IKKE_MOUSE
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 03-AUG-2022, entry version 172.
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 DDX58/RIG-I; interactions are
CC disrupted by the interaction between IKBKE and SIKE1 (By similarity).
CC Interacts with TOPORS; induced by DNA damage (By similarity). Interacts
CC with CYLD, IKBKB, IKBKG and MYD88 (By similarity). Interacts with IFIH1
CC (By similarity). Interacts with DDX3X; the interaction may be induced
CC upon virus infection (By similarity). Interacts with TRIM6 (via SPRY
CC box) (By similarity). Interacts with unanchored K48-linked
CC polyubiquitin chains; this leads to IKBKE activation (By similarity).
CC Interacts with TBK1 (By similarity). Interacts with FKBP5 (By
CC similarity). {ECO:0000250|UniProtKB:Q14164,
CC 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}.
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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; 3.
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; Q9R0T8; -.
DR PRIDE; Q9R0T8; -.
DR ProteomicsDB; 266963; -.
DR Antibodypedia; 73513; 623 antibodies from 45 providers.
DR DNASU; 56489; -.
DR Ensembl; ENSMUST00000062108; ENSMUSP00000054126; ENSMUSG00000042349.
DR GeneID; 56489; -.
DR KEGG; mmu:56489; -.
DR UCSC; uc007cnf.1; mouse.
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; ELQCNNG; -.
DR OrthoDB; 563981at2759; -.
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-936440; Negative regulators of DDX58/IFIH1 signaling.
DR Reactome; R-MMU-936964; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
DR BioGRID-ORCS; 56489; 2 hits in 75 CRISPR screens.
DR PRO; PR:Q9R0T8; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9R0T8; protein.
DR Bgee; ENSMUSG00000042349; Expressed in peripheral lymph node and 136 other tissues.
DR ExpressionAtlas; Q9R0T8; baseline and differential.
DR Genevisible; Q9R0T8; MM.
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:0004704; F:NF-kappaB-inducing kinase activity; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
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:0018105; P:peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0010884; P:positive regulation of lipid storage; IMP:BHF-UCL.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS: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 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 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; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
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
