CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000322
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Inhibitor of nuclear factor kappa-B kinase subunit beta 
Protein Synonyms/Alias
 I-kappa-B-kinase beta; IKK-B; IKK-beta; IkBKB; I-kappa-B kinase 2; IKK2; Nuclear factor NF-kappa-B inhibitor kinase beta; NFKBIKB 
Gene Name
 IKBKB 
Gene Synonyms/Alias
 IKKB 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
44TGEQIAIKQCRQELSubiquitination[1]
106CQGGDLRKYLNQFENubiquitination[1]
147RIIHRDLKPENIVLQubiquitination[1]
163GEQRLIHKIIDLGYAubiquitination[2]
301YGPNGCFKALDDILNubiquitination[1]
337DESLQSLKARIQQDTubiquitination[1]
418SCILQEPKRNLAFFQubiquitination[1]
555QRSPMGRKQGGTLDDubiquitination[1]
659KELWNLLKIACSKVRacetylation[3]
703NSLPEPAKKSEELVAubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [3] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786] 
Functional Description
 Serine kinase that plays an essential role in the NF- kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation. 
Sequence Annotation
 DOMAIN 15 300 Protein kinase.
 NP_BIND 21 29 ATP (By similarity).
 REGION 458 479 Leucine-zipper.
 REGION 737 742 NEMO-binding.
 ACT_SITE 145 145 Proton acceptor (By similarity).
 BINDING 44 44 ATP (By similarity).
 MOD_RES 177 177 Phosphoserine; by TBK1 and PKC/PRKCZ.
 MOD_RES 179 179 S-nitrosocysteine.
 MOD_RES 180 180 O-acetylthreonine; by Yersinia yopJ.
 MOD_RES 181 181 Phosphoserine; by TBK1, PKC/PRKCZ and
 MOD_RES 670 670 Phosphoserine; by autocatalysis
 MOD_RES 672 672 Phosphoserine.
 MOD_RES 675 675 Phosphoserine; by autocatalysis
 MOD_RES 682 682 Phosphoserine; by autocatalysis
 MOD_RES 689 689 Phosphoserine; by autocatalysis
 MOD_RES 692 692 Phosphoserine; by autocatalysis
 MOD_RES 695 695 Phosphoserine; by autocatalysis
 MOD_RES 697 697 Phosphoserine; by autocatalysis
 MOD_RES 705 705 Phosphoserine; by autocatalysis
 MOD_RES 733 733 Phosphoserine; by autocatalysis
 MOD_RES 740 740 Phosphoserine; by autocatalysis
 MOD_RES 750 750 Phosphoserine; by autocatalysis
 CROSSLNK 163 163 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Acetylation; Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Isopeptide bond; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; S-nitrosylation; Serine/threonine-protein kinase; Transferase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 756 AA 
Protein Sequence
MSWSPSLTTQ TCGAWEMKER LGTGGFGNVI RWHNQETGEQ IAIKQCRQEL SPRNRERWCL 60
EIQIMRRLTH PNVVAARDVP EGMQNLAPND LPLLAMEYCQ GGDLRKYLNQ FENCCGLREG 120
AILTLLSDIA SALRYLHENR IIHRDLKPEN IVLQQGEQRL IHKIIDLGYA KELDQGSLCT 180
SFVGTLQYLA PELLEQQKYT VTVDYWSFGT LAFECITGFR PFLPNWQPVQ WHSKVRQKSE 240
VDIVVSEDLN GTVKFSSSLP YPNNLNSVLA ERLEKWLQLM LMWHPRQRGT DPTYGPNGCF 300
KALDDILNLK LVHILNMVTG TIHTYPVTED ESLQSLKARI QQDTGIPEED QELLQEAGLA 360
LIPDKPATQC ISDGKLNEGH TLDMDLVFLF DNSKITYETQ ISPRPQPESV SCILQEPKRN 420
LAFFQLRKVW GQVWHSIQTL KEDCNRLQQG QRAAMMNLLR NNSCLSKMKN SMASMSQQLK 480
AKLDFFKTSI QIDLEKYSEQ TEFGITSDKL LLAWREMEQA VELCGRENEV KLLVERMMAL 540
QTDIVDLQRS PMGRKQGGTL DDLEEQAREL YRRLREKPRD QRTEGDSQEM VRLLLQAIQS 600
FEKKVRVIYT QLSKTVVCKQ KALELLPKVE EVVSLMNEDE KTVVRLQEKR QKELWNLLKI 660
ACSKVRGPVS GSPDSMNASR LSQPGQLMSQ PSTASNSLPE PAKKSEELVA EAHNLCTLLE 720
NAIQDTVREQ DQSFTALDWS WLQTEEEEHS CLEQAS 756 
Gene Ontology
 GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL.
 GO:0008385; C:IkappaB kinase complex; TAS:UniProtKB.
 GO:0009898; C:internal side of plasma membrane; ISS:BHF-UCL.
 GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0008384; F:IkappaB kinase activity; TAS:UniProtKB.
 GO:0001782; P:B cell homeostasis; IEA:Compara.
 GO:0006954; P:inflammatory response; TAS:UniProtKB.
 GO:0045087; P:innate immune response; TAS:UniProtKB.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0043066; P:negative regulation of apoptotic process; TAS:Reactome.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome.
 GO:2001259; P:positive regulation of cation channel activity; IEA:Compara.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; TAS:Reactome.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:UniProtKB.
 GO:0010765; P:positive regulation of sodium ion transport; IEA:Compara.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; NAS:UniProtKB.
 GO:0032481; P:positive regulation of type I interferon production; TAS:Reactome.
 GO:0009615; P:response to virus; TAS:UniProtKB.
 GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. 
Interpro
 IPR022007; IKKbetaNEMObind.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR008271; Ser/Thr_kinase_AS.
 IPR019955; Ubiquitin_supergroup. 
Pfam
 PF12179; IKKbetaNEMObind
 PF00069; Pkinase 
SMART
  
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS