IKBA_HUMAN
ID IKBA_HUMAN Reviewed; 317 AA.
AC P25963; B2R8L6;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 230.
DE RecName: Full=NF-kappa-B inhibitor alpha;
DE AltName: Full=I-kappa-B-alpha;
DE Short=IkB-alpha;
DE Short=IkappaBalpha;
DE AltName: Full=Major histocompatibility complex enhancer-binding protein MAD3;
GN Name=NFKBIA; Synonyms=IKBA, MAD3, NFKBI;
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].
RC TISSUE=Monocyte;
RX PubMed=1829648; DOI=10.1016/0092-8674(91)90022-q;
RA Haskill S., Beg A.A., Tompkins S.M., Morris J.S., Yurochko A.D.,
RA Sampson-Johannes A., Mondal K., Ralph P., Baldwin A.S. Jr.;
RT "Characterization of an immediate-early gene induced in adherent monocytes
RT that encodes I kappa B-like activity.";
RL Cell 65:1281-1289(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Lymph node;
RX PubMed=10637284; DOI=10.1084/jem.191.2.395;
RA Jungnickel B., Staratschek-Jox A., Braeuninger A., Spieker T., Wolf J.,
RA Diehl V., Hansmann M.-L., Rajewsky K., Kueppers R.;
RT "Clonal deleterious mutations in the IkappaB alpha gene in the malignant
RT cells in Hodgkin's lymphoma.";
RL J. Exp. Med. 191:395-402(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Liu B., Huang A.;
RT "Homo sapiens IkBa mRNA.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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 GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Kidney;
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 INTERACTION WITH RELA.
RX PubMed=1493333; DOI=10.1091/mbc.3.12.1339;
RA Ganchi P.A., Sun S.C., Greene W.C., Ballard D.W.;
RT "I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65
RT and requires the transactivation domain to inhibit NF-kappa B p65 DNA
RT binding.";
RL Mol. Biol. Cell 3:1339-1352(1992).
RN [11]
RP UBIQUITINATION AT LYS-21 AND LYS-22, FUNCTION, AND MUTAGENESIS OF LYS-21;
RP LYS-22; LYS-38 AND LYS-47.
RX PubMed=7479976; DOI=10.1073/pnas.92.24.11259;
RA Scherer D.C., Brockman J.A., Chen Z., Maniatis T., Ballard D.W.;
RT "Signal-induced degradation of IkappaB alpha requires site-specific
RT ubiquitination.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:11259-11263(1995).
RN [12]
RP PHOSPHORYLATION AT TYR-42, AND MUTAGENESIS OF TYR-42.
RX PubMed=8797825; DOI=10.1016/s0092-8674(00)80153-1;
RA Imbert V., Rupec R.A., Livolsi A., Pahl H.L., Traenckner E.B.-M.,
RA Mueller-Dieckmann C., Farahifar D., Rossi B., Auberger P., Baeuerle P.A.,
RA Peyron J.-F.;
RT "Tyrosine phosphorylation of IkappaB-alpha activates NF-kappaB without
RT proteolytic degradation of IkappaB-alpha.";
RL Cell 86:787-798(1996).
RN [13]
RP PHOSPHORYLATION AT SER-283; SER-288; SER-293 AND THR-291.
RX PubMed=8622692; DOI=10.1128/mcb.16.3.899;
RA McElhinny J.A., Trushin S.A., Bren G.D., Chester N., Paya C.V.;
RT "Casein kinase II phosphorylates I kappa B alpha at S-283, S-289, S-293,
RT and T-291 and is required for its degradation.";
RL Mol. Cell. Biol. 16:899-906(1996).
RN [14]
RP MUTAGENESIS OF LYS-21; LYS-22; ASP-31; SER-32; ASP-35; SER-36; SER-234;
RP SER-262 AND THR-263.
RX PubMed=8657102; DOI=10.1128/mcb.16.4.1295;
RA DiDonato J.A., Mercurio F., Rosette C., Wu-Li J., Suyang H., Ghosh S.,
RA Karin M.;
RT "Mapping of the inducible IkappaB phosphorylation sites that signal its
RT ubiquitination and degradation.";
RL Mol. Cell. Biol. 16:1295-1304(1996).
RN [15]
RP PHOSPHORYLATION AT THR-291; SER-283 AND THR-299.
RX PubMed=8657113; DOI=10.1128/mcb.16.4.1401;
RA Lin R., Beauparlant P., Makris C., Meloche S., Hiscott J.;
RT "Phosphorylation of IkappaBalpha in the C-terminal PEST domain by casein
RT kinase II affects intrinsic protein stability.";
RL Mol. Cell. Biol. 16:1401-1409(1996).
RN [16]
RP SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF
RP 115-LEU--ILE-120.
RX PubMed=9566872; DOI=10.1128/mcb.18.5.2524;
RA Sachdev S., Hoffmann A., Hannink M.;
RT "Nuclear localization of IkappaB alpha is mediated by the second ankyrin
RT repeat: the IkappaB alpha ankyrin repeats define a novel class of cis-
RT acting nuclear import sequences.";
RL Mol. Cell. Biol. 18:2524-2534(1998).
RN [17]
RP UBIQUITINATION BY THE SCF(FBXW11) COMPLEX.
RX PubMed=10437795; DOI=10.1016/s0014-5793(99)00895-9;
RA Vuillard L., Nicholson J., Hay R.T.;
RT "A complex containing betaTrCP recruits Cdc34 to catalyse ubiquitination of
RT IkappaBalpha.";
RL FEBS Lett. 455:311-314(1999).
RN [18]
RP PHOSPHORYLATION AT SER-32 AND SER-36, MUTAGENESIS OF SER-32 AND SER-36, AND
RP UBIQUITINATION BY UBE2D2 AND UBE2D3.
RX PubMed=10329681; DOI=10.1074/jbc.274.21.14823;
RA Gonen H., Bercovich B., Orian A., Carrano A., Takizawa C., Yamanaka K.,
RA Pagano M., Iwai K., Ciechanover A.;
RT "Identification of the ubiquitin carrier proteins, E2s, involved in signal-
RT induced conjugation and subsequent degradation of IkappaBalpha.";
RL J. Biol. Chem. 274:14823-14830(1999).
RN [19]
RP INTERACTION WITH HEPATITIS B VIRUS/HBV PROTEIN X (MICROBIAL INFECTION).
RX PubMed=10454581; DOI=10.1128/mcb.19.9.6345;
RA Weil R., Sirma H., Giannini C., Kremsdorf D., Bessia C., Dargemont C.,
RA Brechot C., Israel A.;
RT "Direct association and nuclear import of the hepatitis B virus X protein
RT with the NF-kappaB inhibitor IkappaBalpha.";
RL Mol. Cell. Biol. 19:6345-6354(1999).
RN [20]
RP PHOSPHORYLATION AT SER-32 AND SER-36.
RX PubMed=10882136; DOI=10.1016/s1097-2765(00)80445-1;
RA Peters R.T., Liao S.-M., Maniatis T.;
RT "IKK epsilon is part of a novel PMA-inducible IkappaB kinase complex.";
RL Mol. Cell 5:513-522(2000).
RN [21]
RP PHOSPHORYLATION BY TBK1.
RX PubMed=10783893; DOI=10.1038/35008109;
RA Tojima Y., Fujimoto A., Delhase M., Chen Y., Hatakeyama S., Nakayama K.,
RA Kaneko Y., Nimura Y., Motoyama N., Ikeda K., Karin M., Nakanishi M.;
RT "NAK is an IkappaB kinase-activating kinase.";
RL Nature 404:778-782(2000).
RN [22]
RP INTERACTION WITH NKIRAS1 AND NKIRAS2.
RX PubMed=10657303; DOI=10.1126/science.287.5454.869;
RA Fenwick C., Na S.-Y., Voll R.E., Zhong H., Im S.-Y., Lee J.W., Ghosh S.;
RT "A subclass of Ras proteins that regulate the degradation of IkappaB.";
RL Science 287:869-873(2000).
RN [23]
RP SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL, AND MUTAGENESIS OF
RP 45-MET--ILE-52.
RX PubMed=10655476; DOI=10.1073/pnas.97.3.1014;
RA Huang T.T., Kudo N., Yoshida M., Miyamoto S.;
RT "A nuclear export signal in the N-terminal regulatory domain of
RT IkappaBalpha controls cytoplasmic localization of inactive NF-
RT kappaB/IkappaBalpha complexes.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:1014-1019(2000).
RN [24]
RP SUMOYLATION AT LYS-21, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-21 AND
RP LYS-22.
RX PubMed=11124955; DOI=10.1074/jbc.m009476200;
RA Rodriguez M.S., Dargemont C., Hay R.T.;
RT "SUMO-1 conjugation in vivo requires both a consensus modification motif
RT and nuclear targeting.";
RL J. Biol. Chem. 276:12654-12659(2001).
RN [25]
RP INTERACTION WITH PRKACA.
RX PubMed=20356841; DOI=10.1074/jbc.m109.077602;
RA Gambaryan S., Kobsar A., Rukoyatkina N., Herterich S., Geiger J.,
RA Smolenski A., Lohmann S.M., Walter U.;
RT "Thrombin and collagen induce a feedback inhibitory signaling pathway in
RT platelets involving dissociation of the catalytic subunit of protein kinase
RT A from an NFkappaB-IkappaB complex.";
RL J. Biol. Chem. 285:18352-18363(2010).
RN [26]
RP INTERACTION WITH PRMT2, AND SUBCELLULAR LOCATION.
RX PubMed=16648481; DOI=10.1128/mcb.26.10.3864-3874.2006;
RA Ganesh L., Yoshimoto T., Moorthy N.C., Akahata W., Boehm M., Nabel E.G.,
RA Nabel G.J.;
RT "Protein methyltransferase 2 inhibits NF-kappaB function and promotes
RT apoptosis.";
RL Mol. Cell. Biol. 26:3864-3874(2006).
RN [27]
RP INTERACTION WITH HIF1AN, HYDROXYLATION AT ASN-210 AND ASN-244, AND
RP MUTAGENESIS OF ASN-210 AND ASN-244.
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 [28]
RP INTERACTION WITH RWDD3, SUMOYLATION, AND MUTAGENESIS OF LYS-21 AND LYS-22.
RX PubMed=17956732; DOI=10.1016/j.cell.2007.07.044;
RA Carbia-Nagashima A., Gerez J., Perez-Castro C., Paez-Pereda M.,
RA Silberstein S., Stalla G.K., Holsboer F., Arzt E.;
RT "RSUME, a small RWD-containing protein, enhances SUMO conjugation and
RT stabilizes HIF-1alpha during hypoxia.";
RL Cell 131:309-323(2007).
RN [29]
RP INTERACTION WITH MEFV.
RX PubMed=18577712; DOI=10.1182/blood-2008-01-134932;
RA Chae J.J., Wood G., Richard K., Jaffe H., Colburn N.T., Masters S.L.,
RA Gumucio D.L., Shoham N.G., Kastner D.L.;
RT "The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1
RT and activates NF-kappaB through its N-terminal fragment.";
RL Blood 112:1794-1803(2008).
RN [30]
RP UBIQUITINATION AT LYS-21 AND LYS-22.
RX PubMed=20347421; DOI=10.1016/j.molcel.2010.02.025;
RA Wu K., Kovacev J., Pan Z.Q.;
RT "Priming and extending: a UbcH5/Cdc34 E2 handoff mechanism for
RT polyubiquitination on a SCF substrate.";
RL Mol. Cell 37:784-796(2010).
RN [31]
RP DEUBIQUITINATION BY PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME VIRUS
RP NSP2 PROTEIN.
RX PubMed=20504922; DOI=10.1128/jvi.00217-10;
RA Sun Z., Chen Z., Lawson S.R., Fang Y.;
RT "The cysteine protease domain of porcine reproductive and respiratory
RT syndrome virus nonstructural protein 2 possesses deubiquitinating and
RT interferon antagonism functions.";
RL J. Virol. 84:7832-7846(2010).
RN [32]
RP INTERACTION WITH RWDD3.
RX PubMed=23469069; DOI=10.1371/journal.pone.0057795;
RA Gerez J., Fuertes M., Tedesco L., Silberstein S., Sevlever G.,
RA Paez-Pereda M., Holsboer F., Turjanski A.G., Arzt E.;
RT "In silico structural and functional characterization of the RSUME splice
RT variants.";
RL PLoS ONE 8:E57795-E57795(2013).
RN [33]
RP INTERACTION WITH DDRGK1.
RX PubMed=23675531; DOI=10.1371/journal.pone.0064231;
RA Xi P., Ding D., Zhou J., Wang M., Cong Y.S.;
RT "DDRGK1 regulates NF-kappaB activity by modulating IkappaBalpha
RT stability.";
RL PLoS ONE 8:E64231-E64231(2013).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 70-282.
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 [35]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 73-302.
RX PubMed=9865694; DOI=10.1016/s0092-8674(00)81699-2;
RA Huxford T., Huang D.B., Malek S., Ghosh G.;
RT "The crystal structure of the IkappaBalpha/NF-kappaB complex reveals
RT mechanisms of NF-kappaB inactivation.";
RL Cell 95:759-770(1998).
RN [36]
RP VARIANT EDAID2 ILE-32.
RX PubMed=14523047; DOI=10.1172/jci18714;
RA Courtois G., Smahi A., Reichenbach J., Doffinger R., Cancrini C.,
RA Bonnet M., Puel A., Chable-Bessia C., Yamaoka S., Feinberg J.,
RA Dupuis-Girod S., Bodemer C., Livadiotti S., Novelli F., Rossi P.,
RA Fischer A., Israel A., Munnich A., Le Deist F., Casanova J.L.;
RT "A hypermorphic IkappaBalpha mutation is associated with autosomal dominant
RT anhidrotic ectodermal dysplasia and T cell immunodeficiency.";
RL J. Clin. Invest. 112:1108-1115(2003).
RN [37]
RP INVOLVEMENT IN EDAID2.
RX PubMed=18412279; DOI=10.1002/humu.20740;
RA Lopez-Granados E., Keenan J.E., Kinney M.C., Leo H., Jain N., Ma C.A.,
RA Quinones R., Gelfand E.W., Jain A.;
RT "A novel mutation in NFKBIA/IKBA results in a degradation-resistant N-
RT truncated protein and is associated with ectodermal dysplasia with
RT immunodeficiency.";
RL Hum. Mutat. 29:861-868(2008).
