NEMO_MOUSE
ID NEMO_MOUSE Reviewed; 412 AA.
AC O88522; Q924H4;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=NF-kappa-B essential modulator;
DE Short=NEMO;
DE AltName: Full=IkB kinase-associated protein 1;
DE Short=IKKAP1;
DE Short=mFIP-3;
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; Synonyms=Nemo;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=T-cell;
RX PubMed=9657155; DOI=10.1016/s0092-8674(00)81466-x;
RA Yamaoka S., Courtois G., Bessia C., Whiteside S.T., Weil R., Agou F.,
RA Kirk H.E., Kay R.J., Israel A.;
RT "Complementation cloning of NEMO, a component of the I-kappaB kinase
RT complex essential for NF-kappaB activation.";
RL Cell 93:1231-1240(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11410370; DOI=10.1016/s0378-1119(01)00492-9;
RA Galgoczy P., Rosenthal A., Platzer M.;
RT "Human-mouse comparative sequence analysis of the NEMO gene reveals an
RT alternative promoter within the neighboring G6PD gene.";
RL Gene 271:93-98(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Liver;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 85-412, AND PROTEIN SEQUENCE OF 144-159.
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 [8]
RP FUNCTION.
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 [9]
RP IKK COMPLEX, AND SUBUNIT.
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 [10]
RP PHOSPHORYLATION AT SER-369, AND MUTAGENESIS OF SER-369 AND SER-375.
RX PubMed=11971901; DOI=10.1074/jbc.m201393200;
RA Prajapati S., Gaynor R.B.;
RT "Regulation of Ikappa B kinase (IKK)gamma /NEMO function by IKKbeta
RT -mediated phosphorylation.";
RL J. Biol. Chem. 277:24331-24339(2002).
RN [11]
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 [12]
RP INTERACTION WITH TNIP1 AND TNFAIP3.
RX PubMed=16684768; DOI=10.1074/jbc.m601502200;
RA Mauro C., Pacifico F., Lavorgna A., Mellone S., Iannetti A., Acquaviva R.,
RA Formisano S., Vito P., Leonardi A.;
RT "ABIN-1 binds to NEMO/IKKgamma and co-operates with A20 in inhibiting NF-
RT kappaB.";
RL J. Biol. Chem. 281:18482-18488(2006).
RN [13]
RP UBIQUITINATION AT LYS-278; LYS-314; LYS-318; LYS-319 AND LYS-392, AND
RP MUTAGENESIS OF LYS-278; LYS-314; VAL-316; LYS-318; LYS-319 AND LYS-392.
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-380, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [15]
RP INTERACTION WITH TERF2IP.
RX PubMed=20622870; DOI=10.1038/ncb2080;
RA Teo H., Ghosh S., Luesch H., Ghosh A., Wong E.T., Malik N., Orth A.,
RA de Jesus P., Perry A.S., Oliver J.D., Tran N.L., Speiser L.J., Wong M.,
RA Saez E., Schultz P., Chanda S.K., Verma I.M., Tergaonkar V.;
RT "Telomere-independent Rap1 is an IKK adaptor and regulates NF-kappaB-
RT dependent gene expression.";
RL Nat. Cell Biol. 12:758-767(2010).
RN [16]
RP INTERACTION WITH RIPK1.
RX PubMed=31519886; DOI=10.1038/s41467-019-11839-w;
RA Zhang X., Zhang H., Xu C., Li X., Li M., Wu X., Pu W., Zhou B., Wang H.,
RA Li D., Ding Q., Ying H., Wang H., Zhang H.;
RT "Ubiquitination of RIPK1 suppresses programmed cell death by regulating
RT RIPK1 kinase activation during embryogenesis.";
RL Nat. Commun. 10:4158-4158(2019).
RN [17]
RP INTERACTION WITH MARCHF2.
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 [18]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 250-343 IN COMPLEX WITH UBIQUITIN,
RP UBIQUITIN-BINDING, AND MUTAGENESIS OF VAL-293; TYR-301; LYS-302; PHE-305;
RP ARG-309; ARG-312; GLU-313; GLU-313; GLU-317 AND GLU-320.
