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O15111

- IKKA_HUMAN

UniProt

O15111 - IKKA_HUMAN

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Protein
Inhibitor of nuclear factor kappa-B kinase subunit alpha
Gene
CHUK, IKKA, TCF16
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 NCOA3.5 Publications

Catalytic activityi

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

Enzyme regulationi

Activated when phosphorylated and inactivated when dephosphorylated.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei44 – 441ATP By similarity
Active sitei144 – 1441Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi21 – 299ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. IkappaB kinase activity Source: UniProtKB
  3. protein binding Source: UniProtKB
  4. protein heterodimerization activity Source: UniProtKB
  5. protein homodimerization activity Source: UniProtKB
  6. protein kinase activity Source: UniProtKB
  7. scaffold protein binding Source: MGI

GO - Biological processi

  1. Fc-epsilon receptor signaling pathway Source: Reactome
  2. I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  3. I-kappaB phosphorylation Source: ProtInc
  4. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
  5. MyD88-independent toll-like receptor signaling pathway Source: Reactome
  6. Rho protein signal transduction Source: Ensembl
  7. T cell receptor signaling pathway Source: Reactome
  8. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
  9. anatomical structure morphogenesis Source: ProtInc
  10. cellular response to tumor necrosis factor Source: UniProtKB
  11. epidermal growth factor receptor signaling pathway Source: Reactome
  12. fibroblast growth factor receptor signaling pathway Source: Reactome
  13. immune response Source: ProtInc
  14. inflammatory response Source: UniProtKB
  15. innate immune response Source: UniProtKB
  16. lactation Source: Ensembl
  17. mammary gland alveolus development Source: Ensembl
  18. mammary gland epithelial cell proliferation Source: Ensembl
  19. morphogenesis of an epithelial sheet Source: Ensembl
  20. neurotrophin TRK receptor signaling pathway Source: Reactome
  21. nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Source: Reactome
  22. nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
  23. odontogenesis of dentin-containing tooth Source: Ensembl
  24. osteoclast differentiation Source: Ensembl
  25. phosphatidylinositol-mediated signaling Source: Reactome
  26. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Reactome
  27. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  28. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  29. positive regulation of type I interferon production Source: Reactome
  30. protein phosphorylation Source: UniProtKB
  31. response to amino acid Source: Ensembl
  32. response to drug Source: Ensembl
  33. response to hydroperoxide Source: Ensembl
  34. response to lipopolysaccharide Source: Ensembl
  35. response to toxic substance Source: Ensembl
  36. response to virus Source: UniProtKB
  37. skeletal muscle contraction Source: Ensembl
  38. striated muscle cell differentiation Source: Ensembl
  39. toll-like receptor 10 signaling pathway Source: Reactome
  40. toll-like receptor 2 signaling pathway Source: Reactome
  41. toll-like receptor 3 signaling pathway Source: Reactome
  42. toll-like receptor 4 signaling pathway Source: Reactome
  43. toll-like receptor 5 signaling pathway Source: Reactome
  44. toll-like receptor 9 signaling pathway Source: Reactome
  45. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
  46. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
  47. toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.10. 2681.
ReactomeiREACT_118563. RIP-mediated NFkB activation via ZBP1.
REACT_118656. Activation of NF-kappaB in B cells.
REACT_12555. Downstream TCR signaling.
REACT_12564. AKT phosphorylates targets in the cytosol.
REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
REACT_163994. FCERI mediated NF-kB activation.
REACT_21281. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_22442. Interleukin-1 signaling.
REACT_24918. IRAK1 recruits IKK complex.
REACT_24969. TRAF6 mediated NF-kB activation.
REACT_25039. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
REACT_25354. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
REACT_25374. IKK complex recruitment mediated by RIP1.
REACT_75776. NOD1/2 Signaling Pathway.
SABIO-RKO15111.
SignaLinkiO15111.

Names & Taxonomyi

Protein namesi
Recommended name:
Inhibitor of nuclear factor kappa-B kinase subunit alpha (EC:2.7.11.10)
Short name:
I-kappa-B kinase alpha
Short name:
IKK-A
Short name:
IKK-alpha
Short name:
IkBKA
Short name:
IkappaB kinase
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 namesi
Name:CHUK
Synonyms:IKKA, TCF16
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 10

Organism-specific databases

HGNCiHGNC:1974. CHUK.