CC -!- FUNCTION: Inhibits the activity of dimeric NF-kappa-B/REL complexes by
CC trapping REL dimers in the cytoplasm through masking of their nuclear
CC localization signals. On cellular stimulation by immune and pro-
CC inflammatory responses, becomes phosphorylated promoting ubiquitination
CC and degradation, enabling the dimeric RELA to translocate to the
CC nucleus and activate transcription. {ECO:0000269|PubMed:7479976}.
CC -!- SUBUNIT: Interacts with RELA; the interaction requires the nuclear
CC import signal. Interacts with NKIRAS1 and NKIRAS2. Part of a 70-90 kDa
CC complex at least consisting of CHUK, IKBKB, NFKBIA, RELA, ELP1 and
CC MAP3K14. Interacts with isoform 1 and isoform 2 of RWDD3; the
CC interaction enhances sumoylation. Interacts (when phosphorylated at the
CC 2 serine residues in the destruction motif D-S-G-X(2,3,4)-S) with BTRC.
CC Associates with the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC;
CC the association is mediated via interaction with BTRC. Part of a
CC SCF(BTRC)-like complex lacking CUL1, which is associated with RELA;
CC RELA interacts directly with NFKBIA. Interacts with PRMT2. Interacts
CC with PRKACA in platelets; this interaction is disrupted by thrombin and
CC collagen. Interacts with HIF1AN. Interacts with MEFV. Interacts with
CC DDRGK1; positively regulates NFKBIA phosphorylation and degradation.
CC {ECO:0000269|PubMed:10657303, ECO:0000269|PubMed:1493333,
CC ECO:0000269|PubMed:16648481, ECO:0000269|PubMed:17003112,
CC ECO:0000269|PubMed:17956732, ECO:0000269|PubMed:18577712,
CC ECO:0000269|PubMed:20356841, ECO:0000269|PubMed:23469069,
CC ECO:0000269|PubMed:23675531}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HBV protein X.
CC {ECO:0000269|PubMed:10454581}.
CC -!- INTERACTION:
CC P25963; O15111: CHUK; NbExp=15; IntAct=EBI-307386, EBI-81249;
CC P25963; Q8N668: COMMD1; NbExp=3; IntAct=EBI-307386, EBI-1550112;
CC P25963; P35221: CTNNA1; NbExp=5; IntAct=EBI-307386, EBI-701918;
CC P25963; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-307386, EBI-744099;
CC P25963; Q9UKB1: FBXW11; NbExp=2; IntAct=EBI-307386, EBI-355189;
CC P25963; P25098: GRK2; NbExp=2; IntAct=EBI-307386, EBI-3904795;
CC P25963; P34947: GRK5; NbExp=2; IntAct=EBI-307386, EBI-7149314;
CC P25963; Q9NWT6: HIF1AN; NbExp=6; IntAct=EBI-307386, EBI-745632;
CC P25963; O14920: IKBKB; NbExp=27; IntAct=EBI-307386, EBI-81266;
CC P25963; Q9Y6K9: IKBKG; NbExp=6; IntAct=EBI-307386, EBI-81279;
CC P25963; Q14511: NEDD9; NbExp=3; IntAct=EBI-307386, EBI-2108053;
CC P25963; Q14511-2: NEDD9; NbExp=3; IntAct=EBI-307386, EBI-11746523;
CC P25963; P19838: NFKB1; NbExp=8; IntAct=EBI-307386, EBI-300010;
CC P25963; Q00653: NFKB2; NbExp=2; IntAct=EBI-307386, EBI-307326;
CC P25963; P25963: NFKBIA; NbExp=2; IntAct=EBI-307386, EBI-307386;
CC P25963; Q96HA1-2: POM121; NbExp=3; IntAct=EBI-307386, EBI-11956563;
CC P25963; O43242: PSMD3; NbExp=3; IntAct=EBI-307386, EBI-357622;
CC P25963; Q04864: REL; NbExp=3; IntAct=EBI-307386, EBI-307352;
CC P25963; Q04206: RELA; NbExp=25; IntAct=EBI-307386, EBI-73886;
CC P25963; Q04206-2: RELA; NbExp=2; IntAct=EBI-307386, EBI-289947;
CC P25963; P23396: RPS3; NbExp=6; IntAct=EBI-307386, EBI-351193;
CC P25963; P56279: TCL1A; NbExp=3; IntAct=EBI-307386, EBI-749995;
CC P25963; P0CG48: UBC; NbExp=3; IntAct=EBI-307386, EBI-3390054;
CC P25963; Q60680-2: Chuk; Xeno; NbExp=2; IntAct=EBI-307386, EBI-646264;
CC P25963; Q9J0X9: UL54; Xeno; NbExp=3; IntAct=EBI-307386, EBI-7967856;
CC P25963; P14340; Xeno; NbExp=2; IntAct=EBI-307386, EBI-465733;
CC P25963; PRO_0000037965 [P14340]; Xeno; NbExp=2; IntAct=EBI-307386, EBI-9825968;
CC P25963; PRO_0000038062 [P21530]; Xeno; NbExp=4; IntAct=EBI-307386, EBI-12558622;
CC P25963; Q9E7P0; Xeno; NbExp=2; IntAct=EBI-307386, EBI-11361108;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Shuttles between the
CC nucleus and the cytoplasm by a nuclear localization signal (NLS) and a
CC CRM1-dependent nuclear export. {ECO:0000250}.
CC -!- INDUCTION: Induced in adherent monocytes.
CC -!- PTM: Phosphorylated; disables inhibition of NF-kappa-B DNA-binding
CC activity. Phosphorylation at positions 32 and 36 is prerequisite to
CC recognition by UBE2D3 leading to polyubiquitination and subsequent
CC degradation. {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10882136,
CC ECO:0000269|PubMed:20504922}.
CC -!- PTM: Sumoylated; sumoylation requires the presence of the nuclear
CC import signal. Sumoylation blocks ubiquitination and proteasome-
CC mediated degradation of the protein thereby increasing the protein
CC stability. {ECO:0000269|PubMed:11124955, ECO:0000269|PubMed:17956732,
CC ECO:0000269|PubMed:20504922}.
CC -!- PTM: Monoubiquitinated at Lys-21 and/or Lys-22 by UBE2D3. Ubiquitin
CC chain elongation is then performed by CDC34 in cooperation with the
CC SCF(FBXW11) E3 ligase complex, building ubiquitin chains from the
CC UBE2D3-primed NFKBIA-linked ubiquitin. The resulting polyubiquitination
CC leads to protein degradation. Also ubiquitinated by SCF(BTRC) following
CC stimulus-dependent phosphorylation at Ser-32 and Ser-36.
CC {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10882136,
CC ECO:0000269|PubMed:20347421, ECO:0000269|PubMed:20504922,
CC ECO:0000269|PubMed:7479976}.
CC -!- PTM: Deubiquitinated by porcine reproductive and respiratory syndrome
CC virus Nsp2 protein, which thereby interferes with NFKBIA degradation
CC and impairs subsequent NF-kappa-B activation.
CC -!- DISEASE: Ectodermal dysplasia and immunodeficiency 2 (EDAID2)
CC [MIM:612132]: A form of ectoderma dysplasia, a heterogeneous group of
CC disorders due to abnormal development of two or more ectodermal
CC structures. This form of ectodermal dysplasia is associated with
CC decreased production of pro-inflammatory cytokines and certain
CC interferons, rendering patients susceptible to infection. EDAID2
CC inheritance is autosomal dominant. {ECO:0000269|PubMed:14523047,
CC ECO:0000269|PubMed:18412279}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the NF-kappa-B inhibitor family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NFKBIAbase; Note=NFKBIA mutation db;
CC URL="http://structure.bmc.lu.se/idbase/NFKBIAbase/";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/nfkbia/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M69043; AAA16489.1; -; mRNA.
DR EMBL; AJ249294; CAB65556.2; -; Genomic_DNA.
DR EMBL; AJ249295; CAB65556.2; JOINED; Genomic_DNA.
DR EMBL; AJ249283; CAB65556.2; JOINED; Genomic_DNA.
DR EMBL; AJ249284; CAB65556.2; JOINED; Genomic_DNA.
DR EMBL; AJ249285; CAB65556.2; JOINED; Genomic_DNA.
DR EMBL; AJ249286; CAB65556.2; JOINED; Genomic_DNA.
DR EMBL; AY033600; AAK51149.1; -; mRNA.
DR EMBL; BT007091; AAP35754.1; -; mRNA.
DR EMBL; AY496422; AAR29599.1; -; Genomic_DNA.
DR EMBL; AK313421; BAG36213.1; -; mRNA.
DR EMBL; AL133163; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW65875.1; -; Genomic_DNA.
DR EMBL; BC002601; AAH02601.1; -; mRNA.
DR EMBL; BC004983; AAH04983.1; -; mRNA.
DR CCDS; CCDS9656.1; -.
DR PIR; A39935; A39935.
DR RefSeq; NP_065390.1; NM_020529.2.
DR PDB; 1IKN; X-ray; 2.30 A; D=67-302.
DR PDB; 1NFI; X-ray; 2.70 A; E/F=70-282.
DR PDB; 6TTU; EM; 3.70 A; I=21-41.
DR PDB; 6Y1J; X-ray; 1.13 A; P=57-69.
DR PDBsum; 1IKN; -.
DR PDBsum; 1NFI; -.
DR PDBsum; 6TTU; -.
DR PDBsum; 6Y1J; -.
DR AlphaFoldDB; P25963; -.
