Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O15111 (IKKA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 161. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Inhibitor of nuclear factor kappa-B kinase subunit alpha

Short name=I-kappa-B kinase alpha
Short name=IKK-A
Short name=IKK-alpha
Short name=IkBKA
Short name=IkappaB kinase
EC=2.7.11.10
Alternative name(s):
Conserved helix-loop-helix ubiquitous kinase
I-kappa-B kinase 1
Short name=IKK1
Nuclear factor NF-kappa-B inhibitor kinase alpha
Short name=NFKBIKA
Transcription factor 16
Short name=TCF-16
Gene names
Name:CHUK
Synonyms:IKKA, TCF16
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length745 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.17 Ref.22 Ref.25 Ref.27 Ref.29

Catalytic activity

ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein].

Enzyme regulation

Activated when phosphorylated and inactivated when dephosphorylated.

Subunit structure

Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK-beta/IKBKB dimers are associated with four gamma/IKBKG subunits. The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex. The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65. Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Part of a 70-90 kDa complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA, RELA, IKBKAP and MAP3K14. Directly interacts with IKK-gamma/NEMO and TRPC4AP By similarity. May interact with TRAF2. Interacts with NALP2. May interact with MAVS/IPS1. Interacts with ARRB1 and ARRB2. Interacts with NLRC5; prevents CHUK phosphorylation and kinase activity. Interacts with PIAS1; this interaction induces PIAS1 phosphorylation. Interacts with ZNF268 isoform 2;the interaction is further increased in a TNF-alpha-dependent manner. Ref.9 Ref.15 Ref.18 Ref.19 Ref.20 Ref.21 Ref.25 Ref.30

Subcellular location

Cytoplasm. Nucleus. Note: Shuttles between the cytoplasm and the nucleus. Ref.17

Tissue specificity

Widely expressed.

Domain

The kinase domain is located in the N-terminal region. The leucine zipper is important to allow homo- and hetero-dimerization. At the C-terminal region is located the region responsible for the interaction with NEMO/IKBKG. Ref.23

Post-translational modification

Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A. Autophosphorylated. Ref.10 Ref.11 Ref.13 Ref.24

Acetylation of Thr-179 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the I-kappa-B signaling pathway. Ref.8

Involvement in disease

Cocoon syndrome (COCOS) [MIM:613630]: A lethal syndrome characterized by multiple fetal malformations including defective face and seemingly absent limbs, which are bound to the trunk and encased under the skin.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26

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
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

I-kappaB kinase/NF-kappaB signaling

Traceable author statement Ref.23. Source: UniProtKB

I-kappaB phosphorylation

Traceable author statement Ref.2. Source: ProtInc

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

Rho protein signal transduction

Inferred from electronic annotation. Source: Ensembl

T cell receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

anatomical structure morphogenesis

Traceable author statement PubMed 10747982. Source: ProtInc

cellular response to tumor necrosis factor

Inferred from direct assay Ref.30. Source: UniProtKB

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

immune response

Traceable author statement Ref.3. Source: ProtInc

inflammatory response

Traceable author statement Ref.23. Source: UniProtKB

innate immune response

Traceable author statement Ref.23. Source: UniProtKB

lactation

Inferred from electronic annotation. Source: Ensembl

mammary gland alveolus development

Inferred from electronic annotation. Source: Ensembl

mammary gland epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

morphogenesis of an epithelial sheet

Inferred from electronic annotation. Source: Ensembl

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Traceable author statement. Source: Reactome

nucleotide-binding oligomerization domain containing signaling pathway

Traceable author statement. Source: Reactome

odontogenesis of dentin-containing tooth

Inferred from electronic annotation. Source: Ensembl

osteoclast differentiation

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

positive regulation of I-kappaB kinase/NF-kappaB signaling

Traceable author statement. Source: Reactome

positive regulation of NF-kappaB transcription factor activity

Traceable author statement Ref.23. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.30. Source: UniProtKB

positive regulation of type I interferon production

Traceable author statement. Source: Reactome

protein phosphorylation

Inferred from direct assay Ref.25. Source: UniProtKB

response to amino acid

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to hydroperoxide

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to toxic substance

Inferred from electronic annotation. Source: Ensembl

response to virus

Traceable author statement Ref.23. Source: UniProtKB

skeletal muscle contraction

Inferred from electronic annotation. Source: Ensembl

striated muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentCD40 receptor complex

