ID   NEMO_HUMAN              Reviewed;         419 AA.
AC   Q9Y6K9; Q7LBY6; Q7Z7F1;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 2.
DT   29-MAY-2024, entry version 243.
DE   RecName: Full=NF-kappa-B essential modulator {ECO:0000305};
DE            Short=NEMO {ECO:0000305};
DE   AltName: Full=FIP-3;
DE   AltName: Full=IkB kinase-associated protein 1;
DE            Short=IKKAP1;
DE   AltName: Full=Inhibitor of nuclear factor kappa-B kinase subunit gamma;
DE            Short=I-kappa-B kinase subunit gamma;
DE            Short=IKK-gamma;
DE            Short=IKKG;
DE            Short=IkB kinase subunit gamma;
DE   AltName: Full=NF-kappa-B essential modifier;
GN   Name=IKBKG {ECO:0000312|HGNC:HGNC:5961}; Synonyms=FIP3, NEMO;
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 1).
RX   PubMed=9927690; DOI=10.1073/pnas.96.3.1042;
RA   Li Y., Kang J., Friedman J., Tarassishin L., Ye J., Kovalenko A.,
RA   Wallach D., Horwitz M.S.;
RT   "Identification of a cell protein (FIP-3) as a modulator of NF-kappaB
RT   activity and as a target of an adenovirus inhibitor of tumor necrosis
RT   factor alpha-induced apoptosis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:1042-1047(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Mammary cancer;
RX   PubMed=10087442; DOI=10.1007/bf02256442;
RA   Jin D.-Y., Jeang K.-T.;
RT   "Isolation of full-length cDNA and chromosomal localization of human NF-
RT   kappaB modulator NEMO to Xq28.";
RL   J. Biomed. Sci. 6:115-120(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, SUBUNIT,
RP   AND FUNCTION.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=9751060; DOI=10.1038/26261;
RA   Rothwarf D.M., Zandi E., Natoli G., Karin M.;
RT   "IKK-gamma is an essential regulatory subunit of the IkappaB kinase
RT   complex.";
RL   Nature 395:297-300(1998).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT IP VAL-407.
RX   PubMed=10839543; DOI=10.1038/35013114;
RA   Smahi A., Courtois G., Vabres P., Yamaoka S., Heuertz S., Munnich A.,
RA   Israel A., Heiss N.S., Klauck S.M., Kioschis P., Wiemann S., Poustka A.,
RA   Esposito T., Bardaro T., Gianfrancesco F., Ciccodicola A., D'Urso M.,
RA   Woffendin H., Jakins T., Donnai D., Stewart H., Kenwrick S.J., Aradhya S.,
RA   Yamagata T., Levy M., Lewis R.A., Nelson D.L.;
RT   "Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause
RT   of incontinentia pigmenti.";
RL   Nature 405:466-472(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Astrocytoma;
RX   PubMed=10944468; DOI=10.1006/bbrc.2000.3282;
RA   Ye Z., Connor J.R.;
RT   "cDNA cloning by amplification of circularized first strand cDNAs reveals
RT   non-IRE-regulated iron-responsive mRNAs.";
RL   Biochem. Biophys. Res. Commun. 275:223-227(2000).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA   Perelygin A.A., Perelygina L.M.;
RT   "Ikbkg gene modulates the herpes virus susceptibility in mice.";
RL   Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15772651; DOI=10.1038/nature03440;
RA   Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA   Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA   Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA   Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA   Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA   Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA   Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA   Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA   Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA   Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA   Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA   Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA   Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA   Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA   Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA   Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA   Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA   Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA   Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA   Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA   Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA   Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA   Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA   Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA   Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA   Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA   Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA   Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA   Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA   McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA   Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA   Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA   Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA   Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA   Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA   Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA   Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA   Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA   Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA   d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA   Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA   Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA   Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA   Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA   Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA   Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA   Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA   Rogers J., Bentley D.R.;
RT   "The DNA sequence of the human X chromosome.";
RL   Nature 434:325-337(2005).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Lung, Placenta, and Skin;
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 [MRNA] OF 51-419 (ISOFORM 1), PROTEIN SEQUENCE OF
RP   144-159, AND SUBUNIT.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=9891086; DOI=10.1128/mcb.19.2.1526;
RA   Mercurio F., Murray B.W., Shevchenko A., Bennett B.L., Young D.B., Li J.W.,
RA   Pascual G., Motiwala A., Zhu H., Mann M., Manning A.M.;
RT   "IkappaB kinase (IKK)-associated protein 1, a common component of the
RT   heterogeneous IKK complex.";
RL   Mol. Cell. Biol. 19:1526-1538(1999).
RN   [12]
RP   INTERACTION WITH HTLV-1 TAX-1 (MICROBIAL INFECTION), AND FUNCTION
RP   (MICROBIAL INFECTION).
RX   PubMed=10364167; DOI=10.1074/jbc.274.25.17402;
RA   Jin D.-Y., Giordano V., Kibler K.V., Nakano H., Jeang K.-T.;
RT   "Role of adapter function in oncoprotein-mediated activation of NF-kappaB:
RT   human T-cell leukemia virus type I Tax interacts directly with IkappaB
RT   kinase gamma.";
RL   J. Biol. Chem. 274:17402-17405(1999).
RN   [13]
RP   INTERACTION WITH HTLV-1 TAX-1 (MICROBIAL INFECTION), AND FUNCTION
RP   (MICROBIAL INFECTION).
RX   PubMed=11064457; DOI=10.1038/sj.onc.1203894;
RA   Xiao G., Sun S.C.;
RT   "Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax
RT   protein.";
RL   Oncogene 19:5198-5203(2000).
RN   [14]
RP   INTERACTION WITH TNFAIP3.
RX   PubMed=11389905; DOI=10.1016/s0014-5793(01)02504-2;
RA   Klinkenberg M., Van Huffel S., Heyninck K., Beyaert R.;
RT   "Functional redundancy of the zinc fingers of A20 for inhibition of NF-
RT   kappaB activation and protein-protein interactions.";
RL   FEBS Lett. 498:93-97(2001).
RN   [15]
RP   INTERACTION WITH COPS3.
RX   PubMed=11418127; DOI=10.1016/s0014-5793(01)02535-2;
RA   Hong X., Xu L.-G., Li X., Zhai Z., Shu H.-B.;
RT   "CSN3 interacts with IKKgamma and inhibits TNF- but not IL-1-induced NF-
RT   kappaB activation.";
RL   FEBS Lett. 499:133-136(2001).
RN   [16]
RP   SUBUNIT OF THE IKK COMPLEX.
RX   PubMed=11080499; DOI=10.1074/jbc.m008353200;
RA   Li X.-H., Fang X., Gaynor R.B.;
RT   "Role of ikkgamma/nemo in assembly of the IkappaB kinase complex.";
RL   J. Biol. Chem. 276:4494-4500(2001).
RN   [17]
RP   INTERACTION WITH TANK AND IKBKB.
RX   PubMed=12133833; DOI=10.1074/jbc.m205069200;
RA   Chariot A., Leonardi A., Muller J., Bonif M., Brown K., Siebenlist U.;
RT   "Association of the adaptor TANK with the I kappa B kinase (IKK) regulator
RT   NEMO connects IKK complexes with IKK epsilon and TBK1 kinases.";
RL   J. Biol. Chem. 277:37029-37036(2002).
RN   [18]
RP   SUBUNIT OF A COMPLEX CONTAINING CREBBP; NCOA2; NCOA3; IKKA AND IKKB.
RX   PubMed=11971985; DOI=10.1128/mcb.22.10.3549-3561.2002;
RA   Wu R.-C., Qin J., Hashimoto Y., Wong J., Xu J., Tsai S.Y., Tsai M.-J.,
RA   O'Malley B.W.;
RT   "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) coactivator activity by
RT   I kappa B kinase.";
RL   Mol. Cell. Biol. 22:3549-3561(2002).
RN   [19]
RP   SUMOYLATION AT LYS-277 AND LYS-309, UBIQUITINATION AT LYS-277 AND LYS-309,
RP   MUTAGENESIS OF LYS-277 AND LYS-309, SUBCELLULAR LOCATION, AND
RP   CHARACTERIZATION OF VARIANT EDAID1 ARG-417.
RX   PubMed=14651848; DOI=10.1016/s0092-8674(03)00895-x;
RA   Huang T.T., Wuerzberger-Davis S.M., Wu Z.H., Miyamoto S.;
RT   "Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates
RT   NF-kappaB activation by genotoxic stress.";
RL   Cell 115:565-576(2003).
RN   [20]
RP   PHOSPHORYLATION AT SER-31; SER-43 AND SER-376.
RX   PubMed=12657630; DOI=10.1074/jbc.m301705200;
RA   Carter R.S., Pennington K.N., Ungurait B.J., Ballard D.W.;
RT   "In vivo identification of inducible phosphoacceptors in the IKKgamma/NEMO
RT   subunit of human IkappaB kinase.";
RL   J. Biol. Chem. 278:19642-19648(2003).
RN   [21]
RP   SELF-ASSOCIATION, AND COMPOSITION OF THE IKK COMPLEX.
RX   PubMed=12612076; DOI=10.1128/mcb.23.6.2029-2041.2003;
RA   Tegethoff S., Behlke J., Scheidereit C.;
RT   "Tetrameric oligomerization of IkappaB kinase gamma (IKKgamma) is
RT   obligatory for IKK complex activity and NF-kappaB activation.";
RL   Mol. Cell. Biol. 23:2029-2041(2003).
RN   [22]
RP   INTERACTION WITH CYLD.
RX   PubMed=12917691; DOI=10.1038/nature01802;
RA   Kovalenko A., Chable-Bessia C., Cantarella G., Israeel A., Wallach D.,
RA   Courtois G.;
RT   "The tumour suppressor CYLD negatively regulates NF-kappaB signalling by
RT   deubiquitination.";
RL   Nature 424:801-805(2003).
RN   [23]
RP   UBIQUITINATION AT LYS-285, AND MUTAGENESIS OF LYS-115; LYS-224; LYS-285 AND
RP   LYS-399.
RX   PubMed=15620648; DOI=10.1016/j.cub.2004.12.032;
RA   Abbott D.W., Wilkins A., Asara J.M., Cantley L.C.;
RT   "The Crohn's disease protein, NOD2, requires RIP2 in order to induce
RT   ubiquitinylation of a novel site on NEMO.";
RL   Curr. Biol. 14:2217-2227(2004).
RN   [24]
RP   INTERACTION WITH ZFAND5.
RX   PubMed=14754897; DOI=10.1074/jbc.m309491200;
RA   Huang J., Teng L., Li L., Liu T., Li L., Chen D., Xu L.-G., Zhai Z.,
RA   Shu H.-B.;
RT   "ZNF216 is an A20-like and IkappaB kinase gamma-interacting inhibitor of
RT   NFkappaB activation.";
RL   J. Biol. Chem. 279:16847-16853(2004).
RN   [25]
RP   INTERACTION WITH NALP2.
RX   PubMed=15456791; DOI=10.1074/jbc.m406741200;
RA   Bruey J.-M., Bruey-Sedano N., Newman R., Chandler S., Stehlik C.,
RA   Reed J.C.;
RT   "PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-
RT   kappaB and caspase-1 activation in macrophages.";
RL   J. Biol. Chem. 279:51897-51907(2004).
RN   [26]
RP   UBIQUITINATION.
RX   PubMed=15125833; DOI=10.1016/s1097-2765(04)00236-9;
RA   Sun L., Deng L., Ea C.-K., Xia Z.-P., Chen Z.J.;
RT   "The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10
RT   and MALT1 in T lymphocytes.";
RL   Mol. Cell 14:289-301(2004).
RN   [27]
RP   FUNCTION, UBIQUITINATION AT LYS-399, AND MUTAGENESIS OF LYS-399.
RX   PubMed=14695475; DOI=10.1038/nature02273;
RA   Zhou H., Wertz I., O'Rourke K., Ultsch M., Seshagiri S., Eby M., Xiao W.,
RA   Dixit V.M.;
RT   "Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO.";
RL   Nature 427:167-171(2004).
RN   [28]
RP   INTERACTION WITH PIDD1.
RX   PubMed=16360037; DOI=10.1016/j.cell.2005.09.036;
RA   Janssens S., Tinel A., Lippens S., Tschopp J.;
RT   "PIDD mediates NF-kappaB activation in response to DNA damage.";
RL   Cell 123:1079-1092(2005).
RN   [29]
RP   FUNCTION, UBIQUITIN-BINDING, MUTAGENESIS OF LEU-329, AND CHARACTERIZATION
RP   OF VARIANT EDAID1 ASN-311.
RX   PubMed=16547522; DOI=10.1038/ncb1384;
RA   Wu C.J., Conze D.B., Li T., Srinivasula S.M., Ashwell J.D.;
RT   "Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-
RT   kappaB activation.";
RL   Nat. Cell Biol. 8:398-406(2006).
RN   [30]
RP   ERRATUM OF PUBMED:16547522.