DR BMRB; P25963; -.
DR SMR; P25963; -.
DR BioGRID; 110859; 189.
DR CORUM; P25963; -.
DR DIP; DIP-139N; -.
DR ELM; P25963; -.
DR IntAct; P25963; 95.
DR MINT; P25963; -.
DR STRING; 9606.ENSP00000216797; -.
DR BindingDB; P25963; -.
DR ChEMBL; CHEMBL2898; -.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB06543; Astaxanthin.
DR DrugBank; DB05983; Bardoxolone methyl.
DR iPTMnet; P25963; -.
DR MetOSite; P25963; -.
DR PhosphoSitePlus; P25963; -.
DR BioMuta; NFKBIA; -.
DR DMDM; 126682; -.
DR EPD; P25963; -.
DR jPOST; P25963; -.
DR MassIVE; P25963; -.
DR MaxQB; P25963; -.
DR PaxDb; P25963; -.
DR PeptideAtlas; P25963; -.
DR PRIDE; P25963; -.
DR ProteomicsDB; 54304; -.
DR Antibodypedia; 3541; 1894 antibodies from 49 providers.
DR DNASU; 4792; -.
DR Ensembl; ENST00000216797.10; ENSP00000216797.6; ENSG00000100906.11.
DR GeneID; 4792; -.
DR KEGG; hsa:4792; -.
DR MANE-Select; ENST00000216797.10; ENSP00000216797.6; NM_020529.3; NP_065390.1.
DR UCSC; uc001wtf.5; human.
DR CTD; 4792; -.
DR DisGeNET; 4792; -.
DR GeneCards; NFKBIA; -.
DR HGNC; HGNC:7797; NFKBIA.
DR HPA; ENSG00000100906; Tissue enhanced (bone).
DR MalaCards; NFKBIA; -.
DR MIM; 164008; gene.
DR MIM; 612132; phenotype.
DR neXtProt; NX_P25963; -.
DR OpenTargets; ENSG00000100906; -.
DR Orphanet; 251579; Giant cell glioblastoma.
DR Orphanet; 251576; Gliosarcoma.
DR Orphanet; 98813; Hypohidrotic ectodermal dysplasia with immunodeficiency.
DR Orphanet; 150; Nasopharyngeal carcinoma.
DR PharmGKB; PA31601; -.
DR VEuPathDB; HostDB:ENSG00000100906; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000162733; -.
DR InParanoid; P25963; -.
DR OMA; EIRIQPQ; -.
DR OrthoDB; 1341288at2759; -.
DR PhylomeDB; P25963; -.
DR TreeFam; TF320166; -.
DR PathwayCommons; P25963; -.
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-202424; Downstream TCR signaling.
DR Reactome; R-HSA-209560; NF-kB is activated and signals survival.
DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-HSA-445989; TAK1-dependent IKK and NF-kappa-B activation.
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-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-9020702; Interleukin-1 signaling.
DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
DR SABIO-RK; P25963; -.
DR SignaLink; P25963; -.
DR SIGNOR; P25963; -.
DR BioGRID-ORCS; 4792; 21 hits in 1086 CRISPR screens.
DR ChiTaRS; NFKBIA; human.
DR EvolutionaryTrace; P25963; -.
DR GeneWiki; I%CE%BAB%CE%B1; -.
DR GenomeRNAi; 4792; -.
DR Pharos; P25963; Tchem.
DR PRO; PR:P25963; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P25963; protein.
DR Bgee; ENSG00000100906; Expressed in vena cava and 213 other tissues.
DR ExpressionAtlas; P25963; baseline and differential.
DR Genevisible; P25963; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0033256; C:I-kappaB/NF-kappaB complex; TAS:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0051059; F:NF-kappaB binding; IDA:MGI.
DR GO; GO:0008139; F:nuclear localization sequence binding; IPI:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0070417; P:cellular response to cold; NAS:BHF-UCL.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IBA:GO_Central.
DR GO; GO:0007253; P:cytoplasmic sequestering of NF-kappaB; IMP:BHF-UCL.
DR GO; GO:0042994; P:cytoplasmic sequestering of transcription factor; IDA:UniProtKB.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IDA:CAFA.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0043392; P:negative regulation of DNA binding; NAS:UniProtKB.
DR GO; GO:0010888; P:negative regulation of lipid storage; IMP:BHF-UCL.
DR GO; GO:0010745; P:negative regulation of macrophage derived foam cell differentiation; IMP:BHF-UCL.
DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; IEA:Ensembl.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:MGI.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0070427; P:nucleotide-binding oligomerization domain containing 1 signaling pathway; IEA:Ensembl.
DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; IEA:Ensembl.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IMP:BHF-UCL.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IDA:CAFA.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:1901222; P:regulation of NIK/NF-kappaB signaling; NAS:UniProtKB.
DR GO; GO:0043330; P:response to exogenous dsRNA; IEA:Ensembl.
