ID IKKE_MOUSE Reviewed; 717 AA. AC Q9R0T8; Q8C2I3; DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 27-MAR-2024, entry version 181. DE RecName: Full=Inhibitor of nuclear factor kappa-B kinase subunit epsilon; DE Short=I-kappa-B kinase epsilon; DE Short=IKK-E; DE Short=IKK-epsilon; DE Short=IkBKE; DE EC=2.7.11.10 {ECO:0000269|PubMed:10421793}; DE AltName: Full=Inducible I kappa-B kinase; DE Short=IKK-i; GN Name=Ikbke; Synonyms=Ikke, Ikki; 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], FUNCTION, AND CATALYTIC ACTIVITY. RC TISSUE=Macrophage; RX PubMed=10421793; DOI=10.1093/intimm/11.8.1357; RA Shimada T., Kawai T., Takeda K., Matsumoto M., Inoue J., Tatsumi Y., RA Kanamaru A., Akira S.; RT "IKK-i, a novel lipopolysaccharide-inducible kinase that is related to RT IkappaB kinases."; RL Int. Immunol. 11:1357-1362(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, and Thymus; 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 [3] 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 [4] 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 [5] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=15210742; DOI=10.1084/jem.20040520; RA Hemmi H., Takeuchi O., Sato S., Yamamoto M., Kaisho T., Sanjo H., Kawai T., RA Hoshino K., Takeda K., Akira S.; RT "The roles of two IkappaB kinase-related kinases in lipopolysaccharide and RT double stranded RNA signaling and viral infection."; RL J. Exp. Med. 199:1641-1650(2004). RN [6] RP INTERACTION WITH AZI2; TANK AND TBKBP1. RX PubMed=17568778; DOI=10.1038/sj.emboj.7601743; RA Ryzhakov G., Randow F.; RT "SINTBAD, a novel component of innate antiviral immunity, shares a TBK1- RT binding domain with NAP1 and TANK."; RL EMBO J. 26:3180-3190(2007). RN [7] RP FUNCTION IN STAT1 ACTIVATION, PHOSPHORYLATION AT THR-503, DISRUPTION RP PHENOTYPE, TISSUE SPECIFICITY, AND MUTAGENESIS OF LYS-38. RX PubMed=17332413; DOI=10.1126/science.1136567; RA Tenoever B.R., Ng S.L., Chua M.A., McWhirter S.M., Garcia-Sastre A., RA Maniatis T.; RT "Multiple functions of the IKK-related kinase IKKepsilon in interferon- RT mediated antiviral immunity."; RL Science 315:1274-1278(2007). RN [8] RP FUNCTION IN ENERGY BALANCE, DISRUPTION PHENOTYPE, INDUCTION BY HIGH-FAT RP DIET, AND TISSUE SPECIFICITY. RX PubMed=19737522; DOI=10.1016/j.cell.2009.06.046; RA Chiang S.H., Bazuine M., Lumeng C.N., Geletka L.M., Mowers J., White N.M., RA Ma J.T., Zhou J., Qi N., Westcott D., Delproposto J.B., Blackwell T.S., RA Yull F.E., Saltiel A.R.; RT "The protein kinase IKKepsilon regulates energy balance in obese mice."; RL Cell 138:961-975(2009). RN [9] RP FUNCTION IN STAT1 ACTIVATION, AND DISRUPTION PHENOTYPE. RX PubMed=22065572; DOI=10.1074/jbc.m111.285205; RA Perwitasari O., Cho H., Diamond M.S., Gale M. Jr.; RT "Inhibitor of kappaB kinase epsilon (IKK(epsilon)), STAT1, and IFIT2 RT proteins define novel innate immune effector pathway against West Nile RT virus infection."; RL J. Biol. Chem. 286:44412-44423(2011). RN [10] RP FUNCTION REGULATION IN IFN RESPONSE. RX PubMed=22171011; DOI=10.1073/pnas.1119137109; RA Ng S.L., Friedman B.A., Schmid S., Gertz J., Myers R.M., Tenoever B.R., RA Maniatis T.; RT "IkappaB kinase epsilon (IKK(epsilon)) regulates the balance between type I RT and type II interferon responses."; RL Proc. Natl. Acad. Sci. U.S.A. 108:21170-21175(2011). RN [11] RP FUNCTION IN ENERGY BALANCE, DISRUPTION PHENOTYPE, INDUCTION BY HIGH-FAT RP DIET, TISSUE SPECIFICITY, AND ACTIVITY REGULATION. RX PubMed=23396211; DOI=10.1038/nm.3082; RA Reilly S.M., Chiang S.H., Decker S.J., Chang L., Uhm M., Larsen M.J., RA Rubin J.R., Mowers J., White N.M., Hochberg I., Downes M., Yu R.T., RA Liddle C., Evans R.M., Oh D., Li P., Olefsky J.M., Saltiel A.R.; RT "An inhibitor of the protein kinases TBK1 and IKK-[?] improves obesity- RT related metabolic dysfunctions in mice."; RL Nat. Med. 19:313-321(2013). CC -!- FUNCTION: Serine/threonine kinase that plays an essential role in CC regulating inflammatory responses to viral infection, through the CC activation of the type I IFN, NF-kappa-B and STAT signaling. Also CC involved in TNFA and inflammatory cytokines, like Interleukin-1, CC signaling. Following activation of viral RNA sensors, such as RIG-I- CC like receptors, associates with DDX3X and phosphorylates interferon CC regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This CC activity allows subsequent homodimerization and nuclear translocation CC of the IRF3 leading to transcriptional activation of pro-inflammatory CC and antiviral genes including IFNB. In order to establish such an CC antiviral state, IKBKE forms several different complexes whose CC composition depends on the type of cell and cellular stimuli. Thus, CC several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or CC TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. CC Activated by polyubiquitination in response to TNFA and interleukin-1, CC regulates the NF-kappa-B signaling pathway through, at least, the CC phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus CC leading to the dissociation of the inhibitor/NF-kappa-B complex and CC ultimately the degradation of the inhibitor. In addition, is also CC required for the induction of a subset of ISGs which displays antiviral CC activity, may be through the phosphorylation of STAT1 at 'Ser-708'. CC Phosphorylation of STAT1 at 'Ser-708' seems also to promote the CC assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared CC to GAF (STAT1:STAT1) complexes, in this way regulating the balance CC between type I and type II IFN responses. Protects cells against DNA CC damage-induced cell death. Also plays an important role in energy CC balance regulation by sustaining a state of chronic, low-grade CC inflammation in obesity, wich leads to a negative impact on insulin CC sensitivity. Phosphorylates AKT1. {ECO:0000269|PubMed:10421793, CC ECO:0000269|PubMed:15210742, ECO:0000269|PubMed:17332413, CC ECO:0000269|PubMed:19737522, ECO:0000269|PubMed:22065572, CC ECO:0000269|PubMed:22171011, ECO:0000269|PubMed:23396211}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[I-kappa-B protein] = ADP + H(+) + O-phospho-L- CC seryl-[I-kappa-B protein]; Xref=Rhea:RHEA:19073, Rhea:RHEA- CC COMP:13698, Rhea:RHEA-COMP:13699, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, CC ChEBI:CHEBI:456216; EC=2.7.11.10; CC Evidence={ECO:0000269|PubMed:10421793}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19074; CC Evidence={ECO:0000305|PubMed:10421793}; CC -!- ACTIVITY REGULATION: Kinase activity is inhibited competitively by CC amlexanox. {ECO:0000269|PubMed:23396211}. CC -!- SUBUNIT: Homodimer (By similarity). Interacts with MAVS/IPS1 (By CC similarity). Interacts (via protein kinase domain) with TTLL12 (via N- CC terminus); the interaction prevents MAVS binding to IKBKE (By CC similarity). Interacts with the adapter proteins AZI2/NAP1, TANK and CC TBKBP1/SINTBAD (PubMed:17568778). Interacts with SIKE1 (By similarity). CC Interacts with TICAM1/TRIF, IRF3 and RIGI; interactions are disrupted CC by the interaction between IKBKE and SIKE1 (By similarity). Interacts CC with TOPORS; induced by DNA damage (By similarity). Interacts with CC CYLD, IKBKB, IKBKG and MYD88 (By similarity). Interacts with IFIH1 (By CC similarity). Interacts with DDX3X; the interaction may be induced upon CC virus infection (By similarity). Interacts with TRIM6 (via SPRY box) CC (By similarity). Interacts with unanchored K48-linked polyubiquitin CC chains; this leads to IKBKE activation (By similarity). Interacts with CC TBK1 (By similarity). Interacts with FKBP5 (By similarity). CC {ECO:0000250|UniProtKB:Q14164, ECO:0000269|PubMed:17568778}. CC -!- INTERACTION: CC Q9R0T8; Q8N7N6: Traf3ip2; NbExp=3; IntAct=EBI-6664658, EBI-646165; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14164}. Nucleus CC {ECO:0000250|UniProtKB:Q14164}. Nucleus, PML body CC {ECO:0000250|UniProtKB:Q14164}. Note=Targeting to PML nuclear bodies CC upon DNA damage is TOPORS-dependent. Located diffusely throughout the CC cytoplasm but locates to punctate cytoplasmic bodies when coexpressed CC with TRIM6. {ECO:0000250|UniProtKB:Q14164}. CC -!- TISSUE SPECIFICITY: Expressed in bone marrow-derived macrophages and at CC low levels in liver and white adipose tissue (at protein level). CC Detected in muscle and lung. {ECO:0000269|PubMed:17332413, CC ECO:0000269|PubMed:19737522, ECO:0000269|PubMed:23396211}. CC -!- INDUCTION: Induced by lipopolysaccharide (LPS) and TNFA. Under high-fat CC diet, highly induced (via NF-kappa-B) in adipocytes and M1-polarized CC adipose tissue macrophages. {ECO:0000269|PubMed:19737522, CC ECO:0000269|PubMed:23396211}. CC -!- PTM: Sumoylation by TOPORS upon DNA damage is required for protection CC of cells against DNA damage-induced cell death. Desumoylated by SENP1 CC (By similarity). {ECO:0000250}. CC -!- PTM: Autophosphorylated and phosphorylated by IKBKB/IKKB. CC Phosphorylation at Ser-172 is enhanced by the interaction with DDX3X. CC Phosphorylated at Thr-503 upon IFN activation. CC {ECO:0000269|PubMed:17332413}. CC -!- PTM: 'Lys-63'-linked polyubiquitinated at Lys-30 and Lys-403 by CC TRAF2:BIRC2 and TRAF2:BIRC3 complexes. Ubiquitination is induced by CC LPS, TNFA and interleukin-1 and required for full kinase activity and CC KF-kappa-B pathway activation (By similarity). {ECO:0000250}. CC -!- DISRUPTION PHENOTYPE: Animals are hypersusceptible to influenza virus CC infection because of a defect in the activation of a subset of type 1 CC IFN-stimulated genes, however the amounts of IFNB produced are normals. CC Lungs of mice infected 7 days with influenza virus exhibit an CC inflammatory infiltrate consisting of lymphocytes, macrophages and CC neutrophils. After West Nile virus infection, animals display earlier CC neurological symptoms, a higher degree of neurovirulence and a failure CC to recover, compared to wild type. Animals are protected from high-fat CC diet-induced obesity, liver and adipose inflammation, hepatic steatosis CC and insulin resistance. They show an increased energy expenditure and CC thermogenesis and maintain insulin sensitivity in liver and adipose CC tissue. {ECO:0000269|PubMed:15210742, ECO:0000269|PubMed:17332413, CC ECO:0000269|PubMed:19737522, ECO:0000269|PubMed:22065572, CC ECO:0000269|PubMed:23396211}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein CC kinase family. I-kappa-B kinase subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB016589; BAA85154.1; -; mRNA. DR EMBL; AK088580; BAC40434.1; -; mRNA. DR EMBL; AK149911; BAE29161.1; -; mRNA. DR EMBL; CT010206; CAJ18414.1; -; mRNA. DR EMBL; CH466520; EDL39710.1; -; Genomic_DNA. DR CCDS; CCDS15269.1; -. DR RefSeq; NP_062751.2; NM_019777.3. DR RefSeq; XP_011246354.1; XM_011248052.2. DR AlphaFoldDB; Q9R0T8; -. DR SMR; Q9R0T8; -. DR BioGRID; 208014; 6. DR IntAct; Q9R0T8; 2. DR STRING; 10090.ENSMUSP00000054126; -. DR ChEMBL; CHEMBL4296094; -. DR iPTMnet; Q9R0T8; -. DR PhosphoSitePlus; Q9R0T8; -. DR EPD; Q9R0T8; -. DR MaxQB; Q9R0T8; -. DR PaxDb; 10090-ENSMUSP00000054126; -. DR ProteomicsDB; 266963; -. DR Pumba; Q9R0T8; -. DR Antibodypedia; 73513; 714 antibodies from 45 providers. DR DNASU; 56489; -. DR Ensembl; ENSMUST00000062108.10; ENSMUSP00000054126.4; ENSMUSG00000042349.14. DR GeneID; 56489; -. DR KEGG; mmu:56489; -. DR UCSC; uc007cnf.1; mouse. DR AGR; MGI:1929612; -. DR CTD; 9641; -. DR MGI; MGI:1929612; Ikbke. DR VEuPathDB; HostDB:ENSMUSG00000042349; -. DR eggNOG; KOG4250; Eukaryota. DR GeneTree; ENSGT00950000182937; -. DR HOGENOM; CLU_000288_101_1_1; -. DR InParanoid; Q9R0T8; -. DR OMA; AEQAKCW; -. DR OrthoDB; 2957757at2759; -. DR PhylomeDB; Q9R0T8; -. DR TreeFam; TF324269; -. DR BRENDA; 2.7.11.10; 3474. DR Reactome; R-MMU-4755510; SUMOylation of immune response proteins. DR Reactome; R-MMU-5357786; TNFR1-induced proapoptotic signaling. DR Reactome; R-MMU-5357905; Regulation of TNFR1 signaling. DR Reactome; R-MMU-936440; Negative regulators of DDX58/IFIH1 signaling. DR Reactome; R-MMU-936964; Activation of IRF3, IRF7 mediated by TBK1, IKBKE. DR BioGRID-ORCS; 56489; 2 hits in 80 CRISPR screens. DR PRO; PR:Q9R0T8; -. DR Proteomes; UP000000589; Chromosome 1. DR RNAct; Q9R0T8; Protein. DR Bgee; ENSMUSG00000042349; Expressed in peripheral lymph node and 139 other cell types or tissues. DR ExpressionAtlas; Q9R0T8; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0031966; C:mitochondrial membrane; ISO:MGI. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0016605; C:PML body; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0008384; F:IkappaB kinase activity; IDA:MGI. DR GO; GO:0036435; F:K48-linked polyubiquitin modification-dependent protein binding; IDA:UniProtKB. DR GO; GO:0004672; F:protein kinase activity; IDA:MGI. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0098586; P:cellular response to virus; IDA:UniProtKB. DR GO; GO:0010467; P:gene expression; IMP:MGI. DR GO; GO:0006955; P:immune response; IMP:MGI. DR GO; GO:0097400; P:interleukin-17-mediated signaling pathway; IDA:MGI. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISS:UniProtKB. DR GO; GO:0048255; P:mRNA stabilization; IMP:MGI. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISS:UniProtKB. DR GO; GO:0010884; P:positive regulation of lipid storage; IMP:BHF-UCL. DR GO; GO:0032481; P:positive regulation of type I interferon production; ISO:MGI. DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IMP:UniProtKB. DR GO; GO:0043254; P:regulation of protein-containing complex assembly; IMP:MGI. DR GO; GO:0035456; P:response to interferon-beta; ISO:MGI. DR GO; GO:0034340; P:response to type I interferon; IDA:UniProtKB. DR CDD; cd17128; Ubl_IKKE; 1. DR Gene3D; 1.20.1270.420; -; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR041309; TBK1_CCD1. DR InterPro; IPR041087; TBK1_ULD. DR PANTHER; PTHR22969; IKB KINASE; 1. DR PANTHER; PTHR22969:SF10; INHIBITOR OF NUCLEAR FACTOR KAPPA-B KINASE SUBUNIT EPSILON; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF18394; TBK1_CCD1; 1. DR Pfam; PF18396; TBK1_ULD; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR Genevisible; Q9R0T8; MM. PE 1: Evidence at protein level; KW ATP-binding; Cytoplasm; DNA damage; Isopeptide bond; Kinase; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transferase; Ubl conjugation. FT CHAIN 1..717 FT /note="Inhibitor of nuclear factor kappa-B kinase subunit FT epsilon" FT /id="PRO_0000086018" FT DOMAIN 9..315 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 385..650 FT /note="Interaction with DDX3X" FT /evidence="ECO:0000250" FT REGION 452..473 FT /note="Leucine-zipper" FT ACT_SITE 135 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 15..23 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 38 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 172 FT /note="Phosphoserine; by autocatalysis and IKKB" FT /evidence="ECO:0000250|UniProtKB:Q14164" FT MOD_RES 503 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:17332413" FT MOD_RES 665 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q14164" FT CROSSLNK 30 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q14164" FT CROSSLNK 231 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1)" FT /evidence="ECO:0000250|UniProtKB:Q14164" FT CROSSLNK 403 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q14164" FT MUTAGEN 38 FT /note="K->A: Dominant negative." FT /evidence="ECO:0000269|PubMed:17332413" FT CONFLICT 471 FT /note="S -> G (in Ref. 1; BAA85154)" FT /evidence="ECO:0000305" FT CONFLICT 483 FT /note="A -> S (in Ref. 1; BAA85154)" FT /evidence="ECO:0000305" SQ SEQUENCE 717 AA; 80953 MW; 0863ECC180AE385A CRC64; MQSTTNYLWH TDDLLGQGAT ASVYKARNKK SGEVVAVKVF NSASYRRPPE VQVREFEVLR RLNHQNIVKL FAVEETGGSR QKVLIMEYCS SGSLLSVLED PENTFGLSEE EFLVVLRCVV AGMNHLRENG IVHRDIKPGN IMRLVGEEGQ SIYKLSDFGA ARKLDDDEKF VSVYGTEEYL HPDMYERAVL RKPQQKAFGV TVDLWSIGVT LYHAATGSLP FIPFGGPRRN KEIMYRITTE KPAGAISGTQ KQENGPLEWS YSLPITCRLS MGLQNQLVPI LANILEVEED KCWGFDQFFA ETSDILQRTV IHVFSLPQAV LHHVYIHAHN TIAIFLEAVY EQTNVTPKHQ EYLFEGHPCV LEPSLSAQHI AHTAASSPLT LFSMSSDTPK GLAFRDPALD VPKFVPKVDL QADYSTAKGV LGAGYQALWL ARVLLDGQAL MLRGLHWVLE VLQDTCQQTL EVTRTALLYL SSSLGTERFS SGAGMPDVQE RKEATELRTR LQTLSEILSK CSHNVTETQR SLSCLGEELL KNRDQIHEDN KSIQKIQCCL DKMHFIYKQF KKSRMRPGLS YNEEQIHKLD KVNFSHLAKR LLQVFQEECV QTYQVSLVTH GKRMRQVQRA QNHLHLIGHS VATCNSEARG AQESLNKIFD QLLLDRASEQ GAEVSPQPMA PHPGPDPKDL VFHMQELCND MKLLAFDLQD NNRLIERLHR VPSAPDV //