Reviewed, UniProtKB/Swiss-Prot Q9VEZ5 (IKKB_DROME)

Names and origin

Protein names

Recommended name:
    Inhibitor of nuclear factor kappa-B kinase subunit beta
      Short name=DmIKK-beta
    EC=2.7.11.10
Alternative name(s):
    Immune response deficient protein 5
    IKK-like protein
    Lipopolysaccharide-activated kinase
      Short name=DLAK
    Cactus kinase IKK

Gene names

Name:	ird5
Synonyms:	DIK
ORF Names:	CG4201

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	751 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for the activation of the NF-kappa-B factor Relish (Rel) by acting as an essential signaling component in transmitting the lipopolysaccharide (LPS) signal leading to cact degradation, which is required for direct activation of Rel. Phosphorylates inhibitors of NF-kappa-B (cact) thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the NF-kappa-B inhibitor. Essential for antibacterial immune response. Ref.4 Ref.5 Ref.8
Catalytic activity	ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein].
Subunit structure	Interacts with key to form the I-kappa-B kinase complex. In vitro, interacts with cact. Ref.4 Ref.5
Subcellular location	Cytoplasm By similarity. UniProtKB O14920
Developmental stage	Expressed both maternally and zygotically throughout development. Highest expression is in early embryos and third larval instar. Ref.4
Post-translational modification	Autophosphorylated; upon LPS stimulation it is transiently activated, and can be autophosphorylated. Ref.4 Ref.9
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Immune response Innate immunity
Cellular component	Cytoplasm
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	Toll signaling pathway Traceable author statement. Source: FlyBase antibacterial humoral response Ref.8 Inferred from mutant phenotype. Source: FlyBase innate immune response Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-serine phosphorylation Inferred from direct assay. Source: FlyBase positive regulation of antibacterial peptide biosynthetic process Ref.4 Inferred from direct assay. Source: UniProtKB protein catabolic process Ref.5 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Ref.5 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW IkappaB kinase activity Inferred from electronic annotation. Source: EC identical protein binding Ref.4 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-148871,EBI-148871
cact	Q03017	2	EBI-148871,EBI-200600
key	Q9GYV5	2	EBI-148871,EBI-113108

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 751	751	Inhibitor of nuclear factor kappa-B kinase subunit beta		PRO_0000086016
Regions
	Domain	41 – 341	301	Protein kinase
	Domain	489 – 510	22	Leucine-zipper Potential
	Nucleotide binding	47 – 55	9	ATP By similarity UniProtKB O14920
Sites
	Active site	184	1	Proton acceptor By similarity UniProtKB O14920
	Binding site	70	1	ATP UniProtKB O14920
Amino acid modifications
	Modified residue	202	1	Phosphotyrosine Ref.9
	Modified residue	221	1	Phosphoserine By similarity UniProtKB O14920
	Modified residue	225	1	Phosphothreonine Ref.9
Experimental info
	Mutagenesis	70	1	K → A: Loss of kinase activity. Ref.4
	Sequence conflict	16 – 17	2	QI → HE Ref.6
	Sequence conflict	201	1	I → F in AAF27291. Ref.4
	Sequence conflict	335	1	A → G in AAF04130. Ref.1
	Sequence conflict	345	1	L → V in AAF04130. Ref.1
	Sequence conflict	422	1	D → Y in AAF27291. Ref.4
	Sequence conflict	485	1	M → I in AAF27291. Ref.4
	Sequence conflict	548	1	I → S in AAF04348. Ref.6
	Sequence conflict	722	1	P → S in AAF04348. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q9VEZ5-1 [UniParc]. Last modified October 1, 2002. Version 2. Checksum: 0BD2452BED2F8E78	FASTA	751	86,373
	10 20 30 40 50 60 MITVVFCFSD CHGGIQILGR MSSVNKIKLN ENNKMHSFGN WERCRNLGEG GFGLVIHWRN 70 80 90 100 110 120 RTTGREIATK HIKEMGALSA DQQVKLSERW NKELNWSRQF KNFPHIVAGV DIEDPDFLEY 130 140 150 160 170 180 LNGMFSAKLP VIVLEYCNGG DVRKRLQSPE NANGLTEFEV RQILGALRKA LHFLHSQCGI 190 200 210 220 230 240 CHRDLKPDNI VIQRGVDGKK IYKLTDFGLA RGTPDQTMVQ SVVGTRHYYA PEVVENGFYN 250 260 270 280 290 300 STVDLWSFGV IAYELVTGEL PFIPHQTLKN IILNLIKKPA KCIAITEDPE DNTRFVNQFE 310 320 330 340 350 360 LPQTHHLSRP WAAQFTKWLA SPLNSNYKER GQLAANNVPV VFADLDKILN MNVLTIFAVN 370 380 390 400 410 420 NCERLEYAVS AEMTMKDLIA LIVLDTGMDE KELYFVLPTS HPHKTITPKS TPLQLYVEEW 430 440 450 460 470 480 SDTSKDSRKW TKRSNPPVML YIFQVKKECD YKIPEPILSI LSRKFIANKF KTKERWLQKR 490 500 510 520 530 540 VVLDMLYVLT KEQARYEMLV SGINERALSL EDEMMENSFI DSIDKQRIII SFAYDQLTSL 550 560 570 580 590 600 LKEAQAKIPS RQLISSAQWE KLNRNYNFII QSAKSIRSFL EACLREAKDM VKTTNQLRKE 610 620 630 640 650 660 VCEKDLFDCA RFYKKYLCNG AIISPSELNN DAEEFAKSRF KLYNEGEARH LPKSIDHMHY 670 680 690 700 710 720 LYFKTKESIP VLLQQFCDIK KEIFQINLQM LMSASSTPPP KLELSAAMDR LAISSGSPSS 730 740 750 DPFDSLRTIN AIEEAERINN ILVNEMKIDH Y

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"DIK, a IKK-like protein of Drosophila." Inohara N., Nunez G. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION.
[4]	"Lipopolysaccharide-activated kinase, an essential component for the induction of the antimicrobial peptide genes in Drosophila melanogaster cells." Kim Y.-S., Han S.-J., Ryu J.-H., Choi K.-H., Hong Y.-S., Chung Y.-H., Perrot S., Raibaud A., Brey P.T., Lee W.-J. J. Biol. Chem. 275:2071-2079(2000) [PubMed: 10636911] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 11-751, FUNCTION, DEVELOPMENTAL STAGE, AUTOPHOSPHORYLATION, INTERACTION WITH CACT, MUTAGENESIS OF LYS-70.
[5]	"A Drosophila IkappaB kinase complex required for Relish cleavage and antibacterial immunity." Silverman N., Zhou R., Stoeven S., Pandey N., Hultmark D., Maniatis T. Genes Dev. 14:2461-2471(2000) [PubMed: 11018014] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 15-751, FUNCTION, INTERACTION WITH KEY.
[6]	"Cloning and characterization of the Drosophila cactus kinase." Medzhitov R.M., Janeway C.J. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 16-751.
[7]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed: 12537569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 18-751. Strain: Berkeley. Tissue: Embryo.
[8]	"The antibacterial arm of the Drosophila innate immune response requires an IkappaB kinase." Lu Y., Wu L.P., Anderson K.V. Genes Dev. 15:104-110(2001) [PubMed: 11156609] [Abstract] Cited for: FUNCTION.
[9]	"Phosphoproteome analysis of Drosophila melanogaster embryos." Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P. J. Proteome Res. 7:1675-1682(2008) [PubMed: 18327897] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-202 AND THR-225, MASS SPECTROMETRY. Tissue: Embryo.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF190636 mRNA. Translation: AAF04130.1. AE014297 Genomic DNA. Translation: AAF55267.2. AF140766 mRNA. Translation: AAF27291.1. Different initiation. AF294395 mRNA. Translation: AAG02485.1. Different initiation. AF128403 mRNA. Translation: AAF04348.1. Different initiation. AY069472 mRNA. Translation: AAL39617.1. Different initiation.
RefSeq	NP_524751.2.
UniGene	Dm.1435
3D structure databases
HSSP	HSSP built from PDB template 1KWP based on UniProtKB P49137.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9VEZ5. 3 interactions.
STRING	Q9VEZ5.
Genome annotation databases
Ensembl	FBtr0083236; FBpp0082690; FBgn0024222; Drosophila melanogaster. [Genome view]
GeneID	44432.
KEGG	dme:Dmel_CG4201.
NMPDR	fig|7227.3.peg.13087.
Organism-specific databases
CTD	44432.
FlyBase	FBgn0024222. ird5.
Phylogenomic databases
OMA	CIAITED.
Enzyme and pathway databases
BioCyc	DMEL-XXX-02:DMEL-XXX-02-011871-MON.
BRENDA	2.7.11.10. 48.
Gene expression databases
GermOnline	CG4201. Drosophila melanogaster.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	837243.

Entry information

Entry name

IKKB_DROME

Accession

Primary (citable) accession number: Q9VEZ5
Secondary accession number(s): Q9GYV6 , Q9NJI1, Q9U698, Q9U7F5

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	October 1, 2002
Last modified:	November 3, 2009
This is version 78 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project