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Inhibitor of nuclear factor kappa-B kinase subunit beta (I-kappa-B-kinase beta) (IKK-B) (IKK-beta) (IkBKB) (EC 2 7 11 10) (I-kappa-B kinase 2) (IKK2) (Nuclear factor NF-kappa-B inhibitor kinase beta) (NFKBIKB)

 IKKB_MOUSE              Reviewed;         757 AA.
O88351; Q9R1J6;
01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
01-NOV-1998, sequence version 1.
17-JUN-2020, entry version 185.
RecName: Full=Inhibitor of nuclear factor kappa-B kinase subunit beta;
Short=I-kappa-B-kinase beta;
Short=IKK-B;
Short=IKK-beta;
Short=IkBKB;
EC=2.7.11.10;
AltName: Full=I-kappa-B kinase 2;
Short=IKK2;
AltName: Full=Nuclear factor NF-kappa-B inhibitor kinase beta;
Short=NFKBIKB;
Name=Ikbkb; Synonyms=Ikkb;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND PHOSPHORYLATION BY MEKK1.
STRAIN=C57BL/6J; TISSUE=Spleen;
PubMed=9520401; DOI=10.1073/pnas.95.7.3537;
Nakano H., Shindo M., Sakon S., Nishinaka S., Mihara M., Yagita H.,
Okumura K.;
"Differential regulation of IkappaB kinase alpha and beta by two upstream
kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK
kinase kinase-1.";
Proc. Natl. Acad. Sci. U.S.A. 95:3537-3542(1998).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
Hu M.C.-T., Wang Y.-P., Mikhail A., Qiu W.R.;
"Murine IkB kinase-B, a developmentally regulated protein kinase that
constitutively phosphorylates serine residues of IkB.";
Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
[3]
DISRUPTION PHENOTYPE.
PubMed=10229185; DOI=10.1016/s1074-7613(00)80042-4;
Tanaka M., Fuentes M.E., Yamaguchi K., Durnin M.H., Dalrymple S.A.,
Hardy K.L., Goeddel D.V.;
"Embryonic lethality, liver degeneration, and impaired NF-kappa B
activation in IKK-beta-deficient mice.";
Immunity 10:421-429(1999).
[4]
DEVELOPMENTAL STAGE.
PubMed=10523828; DOI=10.1038/sj.onc.1202740;
Hu M.C.-T., Wang Y.-P., Qiu W.R., Mikhail A., Meyer C.F., Tan T.-H.;
"Hematopoietic progenitor kinase-1 (HPK1) stress response signaling pathway
activates IkappaB kinases (IKK-alpha/beta) and IKK-beta is a
developmentally regulated protein kinase.";
Oncogene 18:5514-5524(1999).
[5]
IKK PHOSPHORYLATION.
PubMed=9819420; DOI=10.1128/mcb.18.12.7336;
Nemoto S., DiDonato J.A., Lin A.;
"Coordinate regulation of IkappaB kinases by mitogen-activated protein
kinase kinase kinase 1 and NF-kappaB-inducing kinase.";
Mol. Cell. Biol. 18:7336-7343(1998).
[6]
DISRUPTION PHENOTYPE.
PubMed=10195897; DOI=10.1126/science.284.5412.321;
Li Q., Van Antwerp D., Mercurio F., Lee K.F., Verma I.M.;
"Severe liver degeneration in mice lacking the IkappaB kinase 2 gene.";
Science 284:321-325(1999).
[7]
REVIEW.
PubMed=10712233; DOI=10.1152/ajpcell.2000.278.3.c451;
Jobin C., Sartor R.B.;
"The I kappa B/NF-kappa B system: a key determinant of mucosal inflammation
and protection.";
Am. J. Physiol. 278:C451-C462(2000).
[8]
INTERACTION WITH EIF2AK2.
PubMed=10848580; DOI=10.1128/mcb.20.13.4532-4542.2000;
Bonnet M.C., Weil R., Dam E., Hovanessian A.G., Meurs E.F.;
"PKR stimulates NF-kappaB irrespective of its kinase function by
interacting with the IkappaB kinase complex.";
Mol. Cell. Biol. 20:4532-4542(2000).
[9]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Brown adipose tissue, Kidney, Lung, Pancreas, Spleen, and Testis;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and expression.";
Cell 143:1174-1189(2010).
[10]
INTERACTION WITH TERF2IP.
PubMed=20622870; DOI=10.1038/ncb2080;
Teo H., Ghosh S., Luesch H., Ghosh A., Wong E.T., Malik N., Orth A.,
de Jesus P., Perry A.S., Oliver J.D., Tran N.L., Speiser L.J., Wong M.,
Saez E., Schultz P., Chanda S.K., Verma I.M., Tergaonkar V.;
"Telomere-independent Rap1 is an IKK adaptor and regulates NF-kappaB-
dependent gene expression.";
Nat. Cell Biol. 12:758-767(2010).