Subcellular locationi

Cytoplasm. Nucleus
Note: Shuttles between the cytoplasm and the nucleus.1 Publication

GO - Cellular componenti

  1. CD40 receptor complex Source: BHF-UCL
  2. IkappaB kinase complex Source: UniProtKB
  3. cytoplasm Source: HPA
  4. cytoplasmic side of plasma membrane Source: BHF-UCL
  5. cytosol Source: Reactome
  6. intracellular membrane-bounded organelle Source: HPA
  7. nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi23 – 231T → A: Loss of phosphorylation and decrease of kinase activity. 1 Publication
Mutagenesisi44 – 441K → A: Loss of kinase activity. 2 Publications
Mutagenesisi44 – 441K → M: Loss of autophosphorylation. 2 Publications
Mutagenesisi176 – 1761S → A: Loss of phosphorylation and of activity. 2 Publications
Mutagenesisi176 – 1761S → E: Full activation. 2 Publications
Mutagenesisi179 – 1791T → A: No change in phosphorylation. 1 Publication
Mutagenesisi180 – 1801S → A: No change in phosphorylation. 1 Publication

Organism-specific databases

MIMi613630. phenotype.
PharmGKBiPA26510.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 745745Inhibitor of nuclear factor kappa-B kinase subunit alpha
PRO_0000086011Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei23 – 231Phosphothreonine; by PKB/AKT1 and SGK12 Publications
Modified residuei176 – 1761Phosphoserine; by MAP3K141 Publication
Modified residuei179 – 1791O-acetylthreonine; by Yersinia yopJ
Modified residuei180 – 1801Phosphoserine; by SGK11 Publication

Post-translational modificationi

Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A. Autophosphorylated.4 Publications
Acetylation of Thr-179 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the I-kappa-B signaling pathway.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiO15111.
PaxDbiO15111.
PRIDEiO15111.

PTM databases

PhosphoSiteiO15111.

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

BgeeiO15111.
CleanExiHS_CHUK.
GenevestigatoriO15111.

Organism-specific databases

HPAiCAB004240.
CAB018564.
HPA001402.

Interactioni

Subunit structurei

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.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CDC37Q165433EBI-81249,EBI-295634
CDKN1BP465274EBI-81249,EBI-519280
HSP90AA1P079003EBI-81249,EBI-296047
IKBKBO1492012EBI-81249,EBI-81266
IKBKGQ9Y6K919EBI-81249,EBI-81279
IRF7Q929854EBI-81249,EBI-968267
MAP3K14Q995585EBI-81249,EBI-358011
MYCP011063EBI-81249,EBI-447544
NFKBIAP2596314EBI-81249,EBI-307386
PQ77M192EBI-81249,EBI-6149376From a different organism.
RELAQ042062EBI-81249,EBI-73886
TAX1BP1Q86VP12EBI-81249,EBI-529518
VACWR196P247723EBI-81249,EBI-4291651From a different organism.

Protein-protein interaction databases

BioGridi107569. 118 interactions.
DIPiDIP-27526N.
IntActiO15111. 41 interactions.
MINTiMINT-88648.
STRINGi9606.ENSP00000359424.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi735 – 7373
Helixi741 – 7433

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3BRTX-ray2.25A/C732-745[»]
ProteinModelPortaliO15111.
SMRiO15111. Positions 5-659.

Miscellaneous databases

EvolutionaryTraceiO15111.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini15 – 302288Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni455 – 47622Leucine-zipper
Add
BLAST
Regioni738 – 7436NEMO-binding

Domaini

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.1 Publication

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000038048.
HOVERGENiHBG018241.
InParanoidiO15111.
KOiK04467.
OMAiLQLMLNW.
OrthoDBiEOG7FBRH3.
PhylomeDBiO15111.
TreeFamiTF324269.

Family and domain databases

InterProiIPR022007. 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]
PfamiPF12179. IKKbetaNEMObind. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O15111-1 [UniParc]FASTAAdd to Basket

« Hide

MERPPGLRPG AGGPWEMRER LGTGGFGNVC LYQHRELDLK IAIKSCRLEL    50
STKNRERWCH EIQIMKKLNH ANVVKACDVP EELNILIHDV PLLAMEYCSG 100
GDLRKLLNKP ENCCGLKESQ ILSLLSDIGS GIRYLHENKI IHRDLKPENI 150
VLQDVGGKII HKIIDLGYAK DVDQGSLCTS FVGTLQYLAP ELFENKPYTA 200
TVDYWSFGTM VFECIAGYRP FLHHLQPFTW HEKIKKKDPK CIFACEEMSG 250
EVRFSSHLPQ PNSLCSLVVE PMENWLQLML NWDPQQRGGP VDLTLKQPRC 300
FVLMDHILNL KIVHILNMTS AKIISFLLPP DESLHSLQSR IERETGINTG 350
SQELLSETGI SLDPRKPASQ CVLDGVRGCD SYMVYLFDKS KTVYEGPFAS 400
RSLSDCVNYI VQDSKIQLPI IQLRKVWAEA VHYVSGLKED YSRLFQGQRA 450
AMLSLLRYNA NLTKMKNTLI SASQQLKAKL EFFHKSIQLD LERYSEQMTY 500
GISSEKMLKA WKEMEEKAIH YAEVGVIGYL EDQIMSLHAE IMELQKSPYG 550
RRQGDLMESL EQRAIDLYKQ LKHRPSDHSY SDSTEMVKII VHTVQSQDRV 600
LKELFGHLSK LLGCKQKIID LLPKVEVALS NIKEADNTVM FMQGKRQKEI 650
WHLLKIACTQ SSARSLVGSS LEGAVTPQTS AWLPPTSAEH DHSLSCVVTP 700
QDGETSAQMI EENLNCLGHL STIIHEANEE QGNSMMNLDW SWLTE 745
Length:745
Mass (Da):84,640
Last modified:January 11, 2011 - v2
Checksum:i4EA55C6FFC66FA16
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti126 – 1261S → C.1 Publication
Corresponds to variant rs34427437 [ dbSNP | Ensembl ].
VAR_040565
Natural varianti155 – 1551V → A.1 Publication
Corresponds to variant rs2230803 [ dbSNP | Ensembl ].
VAR_040566
Natural varianti268 – 2681V → I.6 Publications
Corresponds to variant rs2230804 [ dbSNP | Ensembl ].
VAR_021359

