Q9QY78 (IKKB_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 111. History...
Names and origin
|Protein names||Recommended name:|
Inhibitor of nuclear factor kappa-B kinase subunit beta
Short name=I-kappa-B-kinase beta
I-kappa-B kinase 2
Nuclear factor NF-kappa-B inhibitor kinase beta
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||757 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 2 critical 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. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation By similarity.
ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein].
Component of the I-kappa-B-kinase (IKK) canonical 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. Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. Interacts with SQSTM1 through PRKCZ or PRKCI. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6. May interact with MAVS/IPS1. Interacts with NALP2. Interacts with TICAM1. Interacts with FAF1; the interaction disrupts the IKK complex formation. Interacts with ATM. Part of a ternary complex consisting of TANK, IKBKB and IKBKG. Interacts with NIBP; the interaction is direct. Interacts with ARRB1 and ARRB2. Interacts with TRIM21 By similarity. Interacts with NLRC5; prevents IKBKB phosphorylation and kinase activity By similarity. Interacts with PDPK1 By similarity. Ref.3
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.
Upon cytokine stimulation, phosphorylated on Ser-177 and Ser-181 by MEKK1 and/or MAP3K14/NIK as well as TBK1 and PRKCZ; which enhances activity. Once activated, autophosphorylates on the C-terminal serine cluster; which decreases activity and prevents prolonged activation of the inflammatory response. Phosphorylated by the IKK-related kinases TBK1 and IKBKE, which is associated with reduced CHUK/IKKA and IKBKB activity and NF-kappa-B-dependent gene transcription By similarity. Ref.2
Acetylation of Thr-180 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the I-kappa-B pathway By similarity.
Ubiquitinated. Monoubiquitination involves TRIM21 that leads to inhibition of Tax-induced NF-kappa-B signaling. 'Ser-163' may not serve as a monoubiquitination site. Ubiquitination on 'Ser-163' may modulate phosphorylation on C-terminal serine residues. Monoubiquitination by TRIM21 is disrupted by Yersinia yopJ By similarity.
Contains 1 protein kinase domain.
|Technical term||Complete proteome|
|Gene Ontology (GO)|
|Biological_process||I-kappaB phosphorylationpositive regulation of NF-kappaB transcription factor activityregulation of I-kappaB kinase/NF-kappaB cascaderesponse to drugresponse to toxinskeletal muscle contraction|
|Cellular_component||IkappaB kinase complexintracellular membrane-bounded organellemembrane raft|
Inferred from electronic annotation. Source: UniProtKB-SubCellnucleus
Inferred from electronic annotation. Source: UniProtKB-SubCell
|Molecular_function||ATP bindingIkappaB kinase activity|
Inferred from electronic annotation. Source: ECprotein kinase activity
Inferred from sequence or structural similarity. Source: UniProtKB
|Complete GO annotation...|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 757||757||Inhibitor of nuclear factor kappa-B kinase subunit beta||PRO_0000086015|
|Domain||15 – 300||286||Protein kinase|
|Nucleotide binding||21 – 29||9||ATP By similarity|
|Region||458 – 479||22||Leucine-zipper|
|Region||737 – 742||6||NEMO-binding|
|Active site||145||1||Proton acceptor By similarity|
|Binding site||44||1||ATP By similarity|
Amino acid modifications
|Modified residue||177||1||Phosphoserine; by TBK1 and PKC/PRKCZ By similarity|
|Modified residue||181||1||Phosphoserine; by TBK1, PKC/PRKCZ and PDPK1 By similarity|
|Modified residue||670||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||672||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||675||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||682||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||689||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||692||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||697||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||705||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||733||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||740||1||Phosphoserine; by autocatalysis By similarity|
|||"IKK beta in megakaryocyte differentiation."|
Zhang Y., Sun S., Ravid K.
Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"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.
|||"The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination."|
Wooten M.W., Geetha T., Seibenhener M.L., Babu J.R., Diaz-Meco M.T., Moscat J.
J. Biol. Chem. 280:35625-35629(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SQSTM1; PRKCI AND TRAF6.
|||"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.
|+||Additional computationally mapped references.|
|AF115282 mRNA. Translation: AAF21978.1.|
|RefSeq||NP_445807.2. NM_053355.2. |
3D structure databases
|SMR||Q9QY78. Positions 705-743. |
Protein-protein interaction databases
|IntAct||Q9QY78. 3 interactions.|
Protocols and materials databases
Genome annotation databases
|UCSC||RGD:621375. rat. |
|RGD||621375. Ikbkb. |
Enzyme and pathway databases
|BRENDA||18.104.22.168. 5301. |
Gene expression databases
|GermOnline||ENSRNOG00000019073. Rattus norvegicus. |
Family and domain databases
|InterPro||IPR022007. IKKbetaNEMObind. |
|Pfam||PF12179. IKKbetaNEMObind. 1 hit. |
PF00069. Pkinase. 1 hit.
|SUPFAM||SSF56112. Kinase_like. 1 hit. |
|PROSITE||PS00107. PROTEIN_KINASE_ATP. False negative. |
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
|Accession||Primary (citable) accession number: Q9QY78|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families