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Protein Page:
IKKA (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
IKKA a kinase of the IKK family. Phosphorylates inhibitors of NF-kappa-B, leading to their dissociation from NF-kappa-B and ultimately to their degradation. Phosphorylated and activated downstream of growth factor receptors, IL1R, and TNFR by NAK, IRAK and NIK, respectively. Preferentially found as a heterodimer with IKK-beta but also as an homodimer. Directly interacts with IKK-gamma/NEMO and TRPC4AP. Heterodimers form the active complex. The tripartite complex can also bind to MAP3K14/NIK, MEKK1, IKAP and IKB-alpha-p65-p50 complex. Inhibitors are under development to treat arthritis, inflammation, and apoptotic aspects of cancer. Aspirin (sodium salicylate) selectively binds IKK and reduces inflammation. Misexpression and inhibitors show involvement in insulin sensitization in obese rodents. Mutations in IKK-gamma are found in several immune deficiencies: hyper IgM syndrome, incontinentia pigmenti [embryonic lethal in males, defects in skin, hair, teeth in females] and hypohidrotic ectodermal dysplasia; recurrent infections and defects in teeth, hair, and sweat glands]. Inhibitors: CHS 828, NBD peptide, BMS-345541. Note: This description may include information from UniProtKB.
Protein type: Kinase, protein; Protein kinase, Other; EC 2.7.11.10; Protein kinase, Ser/Thr (non-receptor); Other group; IKK family
Chromosomal Location of Human Ortholog: 10q24-q25
Cellular Component: internal side of plasma membrane; intracellular membrane-bound organelle; cytoplasm; nucleolus; IkappaB kinase complex; cytosol; nucleus
Molecular Function: protein binding; protein homodimerization activity; IkappaB kinase activity; protein heterodimerization activity; ATP binding; protein kinase activity
Biological Process: lactation; skeletal muscle contraction; I-kappaB kinase/NF-kappaB cascade; nerve growth factor receptor signaling pathway; response to toxin; response to lipopolysaccharide; toll-like receptor 3 signaling pathway; osteoclast differentiation; protein amino acid phosphorylation; T cell receptor signaling pathway; Rho protein signal transduction; activation of NF-kappaB transcription factor; toll-like receptor 10 signaling pathway; toll-like receptor 5 signaling pathway; morphogenesis of an epithelial sheet; positive regulation of interferon type I production; inflammatory response; toll-like receptor 4 signaling pathway; epidermal growth factor receptor signaling pathway; response to drug; anatomical structure morphogenesis; phosphoinositide-mediated signaling; fibroblast growth factor receptor signaling pathway; positive regulation of I-kappaB kinase/NF-kappaB cascade; MyD88-independent toll-like receptor signaling pathway; response to virus; mammary gland epithelial cell proliferation; response to amino acid stimulus; toll-like receptor 2 signaling pathway; odontogenesis of dentine-containing teeth; MyD88-dependent toll-like receptor signaling pathway; response to hydroperoxide; toll-like receptor signaling pathway; striated muscle cell differentiation; innate immune response; immune response; positive regulation of transcription from RNA polymerase II promoter; toll-like receptor 9 signaling pathway; I-kappaB phosphorylation
Reference #:  O15111 (UniProtKB)
Alt. Names/Synonyms: CHUK; conserved helix-loop ubiquitous kinase; Conserved helix-loop-helix ubiquitous kinase; I-kappa-B kinase 1; I-kappa-B kinase alpha; I-kappa-B kinase-alpha; IkappaB kinase; IkB kinase alpha subunit; IkBKA; IKK-A; IKK-a kinase; IKK-alpha; IKK1; IKKA; Inhibitor of nuclear factor kappa-B kinase subunit alpha; NFKBIKA; Nuclear factor NF-kappa-B inhibitor kinase alpha; Nuclear factor NFkappaB inhibitor kinase alpha; TCF-16; TCF16; Transcription factor 16
Gene Symbols: CHUK
Molecular weight: 84,640 Da
Basal Isoelectric point: 6.27  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

IKKA

Protein Structure Not Found.

Substrate Sequence Logo
Sequence Logo

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Sites Implicated In
apoptosis, altered: T23‑p
apoptosis, inhibited: T23‑p
cell motility, altered: S180‑p
chromatin organization, altered: S180‑p
transcription, altered: T23‑p
transcription, induced: T23‑p, S180‑p
activity, induced: S180‑p
enzymatic activity, induced: T23‑p, S176‑p, S180‑p
phosphorylation: T23‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
6 0 T23-p EMRERLGtGGFGNVC
1 0 S119-ac NCCGLKEsQILSLLS
17 0 S176-p AKDVDQGsLCTsFVG
34 0 S180-p DQGsLCTsFVGTLQY
0 2 K296-ub GPVDLTLkQPRCFVL
0 1 K322-ac ILNMTSAkIISFLLP
0 1 K415-ub NYIVQDSkIQLPIIQ
0 1 K438-ac VHYVSGLkEDYSRLF
0 2 T463-p LRYNANLtKMKNTLI
1 0 S473-p KNTLISAsQQLKAKL
0 1 T499 ERYSEQMTyGISSEK
0 1 Y500-p RYSEQMTyGISSEKM
0 1 K506 TyGISSEKMLKAWKE
1 0 T722-ac NCLGHLStIIHEANE
2078 : Phospho-IKKalpha (Ser176)/IKKbeta (Ser177) (C84E11) Rabbit mAb
2697 : Phospho-IKK-alpha/beta (Ser176/180) (16A6) Rabbit mAb
2697 : Phospho-IKK-alpha/beta (Ser176/180) (16A6) Rabbit mAb
  mouse

 
T23 EMRERLGTGGFGNVS
S119 NCCGLKESQILSLLS
S176-p AKDVDQGsLCTsFVG
S180-p DQGsLCTsFVGTLQY
K296 GPIDLTLKQPRCFAL
K322 ILNMTSAKIISFLLP
K415 NYIVQDSKIQLPIIQ
K438 VHYVSGLKEDYSRLF
T463 LRYNANLTKMKNTLI
S473 KNTLISASQQLKAKL
T499-p ERYSEQMtYGISSEk
Y500 RYSEQMtYGISSEkM
K506-ub tYGISSEkMLKAWKE
T722 NCLGHLSTIIREANE
2078 : Phospho-IKKalpha (Ser176)/IKKbeta (Ser177) (C84E11) Rabbit mAb
2697 : Phospho-IKK-alpha/beta (Ser176/180) (16A6) Rabbit mAb
2697 : Phospho-IKK-alpha/beta (Ser176/180) (16A6) Rabbit mAb
  rat

 
T23 EMRERLGTGGFGNVS
S119 NCCGLKESQILSLLS
S176 AKDVDQGSLCTsFVG
S180-p DQGSLCTsFVGTLQY
K296 GPIDPPLKQPKCFVL
K322 ILNMTSAKIISFLLP
K415 NYIVQDSKIQLPVTQ
K438 VHYVSGLKEDYSRLF
T463 LRYNANLTKMKNTLI
S473 KNTLISASQQLKAKL
T499 ERYSEQMTYGISSEK
Y500 RYSEQMTYGISSEKM
K506 TYGISSEKMLKAWKE
- gap
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