RA   Wu C.J., Conze D.B., Li T., Srinivasula S.M., Ashwell J.D.;
RL   Nat. Cell Biol. 8:424-424(2006).
RN   [31]
RP   INTERACTION WITH ATM, PHOSPHORYLATION AT SER-85, AND MUTAGENESIS OF SER-85.
RX   PubMed=16497931; DOI=10.1126/science.1121513;
RA   Wu Z.H., Shi Y., Tibbetts R.S., Miyamoto S.;
RT   "Molecular linkage between the kinase ATM and NF-kappaB signaling in
RT   response to genotoxic stimuli.";
RL   Science 311:1141-1146(2006).
RN   [32]
RP   UBIQUITINATION.
RX   PubMed=17135271; DOI=10.1074/jbc.m609503200;
RA   Lamothe B., Besse A., Campos A.D., Webster W.K., Wu H., Darnay B.G.;
RT   "Site-specific Lys-63-linked tumor necrosis factor receptor-associated
RT   factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase
RT   activation.";
RL   J. Biol. Chem. 282:4102-4112(2007).
RN   [33]
RP   UBIQUITINATION AT LYS-285, AND MUTAGENESIS OF LYS-285 AND LYS-399.
RX   PubMed=17562858; DOI=10.1128/mcb.00270-07;
RA   Abbott D.W., Yang Y., Hutti J.E., Madhavarapu S., Kelliher M.A.,
RA   Cantley L.C.;
RT   "Coordinated regulation of Toll-like receptor and NOD2 signaling by K63-
RT   linked polyubiquitin chains.";
RL   Mol. Cell. Biol. 27:6012-6025(2007).
RN   [34]
RP   SUBUNIT, AND DISULFIDE BONDS.
RX   PubMed=18164680; DOI=10.1016/j.bbrc.2007.12.123;
RA   Herscovitch M., Comb W., Ennis T., Coleman K., Yong S., Armstead B.,
RA   Kalaitzidis D., Chandani S., Gilmore T.D.;
RT   "Intermolecular disulfide bond formation in the NEMO dimer requires Cys54
RT   and Cys347.";
RL   Biochem. Biophys. Res. Commun. 367:103-108(2008).
RN   [35]
RP   INTERACTION WITH RIPK2.
RX   PubMed=18079694; DOI=10.1038/sj.emboj.7601962;
RA   Hasegawa M., Fujimoto Y., Lucas P.C., Nakano H., Fukase K., Nunez G.,
RA   Inohara N.;
RT   "A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB
RT   activation.";
RL   EMBO J. 27:373-383(2008).
RN   [36]
RP   INTERACTION WITH IKBKB, PHOSPHORYLATION AT SER-68, AND MUTAGENESIS OF
RP   SER-68.
RX   PubMed=17977820; DOI=10.1074/jbc.m708856200;
RA   Palkowitsch L., Leidner J., Ghosh S., Marienfeld R.B.;
RT   "Phosphorylation of serine 68 in the IkappaB kinase (IKK)-binding domain of
RT   NEMO interferes with the structure of the IKK complex and tumor necrosis
RT   factor-alpha-induced NF-kappaB activity.";
RL   J. Biol. Chem. 283:76-86(2008).
RN   [37]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA   Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA   Greff Z., Keri G., Stemmann O., Mann M.;
RT   "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT   kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(2008).
RN   [38]
RP   FUNCTION, UBIQUITIN-BINDING, INTERACTION WITH BCL10, AND MUTAGENESIS OF
RP   LEU-329.
RX   PubMed=18287044; DOI=10.1073/pnas.0712313105;
RA   Wu C.J., Ashwell J.D.;
RT   "NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-
RT   mediated NF-kappaB activation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:3023-3028(2008).
RN   [39]
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   [40]
RP   FUNCTION, UBIQUITIN-BINDING, MUTAGENESIS OF VAL-414 AND MET-415, AND
RP   CHARACTERIZATION OF VARIANT IP VAL-407.
RX   PubMed=19033441; DOI=10.1074/jbc.m806655200;
RA   Cordier F., Grubisha O., Traincard F., Veron M., Delepierre M., Agou F.;
RT   "The zinc finger of NEMO is a functional ubiquitin-binding domain.";
RL   J. Biol. Chem. 284:2902-2907(2009).
RN   [41]
RP   FUNCTION, AND DOMAIN LEUCINE-ZIPPER AND C2HC-TYPE ZINC-FINGER.
RX   PubMed=19854139; DOI=10.1016/j.molcel.2009.09.037;
RA   Zeng W., Xu M., Liu S., Sun L., Chen Z.J.;
RT   "Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of
RT   IRF3.";
RL   Mol. Cell 36:315-325(2009).
RN   [42]
RP   UBIQUITINATION AT LYS-285 AND LYS-309.
RX   PubMed=19136968; DOI=10.1038/ncb1821;
RA   Tokunaga F., Sakata S., Saeki Y., Satomi Y., Kirisako T., Kamei K.,
RA   Nakagawa T., Kato M., Murata S., Yamaoka S., Yamamoto M., Akira S.,
RA   Takao T., Tanaka K., Iwai K.;
RT   "Involvement of linear polyubiquitylation of NEMO in NF-kappaB
RT   activation.";
RL   Nat. Cell Biol. 11:123-132(2009).
RN   [43]
RP   MUTAGENESIS OF GLU-296; PHE-312; GLU-315; ALA-323; LEU-329 AND LEU-336, AND
RP   CHARACTERIZATION OF VARIANTS IMD33 ALA-315 AND PRO-323.
RX   PubMed=19854204; DOI=10.1016/j.jmb.2009.10.018;
RA   Grubisha O., Kaminska M., Duquerroy S., Fontan E., Cordier F., Haouz A.,
RA   Raynal B., Chiaravalli J., Delepierre M., Israel A., Veron M., Agou F.;
RT   "DARPin-assisted crystallography of the CC2-LZ domain of NEMO reveals a
RT   coupling between dimerization and ubiquitin binding.";
RL   J. Mol. Biol. 395:89-104(2010).
RN   [44]
RP   INTERACTION WITH SHIGELLA FLEXNERI IPAH9.8 (MICROBIAL INFECTION), AND
RP   UBIQUITINATION AT LYS-309 AND LYS-321.
RX   PubMed=20010814; DOI=10.1038/ncb2006;
RA   Ashida H., Kim M., Schmidt-Supprian M., Ma A., Ogawa M., Sasakawa C.;
RT   "A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKgamma to dampen
RT   the host NF-kappaB-mediated inflammatory response.";
RL   Nat. Cell Biol. 12:66-73(2010).
RN   [45]
RP   FUNCTION, AND UBIQUITINATION.
RX   PubMed=20724660; DOI=10.1073/pnas.1004621107;
RA   Arimoto K., Funami K., Saeki Y., Tanaka K., Okawa K., Takeuchi O.,
RA   Akira S., Murakami Y., Shimotohno K.;
RT   "Polyubiquitin conjugation to NEMO by tripartite motif protein 23 (TRIM23)
RT   is critical in antiviral defense.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:15856-15861(2010).
RN   [46]
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   [47]
RP   FUNCTION, AND UBIQUITINATION BY TRAF7.
RX   PubMed=21518757; DOI=10.1074/jbc.m110.215426;
RA   Zotti T., Uva A., Ferravante A., Vessichelli M., Scudiero I.,
RA   Ceccarelli M., Vito P., Stilo R.;
RT   "TRAF7 protein promotes Lys-29-linked polyubiquitination of IkappaB kinase
RT   (IKKgamma)/NF-kappaB essential modulator (NEMO) and p65/RelA protein and
RT   represses NF-kappaB activation.";
RL   J. Biol. Chem. 286:22924-22933(2011).
RN   [48]
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   [49]
RP   NEDDYLATION BY TRIM40.
RX   PubMed=21474709; DOI=10.1093/carcin/bgr068;
RA   Noguchi K., Okumura F., Takahashi N., Kataoka A., Kamiyama T., Todo S.,
RA   Hatakeyama S.;
RT   "TRIM40 promotes neddylation of IKKgamma and is downregulated in
RT   gastrointestinal cancers.";
RL   Carcinogenesis 32:995-1004(2011).
RN   [50]
RP   FUNCTION, UBIQUITIN-BINDING, AND CHARACTERIZATION OF VARIANT EDAID1
RP   ASN-311.
RX   PubMed=21606507; DOI=10.1084/jem.20102177;
RA   Nanda S.K., Venigalla R.K., Ordureau A., Patterson-Kane J.C., Powell D.W.,
RA   Toth R., Arthur J.S., Cohen P.;
RT   "Polyubiquitin binding to ABIN1 is required to prevent autoimmunity.";
RL   J. Exp. Med. 208:1215-1228(2011).
RN   [51]
RP   INTERACTION WITH TNFAIP3.
RX   PubMed=22099304; DOI=10.1016/j.molcel.2011.09.015;
RA   Skaug B., Chen J., Du F., He J., Ma A., Chen Z.J.;
RT   "Direct, noncatalytic mechanism of IKK inhibition by A20.";
RL   Mol. Cell 44:559-571(2011).
RN   [52]
RP   UBIQUITINATION BY THE LUBAC COMPLEX.
RX   PubMed=21455173; DOI=10.1038/nature09816;
RA   Gerlach B., Cordier S.M., Schmukle A.C., Emmerich C.H., Rieser E.,
RA   Haas T.L., Webb A.I., Rickard J.A., Anderton H., Wong W.W., Nachbur U.,
RA   Gangoda L., Warnken U., Purcell A.W., Silke J., Walczak H.;
RT   "Linear ubiquitination prevents inflammation and regulates immune
RT   signalling.";
RL   Nature 471:591-596(2011).
RN   [53]
RP   UBIQUITINATION BY THE LUBAC COMPLEX.
RX   PubMed=21455180; DOI=10.1038/nature09815;
RA   Tokunaga F., Nakagawa T., Nakahara M., Saeki Y., Taniguchi M., Sakata S.,
RA   Tanaka K., Nakano H., Iwai K.;
RT   "SHARPIN is a component of the NF-kappaB-activating linear ubiquitin chain
RT   assembly complex.";
RL   Nature 471:633-636(2011).
RN   [54]
RP   UBIQUITINATION AT LYS-277; LYS-285; LYS-309; LYS-326; LYS-111; LYS-143;
RP   LYS-226; LYS-246; LYS-264; LYS-292 AND LYS-302 BY THE LUBAC COMPLEX, AND
RP   UBIQUITINATION AT LYS-139 AND LYS-283.
RX   PubMed=21455181; DOI=10.1038/nature09814;
RA   Ikeda F., Deribe Y.L., Skanland S.S., Stieglitz B., Grabbe C.,
RA   Franz-Wachtel M., van Wijk S.J., Goswami P., Nagy V., Terzic J.,
RA   Tokunaga F., Androulidaki A., Nakagawa T., Pasparakis M., Iwai K.,
RA   Sundberg J.P., Schaefer L., Rittinger K., Macek B., Dikic I.;
RT   "SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappaB
RT   activity and apoptosis.";
RL   Nature 471:637-641(2011).
RN   [55]
RP   INTERACTION WITH NLRP10.
RX   PubMed=22672233; DOI=10.1111/j.1462-5822.2012.01822.x;
RA   Lautz K., Damm A., Menning M., Wenger J., Adam A.C., Zigrino P.,
RA   Kremmer E., Kufer T.A.;
RT   "NLRP10 enhances Shigella-induced pro-inflammatory responses.";
RL   Cell. Microbiol. 14:1568-1583(2012).
RN   [56]
RP   INTERACTION WITH IKBKE.
RX   PubMed=23453969; DOI=10.1016/j.celrep.2013.01.031;
RA   Zhou A.Y., Shen R.R., Kim E., Lock Y.J., Xu M., Chen Z.J., Hahn W.C.;
RT   "IKKepsilon-mediated tumorigenesis requires K63-linked polyubiquitination
RT   by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex.";
RL   Cell Rep. 3:724-733(2013).
RN   [57]
RP   PHOSPHORYLATION AT SER-387.
RX   PubMed=24012789; DOI=10.1016/j.pep.2013.08.020;
RA   Jackson S.S., Coughlin E.E., Coon J.J., Miyamoto S.;
RT   "Identifying post-translational modifications of NEMO by tandem mass
RT   spectrometry after high affinity purification.";
RL   Protein Expr. Purif. 92:48-53(2013).
RN   [58]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-387, 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   [59]
RP   SUBCELLULAR LOCATION, AND DEUBIQUITINATION BY EPSTEIN-BARR VIRUS PROTEIN
RP   BPLF1 (MICROBIAL INFECTION).
RX   PubMed=24586164; DOI=10.1371/journal.ppat.1003960;
RA   van Gent M., Braem S.G., de Jong A., Delagic N., Peeters J.G., Boer I.G.,
RA   Moynagh P.N., Kremmer E., Wiertz E.J., Ovaa H., Griffin B.D., Ressing M.E.;
RT   "Epstein-Barr virus large tegument protein BPLF1 contributes to innate
RT   immune evasion through interference with toll-like receptor signaling.";
RL   PLoS Pathog. 10:e1003960-e1003960(2014).
RN   [60]
RP   INTERACTION WITH IFIT5.
RX   PubMed=26334375; DOI=10.1016/j.cellsig.2015.08.018;
RA   Zheng C., Zheng Z., Zhang Z., Meng J., Liu Y., Ke X., Hu Q., Wang H.;
RT   "IFIT5 positively regulates NF-kappaB signaling through synergizing the
RT   recruitment of IkappaB kinase (IKK) to TGF-beta-activated kinase 1
RT   (TAK1).";
RL   Cell. Signal. 27:2343-2354(2015).
RN   [61]
RP   INTERACTION WITH TANK; USP10 AND ZC3H12A, AND DEUBIQUITINATION BY USP10.
RX   PubMed=25861989; DOI=10.1074/jbc.m115.643767;
RA   Wang W., Huang X., Xin H.B., Fu M., Xue A., Wu Z.H.;
RT   "TRAF family member-associated NF-kappaB activator (TANK) inhibits
RT   genotoxic nuclear factor kappaB activation by facilitating deubiquitinase
RT   USP10-dependent deubiquitination of TRAF6 ligase.";
RL   J. Biol. Chem. 290:13372-13385(2015).
RN   [62]
RP   INTERACTION WITH ARFIP2.
RX   PubMed=26296658; DOI=10.1016/j.cellsig.2015.08.012;
RA   You D.J., Park C.R., Furlong M., Koo O., Lee C., Ahn C., Seong J.Y.,
RA   Hwang J.I.;
RT   "Dimer of arfaptin 2 regulates NF-kappaB signaling by interacting with
RT   IKKbeta/NEMO and inhibiting IKKbeta kinase activity.";
RL   Cell. Signal. 27:2173-2181(2015).
RN   [63]
RP   FUNCTION, UBIQUITIN-BINDING, AND INTERACTION WITH BCL10.
RX   PubMed=27777308; DOI=10.1074/jbc.m116.754028;
RA   Yang Y.K., Yang C., Chan W., Wang Z., Deibel K.E., Pomerantz J.L.;
RT   "Molecular determinants of scaffold-induced linear ubiquitinylation of B
RT   Cell Lymphoma/Leukemia 10 (Bcl10) during T cell receptor and oncogenic
RT   caspase recruitment domain-containing protein 11 (CARD11) signaling.";
RL   J. Biol. Chem. 291:25921-25936(2016).
RN   [64]
RP   INTERACTION WITH MOLLUSCUM CONTAGIOSUM VIRUS PROTEIN MC005 (MICROBIAL
RP   INFECTION).
RX   PubMed=28490597; DOI=10.1128/jvi.00545-17;
RA   Brady G., Haas D.A., Farrell P.J., Pichlmair A., Bowie A.G.;
RT   "Molluscum contagiosum virus protein MC005 inhibits NF-kappaB activation by
RT   targeting NEMO-regulated IkappaB kinase activation.";
RL   J. Virol. 91:0-0(2017).
RN   [65]
RP   IDENTIFICATION IN THE IKK COMPLEX, INTERACTION WITH MARCHF2, UBIQUITINATION
RP   AT LYS-326, AND MUTAGENESIS OF LYS-302; LYS-309; LYS-321; LYS-325; LYS-326;
RP   LYS-342; LYS-344 AND LYS-358.
RX   PubMed=32935379; DOI=10.15252/embj.2020105139;
RA   Chathuranga K., Kim T.H., Lee H., Park J.S., Kim J.H., Chathuranga W.A.G.,
RA   Ekanayaka P., Choi Y.J., Lee C.H., Kim C.J., Jung J.U., Lee J.S.;
RT   "Negative regulation of NEMO signaling by the ubiquitin E3 ligase MARCH2.";
RL   EMBO J. 39:e105139-e105139(2020).
RN   [66]
RP   INTERACTION WITH SARS-COV-2 VIRUS PROTEIN ORF9B (MICROBIAL INFECTION),
RP   UBIQUITINATION, AND FUNCTION.
RX   PubMed=33567255; DOI=10.1016/j.celrep.2021.108761;
RA   Wu J., Shi Y., Pan X., Wu S., Hou R., Zhang Y., Zhong T., Tang H., Du W.,
RA   Wang L., Wo J., Mu J., Qiu Y., Yang K., Zhang L.K., Ye B.C., Qi N.;
RT   "SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting
RT   K63-linked ubiquitination of NEMO.";
RL   Cell Rep. 34:108761-108761(2021).
RN   [67]
RP   STRUCTURE BY NMR OF 394-419 OF WILD-TYPE AND MUTANT PHE-417, AND DOMAIN
RP   ZINC-FINGER.
RX   PubMed=18313693; DOI=10.1016/j.jmb.2008.01.048;
RA   Cordier F., Vinolo E., Veron M., Delepierre M., Agou F.;
RT   "Solution structure of NEMO zinc finger and impact of an anhidrotic
RT   ectodermal dysplasia with immunodeficiency-related point mutation.";
RL   J. Mol. Biol. 377:1419-1432(2008).
RN   [68]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 44-111 IN COMPLEX WITH CHUK AND
RP   IKBKB, AND SUBUNIT.
RX   PubMed=18462684; DOI=10.1016/j.str.2008.02.012;
RA   Rushe M., Silvian L., Bixler S., Chen L.L., Cheung A., Bowes S., Cuervo H.,
RA   Berkowitz S., Zheng T., Guckian K., Pellegrini M., Lugovskoy A.;
RT   "Structure of a NEMO/IKK-associating domain reveals architecture of the
RT   interaction site.";
RL   Structure 16:798-808(2008).
RN   [69]
RP   X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 246-337, FUNCTION,
RP   UBIQUITIN-BINDING, MUTAGENESIS OF VAL-300; LEU-301; GLN-304; ILE-307;
RP   TYR-308; PHE-312; GLN-313 AND GLN-317, CHARACTERIZATION OF VARIANT EDAID1
RP   ASN-311, CHARACTERIZATION OF VARIANT IMD33 ALA-315, AND CHARACTERIZATION OF
RP   VARIANTS GLN-319 AND IP PRO-323.
RX   PubMed=19185524; DOI=10.1016/j.molcel.2009.01.012;
RA   Lo Y.C., Lin S.C., Rospigliosi C.C., Conze D.B., Wu C.J., Ashwell J.D.,
RA   Eliezer D., Wu H.;
RT   "Structural basis for recognition of diubiquitins by NEMO.";
RL   Mol. Cell 33:602-615(2009).
RN   [70]
RP   VARIANTS EDAID1 ARG-417 AND PHE-417.
RX   PubMed=11047757; DOI=10.1086/316914;
RA   Zonana J., Elder M.E., Schneider L.C., Orlow S.J., Moss C., Golabi M.,
RA   Shapira S.K., Farndon P.A., Wara D.W., Emmal S.A., Ferguson B.M.;
RT   "A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal
RT   dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-
RT   gamma (NEMO).";
RL   Am. J. Hum. Genet. 67:1555-1562(2000).
RN   [71]
RP   VARIANTS IP LYS-57 AND VAL-407.
RX   PubMed=11590134; DOI=10.1093/hmg/10.19.2171;
RA   Aradhya S., Woffendin H., Jakins T., Bardaro T., Esposito T., Smahi A.,
RA   Shaw C., Levy M., Munnich A., D'Urso M., Lewis R.A., Kenwrick S.,
RA   Nelson D.L.;
RT   "A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene
RT   accounts for the vast majority of incontinentia pigmenti mutations.";
RL   Hum. Mol. Genet. 10:2171-2179(2001).
RN   [72]
RP   INVOLVEMENT IN EDAID1, AND VARIANTS EDAID1 PRO-175; PRO-227; GLY-288;
RP   ASN-311; ARG-417 AND PHE-417.
RX   PubMed=11242109; DOI=10.1038/85837;
RA   Doeffinger R., Smahi A., Bessia C., Geissmann F., Feinberg J., Durandy A.,
RA   Bodemer C., Kenwrick S.J., Dupuis-Girod S., Blanche S., Wood P.,
RA   Rabia S.H., Headon D.J., Overbeek P.A., Le Deist F., Holland S.M.,
RA   Belani K., Kumararatne D.S., Fischer A., Shapiro R., Conley M.E.,
RA   Reimund E., Kalhoff H., Abinun M., Munnich A., Israael A., Courtois G.,
RA   Casanova J.-L.;
RT   "X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused
RT   by impaired NF-kappa B signaling.";
RL   Nat. Genet. 27:277-285(2001).
RN   [73]
RP   VARIANTS EDAID1 VAL-406 AND ARG-417.
RX   PubMed=11224521; DOI=10.1038/85277;
RA   Jain A., Ma C.A., Liu S., Brown M., Cohen J., Strober W.;
RT   "Specific missense mutations in NEMO result in hyper-IgM syndrome with
RT   hypohydrotic ectodermal dysplasia.";
RL   Nat. Immunol. 2:223-228(2001).
RN   [74]
RP   VARIANTS EDAID1 ARG-153 AND ARG-417.
RX   PubMed=12045264; DOI=10.1172/jci14858;
RA   Orange J.S., Brodeur S.R., Jain A., Bonilla F.A., Schneider L.C.,
RA   Kretschmer R., Nurko S., Rasmussen W.L., Koehler J.R., Gellis S.E.,
RA   Ferguson B.M., Strominger J.L., Zonana J., Ramesh N., Ballas Z.K.,
RA   Geha R.S.;
RT   "Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO
RT   mutations.";
RL   J. Clin. Invest. 109:1501-1509(2002).
RN   [75]
RP   VARIANTS IP LYS-57; LYS-90 DEL AND TRP-123, VARIANT ASN-113,
RP   CHARACTERIZATION OF VARIANTS IP LYS-57; LYS-90 DEL AND TRP-123, AND
RP   CHARACTERIZATION OF VARIANT ASN-113.
RX   PubMed=15229184; DOI=10.1093/hmg/ddh192;
RA   Fusco F., Bardaro T., Fimiani G., Mercadante V., Miano M.G., Falco G.,
RA   Israeel A., Courtois G., D'Urso M., Ursini M.V.;
RT   "Molecular analysis of the genetic defect in a large cohort of IP patients
RT   and identification of novel NEMO mutations interfering with NF-kappaB
RT   activation.";
RL   Hum. Mol. Genet. 13:1763-1773(2004).
RN   [76]
RP   VARIANTS EDAID1 ARG-153 AND ARG-417, AND VARIANT IMD33 TYR-417.
RX   PubMed=15100680; DOI=10.1016/j.jaci.2004.01.762;
RA   Orange J.S., Jain A., Ballas Z.K., Schneider L.C., Geha R.S., Bonilla F.A.;
RT   "The presentation and natural history of immunodeficiency caused by nuclear
RT   factor kappaB essential modulator mutation.";
RL   J. Allergy Clin. Immunol. 113:725-733(2004).
RN   [77]
RP   INVOLVEMENT IN IMD33.
RX   PubMed=15356572; DOI=10.1016/j.jaci.2004.06.052;
RA   Orange J.S., Levy O., Brodeur S.R., Krzewski K., Roy R.M., Niemela J.E.,
RA   Fleisher T.A., Bonilla F.A., Geha R.S.;
RT   "Human nuclear factor kappa B essential modulator mutation can result in
RT   immunodeficiency without ectodermal dysplasia.";
RL   J. Allergy Clin. Immunol. 114:650-656(2004).
RN   [78]
RP   INTERACTION WITH TRIM13.
RX   PubMed=25152375; DOI=10.1016/j.cellsig.2014.08.008;
RA   Tomar D., Singh R.;
RT   "TRIM13 regulates ubiquitination and turnover of NEMO to suppress TNF
RT   induced NF-kappaB activation.";
RL   Cell. Signal. 26:2606-2613(2014).
RN   [79]
RP   CLEAVAGE BY HAV PROTEASE 3C (MICROBIAL INFECTION), CLEAVAGE SITES, AND
RP   MUTAGENESIS OF GLN-304.
RX   PubMed=24920812; DOI=10.1128/jvi.00869-14;
RA   Wang D., Fang L., Wei D., Zhang H., Luo R., Chen H., Li K., Xiao S.;
RT   "Hepatitis A virus 3C protease cleaves NEMO to impair induction of beta
RT   interferon.";
RL   J. Virol. 88:10252-10258(2014).
RN   [80]
RP   INTERACTION WITH TRIM29.
RX   PubMed=27695001; DOI=10.1038/ni.3580;
RA   Xing J., Weng L., Yuan B., Wang Z., Jia L., Jin R., Lu H., Li X.C.,
RA   Liu Y.J., Zhang Z.;
RT   "Identification of a role for TRIM29 in the control of innate immunity in
RT   the respiratory tract.";
RL   Nat. Immunol. 17:1373-1380(2016).
RN   [81]
RP   INVOLVEMENT IN SAIDX.