DR GO; GO:0032495; P:response to muramyl dipeptide; IEA:Ensembl.
DR GO; GO:0035994; P:response to muscle stretch; IEA:Ensembl.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IEA:Ensembl.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:CAFA.
DR DisProt; DP00468; -.
DR Gene3D; 1.25.40.20; -; 1.
DR IDEAL; IID00654; -.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR Pfam; PF00023; Ank; 1.
DR Pfam; PF12796; Ank_2; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 5.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 3.
PE 1: Evidence at protein level;
KW 3D-structure; ANK repeat; Cytoplasm; Disease variant; Ectodermal dysplasia;
KW Host-virus interaction; Hydroxylation; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..317
FT /note="NF-kappa-B inhibitor alpha"
FT /id="PRO_0000066999"
FT REPEAT 73..103
FT /note="ANK 1"
FT REPEAT 110..139
FT /note="ANK 2"
FT REPEAT 143..172
FT /note="ANK 3"
FT REPEAT 182..211
FT /note="ANK 4"
FT REPEAT 216..245
FT /note="ANK 5"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 30..36
FT /note="Destruction motif"
FT MOTIF 45..54
FT /note="Nuclear export signal"
FT MOTIF 110..120
FT /note="Nuclear import signal"
FT COMPBIAS 11..39
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 32
FT /note="Phosphoserine; by IKKA and IKKE"
FT /evidence="ECO:0000269|PubMed:10329681,
FT ECO:0000269|PubMed:10882136"
FT MOD_RES 36
FT /note="Phosphoserine; by IKKA, IKKB, IKKE and TBK1"
FT /evidence="ECO:0000269|PubMed:10329681,
FT ECO:0000269|PubMed:10882136"
FT MOD_RES 42
FT /note="Phosphotyrosine; by Tyr-kinases"
FT /evidence="ECO:0000269|PubMed:8797825"
FT MOD_RES 210
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN; partial"
FT /evidence="ECO:0000269|PubMed:17003112"
FT MOD_RES 244
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN; partial"
FT /evidence="ECO:0000269|PubMed:17003112"
FT MOD_RES 283
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:8622692,
FT ECO:0000269|PubMed:8657113"
FT MOD_RES 288
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:8622692"
FT MOD_RES 291
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000269|PubMed:8622692,
FT ECO:0000269|PubMed:8657113"
FT MOD_RES 293
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:8622692"
FT MOD_RES 299
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000269|PubMed:8657113"
FT CROSSLNK 21
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO or ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:20347421,
FT ECO:0000269|PubMed:7479976"
FT CROSSLNK 21
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1E3"
FT CROSSLNK 22
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:20347421,
FT ECO:0000269|PubMed:7479976"
FT VARIANT 32
FT /note="S -> I (in EDAID2; dbSNP:rs28933100)"
FT /evidence="ECO:0000269|PubMed:14523047"
FT /id="VAR_034871"
FT MUTAGEN 21
FT /note="K->R: Little change in Tax-stimulated
FT transactivation. No sumoylation. Greatly reduced Tax- or
FT cytokine-stimulated transactivation and decrease in
FT ubiquitination and degradation; when associated with R-22."
FT /evidence="ECO:0000269|PubMed:11124955,
FT ECO:0000269|PubMed:17956732, ECO:0000269|PubMed:7479976,
FT ECO:0000269|PubMed:8657102"
FT MUTAGEN 22
FT /note="K->R: Little change in Tax-stimulated
FT transactivation. No sumoylation. Greatly reduced Tax- or
FT cytokine-stimulated transactivation and decrease in
FT ubiquitination and degradation; when associated with R-21."
FT /evidence="ECO:0000269|PubMed:11124955,
FT ECO:0000269|PubMed:17956732, ECO:0000269|PubMed:7479976,
FT ECO:0000269|PubMed:8657102"
FT MUTAGEN 31
FT /note="D->A: Loss of phosphorylation; when associated with
FT A-35."
FT /evidence="ECO:0000269|PubMed:8657102"
FT MUTAGEN 32
FT /note="S->A: Loss of phosphorylation, ubiquitination and
FT degradation; when associated with A-36."
FT /evidence="ECO:0000269|PubMed:10329681,
FT ECO:0000269|PubMed:8657102"
FT MUTAGEN 32
FT /note="S->T: Decrease in phosphorylation and degradation;
FT when associated with T-36."
FT /evidence="ECO:0000269|PubMed:10329681,
FT ECO:0000269|PubMed:8657102"
FT MUTAGEN 35
FT /note="D->A: Loss in phosphorylation; when associated with
FT A-31."
FT /evidence="ECO:0000269|PubMed:8657102"
FT MUTAGEN 35
FT /note="D->G: No change neither in phosphorylation, nor on
FT degradation."
FT /evidence="ECO:0000269|PubMed:8657102"
FT MUTAGEN 36
FT /note="S->A: Loss of phosphorylation, ubiquitination, and
FT degradation; when associated with A-32."