Inferred from sequence or structural similarity. Source: BHF-UCL

IkappaB kinase complex

Traceable author statement Ref.23. Source: UniProtKB

cytoplasm

Inferred from direct assay. Source: HPA

cytoplasmic side of plasma membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

IkappaB kinase activity

Traceable author statement Ref.23. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 10521409PubMed 15125834PubMed 15601829PubMed 18579519Ref.25Ref.30. Source: UniProtKB

protein heterodimerization activity

Inferred from direct assay Ref.30. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay Ref.30. Source: UniProtKB

protein kinase activity

Inferred from direct assay Ref.25. Source: UniProtKB

scaffold protein binding

Inferred from direct assay PubMed 23776175. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 745745Inhibitor of nuclear factor kappa-B kinase subunit alpha
PRO_0000086011

Regions

Domain15 – 302288Protein kinase
Nucleotide binding21 – 299ATP By similarity
Region455 – 47622Leucine-zipper
Region738 – 7436NEMO-binding

Sites

Active site1441Proton acceptor By similarity
Binding site441ATP By similarity

Amino acid modifications

Modified residue231Phosphothreonine; by PKB/AKT1 and SGK1 Ref.11 Ref.24
Modified residue1761Phosphoserine; by MAP3K14 Ref.10
Modified residue1791O-acetylthreonine; by Yersinia yopJ
Modified residue1801Phosphoserine; by SGK1 Ref.24

Natural variations

Natural variant1261S → C. Ref.31
Corresponds to variant rs34427437 [ dbSNP | Ensembl ].
VAR_040565
Natural variant1551V → A. Ref.31
Corresponds to variant rs2230803 [ dbSNP | Ensembl ].
VAR_040566
Natural variant2681V → I. Ref.1 Ref.2 Ref.4 Ref.6 Ref.7 Ref.31
Corresponds to variant rs2230804 [ dbSNP | Ensembl ].
VAR_021359

Experimental info

Mutagenesis231T → A: Loss of phosphorylation and decrease of kinase activity. Ref.11
Mutagenesis441K → A: Loss of kinase activity. Ref.1 Ref.3
Mutagenesis441K → M: Loss of autophosphorylation. Ref.1 Ref.3
Mutagenesis1761S → A: Loss of phosphorylation and of activity. Ref.3 Ref.10
Mutagenesis1761S → E: Full activation. Ref.3 Ref.10
Mutagenesis1791T → A: No change in phosphorylation. Ref.10
Mutagenesis1801S → A: No change in phosphorylation. Ref.10
Sequence conflict5431E → G in AAC51671. Ref.2
Sequence conflict6041L → R in AAC50713. Ref.7
Sequence conflict679 – 6802TS → AY in AAC50713. Ref.7
Sequence conflict6841P → A no nucleotide entry Ref.3
Sequence conflict6841P → A in AAC50713. Ref.7
Sequence conflict686 – 6872TS → DL in AAC50713. Ref.7

Secondary structure

..... 745
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O15111 [UniParc].

Last modified January 11, 2011. Version 2.
Checksum: 4EA55C6FFC66FA16

FASTA74584,640
        10         20         30         40         50         60 
MERPPGLRPG AGGPWEMRER LGTGGFGNVC LYQHRELDLK IAIKSCRLEL STKNRERWCH 

        70         80         90        100        110        120 
EIQIMKKLNH ANVVKACDVP EELNILIHDV PLLAMEYCSG GDLRKLLNKP ENCCGLKESQ 

       130        140        150        160        170        180 
ILSLLSDIGS GIRYLHENKI IHRDLKPENI VLQDVGGKII HKIIDLGYAK DVDQGSLCTS 

       190        200        210        220        230        240 
FVGTLQYLAP ELFENKPYTA TVDYWSFGTM VFECIAGYRP FLHHLQPFTW HEKIKKKDPK 

       250        260        270        280        290        300 
CIFACEEMSG EVRFSSHLPQ PNSLCSLVVE PMENWLQLML NWDPQQRGGP VDLTLKQPRC 

       310        320        330        340        350        360 
FVLMDHILNL KIVHILNMTS AKIISFLLPP DESLHSLQSR IERETGINTG SQELLSETGI 

       370        380        390        400        410        420 
SLDPRKPASQ CVLDGVRGCD SYMVYLFDKS KTVYEGPFAS RSLSDCVNYI VQDSKIQLPI 

       430        440        450        460        470        480 
IQLRKVWAEA VHYVSGLKED YSRLFQGQRA AMLSLLRYNA NLTKMKNTLI SASQQLKAKL 

       490        500        510        520        530        540 
EFFHKSIQLD LERYSEQMTY GISSEKMLKA WKEMEEKAIH YAEVGVIGYL EDQIMSLHAE 

       550        560        570        580        590        600 
IMELQKSPYG RRQGDLMESL EQRAIDLYKQ LKHRPSDHSY SDSTEMVKII VHTVQSQDRV 

       610        620        630        640        650        660 
LKELFGHLSK LLGCKQKIID LLPKVEVALS NIKEADNTVM FMQGKRQKEI WHLLKIACTQ 

       670        680        690        700        710        720 
SSARSLVGSS LEGAVTPQTS AWLPPTSAEH DHSLSCVVTP QDGETSAQMI EENLNCLGHL 

       730        740 
STIIHEANEE QGNSMMNLDW SWLTE 

« Hide

References

« Hide 'large scale' references
[1]"Identification and characterization of an IkappaB kinase."
Regnier C.H., Song H.Y., Gao X., Goeddel D.V., Cao Z., Rothe M.
Cell 90:373-383(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF LYS-44, VARIANT ILE-268.
Tissue: T-cell.
[2]"A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB."
DiDonato J.A., Hayakawa M., Rothwarf D.M., Zandi E., Karin M.
Nature 388:548-554(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANT ILE-268.
[3]"IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation."
Mercurio F., Zhu H., Murray B.W., Shevchenko A., Bennett B.L., Li J.W., Young D.B., Barbosa M., Mann M., Manning A., Rao A.
Science 278:860-866(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, MUTAGENESIS OF LYS-44 AND SER-176.
Tissue: Cervix carcinoma.
[4]"IkappaB kinase-alpha and -beta genes are coexpressed in adult and embryonic tissues but localized to different human chromosomes."
Hu M.C.-T., Wang Y.-P.
Gene 222:31-40(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-268.
Tissue: Heart.
[5]SeattleSNPs variation discovery resource
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-268.
[7]"CHUK, a new member of the helix-loop-helix and leucine zipper families of interacting proteins, contains a serine-threonine kinase catalytic domain."
Connelly M.A., Marcu K.B.
Cell. Mol. Biol. Res. 41:537-549(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 32-745, VARIANT ILE-268.
Tissue: Cervix carcinoma.
[8]"Acetylation of MEK2 and I kappa B kinase (IKK) activation loop residues by YopJ inhibits signaling."
Mittal R., Peak-Chew S.Y., McMahon H.T.
Proc. Natl. Acad. Sci. U.S.A. 103:18574-18579(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 169-181, INACTIVATION BY YERSINIA YOPJ, ACETYLATION AT THR-179, IDENTIFICATION BY MASS SPECTROMETRY.
[9]"IKAP is a scaffold protein of the IkappaB kinase complex."
Cohen L., Henzel W.J., Baeuerle P.A.
Nature 395:292-296(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH IKBKB; NFKBIA; RELA; IKBKAP AND MAP3K14.
[10]"NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176."
Ling L., Cao Z., Goeddel D.V.
Proc. Natl. Acad. Sci. U.S.A. 95:3792-3797(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-176, MUTAGENESIS OF SER-176; THR-179 AND SER-180.
[11]"NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase."
Ozes O.N., Mayo L.D., Gustin J.A., Pfeffer S.R., Pfeffer L.M., Donner D.B.
Nature 401:82-85(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-23, MUTAGENESIS OF THR-23.
[12]"Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation."
Delhase M., Hayakawa M., Chen Y., Karin M.
Science 284:309-313(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: IKKA-IKKB BINDING.
[13]"Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase."
Nemoto S., DiDonato J.A., Lin A.
Mol. Cell. Biol. 18:7336-7343(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: IKK PHOSPHORYLATION.
[14]"The I kappa B/NF-kappa B system: a key determinant of mucosal inflammation and protection."
Jobin C., Sartor R.B.
Am. J. Physiol. 278:C451-C462(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[15]"Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) coactivator activity by I kappa B kinase."
Wu R.-C., Qin J., Hashimoto Y., Wong J., Xu J., Tsai S.Y., Tsai M.-J., O'Malley B.W.
Mol. Cell. Biol. 22:3549-3561(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT OF A COMPLEX CONTAINING CREBBP; NCOA2; NCOA3; IKKB AND IKBKG.
[16]"Tetrameric oligomerization of IkappaB kinase gamma (IKKgamma) is obligatory for IKK complex activity and NF-kappaB activation."
Tegethoff S., Behlke J., Scheidereit C.
Mol. Cell. Biol. 23:2029-2041(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: COMPOSITION OF THE IKK COMPLEX.
[17]"Histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression."
Yamamoto Y., Verma U.N., Prajapati S., Kwak Y.T., Gaynor R.B.
Nature 423:655-659(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, FUNCTION IN PHOSPHORYLATION OF HISTONE H3.
[18]"PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages."
Bruey J.-M., Bruey-Sedano N., Newman R., Chandler S., Stehlik C., Reed J.C.
J. Biol. Chem. 279:51897-51907(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NALP2.
[19]"beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha."
Witherow D.S., Garrison T.R., Miller W.E., Lefkowitz R.J.
Proc. Natl. Acad. Sci. U.S.A. 101:8603-8607(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARRB1 AND ARRB2.
[20]"Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus."
Meylan E., Curran J., Hofmann K., Moradpour D., Binder M., Bartenschlager R., Tschopp J.
Nature 437:1167-1172(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAVS.
[21]"Proinflammatory stimuli induce IKKalpha-mediated phosphorylation of PIAS1 to restrict inflammation and immunity."
Liu B., Yang Y., Chernishof V., Loo R.R., Jang H., Tahk S., Yang R., Mink S., Shultz D., Bellone C.J., Loo J.A., Shuai K.
Cell 129:903-914(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIAS1.
[22]"Phosphorylation of CBP by IKKalpha promotes cell growth by switching the binding preference of CBP from p53 to NF-kappaB."
Huang W.C., Ju T.K., Hung M.C., Chen C.C.
Mol. Cell 26:75-87(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CREBBP.
[23]"The IkappaB kinase complex: master regulator of NF-kappaB signaling."
Solt L.A., May M.J.
Immunol. Res. 42:3-18(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW, DOMAIN.
[24]"SGK1 phosphorylation of IkappaB Kinase alpha and p300 Up-regulates NF-kappaB activity and increases N-Methyl-D-aspartate receptor NR2A and NR2B expression."
Tai D.J., Su C.C., Ma Y.L., Lee E.H.
J. Biol. Chem. 284:4073-4089(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-23 AND SER-180 BY SGK1.
[25]"NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways."
Cui J., Zhu L., Xia X., Wang H.Y., Legras X., Hong J., Ji J., Shen P., Zheng S., Chen Z.J., Wang R.F.
Cell 141:483-496(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NLRC5.
[26]"Mutant CHUK and severe fetal encasement malformation."
Lahtela J., Nousiainen H.O., Stefanovic V., Tallila J., Viskari H., Karikoski R., Gentile M., Saloranta C., Varilo T., Salonen R., Kestila M.
N. Engl. J. Med. 363:1631-1637(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN COCOS.
[27]"Negative feedback in noncanonical NF-kappaB signaling modulates NIK stability through IKKalpha-mediated phosphorylation."
Razani B., Zarnegar B., Ytterberg A.J., Shiba T., Dempsey P.W., Ware C.F., Loo J.A., Cheng G.
Sci. Signal. 3:RA41-RA41(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MAP3K14 PHOSPHORYLATION.
[28]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]"The kinase IKKalpha inhibits activation of the transcription factor NF-kappaB by phosphorylating the regulatory molecule TAX1BP1."
Shembade N., Pujari R., Harhaj N.S., Abbott D.W., Harhaj E.W.
Nat. Immunol. 12:834-843(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TAX1BP1.
[30]"The zinc finger protein ZNF268 is overexpressed in human cervical cancer and contributes to tumorigenesis via enhancing NF-kappaB signaling."
Wang W., Guo M., Hu L., Cai J., Zeng Y., Luo J., Shu Z., Li W., Huang Z.
J. Biol. Chem. 287:42856-42866(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZNF268, SUBUNIT.
[31]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-126; ALA-155 AND ILE-268.
[32]"Structure of a NEMO/IKK-associating domain reveals architecture of the interaction site."
Rushe M., Silvian L., Bixler S., Chen L.L., Cheung A., Bowes S., Cuervo H., Berkowitz S., Zheng T., Guckian K., Pellegrini M., Lugovskoy A.
Structure 16:798-808(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 732-745.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF012890 mRNA. Translation: AAC51662.1.
AF009225 mRNA. Translation: AAC51671.1.
AF080157 mRNA. Translation: AAD08996.1.
AY652653 Genomic DNA. Translation: AAT49098.1.
AL138921 Genomic DNA. Translation: CAH72401.1.
U22512 mRNA. Translation: AAC50713.1.
CCDSCCDS7488.1.
RefSeqNP_001269.3. NM_001278.3.
UniGeneHs.198998.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3BRTX-ray2.25A/C732-745[»]
ProteinModelPortalO15111.
SMRO15111. Positions 5-659.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107569. 116 interactions.
DIPDIP-27526N.
IntActO15111. 41 interactions.
MINTMINT-88648.
STRING9606.ENSP00000359424.