RX   PubMed=31874111; DOI=10.1172/jci129301;
RA   de Jesus A.A., Hou Y., Brooks S., Malle L., Biancotto A., Huang Y.,
RA   Calvo K.R., Marrero B., Moir S., Oler A.J., Deng Z.,
RA   Montealegre Sanchez G.A., Ahmed A., Allenspach E., Arabshahi B.,
RA   Behrens E., Benseler S., Bezrodnik L., Bout-Tabaku S., Brescia A.C.,
RA   Brown D., Burnham J.M., Caldirola M.S., Carrasco R., Chan A.Y., Cimaz R.,
RA   Dancey P., Dare J., DeGuzman M., Dimitriades V., Ferguson I., Ferguson P.,
RA   Finn L., Gattorno M., Grom A.A., Hanson E.P., Hashkes P.J., Hedrich C.M.,
RA   Herzog R., Horneff G., Jerath R., Kessler E., Kim H., Kingsbury D.J.,
RA   Laxer R.M., Lee P.Y., Lee-Kirsch M.A., Lewandowski L., Li S., Lilleby V.,
RA   Mammadova V., Moorthy L.N., Nasrullayeva G., O'Neil K.M., Onel K., Ozen S.,
RA   Pan N., Pillet P., Piotto D.G., Punaro M.G., Reiff A., Reinhardt A.,
RA   Rider L.G., Rivas-Chacon R., Ronis T., Roesen-Wolff A., Roth J., Ruth N.M.,
RA   Rygg M., Schmeling H., Schulert G., Scott C., Seminario G., Shulman A.,
RA   Sivaraman V., Son M.B., Stepanovskiy Y., Stringer E., Taber S.,
RA   Terreri M.T., Tifft C., Torgerson T., Tosi L., Van Royen-Kerkhof A.,
RA   Wampler Muskardin T., Canna S.W., Goldbach-Mansky R.;
RT   "Distinct interferon signatures and cytokine patterns define additional
RT   systemic autoinflammatory diseases.";
RL   J. Clin. Invest. 130:1669-1682(2020).
RN   [82]
RP   INVOLVEMENT IN SAIDX.
RX   PubMed=35289316; DOI=10.1172/jci128808;
RA   Lee Y., Wessel A.W., Xu J., Reinke J.G., Lee E., Kim S.M., Hsu A.P.,
RA   Zilberman-Rudenko J., Cao S., Enos C., Brooks S.R., Deng Z., Lin B.,
RA   de Jesus A.A., Hupalo D.N., Piotto D.G., Terreri M.T., Dimitriades V.R.,
RA   Dalgard C.L., Holland S.M., Goldbach-Mansky R., Siegel R.M., Hanson E.P.;
RT   "Genetically programmed alternative splicing of NEMO mediates an
RT   autoinflammatory disease phenotype.";
RL   J. Clin. Invest. 132:0-0(2022).
RN   [83]
RP   VARIANTS IMD33 ALA-315 AND GLN-319.
RX   PubMed=16818673; DOI=10.1084/jem.20060085;
RA   Filipe-Santos O., Bustamante J., Haverkamp M.H., Vinolo E., Ku C.-L.,
RA   Puel A., Frucht D.M., Christel K., von Bernuth H., Jouanguy E.,
RA   Feinberg J., Durandy A., Senechal B., Chapgier A., Vogt G.,
RA   de Beaucoudrey L., Fieschi C., Picard C., Garfa M., Chemli J., Bejaoui M.,
RA   Tsolia M.N., Kutukculer N., Plebani A., Notarangelo L., Bodemer C.,
RA   Geissmann F., Israeel A., Veron M., Knackstedt M., Barbouche R., Abel L.,
RA   Magdorf K., Gendrel D., Agou F., Holland S.M., Casanova J.-L.;
RT   "X-linked susceptibility to mycobacteria is caused by mutations in NEMO
RT   impairing CD40-dependent IL-12 production.";
RL   J. Exp. Med. 203:1745-1759(2006).
RN   [84]
RP   VARIANT IP PRO-323, CHARACTERIZATION OF VARIANT IP PRO-323, AND INTERACTION
RP   WITH TRAF6.
RX   PubMed=17728323; DOI=10.1093/hmg/ddm237;
RA   Sebban-Benin H., Pescatore A., Fusco F., Pascuale V., Gautheron J.,
RA   Yamaoka S., Moncla A., Ursini M.V., Courtois G.;
RT   "Identification of TRAF6-dependent NEMO polyubiquitination sites through
RT   analysis of a new NEMO mutation causing incontinentia pigmenti.";
RL   Hum. Mol. Genet. 16:2805-2815(2007).
RN   [85]
RP   VARIANT IP HIS-183.
RX   PubMed=20434027; DOI=10.1016/s0929-6646(10)60042-3;
RA   Hsiao P.F., Lin S.P., Chiang S.S., Wu Y.H., Chen H.C., Lin Y.C.;
RT   "NEMO gene mutations in Chinese patients with incontinentia pigmenti.";
RL   J. Formos. Med. Assoc. 109:192-200(2010).
RN   [86]
RP   VARIANTS IP PRO-170; GLN-173; PRO-314; PRO-322 AND TYR-413.
RX   PubMed=24339369; DOI=10.1002/humu.22483;
RA   Conte M.I., Pescatore A., Paciolla M., Esposito E., Miano M.G., Lioi M.B.,
RA   McAleer M.A., Giardino G., Pignata C., Irvine A.D., Scheuerle A.E.,
RA   Royer G., Hadj-Rabia S., Bodemer C., Bonnefont J.P., Munnich A., Smahi A.,
RA   Steffann J., Fusco F., Ursini M.V.;
RT   "Insight into IKBKG/NEMO locus: report of new mutations and complex genomic
RT   rearrangements leading to incontinentia pigmenti disease.";
RL   Hum. Mutat. 35:165-177(2014).
RN   [87]
RP   VARIANT IMD33 GLY-173.
RX   PubMed=16950813; DOI=10.1136/jmg.2006.044446;
RA   Ku C.-L., Picard C., Erdos M., Jeurissen A., Bustamante J., Puel A.,
RA   von Bernuth H., Filipe-Santos O., Chang H.-H., Lawrence T., Raes M.,
RA   Marodi L., Bossuyt X., Casanova J.-L.;
RT   "IRAK4 and NEMO mutations in otherwise healthy children with recurrent
RT   invasive pneumococcal disease.";
RL   J. Med. Genet. 44:16-23(2007).
CC   -!- FUNCTION: Regulatory subunit of the IKK core complex which
CC       phosphorylates inhibitors of NF-kappa-B thus leading to the
CC       dissociation of the inhibitor/NF-kappa-B complex and ultimately the
CC       degradation of the inhibitor (PubMed:14695475, PubMed:20724660,
CC       PubMed:21518757, PubMed:9751060). Its binding to scaffolding
CC       polyubiquitin plays a key role in IKK activation by multiple signaling
CC       receptor pathways (PubMed:16547522, PubMed:18287044, PubMed:19033441,
CC       PubMed:19185524, PubMed:21606507, PubMed:27777308, PubMed:33567255).
CC       Can recognize and bind both 'Lys-63'-linked and linear polyubiquitin
CC       upon cell stimulation, with a much higher affinity for linear
CC       polyubiquitin (PubMed:16547522, PubMed:18287044, PubMed:19033441,
CC       PubMed:19185524, PubMed:21606507, PubMed:27777308). Could be implicated
CC       in NF-kappa-B-mediated protection from cytokine toxicity. Essential for
CC       viral activation of IRF3 (PubMed:19854139). Involved in TLR3- and
CC       IFIH1-mediated antiviral innate response; this function requires 'Lys-
CC       27'-linked polyubiquitination (PubMed:20724660).
CC       {ECO:0000269|PubMed:14695475, ECO:0000269|PubMed:16547522,
CC       ECO:0000269|PubMed:18287044, ECO:0000269|PubMed:19033441,
CC       ECO:0000269|PubMed:19185524, ECO:0000269|PubMed:19854139,
CC       ECO:0000269|PubMed:20724660, ECO:0000269|PubMed:21518757,
CC       ECO:0000269|PubMed:21606507, ECO:0000269|PubMed:27777308,
CC       ECO:0000269|PubMed:33567255, ECO:0000269|PubMed:9751060}.
CC   -!- FUNCTION: (Microbial infection) Also considered to be a mediator for
CC       HTLV-1 Tax oncoprotein activation of NF-kappa-B.
CC       {ECO:0000269|PubMed:10364167, ECO:0000269|PubMed:11064457}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:18164680). Component of
CC       the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and
CC       IKBKG; probably four alpha/CHUK-beta/IKBKB dimers are associated with
CC       four gamma/IKBKG subunits (PubMed:11080499, PubMed:17977820,
CC       PubMed:18462684, PubMed:32935379, PubMed:9751060, PubMed:9891086). The
CC       IKK core complex seems to associate with regulatory or adapter proteins
CC       to form a IKK-signalosome holo-complex (PubMed:11080499,
CC       PubMed:9751060, PubMed:9891086). The IKK complex associates with
CC       TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of
CC       RELA/p65 (By similarity). Part of a complex composed of NCOA2, NCOA3,
CC       CHUK/IKKA, IKBKB, IKBKG and CREBBP (PubMed:11971985). Interacts with
CC       COPS3, CYLD, NALP2, TRPC4AP and PIDD1 (PubMed:11418127,
CC       PubMed:12917691, PubMed:15456791, PubMed:16360037). Interacts with ATM;
CC       the complex is exported from the nucleus (PubMed:16497931). Interacts
CC       with TRAF6 (PubMed:17728323). Interacts with IKBKE (PubMed:23453969).
CC       Interacts with TANK; the interaction is enhanced by IKBKE and TBK1
CC       (PubMed:12133833). Part of a ternary complex consisting of TANK, IKBKB
CC       and IKBKG (PubMed:12133833). Interacts with ZFAND5 (PubMed:14754897).
CC       Interacts with RIPK2 (PubMed:18079694). Interacts with TNIP1 and
CC       TNFAIP3; TNIP1 facilitates the TNFAIP3-mediated de-ubiquitination of
CC       IKBKG (PubMed:11389905, PubMed:22099304). Interacts with TNFAIP3; the
CC       interaction is induced by TNF stimulation and by polyubiquitin
CC       (PubMed:11389905, PubMed:22099304). Binds (via UBAN region)
CC       polyubiquitin; binds both 'Lys-63'-linked and linear polyubiquitin,
CC       with higher affinity for linear ubiquitin (PubMed:16547522,
CC       PubMed:19033441, PubMed:19185524, PubMed:21606507). Interacts with
CC       NLRP10 (PubMed:22672233). Interacts with TANK; this interaction
CC       increases in response to DNA damage (PubMed:25861989). Interacts with
CC       USP10; this interaction increases in response to DNA damage
CC       (PubMed:25861989). Interacts with ZC3H12A; this interaction increases
CC       in response to DNA damage (PubMed:25861989). Interacts with IFIT5; the
CC       interaction synergizes the recruitment of IKK to MAP3K7 and enhances
CC       IKK phosphorylation (PubMed:26334375). Interacts with TRIM29; this
CC       interaction induces IKBKG/NEMO ubiquitination and proteolytic
CC       degradation (PubMed:27695001). Interacts with TRIM13; this interaction
CC       leads to IKBKG/NEMO ubiquitination (PubMed:25152375). Interacts with
CC       ARFIP2 (PubMed:26296658). Interacts with RIPK1 (By similarity).
CC       Interacts with (ubiquitinated) BCL10; interaction with
CC       polyubiquitinated BCL10 via both 'Lys-63'-linked and linear ubiquitin
CC       is required for TCR-induced NF-kappa-B activation (PubMed:18287044,
CC       PubMed:27777308). Interacts with MARCHF2; during the late stages of
CC       macrophage viral and bacterial infection; the interaction leads to
CC       ubiquitination and degradation of IKBKG/NEMO (PubMed:32935379).
CC       {ECO:0000250|UniProtKB:O88522, ECO:0000269|PubMed:11080499,
CC       ECO:0000269|PubMed:11389905, ECO:0000269|PubMed:11418127,
CC       ECO:0000269|PubMed:11971985, ECO:0000269|PubMed:12133833,
CC       ECO:0000269|PubMed:12917691, ECO:0000269|PubMed:14754897,
CC       ECO:0000269|PubMed:15456791, ECO:0000269|PubMed:16360037,
CC       ECO:0000269|PubMed:16497931, ECO:0000269|PubMed:16547522,
CC       ECO:0000269|PubMed:17728323, ECO:0000269|PubMed:17977820,
CC       ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:18164680,
CC       ECO:0000269|PubMed:18287044, ECO:0000269|PubMed:18462684,
CC       ECO:0000269|PubMed:19033441, ECO:0000269|PubMed:19185524,
CC       ECO:0000269|PubMed:21606507, ECO:0000269|PubMed:22099304,
CC       ECO:0000269|PubMed:22672233, ECO:0000269|PubMed:23453969,
CC       ECO:0000269|PubMed:25152375, ECO:0000269|PubMed:25861989,
CC       ECO:0000269|PubMed:26296658, ECO:0000269|PubMed:26334375,
CC       ECO:0000269|PubMed:27695001, ECO:0000269|PubMed:27777308,
CC       ECO:0000269|PubMed:32935379, ECO:0000269|PubMed:9751060,
CC       ECO:0000269|PubMed:9891086}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with Molluscum contagiosum
CC       virus protein MC005; this interaction inhibits NF-kappa-B activation.
CC       {ECO:0000269|PubMed:28490597}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with HTLV-1 Tax oncoprotein;
CC       the interaction activates IKBKG. {ECO:0000269|PubMed:10364167,
CC       ECO:0000269|PubMed:11064457}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with Shigella flexneri
CC       ipah9.8; the interaction promotes TNIP1-dependent 'Lys-27'-linked
CC       polyubiquitination of IKBKG which perturbs NF-kappa-B activation during
CC       bacterial infection. {ECO:0000269|PubMed:20010814}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with SARS coronavirus-2/SARS-
CC       CoV-2 virus protein ORF9B (via N-terminus); the interaction inhibits
CC       polyubiquitination through 'Lys-63' and NF-kappa-B activation.
CC       {ECO:0000269|PubMed:33567255}.
CC   -!- INTERACTION:
CC       Q9Y6K9; Q9NPF8: ADAP2; NbExp=2; IntAct=EBI-81279, EBI-718895;
CC       Q9Y6K9; Q4VCS5: AMOT; NbExp=3; IntAct=EBI-81279, EBI-2511319;
CC       Q9Y6K9; P04083: ANXA1; NbExp=6; IntAct=EBI-81279, EBI-354007;
CC       Q9Y6K9; Q66PJ3: ARL6IP4; NbExp=2; IntAct=EBI-81279, EBI-2683099;
CC       Q9Y6K9; Q13315: ATM; NbExp=4; IntAct=EBI-81279, EBI-495465;
CC       Q9Y6K9; Q13535: ATR; NbExp=2; IntAct=EBI-81279, EBI-968983;
CC       Q9Y6K9; O95999: BCL10; NbExp=7; IntAct=EBI-81279, EBI-958922;
CC       Q9Y6K9; P05937: CALB1; NbExp=3; IntAct=EBI-81279, EBI-4286943;
CC       Q9Y6K9; Q16543: CDC37; NbExp=6; IntAct=EBI-81279, EBI-295634;
CC       Q9Y6K9; P24941: CDK2; NbExp=4; IntAct=EBI-81279, EBI-375096;
CC       Q9Y6K9; O15111: CHUK; NbExp=27; IntAct=EBI-81279, EBI-81249;
CC       Q9Y6K9; Q9UNS2: COPS3; NbExp=2; IntAct=EBI-81279, EBI-350590;
CC       Q9Y6K9; Q2TBE0: CWF19L2; NbExp=3; IntAct=EBI-81279, EBI-5453285;
CC       Q9Y6K9; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-81279, EBI-744099;
CC       Q9Y6K9; P36888: FLT3; NbExp=2; IntAct=EBI-81279, EBI-3946257;
CC       Q9Y6K9; Q14161: GIT2; NbExp=6; IntAct=EBI-81279, EBI-1046878;
CC       Q9Y6K9; Q92917: GPKOW; NbExp=3; IntAct=EBI-81279, EBI-746309;
CC       Q9Y6K9; Q7Z4H3: HDDC2; NbExp=3; IntAct=EBI-81279, EBI-6163836;
CC       Q9Y6K9; P07900: HSP90AA1; NbExp=3; IntAct=EBI-81279, EBI-296047;
CC       Q9Y6K9; P08238: HSP90AB1; NbExp=3; IntAct=EBI-81279, EBI-352572;
CC       Q9Y6K9; O14920: IKBKB; NbExp=36; IntAct=EBI-81279, EBI-81266;
CC       Q9Y6K9; Q9Y6K9: IKBKG; NbExp=8; IntAct=EBI-81279, EBI-81279;
CC       Q9Y6K9; P05783: KRT18; NbExp=3; IntAct=EBI-81279, EBI-297888;
CC       Q9Y6K9; P05787: KRT8; NbExp=2; IntAct=EBI-81279, EBI-297852;
CC       Q9Y6K9; Q96PV6: LENG8; NbExp=3; IntAct=EBI-81279, EBI-739546;
CC       Q9Y6K9; Q9UDY8: MALT1; NbExp=4; IntAct=EBI-81279, EBI-1047372;
CC       Q9Y6K9; Q99558: MAP3K14; NbExp=4; IntAct=EBI-81279, EBI-358011;
CC       Q9Y6K9; P01106: MYC; NbExp=3; IntAct=EBI-81279, EBI-447544;
CC       Q9Y6K9; P25963: NFKBIA; NbExp=6; IntAct=EBI-81279, EBI-307386;
CC       Q9Y6K9; Q9UJX0: OSGIN1; NbExp=3; IntAct=EBI-81279, EBI-9057006;
CC       Q9Y6K9; P67775: PPP2CA; NbExp=4; IntAct=EBI-81279, EBI-712311;
CC       Q9Y6K9; Q99633: PRPF18; NbExp=3; IntAct=EBI-81279, EBI-2798416;
CC       Q9Y6K9; P28074: PSMB5; NbExp=3; IntAct=EBI-81279, EBI-357828;
CC       Q9Y6K9; Q9BYM8: RBCK1; NbExp=9; IntAct=EBI-81279, EBI-2340624;
CC       Q9Y6K9; Q13546: RIPK1; NbExp=8; IntAct=EBI-81279, EBI-358507;
CC       Q9Y6K9; Q96EP0: RNF31; NbExp=10; IntAct=EBI-81279, EBI-948111;
CC       Q9Y6K9; Q9UBF6: RNF7; NbExp=3; IntAct=EBI-81279, EBI-398632;
CC       Q9Y6K9; Q9BVN2-2: RUSC1; NbExp=4; IntAct=EBI-81279, EBI-6257338;
CC       Q9Y6K9; Q9HC62: SENP2; NbExp=3; IntAct=EBI-81279, EBI-714881;
CC       Q9Y6K9; Q9H0F6: SHARPIN; NbExp=14; IntAct=EBI-81279, EBI-3942966;
CC       Q9Y6K9; O95391: SLU7; NbExp=3; IntAct=EBI-81279, EBI-750559;
CC       Q9Y6K9; Q13573: SNW1; NbExp=4; IntAct=EBI-81279, EBI-632715;
CC       Q9Y6K9; Q13501: SQSTM1; NbExp=2; IntAct=EBI-81279, EBI-307104;
CC       Q9Y6K9; P12931: SRC; NbExp=3; IntAct=EBI-81279, EBI-621482;
CC       Q9Y6K9; P63165: SUMO1; NbExp=3; IntAct=EBI-81279, EBI-80140;
CC       Q9Y6K9; P21579: SYT1; NbExp=3; IntAct=EBI-81279, EBI-524909;
CC       Q9Y6K9; Q92844: TANK; NbExp=5; IntAct=EBI-81279, EBI-356349;
CC       Q9Y6K9; Q9UHD2: TBK1; NbExp=4; IntAct=EBI-81279, EBI-356402;
CC       Q9Y6K9; P01375: TNF; NbExp=3; IntAct=EBI-81279, EBI-359977;
CC       Q9Y6K9; P21580: TNFAIP3; NbExp=5; IntAct=EBI-81279, EBI-527670;
CC       Q9Y6K9; Q15025: TNIP1; NbExp=6; IntAct=EBI-81279, EBI-357849;
CC       Q9Y6K9; Q8NFZ5: TNIP2; NbExp=8; IntAct=EBI-81279, EBI-359372;
CC       Q9Y6K9; P0CG48: UBC; NbExp=4; IntAct=EBI-81279, EBI-3390054;
CC       Q9Y6K9; Q9Y2X8: UBE2D4; NbExp=3; IntAct=EBI-81279, EBI-745527;
CC       Q9Y6K9; Q5D1E8: ZC3H12A; NbExp=2; IntAct=EBI-81279, EBI-747793;
CC       Q9Y6K9; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-81279, EBI-6427977;
CC       Q9Y6K9; Q9Y2P0: ZNF835; NbExp=3; IntAct=EBI-81279, EBI-5667516;
CC       Q9Y6K9; P0DTD2: 9b; Xeno; NbExp=3; IntAct=EBI-81279, EBI-25475909;
CC       Q9Y6K9; Q8VSC3: ipaH9.8; Xeno; NbExp=8; IntAct=EBI-81279, EBI-6125799;
CC       Q9Y6K9; PRO_0000449631 [P0DTD1]: rep; Xeno; NbExp=3; IntAct=EBI-81279, EBI-25475920;
CC       Q9Y6K9-1; PRO_0000449623 [P0DTD1]: rep; Xeno; NbExp=2; IntAct=EBI-27121550, EBI-25475864;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14651848,
CC       ECO:0000269|PubMed:24586164}. Nucleus {ECO:0000269|PubMed:14651848}.
CC       Note=Sumoylated NEMO accumulates in the nucleus in response to
CC       genotoxic stress. {ECO:0000269|PubMed:14651848}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q9Y6K9-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9Y6K9-2; Sequence=VSP_041000;
CC       Name=3;
CC         IsoId=Q9Y6K9-3; Sequence=VSP_041001, VSP_041002;
CC   -!- TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal
CC       muscle, kidney and pancreas.
CC   -!- DOMAIN: The leucine-zipper domain and the CCHC NOA-type zinc-fingers
CC       constitute the UBAN region and are essential for polyubiquitin binding
CC       and for the activation of IRF3. {ECO:0000269|PubMed:18313693,
CC       ECO:0000269|PubMed:19854139}.
CC   -!- PTM: Phosphorylation at Ser-68 attenuates aminoterminal
CC       homodimerization. {ECO:0000269|PubMed:17977820}.
CC   -!- PTM: Polyubiquitinated on Lys-285 via 'Lys-63'-linked ubiquitin; the
CC       ubiquitination is mediated downstream of NOD2 and RIPK2 and probably
CC       plays a role in signaling by facilitating interactions with ubiquitin
CC       domain-containing proteins and activates the NF-kappa-B pathway
CC       (PubMed:15620648, PubMed:17562858, PubMed:19136968). Polyubiquitinated
CC       on Lys-285 and Lys-399 through 'Lys-63'-linked ubiquitin; the
CC       ubiquitination is mediated by BCL10, MALT1 and TRAF6 and probably plays
CC       a role in signaling by facilitating interactions with ubiquitin domain-
CC       containing proteins and activates the NF-kappa-B pathway
CC       (PubMed:14695475, PubMed:17562858, PubMed:19136968). Monoubiquitinated
CC       on Lys-277 and Lys-309; promotes nuclear export (PubMed:14651848).
CC       Polyubiquitinated through 'Lys-27' by TRIM23; involved in antiviral
CC       innate and inflammatory responses (PubMed:20724660). Linear
CC       polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-264, Lys-
CC       277, Lys-285, Lys-292, Lys-302, Lys-309 and Lys-326; the head-to-tail
CC       polyubiquitination is mediated by the LUBAC complex and plays a key
CC       role in NF-kappa-B activation (PubMed:21455181). Deubiquitinated by
CC       USP10 in a TANK-dependent and -independent manner, leading to the
CC       negative regulation of NF-kappa-B signaling upon DNA damage
CC       (PubMed:25861989). Ubiquitinated at Lys-326 by MARCHF2 following
CC       bacterial and viral infection which leads to its degradation
CC       (PubMed:32935379). Polyubiquitinated via 'Lys-29'-linked ubiquitin;
CC       leading to lysosomal degradation (PubMed:21518757).
CC       {ECO:0000269|PubMed:14651848, ECO:0000269|PubMed:14695475,
CC       ECO:0000269|PubMed:15620648, ECO:0000269|PubMed:17562858,
CC       ECO:0000269|PubMed:19136968, ECO:0000269|PubMed:20724660,
CC       ECO:0000269|PubMed:21455181, ECO:0000269|PubMed:21518757,
CC       ECO:0000269|PubMed:25861989, ECO:0000269|PubMed:32935379}.
CC   -!- PTM: Sumoylated on Lys-277 and Lys-309 with SUMO1; the modification
CC       results in phosphorylation of Ser-85 by ATM leading to a replacement of
CC       the sumoylation by mono-ubiquitination on these residues.
CC       {ECO:0000269|PubMed:14651848, ECO:0000269|PubMed:16497931,
CC       ECO:0000269|PubMed:19136968, ECO:0000269|PubMed:20010814,
CC       ECO:0000269|PubMed:21455181}.
CC   -!- PTM: Neddylated by TRIM40, resulting in stabilization of NFKBIA and
CC       down-regulation of NF-kappa-B activity. {ECO:0000269|PubMed:21474709}.
CC   -!- PTM: (Microbial infection) Cleaved by hepatitis A virus (HAV) protease
CC       3C allowing the virus to disrupt the host innate immune signaling.
CC       {ECO:0000269|PubMed:24920812}.
CC   -!- PTM: (Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1
CC       on both 'Lys-48' and 'Lys-63'-linked ubiquitin chains; leading to NF-
CC       kappa-B signaling inhibition. {ECO:0000269|PubMed:24586164}.
CC   -!- PTM: (Microbial infection) Polyubiquitinated on Lys-309 and Lys-321 via
CC       'Lys-27'-linked ubiquitin by Shigella flexneri E3 ubiquitin-protein
CC       ligase ipah9.8, leading to its degradation by the proteasome.
CC       {ECO:0000269|PubMed:20010814}.
CC   -!- PTM: (Microbial infection) Polyubiquitination through 'Lys-63' is
CC       interrupted by interaction with SARS coronavirus-2/SARS-CoV-2 virus
CC       protein ORF9B which inhibits the NF-kappa-B pathway.
CC       {ECO:0000269|PubMed:33567255}.
CC   -!- DISEASE: Ectodermal dysplasia and immunodeficiency 1 (EDAID1)
CC       [MIM:300291]: A form of ectoderma dysplasia, a heterogeneous group of
CC       disorders due to abnormal development of two or more ectodermal
CC       structures. EDAID1 is an X-linked recessive disorder characterized by
CC       absence of sweat glands, sparse scalp hair, rare conical teeth and
CC       immunological abnormalities resulting in severe infectious diseases.
CC       Severely affected individuals may also show lymphedema, osteopetrosis,
CC       and, rarely, hematologic abnormalities. The phenotype is highly
CC       variable, and may be fatal in childhood. {ECO:0000269|PubMed:11047757,
CC       ECO:0000269|PubMed:11224521, ECO:0000269|PubMed:11242109,
CC       ECO:0000269|PubMed:12045264, ECO:0000269|PubMed:14651848,
CC       ECO:0000269|PubMed:15100680, ECO:0000269|PubMed:16547522,
CC       ECO:0000269|PubMed:19185524, ECO:0000269|PubMed:21606507}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- DISEASE: Immunodeficiency 33 (IMD33) [MIM:300636]: An X-linked
CC       recessive disorder characterized by variably impaired immunologic
CC       function and early-onset recurrent infections, usually due to
CC       pneumococcus, H. influenzae, and atypical mycobacteria. Features of
CC       hypohidrotic ectodermal dysplasia are generally not present, although
CC       some patients may have conical teeth or hypodontia.
CC       {ECO:0000269|PubMed:15100680, ECO:0000269|PubMed:15356572,
CC       ECO:0000269|PubMed:16818673, ECO:0000269|PubMed:16950813,
CC       ECO:0000269|PubMed:19185524, ECO:0000269|PubMed:19854204}. Note=Disease
CC       susceptibility is associated with variants affecting the gene
CC       represented in this entry.
CC   -!- DISEASE: Incontinentia pigmenti (IP) [MIM:308300]: A genodermatosis
CC       usually prenatally lethal in males. In affected females, it causes
CC       abnormalities of the skin, hair, eyes, nails, teeth, skeleton, heart,
CC       and central nervous system. The prominent skin signs occur in four
CC       classic cutaneous stages: perinatal inflammatory vesicles, verrucous
CC       patches, a distinctive pattern of hyperpigmentation and dermal
CC       scarring. {ECO:0000269|PubMed:10839543, ECO:0000269|PubMed:11590134,
CC       ECO:0000269|PubMed:15229184, ECO:0000269|PubMed:17728323,
CC       ECO:0000269|PubMed:19033441, ECO:0000269|PubMed:20434027,
CC       ECO:0000269|PubMed:24339369}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Autoinflammatory disease, systemic, X-linked (SAIDX)
CC       [MIM:301081]: An X-linked disorder characterized by systemic
CC       autoinflammation appearing in the first months of life. Clinical
CC       manifestations are variable, including lymphadenopathy,
CC       hepatosplenomegaly, fever, panniculitis, and nodular skin rash.
CC       Additional features may include inflammation of the optic nerve,
CC       intracranial hemorrhage, and lipodystrophy.
CC       {ECO:0000269|PubMed:31874111, ECO:0000269|PubMed:35289316}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- WEB RESOURCE: Name=IKBKGbase; Note=IKBKG mutation db;
CC       URL="http://structure.bmc.lu.se/idbase/IKBKGbase/";
CC   -!- WEB RESOURCE: Name=Inhibitor of kappa light polypeptide gene enhancer
CC       in B-cells, kinase gamma (IKBKG); Note=Leiden Open Variation Database
CC       (LOVD);
CC       URL="https://databases.lovd.nl/shared/genes/IKBKG";
CC   ---------------------------------------------------------------------------
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DR   EMBL; AF062089; AAD12183.1; -; mRNA.
DR   EMBL; AF091453; AAD38081.1; -; mRNA.
DR   EMBL; AF074382; AAC36330.1; -; mRNA.
DR   EMBL; AJ271718; CAB93146.1; -; Genomic_DNA.
DR   EMBL; AF261086; AAF99679.1; -; mRNA.
DR   EMBL; AY114157; AAM44073.1; -; mRNA.
DR   EMBL; AK000593; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; BT019621; AAV38427.1; -; mRNA.
DR   EMBL; AF277315; AAL27012.1; -; Genomic_DNA.
DR   EMBL; BC000299; AAH00299.1; -; mRNA.
DR   EMBL; BC012114; AAH12114.1; -; mRNA.
DR   EMBL; BC046922; AAH46922.1; -; mRNA.
DR   EMBL; BC050612; AAH50612.1; -; mRNA.
DR   CCDS; CCDS14757.1; -. [Q9Y6K9-1]
DR   CCDS; CCDS48196.1; -. [Q9Y6K9-2]
DR   CCDS; CCDS48197.1; -. [Q9Y6K9-3]
DR   RefSeq; NP_001093326.2; NM_001099856.4. [Q9Y6K9-2]
DR   RefSeq; NP_001093327.1; NM_001099857.2. [Q9Y6K9-1]
DR   RefSeq; NP_001138727.1; NM_001145255.2. [Q9Y6K9-3]
DR   RefSeq; NP_001308325.1; NM_001321396.1. [Q9Y6K9-1]
DR   RefSeq; NP_001308326.1; NM_001321397.1.
DR   RefSeq; NP_003630.1; NM_003639.4. [Q9Y6K9-1]
DR   PDB; 2JVX; NMR; -; A=394-419.
DR   PDB; 2JVY; NMR; -; A=394-419.
DR   PDB; 3BRT; X-ray; 2.25 A; B/D=44-111.
DR   PDB; 3BRV; X-ray; 2.20 A; B/D=44-111.
DR   PDB; 3CL3; X-ray; 3.20 A; D/E=150-272.
DR   PDB; 3FX0; X-ray; 3.20 A; A/B=246-337.
DR   PDB; 4BWN; X-ray; 2.27 A; A/B=258-344.
DR   PDB; 5AAY; NMR; -; A=392-419.
DR   PDB; 5LDE; X-ray; 3.38 A; R/S=230-249.
DR   PDB; 6MI3; X-ray; 1.78 A; A/B=38-129.
DR   PDB; 6MI4; X-ray; 2.50 A; A/B=38-129.
DR   PDB; 6XX0; X-ray; 2.60 A; A/B=258-344.
DR   PDB; 6YEK; X-ray; 3.20 A; A/B=258-344.
DR   PDB; 7T2U; X-ray; 2.10 A; E/F=226-235.
DR   PDB; 7TV4; X-ray; 4.20 A; B/D=257-346.
DR   PDBsum; 2JVX; -.
DR   PDBsum; 2JVY; -.
DR   PDBsum; 3BRT; -.
DR   PDBsum; 3BRV; -.
DR   PDBsum; 3CL3; -.
DR   PDBsum; 3FX0; -.
DR   PDBsum; 4BWN; -.
DR   PDBsum; 5AAY; -.
DR   PDBsum; 5LDE; -.
DR   PDBsum; 6MI3; -.
DR   PDBsum; 6MI4; -.
DR   PDBsum; 6XX0; -.
DR   PDBsum; 6YEK; -.
DR   PDBsum; 7T2U; -.
DR   PDBsum; 7TV4; -.
DR   AlphaFoldDB; Q9Y6K9; -.
DR   BMRB; Q9Y6K9; -.
DR   SMR; Q9Y6K9; -.
DR   BioGRID; 114089; 452.
DR   ComplexPortal; CPX-3269; IkappaB kinase complex.
DR   CORUM; Q9Y6K9; -.
DR   DIP; DIP-27528N; -.
DR   IntAct; Q9Y6K9; 269.
DR   MINT; Q9Y6K9; -.
DR   STRING; 9606.ENSP00000483825; -.
DR   BindingDB; Q9Y6K9; -.
DR   ChEMBL; CHEMBL4967; -.
DR   DrugBank; DB04998; AGRO100.
DR   DrugBank; DB05289; Tarenflurbil.
DR   MoonDB; Q9Y6K9; Predicted.
DR   GlyGen; Q9Y6K9; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9Y6K9; -.
DR   PhosphoSitePlus; Q9Y6K9; -.
DR   BioMuta; IKBKG; -.
DR   DMDM; 6685695; -.
DR   CPTAC; CPTAC-1044; -.
DR   CPTAC; CPTAC-806; -.
DR   EPD; Q9Y6K9; -.
DR   jPOST; Q9Y6K9; -.
DR   MassIVE; Q9Y6K9; -.
DR   MaxQB; Q9Y6K9; -.
DR   PaxDb; 9606-ENSP00000483825; -.
DR   PeptideAtlas; Q9Y6K9; -.
DR   ProteomicsDB; 86716; -. [Q9Y6K9-1]
DR   ProteomicsDB; 86717; -. [Q9Y6K9-2]
DR   ProteomicsDB; 86718; -. [Q9Y6K9-3]
DR   Pumba; Q9Y6K9; -.
DR   Antibodypedia; 73338; 1437 antibodies from 47 providers.
DR   DNASU; 8517; -.
DR   Ensembl; ENST00000422680.6; ENSP00000390368.3; ENSG00000269335.7. [Q9Y6K9-1]
DR   Ensembl; ENST00000440286.6; ENSP00000394934.2; ENSG00000269335.7. [Q9Y6K9-1]
DR   Ensembl; ENST00000445622.6; ENSP00000395205.2; ENSG00000269335.7. [Q9Y6K9-1]
DR   Ensembl; ENST00000594239.6; ENSP00000471166.1; ENSG00000269335.7. [Q9Y6K9-1]
DR   Ensembl; ENST00000611071.4; ENSP00000479662.1; ENSG00000269335.7. [Q9Y6K9-1]
DR   Ensembl; ENST00000611176.4; ENSP00000478616.1; ENSG00000269335.7. [Q9Y6K9-3]
DR   Ensembl; ENST00000618670.4; ENSP00000483825.1; ENSG00000269335.7. [Q9Y6K9-2]
DR   GeneID; 8517; -.
DR   KEGG; hsa:8517; -.
DR   MANE-Select; ENST00000594239.6; ENSP00000471166.1; NM_001099857.5; NP_001093327.1.
DR   UCSC; uc033fbu.1; human. [Q9Y6K9-1]
DR   AGR; HGNC:5961; -.
DR   CTD; 8517; -.
DR   DisGeNET; 8517; -.
DR   GeneCards; IKBKG; -.
DR   GeneReviews; IKBKG; -.
DR   HGNC; HGNC:5961; IKBKG.
DR   HPA; ENSG00000269335; Low tissue specificity.
DR   MalaCards; IKBKG; -.
DR   MIM; 300248; gene.
DR   MIM; 300291; phenotype.
DR   MIM; 300636; phenotype.
DR   MIM; 301081; phenotype.
DR   MIM; 308300; phenotype.
DR   neXtProt; NX_Q9Y6K9; -.
DR   OpenTargets; ENSG00000269335; -.
DR   Orphanet; 69088; Anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome.
DR   Orphanet; 98813; Hypohidrotic ectodermal dysplasia with immunodeficiency.
DR   Orphanet; 464; Incontinentia pigmenti.
DR   Orphanet; 319612; X-linked mendelian susceptibility to mycobacterial diseases due to IKBKG deficiency.
DR   PharmGKB; PA29777; -.
DR   VEuPathDB; HostDB:ENSG00000269335; -.
DR   eggNOG; ENOG502R4ZD; Eukaryota.
DR   GeneTree; ENSGT00530000063808; -.
DR   InParanoid; Q9Y6K9; -.
DR   OMA; VAMRKNF; -.
DR   OrthoDB; 5406882at2759; -.
DR   PhylomeDB; Q9Y6K9; -.
DR   TreeFam; TF326608; -.
DR   PathwayCommons; Q9Y6K9; -.
DR   Reactome; R-HSA-1169091; Activation of NF-kappaB in B cells.
DR   Reactome; R-HSA-1236974; ER-Phagosome pathway.
DR   Reactome; R-HSA-168638; NOD1/2 Signaling Pathway.
DR   Reactome; R-HSA-168927; TICAM1, RIP1-mediated IKK complex recruitment.
DR   Reactome; R-HSA-1810476; RIP-mediated NFkB activation via ZBP1.
DR   Reactome; R-HSA-202424; Downstream TCR signaling.
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-450302; activated TAK1 mediates p38 MAPK activation.
DR   Reactome; R-HSA-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR   Reactome; R-HSA-4755510; SUMOylation of immune response proteins.
DR   Reactome; R-HSA-5357905; Regulation of TNFR1 signaling.
DR   Reactome; R-HSA-5357956; TNFR1-induced NF-kappa-B signaling pathway.
DR   Reactome; R-HSA-5602636; IKBKB deficiency causes SCID.
DR   Reactome; R-HSA-5603027; IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR).
DR   Reactome; R-HSA-5603029; IkBA variant leads to EDA-ID.
DR   Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling.
DR   Reactome; R-HSA-5684264; MAP3K8 (TPL2)-dependent MAPK1/3 activation.
DR   Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR   Reactome; R-HSA-5689896; Ovarian tumor domain proteases.
DR   Reactome; R-HSA-9020702; Interleukin-1 signaling.
DR   Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
DR   Reactome; R-HSA-933543; NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
DR   Reactome; R-HSA-937039; IRAK1 recruits IKK complex.
DR   Reactome; R-HSA-937041; IKK complex recruitment mediated by RIP1.
DR   Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR   Reactome; R-HSA-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
DR   Reactome; R-HSA-9758274; Regulation of NF-kappa B signaling.
DR   Reactome; R-HSA-9833482; PKR-mediated signaling.
DR   SABIO-RK; Q9Y6K9; -.
DR   SignaLink; Q9Y6K9; -.
DR   SIGNOR; Q9Y6K9; -.
DR   BioGRID-ORCS; 8517; 75 hits in 782 CRISPR screens.
DR   ChiTaRS; IKBKG; human.
DR   EvolutionaryTrace; Q9Y6K9; -.
DR   GeneWiki; IKBKG; -.
DR   GenomeRNAi; 8517; -.
DR   Pharos; Q9Y6K9; Tbio.
DR   PRO; PR:Q9Y6K9; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; Q9Y6K9; Protein.
DR   Bgee; ENSG00000269335; Expressed in granulocyte and 95 other cell types or tissues.
DR   ExpressionAtlas; Q9Y6K9; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0008385; C:IkappaB kinase complex; IDA:MGI.
DR   GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR   GO; GO:0000922; C:spindle pole; IDA:UniProtKB.
DR   GO; GO:0000151; C:ubiquitin ligase complex; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR   GO; GO:1990450; F:linear polyubiquitin binding; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IDA:UniProt.
DR   GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR   GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0035591; F:signaling adaptor activity; IDA:UniProt.
DR   GO; GO:1990459; F:transferrin receptor binding; IPI:ARUK-UCL.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0043276; P:anoikis; ISS:BHF-UCL.
DR   GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR   GO; GO:0007249; P:canonical NF-kappaB signal transduction; TAS:UniProtKB.
DR   GO; GO:0042742; P:defense response to bacterium; IDA:UniProt.
DR   GO; GO:0006974; P:DNA damage response; IDA:UniProtKB.
DR   GO; GO:0051650; P:establishment of vesicle localization; IMP:UniProtKB.
DR   GO; GO:0006955; P:immune response; TAS:ProtInc.
DR   GO; GO:0006954; P:inflammatory response; TAS:UniProtKB.
DR   GO; GO:0045087; P:innate immune response; TAS:UniProtKB.
DR   GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:UniProtKB.
DR   GO; GO:0016239; P:positive regulation of macroautophagy; ISS:BHF-UCL.
DR   GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR   GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; TAS:UniProt.
DR   GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
DR   GO; GO:0009615; P:response to virus; TAS:UniProtKB.
DR   GO; GO:0050852; P:T cell receptor signaling pathway; NAS:UniProtKB.
DR   DisProt; DP02269; -.
DR   Gene3D; 1.20.5.390; L1 transposable element, trimerization domain; 2.
DR   Gene3D; 1.20.5.990; Nemo cc2-lz domain - 1d5 darpin complex; 1.
DR   IDEAL; IID00745; -.
DR   InterPro; IPR032419; CC2-LZ_dom.
DR   InterPro; IPR021063; NEMO_N.
DR   InterPro; IPR034735; NEMO_ZF.
DR   PANTHER; PTHR31553; NF-KAPPA-B ESSENTIAL MODULATOR; 1.
DR   PANTHER; PTHR31553:SF3; NF-KAPPA-B ESSENTIAL MODULATOR; 1.
DR   Pfam; PF16516; CC2-LZ; 1.
DR   Pfam; PF11577; NEMO; 1.
DR   Pfam; PF18414; zf_C2H2_10; 1.
DR   PROSITE; PS51801; ZF_CCHC_NOA; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Coiled coil; Cytoplasm;
KW   Direct protein sequencing; Disease variant; Disulfide bond; DNA damage;
KW   Ectodermal dysplasia; Host-virus interaction; Isopeptide bond;
KW   Metal-binding; Nucleus; Osteopetrosis; Phosphoprotein; Reference proteome;
KW   Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW   Zinc-finger.
FT   CHAIN           1..419
FT                   /note="NF-kappa-B essential modulator"
FT                   /id="PRO_0000096782"
FT   ZN_FING         389..419
FT                   /note="CCHC NOA-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT   REGION          1..197
FT                   /note="Required for interaction with and ubiquitination by
FT                   MARCHF2"
FT                   /evidence="ECO:0000269|PubMed:32935379"
FT   REGION          44..111
FT                   /note="Interaction with CHUK/IKBKB"
FT   REGION          150..257
FT                   /note="Interaction with TANK"
FT   REGION          242..350
FT                   /note="Ubiquitin-binding (UBAN)"
FT   REGION          246..365
FT                   /note="Self-association"
FT   REGION          251..419
FT                   /note="Required for interaction with TNFAIP3"
FT   REGION          322..343
FT                   /note="Leucine-zipper"
FT                   /evidence="ECO:0000255"
FT   REGION          358..395
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          382..419
FT                   /note="Interaction with CYLD"
FT                   /evidence="ECO:0000269|PubMed:12917691"
FT   COILED          49..356
FT                   /evidence="ECO:0000255"
FT   BINDING         397
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT   BINDING         400
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT   BINDING         413
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT   BINDING         417
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT   MOD_RES         31
FT                   /note="Phosphoserine; by IKKB"
FT                   /evidence="ECO:0000269|PubMed:12657630"
FT   MOD_RES         43
FT                   /note="Phosphoserine; by IKKB"
FT                   /evidence="ECO:0000269|PubMed:12657630"
FT   MOD_RES         68
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:17977820"
FT   MOD_RES         85
FT                   /note="Phosphoserine; by ATM"
FT                   /evidence="ECO:0000269|PubMed:16497931"
FT   MOD_RES         376
FT                   /note="Phosphoserine; by IKKB"
FT                   /evidence="ECO:0000269|PubMed:12657630"
FT   MOD_RES         387
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:24012789,
FT                   ECO:0007744|PubMed:24275569"
FT   DISULFID        54
FT                   /note="Interchain"
FT                   /evidence="ECO:0000269|PubMed:18164680"
FT   DISULFID        347
FT                   /note="Interchain"
FT                   /evidence="ECO:0000269|PubMed:18164680"
FT   CROSSLNK        111
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:21455181"
FT   CROSSLNK        139
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:21455181"
FT   CROSSLNK        143
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:21455181"
FT   CROSSLNK        226
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:21455181"
FT   CROSSLNK        246
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:21455181"
FT   CROSSLNK        264
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:21455181"
FT   CROSSLNK        277
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO); alternate"
FT                   /evidence="ECO:0000269|PubMed:14651848"
FT   CROSSLNK        277
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin); alternate"
FT                   /evidence="ECO:0000269|PubMed:14651848,
FT                   ECO:0000269|PubMed:21455181"
FT   CROSSLNK        283
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:21455181"
FT   CROSSLNK        285
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:15620648,
FT                   ECO:0000269|PubMed:17562858, ECO:0000269|PubMed:19136968,
FT                   ECO:0000269|PubMed:21455181"
FT   CROSSLNK        292
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:21455181"
FT   CROSSLNK        302
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:21455181"
FT   CROSSLNK        309
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO); alternate"
FT                   /evidence="ECO:0000269|PubMed:14651848"
FT   CROSSLNK        309
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin); alternate"
FT                   /evidence="ECO:0000269|PubMed:14651848,
FT                   ECO:0000269|PubMed:19136968, ECO:0000269|PubMed:20010814,
FT                   ECO:0000269|PubMed:21455181"
FT   CROSSLNK        321
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:20010814"
FT   CROSSLNK        325
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:O88522"
FT   CROSSLNK        326
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin and interchain with MARCHF2)"
FT                   /evidence="ECO:0000269|PubMed:21455181,
FT                   ECO:0000269|PubMed:32935379"
FT   CROSSLNK        399
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:14695475"
FT   VAR_SEQ         1
FT                   /note="M -> MALVIQVGKLRPREVRTPQTINPSLFPSLPVKLSSIIEVPSGGERCC
FT                   SRRTLVYKARAFWKGAPLPCWM (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.6"
FT                   /id="VSP_041000"
FT   VAR_SEQ         174..224
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_041001"
FT   VAR_SEQ         257..304
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_041002"
FT   VARIANT         57
FT                   /note="E -> K (in IP; shows the same luciferase activity as
FT                   the control; dbSNP:rs148695964)"
FT                   /evidence="ECO:0000269|PubMed:11590134,
FT                   ECO:0000269|PubMed:15229184"
FT                   /id="VAR_026491"
FT   VARIANT         90
FT                   /note="Missing (in IP; only 46.3% of the activation
FT                   obtained with the wild-type protein)"
FT                   /evidence="ECO:0000269|PubMed:15229184"
FT                   /id="VAR_026492"
FT   VARIANT         113
FT                   /note="D -> N (in dbSNP:rs179363896)"
FT                   /evidence="ECO:0000269|PubMed:15229184"
FT                   /id="VAR_026493"
FT   VARIANT         123
FT                   /note="R -> W (in IP; shows the same luciferase activity as
FT                   the control; dbSNP:rs179363895)"
FT                   /evidence="ECO:0000269|PubMed:15229184"
FT                   /id="VAR_026494"
FT   VARIANT         153
FT                   /note="L -> R (in EDAID1; dbSNP:rs137853328)"
FT                   /evidence="ECO:0000269|PubMed:12045264,
FT                   ECO:0000269|PubMed:15100680"
FT                   /id="VAR_026495"
FT   VARIANT         170
FT                   /note="L -> P (in IP)"
FT                   /evidence="ECO:0000269|PubMed:24339369"
FT                   /id="VAR_072603"
FT   VARIANT         173
FT                   /note="R -> G (in IMD33; dbSNP:rs179363866)"
FT                   /evidence="ECO:0000269|PubMed:16950813"
FT                   /id="VAR_031958"
FT   VARIANT         173
FT                   /note="R -> Q (in IP; dbSNP:rs1057520292)"
FT                   /evidence="ECO:0000269|PubMed:24339369"
FT                   /id="VAR_072604"
FT   VARIANT         175
FT                   /note="R -> P (in EDAID1; dbSNP:rs179363868)"
FT                   /evidence="ECO:0000269|PubMed:11242109"
FT                   /id="VAR_011320"
FT   VARIANT         183
FT                   /note="Q -> H (in IP; dbSNP:rs1198984417)"
FT                   /evidence="ECO:0000269|PubMed:20434027"
FT                   /id="VAR_072605"
FT   VARIANT         227
FT                   /note="L -> P (in EDAID1; dbSNP:rs179363869)"
FT                   /evidence="ECO:0000269|PubMed:11242109"
FT                   /id="VAR_011321"
FT   VARIANT         288
FT                   /note="A -> G (in EDAID1; dbSNP:rs137853330)"
FT                   /evidence="ECO:0000269|PubMed:11242109"
FT                   /id="VAR_011322"
FT   VARIANT         311
FT                   /note="D -> N (in EDAID1; abolishes binding to
FT                   polyubiquitin ('K63'-linked and linear) and greatly impairs
FT                   tandem ubiquitin binding; dbSNP:rs179363867)"
FT                   /evidence="ECO:0000269|PubMed:11242109,
FT                   ECO:0000269|PubMed:16547522, ECO:0000269|PubMed:19185524,
FT                   ECO:0000269|PubMed:21606507"
FT                   /id="VAR_011323"
FT   VARIANT         314
FT                   /note="A -> P (in IP)"
FT                   /evidence="ECO:0000269|PubMed:24339369"
FT                   /id="VAR_072606"
FT   VARIANT         315
FT                   /note="E -> A (in IMD33; greatly impairs tandem ubiquitin
FT                   binding. Impairs oligomerization, impairs binding of 'Lys-
FT                   63'-linked ubiuitin and linear tetra-ubiquitin, impairs
FT                   TNF-induced NF-kappa-B activation; dbSNP:rs137853331)"
FT                   /evidence="ECO:0000269|PubMed:16818673,
FT                   ECO:0000269|PubMed:19185524, ECO:0000269|PubMed:19854204"
FT                   /id="VAR_031959"
FT   VARIANT         319
FT                   /note="R -> Q (in IMD33; impairs tandem ubiquitin binding;
FT                   dbSNP:rs137853332)"
FT                   /evidence="ECO:0000269|PubMed:16818673,
FT                   ECO:0000269|PubMed:19185524"
FT                   /id="VAR_031960"
FT   VARIANT         322
FT                   /note="L -> P (in IP)"
FT                   /evidence="ECO:0000269|PubMed:24339369"
FT                   /id="VAR_072607"
FT   VARIANT         323
FT                   /note="A -> P (in IP; diminishes interaction with TRAF6 and
FT                   polyubiquitination, greatly impairs tandem ubiquitin
FT                   binding. Impairs oligomerization, greatly impairs binding
FT                   of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin,
FT                   impairs TNF-induced NF-kappa-B activation;
FT                   dbSNP:rs179363865)"
FT                   /evidence="ECO:0000269|PubMed:17728323,
FT                   ECO:0000269|PubMed:19185524, ECO:0000269|PubMed:19854204"
FT                   /id="VAR_042666"
FT   VARIANT         406
FT                   /note="D -> V (in EDAID1; dbSNP:rs137853327)"
FT                   /evidence="ECO:0000269|PubMed:11224521"
FT                   /id="VAR_011324"
FT   VARIANT         407
FT                   /note="M -> V (in IP; impairs binding to ubiquitin;
FT                   dbSNP:rs137853322)"
FT                   /evidence="ECO:0000269|PubMed:10839543,
FT                   ECO:0000269|PubMed:11590134, ECO:0000269|PubMed:19033441"
FT                   /id="VAR_009182"
FT   VARIANT         413
FT                   /note="H -> Y (in IP)"
FT                   /evidence="ECO:0000269|PubMed:24339369"
FT                   /id="VAR_072608"
FT   VARIANT         417
FT                   /note="C -> F (in EDAID1; dbSNP:rs137853326)"
FT                   /evidence="ECO:0000269|PubMed:11047757,
FT                   ECO:0000269|PubMed:11242109"
FT                   /id="VAR_011325"
FT   VARIANT         417
FT                   /note="C -> R (in EDAID1; loss of sumoylation;
FT                   dbSNP:rs137853325)"
FT                   /evidence="ECO:0000269|PubMed:11047757,
FT                   ECO:0000269|PubMed:11224521, ECO:0000269|PubMed:11242109,
FT                   ECO:0000269|PubMed:12045264, ECO:0000269|PubMed:14651848,
FT                   ECO:0000269|PubMed:15100680"
FT                   /id="VAR_011326"
FT   VARIANT         417
FT                   /note="C -> Y (in IMD33; dbSNP:rs137853326)"
FT                   /evidence="ECO:0000269|PubMed:15100680"
FT                   /id="VAR_026496"
FT   MUTAGEN         68
FT                   /note="S->A: Increases formation of homodimers."
FT                   /evidence="ECO:0000269|PubMed:17977820"
FT   MUTAGEN         68
FT                   /note="S->E: Abolishes interaction with IKBKB; abolishes
FT                   TNF-alpha induced NF-kappa-B activity."
FT                   /evidence="ECO:0000269|PubMed:17977820"
FT   MUTAGEN         85
FT                   /note="S->A: Decreases ubiquitination and abolishes nuclear
FT                   export."
FT                   /evidence="ECO:0000269|PubMed:16497931"
FT   MUTAGEN         115
FT                   /note="K->R: No change in the ubiquitination level; when
FT                   associated with R-399."
FT                   /evidence="ECO:0000269|PubMed:15620648"
FT   MUTAGEN         224
FT                   /note="K->R: No change in the ubiquitination level; when
FT                   associated with R-399."
FT                   /evidence="ECO:0000269|PubMed:15620648"
FT   MUTAGEN         277
FT                   /note="K->A: Partial abolition of sumoylation. Abolishes
FT                   sumoylation and IKK activation; when associated with A-
FT                   309."
FT                   /evidence="ECO:0000269|PubMed:14651848"
FT   MUTAGEN         285
FT                   /note="K->R: Decreased ability to activate NF-kappa-B.
FT                   Important decrease in the ubiquitination level; when
FT                   associated with R-399."
FT                   /evidence="ECO:0000269|PubMed:15620648,
FT                   ECO:0000269|PubMed:17562858"
FT   MUTAGEN         296
FT                   /note="E->A: No effet on oligomerization,impairs binding of
FT                   'Lys-63'-linked ubiuitin and linear tetra-ubiquitin,
FT                   impairs TNF-induced NF-kappa-B activation."
FT                   /evidence="ECO:0000269|PubMed:19854204"
FT   MUTAGEN         300
FT                   /note="V->D: Greatly impairs tandem ubiquitin binding."
FT                   /evidence="ECO:0000269|PubMed:19185524"
FT   MUTAGEN         301
FT                   /note="L->A: Impairs tandem ubiquitin binding."
FT                   /evidence="ECO:0000269|PubMed:19185524"
FT   MUTAGEN         302
FT                   /note="K->R: No effect on MARCH2F-mediated K48-linked
FT                   ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:32935379"
FT   MUTAGEN         304
FT                   /note="Q->A: Complete loss of cleavage by HAV protease 3c."
FT                   /evidence="ECO:0000269|PubMed:24920812"
FT   MUTAGEN         304
FT                   /note="Q->A: Impairs tandem ubiquitin binding."
FT                   /evidence="ECO:0000269|PubMed:19185524"
FT   MUTAGEN         307
FT                   /note="I->N: Greatly impairs tandem ubiquitin binding."
FT                   /evidence="ECO:0000269|PubMed:19185524"
FT   MUTAGEN         308
FT                   /note="Y->A: Greatly impairs tandem ubiquitin binding."
FT                   /evidence="ECO:0000269|PubMed:19185524"
FT   MUTAGEN         309
FT                   /note="K->A: Partial abolition of sumoylation. Abolishes
FT                   sumoylation and IKK activation; when associated with A-277.
FT                   No effect on MARCH2F-mediated K48-linked ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:14651848,
FT                   ECO:0000269|PubMed:32935379"
FT   MUTAGEN         312
FT                   /note="F->A: Greatly impairs tandem ubiquitin
FT                   binding,impairs oligomerization, impairs TNF-induced NF-
FT                   kappa-B activation."
FT                   /evidence="ECO:0000269|PubMed:19185524,
FT                   ECO:0000269|PubMed:19854204"
FT   MUTAGEN         312
FT                   /note="F->W: MNo effet on oligomerization, preferentially
FT                   binds tri-ubiquitin chains ('Lys-48' or 'Lys-63'-linked)."
FT                   /evidence="ECO:0000269|PubMed:19185524,
FT                   ECO:0000269|PubMed:19854204"
FT   MUTAGEN         312
FT                   /note="F->Y: Impairs tandem ubiquitin binding."
FT                   /evidence="ECO:0000269|PubMed:19185524,
FT                   ECO:0000269|PubMed:19854204"
FT   MUTAGEN         313
FT                   /note="Q->A: Impairs tandem ubiquitin binding."
FT                   /evidence="ECO:0000269|PubMed:19185524"
FT   MUTAGEN         315
FT                   /note="E->Q: Greatly impairs tandem ubiquitin binding."
FT                   /evidence="ECO:0000269|PubMed:19854204"
FT   MUTAGEN         317
FT                   /note="Q->A,W: Greatly impairs tandem ubiquitin binding."
FT                   /evidence="ECO:0000269|PubMed:19185524"
FT   MUTAGEN         321
FT                   /note="K->R: No effect on MARCH2F-mediated K48-linked
FT                   ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:32935379"
FT   MUTAGEN         323
FT                   /note="A->D: Greatly impairs tandem ubiquitin binding."
FT                   /evidence="ECO:0000269|PubMed:19854204"
FT   MUTAGEN         325
FT                   /note="K->R: No effect on MARCH2F-mediated K48-linked
FT                   ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:32935379"
FT   MUTAGEN         326
FT                   /note="K->R: Abolishes MARCH2F-mediated K48-linked
FT                   ubiquitination and subsequent suppression of antiviral and
FT                   antibacterial innate immune response."
FT                   /evidence="ECO:0000269|PubMed:32935379"
FT   MUTAGEN         329
FT                   /note="L->A: Impairs oligomerization, impairs binding of
FT                   'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B
FT                   activation; when associated with A-336."
FT                   /evidence="ECO:0000269|PubMed:16547522,
FT                   ECO:0000269|PubMed:19854204"
FT   MUTAGEN         329
FT                   /note="L->P: Abolished ubiquitin-binding."
FT                   /evidence="ECO:0000269|PubMed:16547522,
FT                   ECO:0000269|PubMed:18287044, ECO:0000269|PubMed:19854204"
FT   MUTAGEN         336
FT                   /note="L->A: Impairs oligomerization, impairs binding of
FT                   'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B
FT                   activation; when associated with A-329."
FT                   /evidence="ECO:0000269|PubMed:19854204"
FT   MUTAGEN         342
FT                   /note="K->R: No effect on MARCH2F-mediated K48-linked
FT                   ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:32935379"
FT   MUTAGEN         344
FT                   /note="K->R: No effect on MARCH2F-mediated K48-linked
FT                   ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:32935379"
FT   MUTAGEN         358
FT                   /note="K->R: No effect on MARCH2F-mediated K48-linked
FT                   ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:32935379"
FT   MUTAGEN         399
FT                   /note="K->R: Abolishes BCL10-mediated but not RIPK2-
FT                   mediated ubiquitination. Important decrease in the
FT                   ubiquitination level; when associated with R-285. No change
FT                   in the ubiquitination level; when associated with R-115 or
FT                   R-224."
FT                   /evidence="ECO:0000269|PubMed:14695475,
FT                   ECO:0000269|PubMed:15620648"
FT   MUTAGEN         414
FT                   /note="V->S: Abolishes binding to polyubiquitin."
FT                   /evidence="ECO:0000269|PubMed:19033441"
FT   MUTAGEN         415
FT                   /note="M->S: Impairs binding to polyubiquitin."
FT                   /evidence="ECO:0000269|PubMed:19033441"
FT   CONFLICT        341
FT                   /note="S -> R (in Ref. 1; AAD12183)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        387
FT                   /note="S -> R (in Ref. 1; AAD12183)"
FT                   /evidence="ECO:0000305"
FT   HELIX           38..129
FT                   /evidence="ECO:0007829|PDB:6MI3"
FT   TURN            194..196
FT                   /evidence="ECO:0007829|PDB:3CL3"
FT   HELIX           197..249
FT                   /evidence="ECO:0007829|PDB:3CL3"
FT   HELIX           260..268
FT                   /evidence="ECO:0007829|PDB:4BWN"
FT   HELIX           271..295
FT                   /evidence="ECO:0007829|PDB:4BWN"
FT   HELIX           297..341
FT                   /evidence="ECO:0007829|PDB:4BWN"
FT   STRAND          394..396
FT                   /evidence="ECO:0007829|PDB:2JVY"
FT   TURN            398..400
FT                   /evidence="ECO:0007829|PDB:5AAY"
FT   STRAND          403..406
FT                   /evidence="ECO:0007829|PDB:2JVX"
FT   HELIX           407..416
FT                   /evidence="ECO:0007829|PDB:2JVX"
SQ   SEQUENCE   419 AA;  48198 MW;  322D1037881447FF CRC64;
     MNRHLWKSQL CEMVQPSGGP AADQDVLGEE SPLGKPAMLH LPSEQGAPET LQRCLEENQE
     LRDAIRQSNQ ILRERCEELL HFQASQREEK EFLMCKFQEA RKLVERLGLE KLDLKRQKEQ
     ALREVEHLKR CQQQMAEDKA SVKAQVTSLL GELQESQSRL EAATKECQAL EGRARAASEQ
     ARQLESEREA LQQQHSVQVD QLRMQGQSVE AALRMERQAA SEEKRKLAQL QVAYHQLFQE
     YDNHIKSSVV GSERKRGMQL EDLKQQLQQA EEALVAKQEV IDKLKEEAEQ HKIVMETVPV
     LKAQADIYKA DFQAERQARE KLAEKKELLQ EQLEQLQREY SKLKASCQES ARIEDMRKRH
     VEVSQAPLPP APAYLSSPLA LPSQRRSPPE EPPDFCCPKC QYQAPDMDTL QIHVMECIE
//