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Protein

Inhibitor of nuclear factor kappa-B kinase subunit beta

Gene

Ikbkb

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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)DescriptionActionsGraphical viewLength
Binding sitei44ATPPROSITE-ProRule annotation1
Active sitei145Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi21 – 29ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: RGD
  • IkappaB kinase activity Source: UniProtKB-EC
  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: UniProtKB
  • protein kinase activity Source: UniProtKB

GO - Biological processi

  • cellular response to tumor necrosis factor Source: UniProtKB
  • neuron projection development Source: RGD
  • positive regulation of cell proliferation Source: RGD
  • positive regulation of neuron death Source: RGD
  • positive regulation of neuron projection development Source: RGD
  • positive regulation of NF-kappaB transcription factor activity Source: RGD
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • response to drug Source: RGD
  • response to fatty acid Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to toxic substance Source: RGD
  • skeletal muscle contraction Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.10. 5301.

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
Synonyms:Ikkb
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621375. Ikbkb.

Subcellular locationi

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

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

GO - Cellular componenti

  • cytosol Source: RGD
  • IkappaB kinase complex Source: RGD
  • intracellular membrane-bounded organelle Source: RGD
  • membrane raft Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000860151 – 757Inhibitor of nuclear factor kappa-B kinase subunit betaAdd BLAST757

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki163Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei177Phosphoserine; by TBK1 and PKC/PRKCZBy similarity1
Modified residuei179S-nitrosocysteineBy similarity1
Modified residuei181Phosphoserine; by TBK1, PKC/PRKCZ and PDPK1By similarity1
Modified residuei191HydroxyprolineBy similarity1
Modified residuei670Phosphoserine; by autocatalysisBy similarity1
Modified residuei672PhosphoserineCombined sources1
Modified residuei675Phosphoserine; by autocatalysisBy similarity1
Modified residuei682Phosphoserine; by autocatalysisBy similarity1
Modified residuei689Phosphoserine; by autocatalysisBy similarity1
Modified residuei692Phosphoserine; by autocatalysisBy similarity1
Modified residuei697Phosphoserine; by autocatalysisBy similarity1
Modified residuei705Phosphoserine; by autocatalysisBy similarity1
Modified residuei733Phosphoserine; by autocatalysisBy similarity1
Modified residuei740Phosphoserine; by autocatalysisBy similarity1

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

PaxDbiQ9QY78.
PRIDEiQ9QY78.

PTM databases

iPTMnetiQ9QY78.
PhosphoSitePlusiQ9QY78.

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 (By similarity). Interacts with SQSTM1 through PRKCZ or PRKCI (PubMed:16079148). Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6 (PubMed:16079148). 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 isoform 2; 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 (By similarity). Interacts with AKAP13 (PubMed:23090968).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Snap23O703772EBI-1812464,EBI-1573765

GO - Molecular functioni

  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi249911. 1 interactor.
IntActiQ9QY78. 4 interactors.
STRINGi10116.ENSRNOP00000025851.

Structurei

3D structure databases

ProteinModelPortaliQ9QY78.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini15 – 300Protein kinasePROSITE-ProRule annotationAdd BLAST286

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni458 – 479Leucine-zipperAdd BLAST22
Regioni737 – 742NEMO-binding6

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.
HOGENOMiHOG000038048.
HOVERGENiHBG018241.
InParanoidiQ9QY78.
KOiK07209.
PhylomeDBiQ9QY78.

Family and domain databases

InterProiIPR022007. IKKbetaNEMObind.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF12179. IKKbetaNEMObind. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM01239. IKKbetaNEMObind. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9QY78-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSWSPSLPTQ TCGAWEMKER LGTGGFGNVI RWHNQVTGEQ IAIKQCRQEL
60 70 80 90 100
SPKNRDRWCL EIQIMRRLNH PNVVAARDVP EGMQNLAPND LPLLAMEYCQ
110 120 130 140 150
GGDLRRYLNQ FENCCGLREG AILTLLSDIA SALRYLHENR IIHRDLKPEN
160 170 180 190 200
IVLQQGEKRL IHKIIDLGYA KELDQGSLCT SFVGTLQYLA PELLEQQKYT
210 220 230 240 250
VTVDYWSFGT LAFECITGFR PFLPNWQPVQ WHSKVRQKSE VDIVVSEDLN
260 270 280 290 300
GTVKFSSSSP FPNNLNSVLA ERLEKWLQLM LTWQPRQRGV DPQYGPNGCF
310 320 330 340 350
RALDDILNLK LVHILNMVTG TIHTYPVMED ESLQSLKTRI REDTGILETD
360 370 380 390 400
QELLQEAGLV LLPDKPATQC ISDSKTNEGL TLDMDLVFLF DNSKMSYETQ
410 420 430 440 450
ITPRPQPESV SCVLQEPKRN LSFFQMRKVW GQVWHSIQTL KEDCNRLQQG
460 470 480 490 500
QRAAMMNLLR NNSCLSKMKN AMASTAQQLK AKLDFFKTSI QIDLEKYREQ
510 520 530 540 550
TEFGITSDKL LLAWREMEQA VEQCGRENDV KVLVERMMAL QTDIVDLQRS
560 570 580 590 600
PMGRKQGGTL DDLEEQAREL YRRLREKPRD QRTEGDSQDM VRLLLQAIQS
610 620 630 640 650
FEKKVRVIYS QLSKTVVCKQ KALELLPKVE EVVRLMNEDE KTVVRLQEKR
660 670 680 690 700
QKELWNLLKI ACSKVRGPVS GSPDSMNVSR LSHPGHLMSQ PSSACDSLPD
710 720 730 740 750
SDKKSEELVA EAHALCSRLE SALQDTVKQQ DRSFTTLDWS WLQMEDEERC

GLEQACD
Length:757
Mass (Da):86,866
Last modified:May 1, 2000 - v1
Checksum:i3AFFE46A7DF91F9C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF115282 mRNA. Translation: AAF21978.1.
RefSeqiNP_445807.2. NM_053355.2.
UniGeneiRn.19222.

Genome annotation databases

GeneIDi84351.
KEGGirno:84351.
UCSCiRGD:621375. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF115282 mRNA. Translation: AAF21978.1.
RefSeqiNP_445807.2. NM_053355.2.
UniGeneiRn.19222.

3D structure databases

ProteinModelPortaliQ9QY78.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249911. 1 interactor.
IntActiQ9QY78. 4 interactors.
STRINGi10116.ENSRNOP00000025851.

PTM databases

iPTMnetiQ9QY78.
PhosphoSitePlusiQ9QY78.

Proteomic databases

PaxDbiQ9QY78.
PRIDEiQ9QY78.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi84351.
KEGGirno:84351.
UCSCiRGD:621375. rat.

Organism-specific databases

CTDi3551.
RGDi621375. Ikbkb.

Phylogenomic databases

eggNOGiKOG4250. Eukaryota.
ENOG410XRMU. LUCA.
HOGENOMiHOG000038048.
HOVERGENiHBG018241.
InParanoidiQ9QY78.
KOiK07209.
PhylomeDBiQ9QY78.

Enzyme and pathway databases

BRENDAi2.7.11.10. 5301.

Miscellaneous databases

PROiQ9QY78.

Family and domain databases

InterProiIPR022007. IKKbetaNEMObind.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF12179. IKKbetaNEMObind. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM01239. IKKbetaNEMObind. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIKKB_RAT
AccessioniPrimary (citable) accession number: Q9QY78
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: May 1, 2000
Last modified: November 2, 2016
This is version 139 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.