dbPAF Protein Information

Tag Content
dbPAF ID dbPAF-0000858
Uniprot Accession O15111; IKKA_HUMAN; O14666; Q13132; Q5W0I4; Q92467;
Genbank Protein ID NP_001269.3;
Genbank Nucleotide ID NM_001278.3;
Protein Name Inhibitor of nuclear factor kappa-B kinase subunit alpha
Protein Synonyms/Alias
Gene Name CHUK
Gene Synonyms/Alias IKKA;TCF16;
Organism Homo sapiens(Human)
NCBI Taxa ID 9606
Functional Description
(View all)		 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. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260).
Phosphorylation Sites
 dbPAF PTMs: 12
PositionPeptidesSourceReferences ( PMIDs )
23EMRERLGTGGFGNVCdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoPep 2.0;PhosphoSitePlus;curated10485710; 19088076; 16381945; 23193290; 12048203; 18515365;
45DLKIAIKSCRLELSTcurated23090842
52SCRLELSTKNRERWCcurated23090842
123LKESQILSLLSDIGScurated20873877
126SQILSLLSDIGSGIRcurated20873877
168HKIIDLGYAKDVDQGPhosphoSitePlus22135298
176AKDVDQGSLCTSFVGdbPTM 3.0;HPRD 9;PhosphoSitePlus;curated9520446; 16381945; 23193290; 10195894; 16735506; 17595324; 1
179VDQGSLCTSFVGTLQPhosphoSitePlus22135298
180DQGSLCTSFVGTLQYdbPTM 3.0;PhosphoSitePlus19088076; 16381945; 23193290; 10195894; 12409308; 15128824;
463LRYNANLTKMKNTLIPhosphoSitePlus22135298
473KNTLISASQQLKAKLdbPTM 3.0;PhosphoSitePlus;curated17700524; 16381945; 23193290; 22135298; 22817900
500RYSEQMTYGISSEKMPhosphoSitePlus22135298
Sequence
(Fasta)		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 746
Keyword

KW-0002--3D-structure
KW-0007--Acetylation
KW-0067--ATP-binding
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0903--Direct protein sequencing
KW-0418--Kinase
KW-0547--Nucleotide-binding
KW-0539--Nucleus
KW-0597--Phosphoprotein
KW-0621--Polymorphism
KW-1185--Reference proteome
KW-0723--Serine/threonine-protein kinase
KW-0808--Transferase
Interpro

IPR022007--IKKbetaNEMObind
IPR011009--Kinase-like_dom
IPR000719--Prot_kinase_dom
IPR017441--Protein_kinase_ATP_BS
IPR002290--Ser/Thr_dual-sp_kinase
IPR008271--Ser/Thr_kinase_AS
PROSITE

PS00107--PROTEIN_KINASE_ATP
PS50011--PROTEIN_KINASE_DOM
PS00108--PROTEIN_KINASE_ST
Pfam

PF12179--IKKbetaNEMObind
PF00069--Pkinase
Gene Ontology

GO:0035631--C:CD40 receptor complex
GO:0005737--C:cytoplasm
GO:0009898--C:cytoplasmic side of plasma membrane
GO:0005829--C:cytosol
GO:0008385--C:IkappaB kinase complex
GO:0043231--C:intracellular membrane-bounded organelle
GO:0005654--C:nucleoplasm
GO:0005524--F:ATP binding
GO:0008384--F:IkappaB kinase activity
GO:0046982--F:protein heterodimerization activity
GO:0042803--F:protein homodimerization activity
GO:0004672--F:protein kinase activity
GO:0097110--F:scaffold protein binding
GO:0009653--P:anatomical structure morphogenesis
GO:0007166--P:cell surface receptor signaling pathway
GO:0071356--P:cellular response to tumor necrosis factor
GO:0007173--P:epidermal growth factor receptor signaling pathway
GO:0038095--P:Fc-epsilon receptor signaling pathway
GO:0008543--P:fibroblast growth factor receptor signaling pathway
GO:0007249--P:I-kappaB kinase/NF-kappaB signaling
GO:0007252--P:I-kappaB phosphorylation
GO:0006955--P:immune response
GO:0006954--P:inflammatory response
GO:0045087--P:innate immune response
GO:0007595--P:lactation
GO:0060749--P:mammary gland alveolus development
GO:0033598--P:mammary gland epithelial cell proliferation
GO:0002011--P:morphogenesis of an epithelial sheet
GO:0002755--P:MyD88-dependent toll-like receptor signaling pathway
GO:0002756--P:MyD88-independent toll-like receptor signaling pathway
GO:0048011--P:neurotrophin TRK receptor signaling pathway
GO:0038061--P:NIK/NF-kappaB signaling
GO:0035872--P:nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0070423--P:nucleotide-binding oligomerization domain containing signaling pathway
GO:0042475--P:odontogenesis of dentin-containing tooth
GO:0030316--P:osteoclast differentiation
GO:0048015--P:phosphatidylinositol-mediated signaling
GO:0043123--P:positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0051092--P:positive regulation of NF-kappaB transcription factor activity
GO:0045944--P:positive regulation of transcription from RNA polymerase II promoter
GO:0032481--P:positive regulation of type I interferon production
GO:0006468--P:protein phosphorylation
GO:0010803--P:regulation of tumor necrosis factor-mediated signaling pathway
GO:0010034--P:response to acetate
GO:0043200--P:response to amino acid
GO:0042493--P:response to drug
GO:0033194--P:response to hydroperoxide
GO:0032496--P:response to lipopolysaccharide
GO:0035994--P:response to muscle stretch
GO:0009636--P:response to toxic substance
GO:0009615--P:response to virus
GO:0007266--P:Rho protein signal transduction
GO:0003009--P:skeletal muscle contraction
GO:0002223--P:stimulatory C-type lectin receptor signaling pathway
GO:0051403--P:stress-activated MAPK cascade
GO:0051146--P:striated muscle cell differentiation
GO:0050852--P:T cell receptor signaling pathway
GO:0034166--P:toll-like receptor 10 signaling pathway
GO:0034134--P:toll-like receptor 2 signaling pathway
GO:0034138--P:toll-like receptor 3 signaling pathway
GO:0034142--P:toll-like receptor 4 signaling pathway
GO:0034146--P:toll-like receptor 5 signaling pathway
GO:0034162--P:toll-like receptor 9 signaling pathway
GO:0002224--P:toll-like receptor signaling pathway
GO:0038123--P:toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124--P:toll-like receptor TLR6:TLR2 signaling pathway
GO:0035666--P:TRIF-dependent toll-like receptor signaling pathway
GO:0033209--P:tumor necrosis factor-mediated signaling pathway