IKKB_DROME
ID IKKB_DROME Reviewed; 751 AA.
AC Q9VEZ5; Q9GYV6; Q9NJI1; Q9U698; Q9U7F5;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Inhibitor of nuclear factor kappa-B kinase subunit beta {ECO:0000305};
DE Short=I-kappaB kinase subunit beta {ECO:0000312|FlyBase:FBgn0024222};
DE EC=2.7.11.10;
DE AltName: Full=Cactus kinase IKK {ECO:0000303|Ref.6};
DE AltName: Full=IKK-like protein {ECO:0000303|Ref.1};
DE AltName: Full=Immune response deficient protein 5 {ECO:0000303|PubMed:11156609};
DE AltName: Full=Lipopolysaccharide-activated kinase {ECO:0000303|PubMed:10636911};
DE Short=DLAK {ECO:0000303|PubMed:10636911};
GN Name=IKKbeta {ECO:0000312|FlyBase:FBgn0024222};
GN Synonyms=DIK {ECO:0000303|Ref.1}, ird5 {ECO:0000303|PubMed:11156609};
GN ORFNames=CG4201 {ECO:0000312|FlyBase:FBgn0024222};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|EMBL:AAF55267.2};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Inohara N., Nunez G.;
RT "DIK, a IKK-like protein of Drosophila.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3] {ECO:0000305}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-751, FUNCTION, DEVELOPMENTAL STAGE,
RP AUTOPHOSPHORYLATION, INTERACTION WITH CACT, AND MUTAGENESIS OF LYS-70.
RX PubMed=10636911; DOI=10.1074/jbc.275.3.2071;
RA Kim Y.-S., Han S.-J., Ryu J.-H., Choi K.-H., Hong Y.-S., Chung Y.-H.,
RA Perrot S., Raibaud A., Brey P.T., Lee W.-J.;
RT "Lipopolysaccharide-activated kinase, an essential component for the
RT induction of the antimicrobial peptide genes in Drosophila melanogaster
RT cells.";
RL J. Biol. Chem. 275:2071-2079(2000).
RN [5] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE OF 15-751, FUNCTION, AND INTERACTION WITH KEY.
RX PubMed=11018014; DOI=10.1101/gad.817800;
RA Silverman N., Zhou R., Stoeven S., Pandey N., Hultmark D., Maniatis T.;
RT "A Drosophila IkappaB kinase complex required for Relish cleavage and
RT antibacterial immunity.";
RL Genes Dev. 14:2461-2471(2000).
RN [6] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-751.
RA Medzhitov R.M., Janeway C.J.;
RT "Cloning and characterization of the Drosophila cactus kinase.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [7] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 18-751.
RC STRAIN=Berkeley {ECO:0000269|PubMed:12537569};
RC TISSUE=Embryo {ECO:0000269|PubMed:12537569};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [8]
RP FUNCTION.
RX PubMed=11156609; DOI=10.1101/gad.856901;
RA Lu Y., Wu L.P., Anderson K.V.;
RT "The antibacterial arm of the Drosophila innate immune response requires an
RT IkappaB kinase.";
RL Genes Dev. 15:104-110(2001).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-202 AND THR-225, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [10]
RP FUNCTION.
RX PubMed=30119996; DOI=10.1016/j.immuni.2018.07.013;
RA Goto A., Okado K., Martins N., Cai H., Barbier V., Lamiable O., Troxler L.,
RA Santiago E., Kuhn L., Paik D., Silverman N., Holleufer A., Hartmann R.,
RA Liu J., Peng T., Hoffmann J.A., Meignin C., Daeffler L., Imler J.L.;
RT "The kinase IKKbeta regulates a STING- and NF-kappaB-dependent antiviral
RT response pathway in Drosophila.";
RL Immunity 49:225-234(2018).
CC -!- FUNCTION: Required for the activation of the NF-kappa-B factor Relish
CC (Rel) by acting as an essential signaling component in transmitting the
CC lipopolysaccharide (LPS) signal leading to cact degradation, which is
CC required for direct activation of Rel (PubMed:10636911,
CC PubMed:11018014, PubMed:11156609, PubMed:30119996). Phosphorylates
CC inhibitors of NF-kappa-B (cact) thus leading to the dissociation of the
CC inhibitor/NF-kappa-B complex and ultimately the degradation of the NF-
CC kappa-B inhibitor (PubMed:10636911, PubMed:11018014, PubMed:11156609).
CC Essential for antibacterial immune response (PubMed:11018014). Also
CC required for antiviral immune response (PubMed:30119996).
CC {ECO:0000269|PubMed:10636911, ECO:0000269|PubMed:11018014,
CC ECO:0000269|PubMed:11156609, ECO:0000269|PubMed:30119996}.
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 -!- SUBUNIT: Interacts with key to form the I-kappa-B kinase complex. In
CC vitro, interacts with cact. {ECO:0000269|PubMed:10636911,
CC ECO:0000269|PubMed:11018014}.
CC -!- INTERACTION:
CC Q9VEZ5; Q03017: cact; NbExp=2; IntAct=EBI-148871, EBI-200600;
CC Q9VEZ5; Q9VEZ5: IKKbeta; NbExp=2; IntAct=EBI-148871, EBI-148871;
CC Q9VEZ5; Q9GYV5: key; NbExp=3; IntAct=EBI-148871, EBI-113108;
CC Q9VEZ5; Q94527-1: Rel; NbExp=2; IntAct=EBI-148871, EBI-15786027;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically
CC throughout development. Highest expression is in early embryos and
CC third larval instar. {ECO:0000269|PubMed:10636911}.
CC -!- PTM: Autophosphorylated; upon LPS stimulation it is transiently
CC activated, and can be autophosphorylated.
CC {ECO:0000269|PubMed:18327897}.
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 -!- SEQUENCE CAUTION:
CC Sequence=AAF04348.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAF27291.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAG02485.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAL39617.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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; AF190636; AAF04130.1; -; mRNA.
DR EMBL; AE014297; AAF55267.2; -; Genomic_DNA.
DR EMBL; AF140766; AAF27291.1; ALT_INIT; mRNA.
DR EMBL; AF294395; AAG02485.1; ALT_INIT; mRNA.
DR EMBL; AF128403; AAF04348.1; ALT_INIT; mRNA.
DR EMBL; AY069472; AAL39617.1; ALT_INIT; mRNA.
DR RefSeq; NP_524751.3; NM_080012.4.
DR AlphaFoldDB; Q9VEZ5; -.
DR SMR; Q9VEZ5; -.
DR BioGRID; 69058; 173.
DR DIP; DIP-31307N; -.
DR IntAct; Q9VEZ5; 7.
DR STRING; 7227.FBpp0293344; -.
DR iPTMnet; Q9VEZ5; -.
DR PaxDb; Q9VEZ5; -.
DR PRIDE; Q9VEZ5; -.
DR EnsemblMetazoa; FBtr0304804; FBpp0293344; FBgn0024222.
DR GeneID; 44432; -.
DR KEGG; dme:Dmel_CG4201; -.
DR CTD; 44432; -.
DR FlyBase; FBgn0024222; IKKbeta.
DR VEuPathDB; VectorBase:FBgn0024222; -.
DR eggNOG; KOG4250; Eukaryota.
DR GeneTree; ENSGT00950000182937; -.
DR HOGENOM; CLU_022451_0_0_1; -.
DR InParanoid; Q9VEZ5; -.
DR OrthoDB; 1013139at2759; -.
DR PhylomeDB; Q9VEZ5; -.
DR Reactome; R-DME-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-DME-209447; Activation of the IkappaB kinase complex, KEY:IRD5 dimer:KEY.
DR Reactome; R-DME-214399; Activated IkappaB kinase (IKK) complex, Phospho IRD5:KEY dimer, phosphorylates REL in the PGN:PGRP-LC/LE receptor 'signalling complex'.
DR Reactome; R-DME-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
DR Reactome; R-DME-5676590; NIK-->noncanonical NF-kB signaling.
DR Reactome; R-DME-9020702; Interleukin-1 signaling.
DR SignaLink; Q9VEZ5; -.
DR BioGRID-ORCS; 44432; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 44432; -.
DR PRO; PR:Q9VEZ5; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0024222; Expressed in adult abdomen and 21 other tissues.
DR Genevisible; Q9VEZ5; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008384; F:IkappaB kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:FlyBase.
DR GO; GO:0019731; P:antibacterial humoral response; IMP:FlyBase.
DR GO; GO:0071456; P:cellular response to hypoxia; IMP:FlyBase.
DR GO; GO:0051607; P:defense response to virus; IMP:FlyBase.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0061057; P:peptidoglycan recognition protein signaling pathway; IMP:FlyBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0006963; P:positive regulation of antibacterial peptide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IMP:FlyBase.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:FlyBase.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:FlyBase.
DR GO; GO:0030163; P:protein catabolic process; IDA:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; IMP:FlyBase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Antiviral defense; ATP-binding; Cytoplasm; Immunity; Innate immunity;
KW Kinase; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..751
FT /note="Inhibitor of nuclear factor kappa-B kinase subunit
FT beta"
FT /id="PRO_0000086016"
FT DOMAIN 41..341
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000305"
FT REGION 489..510
FT /note="Leucine-zipper"
FT ACT_SITE 184
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O14920,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 47..55
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O14920,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 70
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 202
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 221
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14920"
FT MOD_RES 225
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MUTAGEN 70
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:10636911"
FT CONFLICT 16..17
FT /note="QI -> HE (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="I -> F (in Ref. 4; AAF27291)"
FT /evidence="ECO:0000305"
FT CONFLICT 335
FT /note="A -> G (in Ref. 1; AAF04130)"
FT /evidence="ECO:0000305"
FT CONFLICT 345
FT /note="L -> V (in Ref. 1; AAF04130)"
FT /evidence="ECO:0000305"
FT CONFLICT 422
FT /note="D -> Y (in Ref. 4; AAF27291)"
FT /evidence="ECO:0000305"
FT CONFLICT 485
FT /note="M -> I (in Ref. 4; AAF27291)"
FT /evidence="ECO:0000305"
FT CONFLICT 548
FT /note="I -> S (in Ref. 6; AAF04348)"
FT /evidence="ECO:0000305"
FT CONFLICT 722
FT /note="P -> S (in Ref. 6; AAF04348)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 751 AA; 86373 MW; 0BD2452BED2F8E78 CRC64;
MITVVFCFSD CHGGIQILGR MSSVNKIKLN ENNKMHSFGN WERCRNLGEG GFGLVIHWRN
RTTGREIATK HIKEMGALSA DQQVKLSERW NKELNWSRQF KNFPHIVAGV DIEDPDFLEY
LNGMFSAKLP VIVLEYCNGG DVRKRLQSPE NANGLTEFEV RQILGALRKA LHFLHSQCGI
CHRDLKPDNI VIQRGVDGKK IYKLTDFGLA RGTPDQTMVQ SVVGTRHYYA PEVVENGFYN
STVDLWSFGV IAYELVTGEL PFIPHQTLKN IILNLIKKPA KCIAITEDPE DNTRFVNQFE
LPQTHHLSRP WAAQFTKWLA SPLNSNYKER GQLAANNVPV VFADLDKILN MNVLTIFAVN
NCERLEYAVS AEMTMKDLIA LIVLDTGMDE KELYFVLPTS HPHKTITPKS TPLQLYVEEW
SDTSKDSRKW TKRSNPPVML YIFQVKKECD YKIPEPILSI LSRKFIANKF KTKERWLQKR
VVLDMLYVLT KEQARYEMLV SGINERALSL EDEMMENSFI DSIDKQRIII SFAYDQLTSL
LKEAQAKIPS RQLISSAQWE KLNRNYNFII QSAKSIRSFL EACLREAKDM VKTTNQLRKE
VCEKDLFDCA RFYKKYLCNG AIISPSELNN DAEEFAKSRF KLYNEGEARH LPKSIDHMHY
LYFKTKESIP VLLQQFCDIK KEIFQINLQM LMSASSTPPP KLELSAAMDR LAISSGSPSS
DPFDSLRTIN AIEEAERINN ILVNEMKIDH Y
