11239468"
FT CONFLICT 144
FT /note="K -> E (in Ref. 2; AAB21124)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="I -> T (in Ref. 1; CAA43715/CAA43716 and 11;
FT AAA68171)"
FT /evidence="ECO:0000305"
FT CONFLICT 396
FT /note="G -> R (in Ref. 1; CAA43715)"
FT /evidence="ECO:0000305"
FT CONFLICT 433..434
FT /note="EP -> DA (in Ref. 2; AAB21124)"
FT /evidence="ECO:0000305"
FT CONFLICT 459
FT /note="R -> K (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 465
FT /note="G -> C (in Ref. 1; CAA43715)"
FT /evidence="ECO:0000305"
FT CONFLICT 470
FT /note="A -> R (in Ref. 1; CAA43715 and 2; AAB21124)"
FT /evidence="ECO:0000305"
FT CONFLICT 741
FT /note="K -> L (in Ref. 1; CAA43715)"
FT /evidence="ECO:0000305"
FT CONFLICT 860
FT /note="A -> T (in Ref. 2; AAB21124)"
FT /evidence="ECO:0000305"
FT CONFLICT 876
FT /note="E -> K (in Ref. 2; AAB21124)"
FT /evidence="ECO:0000305"
FT CONFLICT 891
FT /note="C -> S (in Ref. 1; CAA43715)"
FT /evidence="ECO:0000305"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:7W7L"
FT STRAND 39..44
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:1A3Q"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:7W7L"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 87..96
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 106..111
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:7W7L"
FT STRAND 120..124
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 136..140
FT /evidence="ECO:0007829|PDB:1A3Q"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:1A3Q"
FT HELIX 146..158
FT /evidence="ECO:0007829|PDB:1A3Q"
FT TURN 159..161
FT /evidence="ECO:0007829|PDB:1A3Q"
FT HELIX 168..182
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 189..198
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:7CLI"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:3DO7"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:3DO7"
FT TURN 223..225
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 230..234
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 236..239
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:3DO7"
FT STRAND 245..252
FT /evidence="ECO:0007829|PDB:1A3Q"
FT TURN 255..257
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 258..264
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 270..273
FT /evidence="ECO:0007829|PDB:1A3Q"
FT HELIX 278..280
FT /evidence="ECO:0007829|PDB:1A3Q"
FT TURN 283..285
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 286..290
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 303..311
FT /evidence="ECO:0007829|PDB:1A3Q"
FT TURN 312..314
FT /evidence="ECO:0007829|PDB:1A3Q"
FT STRAND 321..326
FT /evidence="ECO:0007829|PDB:1A3Q"
FT HELIX 439..467
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 470..475
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 476..480
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 491..497
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 501..512
FT /evidence="ECO:0007829|PDB:4OT9"
FT TURN 513..515
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 519..521
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 530..536
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 540..548
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 563..567
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 575..582
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 586..588
FT /evidence="ECO:0007829|PDB:4OT9"
FT TURN 589..593
FT /evidence="ECO:0007829|PDB:4OT9"
FT TURN 597..599
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 603..609
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 613..621
FT /evidence="ECO:0007829|PDB:4OT9"
FT TURN 631..633
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 637..643
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 647..654
FT /evidence="ECO:0007829|PDB:4OT9"
FT TURN 655..657
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 671..678
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 681..689
FT /evidence="ECO:0007829|PDB:4OT9"
FT TURN 733..735
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 740..751
FT /evidence="ECO:0007829|PDB:4OT9"
FT STRAND 752..754
FT /evidence="ECO:0007829|PDB:4OT9"
FT HELIX 772..782
FT /evidence="ECO:0007829|PDB:2D96"
FT STRAND 783..786
FT /evidence="ECO:0007829|PDB:2D96"
FT HELIX 791..798
FT /evidence="ECO:0007829|PDB:2D96"
FT HELIX 801..808
FT /evidence="ECO:0007829|PDB:2D96"
FT HELIX 813..823
FT /evidence="ECO:0007829|PDB:2D96"
FT HELIX 828..838
FT /evidence="ECO:0007829|PDB:2D96"
FT HELIX 841..848
FT /evidence="ECO:0007829|PDB:2D96"
SQ SEQUENCE 900 AA; 96749 MW; 6BAD7038834783CA CRC64;
MESCYNPGLD GIIEYDDFKL NSSIVEPKEP APETADGPYL VIVEQPKQRG FRFRYGCEGP
SHGGLPGASS EKGRKTYPTV KICNYEGPAK IEVDLVTHSD PPRAHAHSLV GKQCSELGIC
AVSVGPKDMT AQFNNLGVLH VTKKNMMGTM IQKLQRQRLR SRPQGLTEAE QRELEQEAKE
LKKVMDLSIV RLRFSAFLRA SDGSFSLPLK PVISQPIHDS KSPGASNLKI SRMDKTAGSV
RGGDEVYLLC DKVQKDDIEV RFYEDDENGW QAFGDFSPTD VHKQYAIVFR TPPYHKMKIE
RPVTVFLQLK RKRGGDVSDS KQFTYYPLVE DKEEVQRKRR KALPTFSQPF GGGSHMGGGS
GGAAGGYGGA GGGGSLGFFP SSLAYSPYQS GAGPMGCYPG GGGGAQMAAT VPSRDSGEEA
AEPSAPSRTP QCEPQAPEML QRAREYNARL FGLAQRSARA LLDYGVTADA RALLAGQRHL
LTAQDENGDT PLHLAIIHGQ TSVIEQIVYV IHHAQDLGVV NLTNHLHQTP LHLAVITGQT
SVVSFLLRVG ADPALLDRHG DSAMHLALRA GAGAPELLRA LLQSGAPAVP QLLHMPDFEG
LYPVHLAVRA RSPECLDLLV DSGAEVEATE RQGGRTALHL ATEMEELGLV THLVTKLRAN
VNARTFAGNT PLHLAAGLGY PTLTRLLLKA GADIHAENEE PLCPLPSPPT SDSDSDSEGP
EKDTRSSFRG HTPLDLTCST KVKTLLLNAA QNTMEPPLTP PSPAGPGLSL GDTALQNLEQ
LLDGPEAQGS WAELAERLGL RSLVDTYRQT TSPSGSLLRS YELAGGDLAG LLEALSDMGL
EEGVRLLRGP ETRDKLPSTA EVKEDSAYGS QSVEQEAEKL GPPPEPPGGL CHGHPQPQVH