Chemistry

BindingDBO15111.
ChEMBLCHEMBL3476.
GuidetoPHARMACOLOGY1989.

PTM databases

PhosphoSiteO15111.

Proteomic databases

MaxQBO15111.
PaxDbO15111.
PRIDEO15111.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000370397; ENSP00000359424; ENSG00000213341.
GeneID1147.
KEGGhsa:1147.
UCSCuc001kqp.3. human.

Organism-specific databases

CTD1147.
GeneCardsGC10M101938.
H-InvDBHIX0201495.
HGNCHGNC:1974. CHUK.
HPACAB004240.
CAB018564.
HPA001402.
MIM600664. gene.
613630. phenotype.
neXtProtNX_O15111.
PharmGKBPA26510.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000038048.
HOVERGENHBG018241.
InParanoidO15111.
KOK04467.
OMALQLMLNW.
OrthoDBEOG7FBRH3.
PhylomeDBO15111.
TreeFamTF324269.

Enzyme and pathway databases

BRENDA2.7.11.10. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SABIO-RKO15111.
SignaLinkO15111.

Gene expression databases

BgeeO15111.
CleanExHS_CHUK.
GenevestigatorO15111.

Family and domain databases

InterProIPR022007. IKKbetaNEMObind.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF12179. IKKbetaNEMObind. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCHUK. human.
EvolutionaryTraceO15111.
GeneWikiCHUK.
GenomeRNAi1147.
NextBio4772.
PROO15111.
SOURCESearch...

Entry information

Entry nameIKKA_HUMAN
AccessionPrimary (citable) accession number: O15111
Secondary accession number(s): O14666 expand/collapse secondary AC list , Q13132, Q5W0I4, Q92467
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: January 11, 2011
Last modified: July 9, 2014
This is version 161 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM