CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000377
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Inhibitor of nuclear factor kappa-B kinase subunit alpha 
Protein Synonyms/Alias
 I-kappa-B kinase alpha; IKK-A; IKK-alpha; IkBKA; IkappaB kinase; Conserved helix-loop-helix ubiquitous kinase; I-kappa-B kinase 1; IKK1; Nuclear factor NF-kappa-B inhibitor kinase alpha; NFKBIKA; Transcription factor 16; TCF-16 
Gene Name
 CHUK 
Gene Synonyms/Alias
 IKKA; TCF16 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
44LDLKIAIKSCRLELSubiquitination[1]
53CRLELSTKNRERWCHubiquitination[1]
105CSGGDLRKLLNKPENubiquitination[1]
109DLRKLLNKPENCCGLubiquitination[1]
117PENCCGLKESQILSLubiquitination[1]
139IRYLHENKIIHRDLKubiquitination[1]
146KIIHRDLKPENIVLQubiquitination[1]
158VLQDVGGKIIHKIIDubiquitination[1]
296GPVDLTLKQPRCFVLubiquitination[1, 2, 3]
366GISLDPRKPASQCVLubiquitination[1]
389YMVYLFDKSKTVYEGubiquitination[4]
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] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 
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 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. Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa- B RelB-p52 complexes. In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Participates also in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities. Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP. Additionally, phosphorylates the CREBBP-interacting protein NCOA3. 
Sequence Annotation
 DOMAIN 15 302 Protein kinase.
 NP_BIND 21 29 ATP (By similarity).
 REGION 455 476 Leucine-zipper.
 REGION 738 743 NEMO-binding.
 ACT_SITE 144 144 Proton acceptor (By similarity).
 BINDING 44 44 ATP (By similarity).
 MOD_RES 23 23 Phosphothreonine; by PKB/AKT1 and SGK1.
 MOD_RES 176 176 Phosphoserine; by MAP3K14.
 MOD_RES 179 179 O-acetylthreonine; by Yersinia yopJ.
 MOD_RES 180 180 Phosphoserine; by SGK1.  
Keyword
 3D-structure; Acetylation; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 745 AA 
Protein Sequence
MERPPGLRPG AGGPWEMRER LGTGGFGNVC LYQHRELDLK IAIKSCRLEL STKNRERWCH 60
EIQIMKKLNH ANVVKACDVP EELNILIHDV PLLAMEYCSG GDLRKLLNKP ENCCGLKESQ 120
ILSLLSDIGS GIRYLHENKI IHRDLKPENI VLQDVGGKII HKIIDLGYAK DVDQGSLCTS 180
FVGTLQYLAP ELFENKPYTA TVDYWSFGTM VFECIAGYRP FLHHLQPFTW HEKIKKKDPK 240
CIFACEEMSG EVRFSSHLPQ PNSLCSLVVE PMENWLQLML NWDPQQRGGP VDLTLKQPRC 300
FVLMDHILNL KIVHILNMTS AKIISFLLPP DESLHSLQSR IERETGINTG SQELLSETGI 360
SLDPRKPASQ CVLDGVRGCD SYMVYLFDKS KTVYEGPFAS RSLSDCVNYI VQDSKIQLPI 420
IQLRKVWAEA VHYVSGLKED YSRLFQGQRA AMLSLLRYNA NLTKMKNTLI SASQQLKAKL 480
EFFHKSIQLD LERYSEQMTY GISSEKMLKA WKEMEEKAIH YAEVGVIGYL EDQIMSLHAE 540
IMELQKSPYG RRQGDLMESL EQRAIDLYKQ LKHRPSDHSY SDSTEMVKII VHTVQSQDRV 600
LKELFGHLSK LLGCKQKIID LLPKVEVALS NIKEADNTVM FMQGKRQKEI WHLLKIACTQ 660
SSARSLVGSS LEGAVTPQTS AWLPPTSAEH DHSLSCVVTP QDGETSAQMI EENLNCLGHL 720
STIIHEANEE QGNSMMNLDW SWLTE 745 
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:0005634; C:nucleus; IDA:HPA.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0008384; F:IkappaB kinase activity; TAS:UniProtKB.
 GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0006954; P:inflammatory response; TAS:UniProtKB.
 GO:0045087; P:innate immune response; TAS:UniProtKB.
 GO:0007595; P:lactation; IEA:Compara.
 GO:0060749; P:mammary gland alveolus development; IEA:Compara.
 GO:0033598; P:mammary gland epithelial cell proliferation; IEA:Compara.
 GO:0002011; P:morphogenesis of an epithelial sheet; IEA:Compara.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; 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:0042475; P:odontogenesis of dentin-containing tooth; IEA:Compara.
 GO:0030316; P:osteoclast differentiation; IEA:Compara.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 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:0032481; P:positive regulation of type I interferon production; TAS:Reactome.
 GO:0043200; P:response to amino acid stimulus; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0033194; P:response to hydroperoxide; IEA:Compara.
 GO:0032496; P:response to lipopolysaccharide; IEA:Compara.
 GO:0009636; P:response to toxic substance; IEA:Compara.
 GO:0009615; P:response to virus; TAS:UniProtKB.
 GO:0007266; P:Rho protein signal transduction; IEA:Compara.
 GO:0003009; P:skeletal muscle contraction; IEA:Compara.
 GO:0051146; P:striated muscle cell differentiation; IEA:Compara.
 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.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF12179; IKKbetaNEMObind
 PF00069; Pkinase 
SMART
 SM00220; S_TKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS