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Q9QY78 (IKKB_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Inhibitor of nuclear factor kappa-B kinase subunit beta
Short name=I-kappa-B-kinase beta
Short name=IKK-B
Short name=IKK-beta
Short name=IkBKB
EC=2.7.11.10
Alternative name(s):
I-kappa-B kinase 2
Short name=IKK2
Nuclear factor NF-kappa-B inhibitor kinase beta
Short name=NFKBIKB
Gene names
Name:Ikbkb
Synonyms:Ikkb
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length757 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 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.

Catalytic activity

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

Subunit structure

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

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Membrane raft By similarity. Note: Colocalized with DPP4 in membrane rafts By similarity.

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 By similarity.

Post-translational modification

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.

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.

Contains 1 protein kinase domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Snap23O703772EBI-1812464,EBI-1573765

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 757757Inhibitor of nuclear factor kappa-B kinase subunit beta
PRO_0000086015

Regions

Domain15 – 300286Protein kinase
Nucleotide binding21 – 299ATP By similarity
Region458 – 47922Leucine-zipper
Region737 – 7426NEMO-binding

Sites

Active site1451Proton acceptor By similarity
Binding site441ATP By similarity

Amino acid modifications

Modified residue1771Phosphoserine; by TBK1 and PKC/PRKCZ By similarity
Modified residue1811Phosphoserine; by TBK1, PKC/PRKCZ and PDPK1 By similarity
Modified residue6701Phosphoserine; by autocatalysis By similarity
Modified residue6721Phosphoserine; by autocatalysis By similarity
Modified residue6751Phosphoserine; by autocatalysis By similarity
Modified residue6821Phosphoserine; by autocatalysis By similarity
Modified residue6891Phosphoserine; by autocatalysis By similarity
Modified residue6921Phosphoserine; by autocatalysis By similarity
Modified residue6971Phosphoserine; by autocatalysis By similarity
Modified residue7051Phosphoserine; by autocatalysis By similarity
Modified residue7331Phosphoserine; by autocatalysis By similarity
Modified residue7401Phosphoserine; by autocatalysis By similarity

Sequences

Sequence LengthMass (Da)Tools
Q9QY78 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 3AFFE46A7DF91F9C

FASTA75786,866
        10         20         30         40         50         60 
MSWSPSLPTQ TCGAWEMKER LGTGGFGNVI RWHNQVTGEQ IAIKQCRQEL SPKNRDRWCL 

        70         80         90        100        110        120 
EIQIMRRLNH PNVVAARDVP EGMQNLAPND LPLLAMEYCQ GGDLRRYLNQ FENCCGLREG 

       130        140        150        160        170        180 
AILTLLSDIA SALRYLHENR IIHRDLKPEN IVLQQGEKRL IHKIIDLGYA KELDQGSLCT 

       190        200        210        220        230        240 
SFVGTLQYLA PELLEQQKYT VTVDYWSFGT LAFECITGFR PFLPNWQPVQ WHSKVRQKSE 

       250        260        270        280        290        300 
VDIVVSEDLN GTVKFSSSSP FPNNLNSVLA ERLEKWLQLM LTWQPRQRGV DPQYGPNGCF 

       310        320        330        340        350        360 
RALDDILNLK LVHILNMVTG TIHTYPVMED ESLQSLKTRI REDTGILETD QELLQEAGLV 

       370        380        390        400        410        420 
LLPDKPATQC ISDSKTNEGL TLDMDLVFLF DNSKMSYETQ ITPRPQPESV SCVLQEPKRN 

       430        440        450        460        470        480 
LSFFQMRKVW GQVWHSIQTL KEDCNRLQQG QRAAMMNLLR NNSCLSKMKN AMASTAQQLK 

       490        500        510        520        530        540 
AKLDFFKTSI QIDLEKYREQ TEFGITSDKL LLAWREMEQA VEQCGRENDV KVLVERMMAL 

       550        560        570        580        590        600 
QTDIVDLQRS PMGRKQGGTL DDLEEQAREL YRRLREKPRD QRTEGDSQDM VRLLLQAIQS 

       610        620        630        640        650        660 
FEKKVRVIYS QLSKTVVCKQ KALELLPKVE EVVRLMNEDE KTVVRLQEKR QKELWNLLKI 

       670        680        690        700        710        720 
ACSKVRGPVS GSPDSMNVSR LSHPGHLMSQ PSSACDSLPD SDKKSEELVA EAHALCSRLE 

       730        740        750 
SALQDTVKQQ DRSFTTLDWS WLQMEDEERC GLEQACD

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References

[1]"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].
[2]"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.
[3]"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.
[4]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF115282 mRNA. Translation: AAF21978.1.
IPIIPI00213608.
RefSeqNP_445807.2. NM_053355.2.
UniGeneRn.19222.

3D structure databases

ProteinModelPortalQ9QY78.
SMRQ9QY78. Positions 705-743.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9QY78. 3 interactions.
STRING10116.ENSRNOP00000025851.

PTM databases

PhosphoSiteQ9QY78.

Proteomic databases

PaxDbQ9QY78.
PRIDEQ9QY78.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID84351.
KEGGrno:84351.
UCSCRGD:621375. rat.

Organism-specific databases

CTD3551.
RGD621375. Ikbkb.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000038048.
HOVERGENHBG018241.
InParanoidQ9QY78.
KOK07209.
OrthoDBEOG4PK276.

Enzyme and pathway databases

BRENDA2.7.11.10. 5301.

Gene expression databases

ArrayExpressQ9QY78.
GenevestigatorQ9QY78.
GermOnlineENSRNOG00000019073. Rattus norvegicus.

Family and domain databases

InterProIPR022007. IKKbetaNEMObind.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF12179. IKKbetaNEMObind. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMSSF56112. Kinase_like. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio616659.

Entry information

Entry nameIKKB_RAT
AccessionPrimary (citable) accession number: Q9QY78
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: May 1, 2000
Last modified: April 3, 2013
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents