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Protein

Inhibitor of nuclear factor kappa-B kinase subunit beta

Gene

IKBKB

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 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. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor. 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 activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei44 – 441ATPPROSITE-ProRule annotation
Active sitei145 – 1451Proton 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-202424. Downstream TCR signaling.
R-BTA-209543. p75NTR recruits signalling complexes.
R-BTA-209560. NF-kB is activated and signals survival.
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-5607764. CLEC7A (Dectin-1) 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 beta (EC:2.7.11.10)
Short name:
I-kappa-B-kinase beta
Short name:
IKK-B
Short name:
IKK-beta
Short name:
IkBKB
Alternative name(s):
I-kappa-B kinase 2
Short name:
IKK2
Nuclear factor NF-kappa-B inhibitor kinase beta
Short name:
NFKBIKB
Gene namesi
Name:IKBKB
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 27

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity
  • Membrane raft By similarity

  • Note: Colocalized with DPP4 in membrane rafts.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 756756Inhibitor of nuclear factor kappa-B kinase subunit betaPRO_0000248284Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki163 – 163Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei177 – 1771Phosphoserine; by TBK1 and PKC/PRKCZBy similarity
Modified residuei179 – 1791S-nitrosocysteineBy similarity
Modified residuei181 – 1811Phosphoserine; by TBK1, PKC/PRKCZ and PDPK1By similarity
Modified residuei191 – 1911HydroxyprolineBy similarity
Modified residuei670 – 6701Phosphoserine; by autocatalysisBy similarity
Modified residuei672 – 6721Phosphoserine; by autocatalysisBy similarity
Modified residuei675 – 6751Phosphoserine; by autocatalysisBy similarity
Modified residuei682 – 6821Phosphoserine; by autocatalysisBy similarity
Modified residuei689 – 6891Phosphoserine; by autocatalysisBy similarity
Modified residuei697 – 6971Phosphoserine; by autocatalysisBy similarity
Modified residuei705 – 7051Phosphoserine; by autocatalysisBy similarity
Modified residuei733 – 7331Phosphoserine; by autocatalysisBy similarity
Modified residuei740 – 7401Phosphoserine; by autocatalysisBy similarity

Post-translational modificationi

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. Dephosphorylated at Ser-177 and Ser-181 by PPM1A and PPM1B.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.By similarity
Hydroxylated by PHD1/EGLN2, loss of hydroxylation under hypoxic conditions results in activation of NF-kappa-B.By similarity

Keywords - PTMi

Hydroxylation, Isopeptide bond, Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

PaxDbiQ95KV0.
PRIDEiQ95KV0.

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. 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. Interacts with NLRC5; prevents IKBKB phosphorylation and kinase activity. Interacts with PDPK1. Interacts with EIF2AK2/PKR. The phosphorylated form interacts with PPM1A and PPM1B. Interacts with ZNF268; the interaction is further increased in a TNF-alpha-dependent manner. Interacts with IKBKE. Interacts with NAA10, leading to NAA10 degradation. Interacts with FOXO3. Interacts with ZC3H12A. Interacts with AKAP13 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi159165. 2 interactions.
STRINGi9913.ENSBTAP00000009995.

Structurei

3D structure databases

ProteinModelPortaliQ95KV0.
SMRiQ95KV0. Positions 705-743.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini15 – 300286Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni458 – 47922Leucine-zipperAdd
BLAST
Regioni737 – 7426NEMO-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.
InParanoidiQ95KV0.
KOiK07209.
OMAiVYGPNGC.
OrthoDBiEOG7FBRH3.
TreeFamiTF324269.

Family and domain databases

InterProiIPR022007. IKKbetaNEMObind.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF12179. IKKbetaNEMObind. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM01239. IKKbetaNEMObind. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q95KV0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSWSPSLPTQ TCGAWEMKER LGTGGFGNVI RWHNQETGEQ IAIKQCRQEL
60 70 80 90 100
SPRNRERWCL EIQIMRRLNH PNVVAARDVP EGMQSLAPND LPLLAMEYCQ
110 120 130 140 150
GGDLRKYLNQ FENCCGLREG AILTLLSDIA SALRYLHENR IIHRDLKPEN
160 170 180 190 200
IVLQQGEQRL IHKIIDLGYA KELDQGSLCT SFVGTLQYLA PELLEQQKYT
210 220 230 240 250
VTVDYWSFGT LAFECITGFR PFLPNWQPVQ WHSKVRQKSE MDIVVSEDLN
260 270 280 290 300
GAVKFSSSLP HPNNLNSVLA QRLEKWLQLM LMWHPRQRGT DPVYGPNGCF
310 320 330 340 350
KALDDILNLK LLHVLNMVTG TLHTYPVTED ESLQSLKARI RQDTGILEED
360 370 380 390 400
QELLQEAGLA LIPDKPAAQC LSDGKLNEGR TLDMDLVFLF DNSRVTYESQ
410 420 430 440 450
VSPQPQPESV SCILQEPKRN LPFFQLRKVW GQVWHSIQAL KEDCSRLQQG
460 470 480 490 500
QRAAMMNLLR NNSCLSKMKN SMASMSQQLK AKLDFFKTSI QIDLEKYREQ
510 520 530 540 550
TEFGITSDKL LLAWREMEQA VELCGRENEV KHLVERMMAL QTDIVDLQRS
560 570 580 590 600
PMGRKQGGTL DDLEEQAREL YRRLREKPRD QRTDGDSQEM VRLLLQAIQG
610 620 630 640 650
FEKKVRVIYT QLSKTVVCKQ KALELLPKVE EVVSLMSEDE KMVVRLQEKR
660 670 680 690 700
QKELWNLLKI ACSKVRGPVS GSPDSMNASR LSHPCQLMSQ PCTAPDSLPE
710 720 730 740 750
AAEKSEDLVA EAHTLCTQLE NALQDTMKEQ DQSLRSLDWS WLQSEEEEQQ

SLERAS
Length:756
Mass (Da):86,647
Last modified:December 1, 2001 - v1
Checksum:iA072D15614A176E5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ414556 mRNA. Translation: CAC93687.1.
BT021585 mRNA. Translation: AAX46432.1.
RefSeqiNP_776778.1. NM_174353.2.
UniGeneiBt.9023.

Genome annotation databases

EnsembliENSBTAT00000009995; ENSBTAP00000009995; ENSBTAG00000007599.
GeneIDi281854.
KEGGibta:281854.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ414556 mRNA. Translation: CAC93687.1.
BT021585 mRNA. Translation: AAX46432.1.
RefSeqiNP_776778.1. NM_174353.2.
UniGeneiBt.9023.

3D structure databases

ProteinModelPortaliQ95KV0.
SMRiQ95KV0. Positions 705-743.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi159165. 2 interactions.
STRINGi9913.ENSBTAP00000009995.

Proteomic databases

PaxDbiQ95KV0.
PRIDEiQ95KV0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000009995; ENSBTAP00000009995; ENSBTAG00000007599.
GeneIDi281854.
KEGGibta:281854.

Organism-specific databases

CTDi3551.

Phylogenomic databases

eggNOGiKOG4250. Eukaryota.
ENOG410XRMU. LUCA.
GeneTreeiENSGT00820000127009.
HOGENOMiHOG000038048.
HOVERGENiHBG018241.
InParanoidiQ95KV0.
KOiK07209.
OMAiVYGPNGC.
OrthoDBiEOG7FBRH3.
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-202424. Downstream TCR signaling.
R-BTA-209543. p75NTR recruits signalling complexes.
R-BTA-209560. NF-kB is activated and signals survival.
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-5607764. CLEC7A (Dectin-1) 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.

Family and domain databases

InterProiIPR022007. IKKbetaNEMObind.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF12179. IKKbetaNEMObind. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM01239. IKKbetaNEMObind. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].

Entry informationi

Entry nameiIKKB_BOVIN
AccessioniPrimary (citable) accession number: Q95KV0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: December 1, 2001
Last modified: July 6, 2016
This is version 118 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.