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Protein

Inhibitor of nuclear factor kappa-B kinase subunit alpha

Gene

CHUK

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: 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. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor.By similarity

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 – 441ATPPROSITE-ProRule annotation
Active sitei144 – 1441Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi21 – 299ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-BTA-1169091. Activation of NF-kappaB in B cells.
R-BTA-168638. NOD1/2 Signaling Pathway.
R-BTA-1810476. RIP-mediated NFkB activation via ZBP1.
R-BTA-198323. AKT phosphorylates targets in the cytosol.
R-BTA-202424. Downstream TCR signaling.
R-BTA-2871837. FCERI mediated NF-kB activation.
R-BTA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-BTA-446652. Interleukin-1 signaling.
R-BTA-5357905. Regulation of TNFR1 signaling.
R-BTA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-BTA-5607761. Dectin-1 mediated noncanonical NF-kB signaling.
R-BTA-5607764. CLEC7A (Dectin-1) signaling.
R-BTA-5676590. NIK-->noncanonical NF-kB signaling.
R-BTA-5684264. MAP3K8 (TPL2)-dependent MAPK1/3 activation.
R-BTA-933542. TRAF6 mediated NF-kB activation.
R-BTA-937039. IRAK1 recruits IKK complex.
R-BTA-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.

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
Alternative name(s):
I-kappa-B kinase 1
Short name:
IKK1
Nuclear factor NF-kappa-B inhibitor kinase alpha
Short name:
NFKBIKA
Gene namesi
Name:CHUK
Synonyms:IKKA
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 26

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Shuttles between the cytoplasm and the nucleus.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 740740Inhibitor of nuclear factor kappa-B kinase subunit alphaPRO_0000268159Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei23 – 231Phosphothreonine; by PKB/AKT1By similarity
Modified residuei176 – 1761Phosphoserine; by MAP3K14By similarity
Modified residuei180 – 1801PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A. Autophosphorylated (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ95KV1.
PRIDEiQ95KV1.

Expressioni

Gene expression databases

BgeeiENSBTAG00000007591.

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 (PubMed:12459277). 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 TRPC4AP. 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 (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CHEK1O147573EBI-7669068,EBI-974488From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi158442. 2 interactions.
DIPiDIP-44031N.
IntActiQ95KV1. 2 interactions.
STRINGi9913.ENSBTAP00000009985.

Structurei

3D structure databases

ProteinModelPortaliQ95KV1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini15 – 302288Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni455 – 47622Leucine-zipperAdd
BLAST
Regioni733 – 7386NEMO-bindingBy similarity

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 (By similarity).By similarity

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG4250. Eukaryota.
ENOG410XRMU. LUCA.
GeneTreeiENSGT00820000127009.
HOGENOMiHOG000038048.
HOVERGENiHBG018241.
InParanoidiQ95KV1.
KOiK04467.
OMAiFVLMDHI.
OrthoDBiEOG091G02VC.
TreeFamiTF324269.

Family and domain databases

InterProiIPR022007. IKKbetaNEMObind.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF12179. IKKbetaNEMObind. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM01239. IKKbetaNEMObind. 1 hit.
SM00220. 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.

Q95KV1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MERPPGLRPG AGGPWEMRER LGTGGFGNVC LYQHRELDLK IAIKSCRLEL
60 70 80 90 100
STKNRERWCH EIQIMKKLNH ANVVKACDVP EELNFLINDV PLLAMEYCSG
110 120 130 140 150
GDLRKLLNKP ENCCGLKESQ ILSLLSDIGS GIRYLHENKI IHRDLKPENI
160 170 180 190 200
VLQDVGGKIM HKIIDLGYAK DVDQGSLCTS FVGTLQYLAP ELFENKPYTA
210 220 230 240 250
TVDYWSFGTM VFECIAGYRP FLHHLQPFTW HEKIKKKDPK CIFACEEMTG
260 270 280 290 300
EVRFSSHLPQ PNSLCSLIVE PMENWLQLML NWDPQQRGGP VDLTLKQPRC
310 320 330 340 350
FVLMDHILNL KIVHILNMTS AKIISFLLPP DESLHSLQSR IERETGINTG
360 370 380 390 400
SQELLSEMGI SLDPRKPASQ CVLDGVRGCD SYMVYLFDKS KTVYEGPFAS
410 420 430 440 450
RSLSDCVNYI VQDSKIQLPI IQLRKVWAEA VHYVSGLKED YSRLFQGQRA
460 470 480 490 500
AMLSLLRYNT NLTKMKNTLI SASQQLKAKL EFFHKSIQLD LERYSEQMTY
510 520 530 540 550
GISSEKMLKA WKEMEEKAIH YAEVGVIGYL EDQIMSLHTE IMELQKSPYG
560 570 580 590 600
RRQGDLMESL EQRAIDLYKQ LKHRPSDHSY SDSTEMVKII VHTVQSQDRV
610 620 630 640 650
LKELFGHLSK LLGCKQKIID LLPKVEMALS NIKEADSTVM FMQGKRQKEI
660 670 680 690 700
WHLLKIACTQ SSARSLVGSS LEGVTPQLPP TSAEREHPLS CVVTPQDGET
710 720 730 740
LAQMIEENLN CLGHLSTIIH EANEKQGNNM MSLDWSWLTE
Length:740
Mass (Da):84,344
Last modified:December 1, 2001 - v1
Checksum:i01903BE11F44D176
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ414555 mRNA. Translation: CAC93686.1.
BC134510 mRNA. Translation: AAI34511.1.
RefSeqiNP_776446.1. NM_174021.2.
UniGeneiBt.63925.

Genome annotation databases

EnsembliENSBTAT00000009985; ENSBTAP00000009985; ENSBTAG00000007591.
GeneIDi281073.
KEGGibta:281073.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ414555 mRNA. Translation: CAC93686.1.
BC134510 mRNA. Translation: AAI34511.1.
RefSeqiNP_776446.1. NM_174021.2.
UniGeneiBt.63925.

3D structure databases

ProteinModelPortaliQ95KV1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi158442. 2 interactions.
DIPiDIP-44031N.
IntActiQ95KV1. 2 interactions.
STRINGi9913.ENSBTAP00000009985.

Proteomic databases

PaxDbiQ95KV1.
PRIDEiQ95KV1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000009985; ENSBTAP00000009985; ENSBTAG00000007591.
GeneIDi281073.
KEGGibta:281073.

Organism-specific databases

CTDi1147.

Phylogenomic databases

eggNOGiKOG4250. Eukaryota.
ENOG410XRMU. LUCA.
GeneTreeiENSGT00820000127009.
HOGENOMiHOG000038048.
HOVERGENiHBG018241.
InParanoidiQ95KV1.
KOiK04467.
OMAiFVLMDHI.
OrthoDBiEOG091G02VC.
TreeFamiTF324269.

Enzyme and pathway databases

ReactomeiR-BTA-1169091. Activation of NF-kappaB in B cells.
R-BTA-168638. NOD1/2 Signaling Pathway.
R-BTA-1810476. RIP-mediated NFkB activation via ZBP1.
R-BTA-198323. AKT phosphorylates targets in the cytosol.
R-BTA-202424. Downstream TCR signaling.
R-BTA-2871837. FCERI mediated NF-kB activation.
R-BTA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-BTA-446652. Interleukin-1 signaling.
R-BTA-5357905. Regulation of TNFR1 signaling.
R-BTA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-BTA-5607761. Dectin-1 mediated noncanonical NF-kB signaling.
R-BTA-5607764. CLEC7A (Dectin-1) signaling.
R-BTA-5676590. NIK-->noncanonical NF-kB signaling.
R-BTA-5684264. MAP3K8 (TPL2)-dependent MAPK1/3 activation.
R-BTA-933542. TRAF6 mediated NF-kB activation.
R-BTA-937039. IRAK1 recruits IKK complex.
R-BTA-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.

Gene expression databases

BgeeiENSBTAG00000007591.

Family and domain databases

InterProiIPR022007. IKKbetaNEMObind.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF12179. IKKbetaNEMObind. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM01239. IKKbetaNEMObind. 1 hit.
SM00220. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiIKKA_BOVIN
AccessioniPrimary (citable) accession number: Q95KV1
Secondary accession number(s): A7YWD1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: December 1, 2001
Last modified: September 7, 2016
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.