FT /evidence="ECO:0000269|PubMed:10329681,
FT ECO:0000269|PubMed:8657102"
FT MUTAGEN 36
FT /note="S->T: Decrease in phosphorylation and degradation;
FT when associated with T-32."
FT /evidence="ECO:0000269|PubMed:10329681,
FT ECO:0000269|PubMed:8657102"
FT MUTAGEN 38
FT /note="K->R: No change in Tax-stimulated transactivation.
FT No change in Tax-stimulated transactivation; when
FT associated with R-47."
FT /evidence="ECO:0000269|PubMed:7479976"
FT MUTAGEN 42
FT /note="Y->F: No phosphorylation."
FT /evidence="ECO:0000269|PubMed:8797825"
FT MUTAGEN 45..52
FT /note="MVKELQEI->AAKEAQEA: No nuclear export."
FT /evidence="ECO:0000269|PubMed:10655476"
FT MUTAGEN 47
FT /note="K->R: Little change in Tax-stimulated
FT transactivation. No change in Tax-stimulated
FT transactivation; when associated with R-38."
FT /evidence="ECO:0000269|PubMed:7479976"
FT MUTAGEN 115..120
FT /note="LHLAVI->AHAAVA: Greatly reduced nuclear
FT localization. Great reduction in its ability to inhibit DNA
FT binding of RELA."
FT /evidence="ECO:0000269|PubMed:9566872"
FT MUTAGEN 210
FT /note="N->A: Almost abolished ability to inhibit NF-kappa-B
FT DNA-binding activity; when associated with A-244."
FT /evidence="ECO:0000269|PubMed:17003112"
FT MUTAGEN 234
FT /note="S->A: No inducible ubiquitination nor protein
FT degradation."
FT /evidence="ECO:0000269|PubMed:8657102"
FT MUTAGEN 244
FT /note="N->A: Almost abolished ability to inhibit NF-kappa-B
FT DNA-binding activity; when associated with A-210."
FT /evidence="ECO:0000269|PubMed:17003112"
FT MUTAGEN 262
FT /note="S->A: No inducible ubiquitination nor protein
FT degradation."
FT /evidence="ECO:0000269|PubMed:8657102"
FT MUTAGEN 263
FT /note="T->A: No inducible ubiquitination nor protein
FT degradation."
FT /evidence="ECO:0000269|PubMed:8657102"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:1NFI"
FT HELIX 79..83
FT /evidence="ECO:0007829|PDB:1IKN"
FT STRAND 87..91
FT /evidence="ECO:0007829|PDB:1IKN"
FT HELIX 101..104
FT /evidence="ECO:0007829|PDB:1NFI"
FT HELIX 114..120
FT /evidence="ECO:0007829|PDB:1IKN"
FT HELIX 124..128
FT /evidence="ECO:0007829|PDB:1IKN"
FT HELIX 147..154
FT /evidence="ECO:0007829|PDB:1IKN"
FT HELIX 157..165
FT /evidence="ECO:0007829|PDB:1IKN"
FT TURN 167..170
FT /evidence="ECO:0007829|PDB:1IKN"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:1IKN"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:1IKN"
FT HELIX 186..192
FT /evidence="ECO:0007829|PDB:1IKN"
FT HELIX 196..205
FT /evidence="ECO:0007829|PDB:1IKN"
FT TURN 214..216
FT /evidence="ECO:0007829|PDB:1IKN"
FT HELIX 220..226
FT /evidence="ECO:0007829|PDB:1IKN"
FT HELIX 230..237
FT /evidence="ECO:0007829|PDB:1IKN"
FT TURN 238..240
FT /evidence="ECO:0007829|PDB:1IKN"
FT HELIX 253..256
FT /evidence="ECO:0007829|PDB:1IKN"
FT HELIX 263..270
FT /evidence="ECO:0007829|PDB:1IKN"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:1IKN"
FT TURN 285..287
FT /evidence="ECO:0007829|PDB:1IKN"
SQ SEQUENCE 317 AA; 35609 MW; 088B313226786395 CRC64;
MFQAAERPQE WAMEGPRDGL KKERLLDDRH DSGLDSMKDE EYEQMVKELQ EIRLEPQEVP
RGSEPWKQQL TEDGDSFLHL AIIHEEKALT MEVIRQVKGD LAFLNFQNNL QQTPLHLAVI
TNQPEIAEAL LGAGCDPELR DFRGNTPLHL ACEQGCLASV GVLTQSCTTP HLHSILKATN
YNGHTCLHLA SIHGYLGIVE LLVSLGADVN AQEPCNGRTA LHLAVDLQNP DLVSLLLKCG
ADVNRVTYQG YSPYQLTWGR PSTRIQQQLG QLTLENLQML PESEDEESYD TESEFTEFTE
DELPYDDCVF GGQRLTL
