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Q95KV0 (IKKB_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 88. 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·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
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length756 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript 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) 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. 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. Interacts with EIF2AK2/PKR By similarity.

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.

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 756756Inhibitor of nuclear factor kappa-B kinase subunit beta
PRO_0000248284

Regions

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

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 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
Q95KV0 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: A072D15614A176E5

FASTA75686,647
        10         20         30         40         50         60 
MSWSPSLPTQ TCGAWEMKER LGTGGFGNVI RWHNQETGEQ IAIKQCRQEL SPRNRERWCL 

        70         80         90        100        110        120 
EIQIMRRLNH PNVVAARDVP EGMQSLAPND LPLLAMEYCQ GGDLRKYLNQ FENCCGLREG 

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

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

       250        260        270        280        290        300 
MDIVVSEDLN GAVKFSSSLP HPNNLNSVLA QRLEKWLQLM LMWHPRQRGT DPVYGPNGCF 

       310        320        330        340        350        360 
KALDDILNLK LLHVLNMVTG TLHTYPVTED ESLQSLKARI RQDTGILEED QELLQEAGLA 

       370        380        390        400        410        420 
LIPDKPAAQC LSDGKLNEGR TLDMDLVFLF DNSRVTYESQ VSPQPQPESV SCILQEPKRN 

       430        440        450        460        470        480 
LPFFQLRKVW GQVWHSIQAL KEDCSRLQQG QRAAMMNLLR NNSCLSKMKN SMASMSQQLK 

       490        500        510        520        530        540 
AKLDFFKTSI QIDLEKYREQ TEFGITSDKL LLAWREMEQA VELCGRENEV KHLVERMMAL 

       550        560        570        580        590        600 
QTDIVDLQRS PMGRKQGGTL DDLEEQAREL YRRLREKPRD QRTDGDSQEM VRLLLQAIQG 

       610        620        630        640        650        660 
FEKKVRVIYT QLSKTVVCKQ KALELLPKVE EVVSLMSEDE KMVVRLQEKR QKELWNLLKI 

       670        680        690        700        710        720 
ACSKVRGPVS GSPDSMNASR LSHPCQLMSQ PCTAPDSLPE AAEKSEDLVA EAHTLCTQLE 

       730        740        750 
NALQDTMKEQ DQSLRSLDWS WLQSEEEEQQ SLERAS

« Hide

References

« Hide 'large scale' references
[1]"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].
[2]"Characterization of 954 bovine full-CDS cDNA sequences."
Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.
BMC Genomics 6:166-166(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AJ414556 mRNA. Translation: CAC93687.1.
BT021585 mRNA. Translation: AAX46432.1.
IPIIPI00903663.
RefSeqNP_776778.1. NM_174353.2.
UniGeneBt.9023.

3D structure databases

ProteinModelPortalQ95KV0.
SMRQ95KV0. Positions 705-743.
ModBaseSearch...

Proteomic databases

PRIDEQ95KV0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000009995; ENSBTAP00000009995; ENSBTAG00000007599.
GeneID281854.
KEGGbta:281854.

Organism-specific databases

CTD3551.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00530000063051.
HOGENOMHOG000038048.
HOVERGENHBG018241.
KOK07209.
OMACTQLENA.

Enzyme and pathway databases

BioCycCATTLE:281854-MONOMER.

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

NextBio20805758.

Entry information

Entry nameIKKB_BOVIN
AccessionPrimary (citable) accession number: Q95KV0
Entry history
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: December 1, 2001
Last modified: May 29, 2013
This is version 88 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

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