Q95KV1 (IKKA_BOVIN) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 81. History...
Names and origin
|Protein names||Recommended name:|
Inhibitor of nuclear factor kappa-B kinase subunit alpha
Short name=I-kappa-B kinase alpha
I-kappa-B kinase 1
Nuclear factor NF-kappa-B inhibitor kinase alpha
|Organism||Bos taurus (Bovine) [Reference proteome]|
|Taxonomic identifier||9913 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos|
|Sequence length||740 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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 By similarity.
ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein].
Activated when phosphorylated and inactivated when dephosphorylated.
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. May interact with TRAF2. Interacts with NALP2. May interact with MAVS/IPS1. Interacts with ARRB1 and ARRB2 By similarity. Interacts with NLRC5; prevents CHUK phosphorylation and kinase activity. Interacts with PIAS1; this interaction induces PIAS1 phosphorylation By similarity. Ref.1
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.
Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A. Autophosphorylated By similarity.
Contains 1 protein kinase domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 740||740||Inhibitor of nuclear factor kappa-B kinase subunit alpha||PRO_0000268159|
|Domain||15 – 302||288||Protein kinase|
|Nucleotide binding||21 – 29||9||ATP By similarity|
|Region||455 – 476||22||Leucine-zipper|
|Region||733 – 738||6||NEMO-binding By similarity|
|Active site||144||1||Proton acceptor By similarity|
|Binding site||44||1||ATP By similarity|
Amino acid modifications
|Modified residue||23||1||Phosphothreonine; by PKB/AKT1 By similarity|
|Modified residue||176||1||Phosphoserine; by MAP3K14 By similarity|
|Modified residue||180||1||Phosphoserine By similarity|
|||"Characterization of the bovine IkappaB kinases (IKK)alpha and IKKbeta, the regulatory subunit NEMO and their substrate IkappaBalpha."|
Rottenberg S., Schmuckli-Maurer J., Grimm S., Heussler V.T., Dobbelaere D.A.E.
Gene 299:293-300(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH IKKB AND IKBKG.
|||NIH - Mammalian Gene Collection (MGC) project|
Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Ascending colon.
|AJ414555 mRNA. Translation: CAC93686.1.|
BC134510 mRNA. Translation: AAI34511.1.
|RefSeq||NP_776446.1. NM_174021.2. |
3D structure databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSBTAT00000009985; ENSBTAP00000009985; ENSBTAG00000007591. |
Family and domain databases
|InterPro||IPR022007. IKKbetaNEMObind. |
|Pfam||PF12179. IKKbetaNEMObind. 1 hit. |
PF00069. Pkinase. 1 hit.
|SMART||SM00220. S_TKc. 1 hit. |
|SUPFAM||SSF56112. Kinase_like. 1 hit. |
|PROSITE||PS00107. PROTEIN_KINASE_ATP. 1 hit. |
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
|Accession||Primary (citable) accession number: Q95KV1|
Secondary accession number(s): A7YWD1
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families