RX PubMed=19303852; DOI=10.1016/j.cell.2009.03.007;
RA Rahighi S., Ikeda F., Kawasaki M., Akutsu M., Suzuki N., Kato R.,
RA Kensche T., Uejima T., Bloor S., Komander D., Randow F., Wakatsuki S.,
RA Dikic I.;
RT "Specific recognition of linear ubiquitin chains by NEMO is important for
RT NF-kappaB activation.";
RL Cell 136:1098-1109(2009).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 251-337, UBIQUITIN-BINDING, AND
RP OLIGOMETRIZATION.
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).
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:9927690). Its binding to
CC scaffolding polyubiquitin plays a key role in IKK activation by
CC multiple signaling receptor pathways. Can recognize and bind both 'Lys-
CC 63'-linked and linear polyubiquitin upon cell stimulation, with a much
CC highr affinity for linear polyubiquitin. Could be implicated in NF-
CC kappa-B-mediated protection from cytokine toxicity. Essential for viral
CC activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral
CC innate response; this function requires 'Lys-27'-linked
CC polyubiquitination (By similarity). {ECO:0000250|UniProtKB:Q9Y6K9,
CC ECO:0000269|PubMed:9927690}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Component of the
CC 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). The IKK core complex seems
CC to associate with regulatory or adapter proteins to form a IKK-
CC signalosome holo-complex (PubMed:11080499). The IKK complex associates
CC with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of
CC RELA/p65 (PubMed:20622870). Part of a complex composed of NCOA2, NCOA3,
CC CHUK/IKKA, IKBKB, IKBKG and CREBBP (By similarity). Interacts with
CC COPS3, CYLD, NALP2, TRPC4AP and PIDD1 (By similarity). Interacts with
CC ATM; the complex is exported from the nucleus (By similarity).
CC Interacts with TRAF6 (By similarity). Interacts with IKBKE (By
CC similarity). Interacts with TANK; the interaction is enhanced by IKBKE
CC and TBK1 (By similarity). Part of a ternary complex consisting of TANK,
CC IKBKB and IKBKG (PubMed:12133833). Interacts with ZFAND5 (By
CC similarity). Interacts with RIPK2 (By similarity). Interacts with TNIP1
CC and TNFAIP3; TNIP1 facilitates the TNFAIP3-mediated de-ubiquitination
CC of IKBKG (By similarity). Interacts with TNFAIP3; the interaction is
CC induced by TNF stimulation and by polyubiquitin (By similarity). Binds
CC (via UBAN region) polyubiquitin; binds both 'Lys-63'-linked and linear
CC polyubiquitin, with higher affinity for linear ubiquitin
CC (PubMed:19303852, PubMed:19854204). Interacts with NLRP10 (By
CC similarity). Interacts with TANK; this interaction increases in
CC response to DNA damage (By similarity). Interacts with USP10; this
CC interaction increases in response to DNA damage (By similarity).
CC Interacts with ZC3H12A; this interaction increases in response to DNA
CC damage (By similarity). Interacts with IFIT5; the interaction
CC synergizes the recruitment of IKK to MAP3K7 and enhances IKK
CC phosphorylation (By similarity). Interacts with TRIM29; this
CC interaction induces IKBKG/NEMO ubiquitination and proteolytic
CC degradation (By similarity). Interacts with TRIM13; this interaction
CC leads to IKBKG/NEMO ubiquitination (By similarity). Interacts with
CC ARFIP2 (By similarity). Interacts with RIPK1 (PubMed:31519886).
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 (By similarity).
CC Interacts with MARCHF2; during the late stages of macrophage viral and
CC bacterial infection; the interaction leads to ubiquitination and
CC degradation of IKBKG/NEMO (PubMed:32935379).
CC {ECO:0000250|UniProtKB:Q9Y6K9, ECO:0000269|PubMed:11080499,
CC ECO:0000269|PubMed:12133833, ECO:0000269|PubMed:19303852,
CC ECO:0000269|PubMed:19854204, ECO:0000269|PubMed:20622870,
CC ECO:0000269|PubMed:31519886, ECO:0000269|PubMed:32935379}.
CC -!- INTERACTION:
CC O88522; Q60680: Chuk; NbExp=6; IntAct=EBI-998011, EBI-646245;
CC O88522; O88351: Ikbkb; NbExp=8; IntAct=EBI-998011, EBI-447960;
CC O88522; O88522: Ikbkg; NbExp=2; IntAct=EBI-998011, EBI-998011;
CC O88522; Q924T7: Rnf31; NbExp=7; IntAct=EBI-998011, EBI-647680;
CC O88522; P62991: Ubc; NbExp=3; IntAct=EBI-998011, EBI-413074;
CC O88522; P0CG48: UBC; Xeno; NbExp=3; IntAct=EBI-998011, EBI-3390054;
CC O88522; P24772: VACWR196; Xeno; NbExp=2; IntAct=EBI-998011, EBI-4291651;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y6K9}. Nucleus
CC {ECO:0000250|UniProtKB:Q9Y6K9}. Note=Sumoylated NEMO accumulates in the
CC nucleus in response to genotoxic stress.
CC {ECO:0000250|UniProtKB:Q9Y6K9}.
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:0000250|UniProtKB:Q9Y6K9}.
CC -!- PTM: Phosphorylation at Ser-68 attenuates aminoterminal
CC homodimerization. {ECO:0000250|UniProtKB:Q9Y6K9}.
CC -!- PTM: Polyubiquitinated on Lys-278 through 'Lys-63'; the ubiquitination
CC is mediated by NOD2 and RIPK2 and probably plays a role in signaling by
CC facilitating interactions with ubiquitin domain-containing proteins and
CC activates the NF-kappa-B pathway. Polyubiquitinated on Lys-392 through
CC 'Lys-63'; the ubiquitination is mediated by BCL10, MALT1 and TRAF6 and
CC probably plays a role in signaling by facilitating interactions with
CC ubiquitin domain-containing proteins and activates the NF-kappa-B
CC pathway. Monoubiquitinated on Lys-270 and Lys-302; promotes nuclear
CC export. Polyubiquitinated through 'Lys-27' by TRIM23; involved in
CC antiviral innate and inflammatory responses. Linear polyubiquitinated
CC on Lys-111, Lys-143, Lys-226, Lys-246, Lys-270, Lys-278, Lys-285, Lys-
CC 295, Lys-302 and Lys-319; the head-to-tail polyubiquitination is
CC mediated by the LUBAC complex and plays a key role in NF-kappa-B
CC activation. Deubiquitinated by USP10 in a TANK-dependent and
CC -independent manner, leading to the negative regulation of NF-kappa-B
CC signaling upon DNA damage (By similarity). Ubiquitinated at Lys-319 by
CC MARCHF2 following bacterial and viral infection which leads to its
CC degradation (By similarity). {ECO:0000250|UniProtKB:Q9Y6K9}.
CC -!- PTM: Sumoylated on Lys-270 and Lys-302 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:0000250|UniProtKB:Q9Y6K9}.
CC -!- PTM: Neddylated by TRIM40, resulting in stabilization of NFKBIA and
CC down-regulation of NF-kappa-B activity. {ECO:0000250|UniProtKB:Q9Y6K9}.
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DR EMBL; AF069542; AAC40153.1; -; mRNA.
DR EMBL; AF326207; AAK69186.1; -; Genomic_DNA.
DR EMBL; AF513109; AAP47160.1; -; mRNA.
DR EMBL; AK154095; BAE32372.1; -; mRNA.
DR EMBL; AL669976; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466650; EDL29810.1; -; Genomic_DNA.
DR CCDS; CCDS41023.1; -.
DR RefSeq; NP_001154895.1; NM_001161423.1.
DR RefSeq; NP_034677.2; NM_010547.2.
DR RefSeq; XP_006527913.1; XM_006527850.2.
DR RefSeq; XP_006527914.1; XM_006527851.2.
DR RefSeq; XP_006527915.1; XM_006527852.2.
DR RefSeq; XP_011245829.1; XM_011247527.2.
DR PDB; 2V4H; X-ray; 2.90 A; A/B=251-337.
DR PDB; 2ZVN; X-ray; 3.00 A; B/D/F/H=253-337.
DR PDB; 2ZVO; X-ray; 2.90 A; B/D=250-339.
DR PDB; 3F89; X-ray; 2.80 A; A/B=250-339.
DR PDB; 3JSV; X-ray; 2.70 A; C/D=250-343.
DR PDB; 4OWF; X-ray; 2.00 A; A/B=250-339.
DR PDBsum; 2V4H; -.
DR PDBsum; 2ZVN; -.
DR PDBsum; 2ZVO; -.
DR PDBsum; 3F89; -.
DR PDBsum; 3JSV; -.
DR PDBsum; 4OWF; -.
DR AlphaFoldDB; O88522; -.
DR BMRB; O88522; -.
DR SMR; O88522; -.
DR BioGRID; 200602; 51.
DR ComplexPortal; CPX-3270; IkappaB kinase complex.
DR CORUM; O88522; -.
DR DIP; DIP-29811N; -.
DR IntAct; O88522; 27.
DR MINT; O88522; -.
DR STRING; 10090.ENSMUSP00000109762; -.
DR ChEMBL; CHEMBL4524000; -.
DR iPTMnet; O88522; -.
DR PhosphoSitePlus; O88522; -.
DR EPD; O88522; -.
DR jPOST; O88522; -.
DR MaxQB; O88522; -.
DR PaxDb; O88522; -.
DR PRIDE; O88522; -.
DR ProteomicsDB; 252822; -.
DR Antibodypedia; 73338; 1291 antibodies from 47 providers.
DR DNASU; 16151; -.
DR Ensembl; ENSMUST00000114127; ENSMUSP00000109762; ENSMUSG00000004221.
DR Ensembl; ENSMUST00000114128; ENSMUSP00000109763; ENSMUSG00000004221.
DR Ensembl; ENSMUST00000114133; ENSMUSP00000109768; ENSMUSG00000004221.
DR Ensembl; ENSMUST00000164101; ENSMUSP00000126770; ENSMUSG00000004221.
DR GeneID; 16151; -.
DR KEGG; mmu:16151; -.
DR UCSC; uc009toz.2; mouse.
DR CTD; 8517; -.
DR MGI; MGI:1338074; Ikbkg.
DR VEuPathDB; HostDB:ENSMUSG00000004221; -.
DR eggNOG; ENOG502R4ZD; Eukaryota.
DR GeneTree; ENSGT00530000063808; -.
DR HOGENOM; CLU_034097_0_0_1; -.
DR InParanoid; O88522; -.
DR OMA; QHRCIEH; -.
DR TreeFam; TF326608; -.
DR Reactome; R-MMU-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-MMU-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-MMU-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-MMU-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-MMU-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-MMU-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR Reactome; R-MMU-4755510; SUMOylation of immune response proteins.
DR Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-MMU-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-MMU-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-MMU-5684264; MAP3K8 (TPL2)-dependent MAPK1/3 activation.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases.
DR Reactome; R-MMU-9020702; Interleukin-1 signaling.
DR Reactome; R-MMU-933542; TRAF6 mediated NF-kB activation.
DR Reactome; R-MMU-937039; IRAK1 recruits IKK complex.
DR Reactome; R-MMU-937041; IKK complex recruitment mediated by RIP1.
DR Reactome; R-MMU-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
DR BioGRID-ORCS; 16151; 28 hits in 79 CRISPR screens.
DR ChiTaRS; Ikbkg; mouse.
DR EvolutionaryTrace; O88522; -.
DR PRO; PR:O88522; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; O88522; protein.
DR Bgee; ENSMUSG00000004221; Expressed in left lobe of liver and 265 other tissues.
DR ExpressionAtlas; O88522; baseline and differential.
DR Genevisible; O88522; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0008385; C:IkappaB kinase complex; ISO:MGI.
DR GO; GO:0072686; C:mitotic spindle; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0000922; C:spindle pole; ISO:MGI.
DR GO; GO:0000151; C:ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IDA:MGI.
DR GO; GO:1990450; F:linear polyubiquitin binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042975; F:peroxisome proliferator activated receptor binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:1990459; F:transferrin receptor binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; IDA:MGI.
DR GO; GO:0043276; P:anoikis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0001782; P:B cell homeostasis; IMP:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0051650; P:establishment of vesicle localization; ISO:MGI.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:ParkinsonsUK-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR InterPro; IPR032419; CC2-LZ_dom.
DR InterPro; IPR021063; NEMO_N.
DR InterPro; IPR034735; NEMO_ZF.
DR Pfam; PF16516; CC2-LZ; 1.
DR Pfam; PF11577; NEMO; 1.
DR PROSITE; PS51801; ZF_CCHC_NOA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; DNA damage; Isopeptide bond; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..412
FT /note="NF-kappa-B essential modulator"
FT /id="PRO_0000096783"
FT ZN_FING 382..412
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:0000250|UniProtKB:Q9Y6K9"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 44..111
FT /note="Interaction with CHUK/IKBKB"
FT /evidence="ECO:0000250"
FT REGION 150..250
FT /note="Interaction with TANK"
FT /evidence="ECO:0000269|PubMed:12133833"
FT REGION 242..343
FT /note="Ubiquitin-binding (UBAN)"
FT REGION 246..358
FT /note="Self-association"
FT /evidence="ECO:0000250"
FT REGION 249..412
FT /note="Required for interaction with TNFAIP3"
FT /evidence="ECO:0000250"
FT REGION 250..339
FT /note="Linear polyubiquitin-binding, does not bind to 'Lys-
FT 63'-linked polyubiquitin"
FT REGION 315..336
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255"
FT REGION 375..412
FT /note="Interaction with CYLD"
FT /evidence="ECO:0000250"
FT COILED 49..345
FT /evidence="ECO:0000255"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 390
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 393
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 406
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 410
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:0000250|UniProtKB:Q9Y6K9"
FT MOD_RES 43
FT /note="Phosphoserine; by IKKB"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT MOD_RES 85
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT MOD_RES 369
FT /note="Phosphoserine; by IKKB"
FT /evidence="ECO:0000269|PubMed:11971901"
FT MOD_RES 380
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT DISULFID 54
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 340
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT CROSSLNK 111
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 139
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 143
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 226
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 246
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 270
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 270
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 276
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 278
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17728323"
FT CROSSLNK 285
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 295
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 302
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 302
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K9"
FT CROSSLNK 314
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17728323"
FT CROSSLNK 318
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17728323"
FT CROSSLNK 319
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17728323"
FT CROSSLNK 392
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17728323"
FT MUTAGEN 278
FT /note="K->R: Slight decrease in TRAF6-induced
FT polyubiquitination."
FT /evidence="ECO:0000269|PubMed:17728323"
FT MUTAGEN 293
FT /note="V->A: Abolishes linear polyubiquitin-binding,
FT impairs 'Lys-63'-linked polyubiquitin-binding and impairs
FT NF-kappa-B activation; when associated with A-301 and A-
FT 302."
FT /evidence="ECO:0000269|PubMed:19303852"
FT MUTAGEN 301
FT /note="Y->A: Abolishes linear polyubiquitin-binding,
FT impairs 'Lys-63'-linked polyubiquitin-binding and impairs
FT NF-kappa-B activation; when associated with A-293 and A-
FT 302."
FT /evidence="ECO:0000269|PubMed:19303852"
FT MUTAGEN 302
FT /note="K->A: Abolishes linear polyubiquitin-binding,
FT impairs 'Lys-63'-linked polyubiquitin-binding and impairs
FT NF-kappa-B activation; when associated with A-293 and A-
FT 301."
FT /evidence="ECO:0000269|PubMed:19303852"
FT MUTAGEN 305
FT /note="F->A: Abolishes linear polyubiquitin-binding,
FT impairs 'Lys-63'-linked polyubiquitin-binding and impairs
FT of NF-kappa-B activation."
FT /evidence="ECO:0000269|PubMed:19303852"
FT MUTAGEN 309
FT /note="R->A: Abolishes linear polyubiquitin-binding, no
FT effect on 'Lys-63'-linked polyubiquitin-binding and impairs
FT NF-kappa-B activation; when associated with A-312 and A-
FT 313."
FT /evidence="ECO:0000269|PubMed:19303852"
FT MUTAGEN 312
FT /note="R->A: Abolishes linear polyubiquitin-binding, no
FT effect on 'Lys-63'-linked polyubiquitin-binding and impairs
FT NF-kappa-B activation; when associated with A-309 and A-
FT 313."
FT /evidence="ECO:0000269|PubMed:19303852"
FT MUTAGEN 313
FT /note="E->A: Impairs linear polyubiquitin-binding.
FT Abolishes linear polyubiquitin-binding, no effect on 'Lys-
FT 63'-linked polyubiquitin-binding and impairs NF-kappa-B
FT activation; when associated with A-309 and A-312. Abolishes
FT linear polyubiquitin-binding; when associated with A-317
FT and A-320."
FT /evidence="ECO:0000269|PubMed:19303852"
FT MUTAGEN 314
FT /note="K->R: Slight decrease in TRAF6-induced
FT polyubiquitination. Important decrease in TRAF6-induced
FT polyubiquitination; when associated with R-318 and R-319."
FT /evidence="ECO:0000269|PubMed:17728323"
FT MUTAGEN 316
FT /note="V->P: Loss of interaction with TRAF6 and TRAF6-
FT induced polyubiquitination."
FT /evidence="ECO:0000269|PubMed:17728323"
FT MUTAGEN 317
FT /note="E->A: Abolishes linear polyubiquitin-binding; when
FT associated with A-313 and A-320."
FT /evidence="ECO:0000269|PubMed:19303852"
FT MUTAGEN 318
FT /note="K->R: Slight decrease in TRAF6-induced
FT polyubiquitination. Decrease in TRAF6-induced
FT polyubiquitination; when associated with R-319. Important
FT decrease in TRAF6-induced polyubiquitination; when
FT associated with R-314 and R-319."
FT /evidence="ECO:0000269|PubMed:17728323"
FT MUTAGEN 319
FT /note="K->R: Slight decrease in TRAF6-induced
FT polyubiquitination. Decrease in TRAF6-induced
FT polyubiquitination; when associated with R-318. Important
FT decrease in TRAF6-induced polyubiquitination; when
FT associated with R-314 and R-318."
FT /evidence="ECO:0000269|PubMed:17728323"
FT MUTAGEN 320
FT /note="E->A: Abolishes linear polyubiquitin-binding; when
FT associated with A-313 and A-317."
FT /evidence="ECO:0000269|PubMed:19303852"
FT MUTAGEN 369
FT /note="S->A: Decreases phosphorylation and increases NF-
FT kappa-B activity."
FT /evidence="ECO:0000269|PubMed:11971901"
FT MUTAGEN 375
FT /note="S->A: Decreases phosphorylation and increases NF-
FT kappa-B activity."
FT /evidence="ECO:0000269|PubMed:11971901"
FT MUTAGEN 392
FT /note="K->R: 40% decrease in IL1-induced NF-kappa-B
FT activation."
FT /evidence="ECO:0000269|PubMed:17728323"
FT CONFLICT 13
FT /note="M -> T (in Ref. 1; AAC40153)"
FT /evidence="ECO:0000305"
FT HELIX 253..289
FT /evidence="ECO:0007829|PDB:4OWF"
FT HELIX 291..333
FT /evidence="ECO:0007829|PDB:4OWF"
FT HELIX 337..340
FT /evidence="ECO:0007829|PDB:3JSV"
SQ SEQUENCE 412 AA; 47972 MW; 66C693C857A2D5E6 CRC64;
MNKHPWKNQL SEMVQPSGGP AEDQDMLGEE SSLGKPAMLH LPSEQGTPET LQRCLEENQE
LRDAIRQSNQ MLRERCEELL HFQVSQREEK EFLMCKFQEA RKLVERLSLE KLDLRSQREQ
ALKELEQLKK CQQQMAEDKA SVKAQVTSLL GELQESQSRL EAATKDRQAL EGRIRAVSEQ
VRQLESEREV LQQQHSVQVD QLRMQNQSVE AALRMERQAA SEEKRKLAQL QAAYHQLFQD
YDSHIKSSKG MQLEDLRQQL QQAEEALVAK QELIDKLKEE AEQHKIVMET VPVLKAQADI
YKADFQAERH AREKLVEKKE YLQEQLEQLQ REFNKLKVGC HESARIEDMR KRHVETPQPP
LLPAPAHHSF HLALSNQRRS PPEEPPDFCC PKCQYQAPDM DTLQIHVMEC IE