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti543 – 5431E → G in AAC51671. 1 Publication
Sequence conflicti604 – 6041L → R in AAC50713. 1 Publication
Sequence conflicti679 – 6802TS → AY in AAC50713. 1 Publication
Sequence conflicti684 – 6841P → A no nucleotide entry 1 Publication
Sequence conflicti684 – 6841P → A in AAC50713. 1 Publication
Sequence conflicti686 – 6872TS → DL in AAC50713. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS7488.1.
RefSeqiNP_001269.3. NM_001278.3.
UniGeneiHs.198998.

Genome annotation databases

EnsembliENST00000370397; ENSP00000359424; ENSG00000213341.
GeneIDi1147.
KEGGihsa:1147.
UCSCiuc001kqp.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS7488.1.
RefSeqi NP_001269.3. NM_001278.3.
UniGenei Hs.198998.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3BRT X-ray 2.25 A/C 732-745 [» ]
ProteinModelPortali O15111.
SMRi O15111. Positions 5-659.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107569. 118 interactions.
DIPi DIP-27526N.
IntActi O15111. 41 interactions.
MINTi MINT-88648.
STRINGi 9606.ENSP00000359424.

Chemistry

BindingDBi O15111.
ChEMBLi CHEMBL3476.
GuidetoPHARMACOLOGYi 1989.

PTM databases

PhosphoSitei O15111.

Proteomic databases

MaxQBi O15111.
PaxDbi O15111.
PRIDEi O15111.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000370397 ; ENSP00000359424 ; ENSG00000213341 .
GeneIDi 1147.
KEGGi hsa:1147.
UCSCi uc001kqp.3. human.

Organism-specific databases

CTDi 1147.
GeneCardsi GC10M101938.
H-InvDB HIX0201495.
HGNCi HGNC:1974. CHUK.
HPAi CAB004240.
CAB018564.
HPA001402.
MIMi 600664. gene.
613630. phenotype.
neXtProti NX_O15111.
PharmGKBi PA26510.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000038048.
HOVERGENi HBG018241.
InParanoidi O15111.
KOi K04467.
OMAi LQLMLNW.
OrthoDBi EOG7FBRH3.
PhylomeDBi O15111.
TreeFami TF324269.

Enzyme and pathway databases

BRENDAi 2.7.11.10. 2681.
Reactomei REACT_118563. RIP-mediated NFkB activation via ZBP1.
REACT_118656. Activation of NF-kappaB in B cells.
REACT_12555. Downstream TCR signaling.
REACT_12564. AKT phosphorylates targets in the cytosol.
REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
REACT_163994. FCERI mediated NF-kB activation.
REACT_21281. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_22442. Interleukin-1 signaling.
REACT_24918. IRAK1 recruits IKK complex.
REACT_24969. TRAF6 mediated NF-kB activation.
REACT_25039. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
REACT_25354. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
REACT_25374. IKK complex recruitment mediated by RIP1.
REACT_75776. NOD1/2 Signaling Pathway.
SABIO-RK O15111.
SignaLinki O15111.

Miscellaneous databases

ChiTaRSi CHUK. human.
EvolutionaryTracei O15111.
GeneWikii CHUK.
GenomeRNAii 1147.
NextBioi 4772.
PROi O15111.
SOURCEi Search...

Gene expression databases

Bgeei O15111.
CleanExi HS_CHUK.
Genevestigatori O15111.

Family and domain databases

InterProi IPR022007. 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 ]
Pfami PF12179. IKKbetaNEMObind. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. 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.
    , 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.

Entry informationi

Entry nameiIKKA_HUMAN
AccessioniPrimary (citable) accession number: O15111
Secondary accession number(s): O14666
, Q13132, Q5W0I4, Q92467
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: January 11, 2011
Last modified: September 3, 2014
This is version 162 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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