[11]
INTERACTION WITH ZC3H12A.
PubMed=22037600; DOI=10.1038/ni.2137;
Iwasaki H., Takeuchi O., Teraguchi S., Matsushita K., Uehata T.,
Kuniyoshi K., Satoh T., Saitoh T., Matsushita M., Standley D.M., Akira S.;
"The IkappaB kinase complex regulates the stability of cytokine-encoding
mRNA induced by TLR-IL-1R by controlling degradation of regnase-1.";
Nat. Immunol. 12:1167-1175(2011).
[12]
INTERACTION WITH AKAP13, IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE
SPECIFICITY.
PubMed=23090968; DOI=10.1128/mcb.00887-12;
del Vescovo C.D., Cotecchia S., Diviani D.;
"A-kinase-anchoring protein-Lbc anchors IkappaB kinase beta to support
interleukin-6-mediated cardiomyocyte hypertrophy.";
Mol. Cell. Biol. 33:14-27(2013).
[13]
FUNCTION.
PubMed=30988283; DOI=10.1038/s41467-019-09690-0;
Dondelinger Y., Delanghe T., Priem D., Wynosky-Dolfi M.A., Sorobetea D.,
Rojas-Rivera D., Giansanti P., Roelandt R., Gropengiesser J.,
Ruckdeschel K., Savvides S.N., Heck A.J.R., Vandenabeele P., Brodsky I.E.,
Bertrand M.J.M.;
"Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in
models of infection and inflammation.";
Nat. Commun. 10:1729-1729(2019).
-!- 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. 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). Phosphorylates RIPK1 at
'Ser-25' which represses its kinase activity and consequently prevents
TNF-mediated RIPK1-dependent cell death (PubMed:30988283).
{ECO:0000250|UniProtKB:O14920, ECO:0000269|PubMed:30988283}.
-!- CATALYTIC ACTIVITY:
Reaction=[I-kappa-B protein]-L-serine + ATP = [I-kappa-B protein]-O-
phospho-L-serine + ADP + H(+); Xref=Rhea:RHEA:19073, Rhea:RHEA-
COMP:13698, Rhea:RHEA-COMP:13699, ChEBI:CHEBI:15378,
ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421,
ChEBI:CHEBI:456216; EC=2.7.11.10;
-!- SUBUNIT: 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 (By similarity). The IKK complex
associates with TERF2IP/RAP1, leading to promote IKK-mediated
phosphorylation of RELA/p65 (PubMed:20622870). 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, ELP1 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 (By similarity). Interacts with
EIF2AK2/PKR (PubMed:10848580). 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 (By similarity). Interacts with ZC3H12A (PubMed:22037600).
Interacts with AKAP13 (PubMed:23090968). Interacts with LRRC14;
disrupts IKBKB-IKBKG interaction preventing I-kappa-B-kinase (IKK) core
complex formation and leading to a decrease of IKBKB phosphorylation
and NF-kappaB activation (By similarity). Interacts with SASH1 (By
similarity). Interacts with ARFIP2 (By similarity).
{ECO:0000250|UniProtKB:O14920, ECO:0000269|PubMed:10848580,
ECO:0000269|PubMed:20622870, ECO:0000269|PubMed:22037600}.
-!- INTERACTION:
O88351; Q60680: Chuk; NbExp=4; IntAct=EBI-447960, EBI-646245;
O88351; O88522: Ikbkg; NbExp=7; IntAct=EBI-447960, EBI-998011;
O88351; P68040: Rack1; NbExp=4; IntAct=EBI-447960, EBI-296749;
O88351; Q14145: KEAP1; Xeno; NbExp=2; IntAct=EBI-447960, EBI-751001;
O88351; P01375: TNF; Xeno; NbExp=3; IntAct=EBI-447960, EBI-359977;
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O14920}. Nucleus
{ECO:0000250|UniProtKB:O14920}. Membrane raft
{ECO:0000250|UniProtKB:O14920}. Note=Colocalized with DPP4 in membrane
rafts. {ECO:0000250|UniProtKB:O14920}.
-!- TISSUE SPECIFICITY: Detected in heart (at protein level)
(PubMed:23090968). Expressed in liver, kidney and spleen.
{ECO:0000269|PubMed:23090968}.
-!- DEVELOPMENTAL STAGE: While it is expressed ubiquitously throughout the
mouse embryo, at 9.5 dpc its expression begins to be localized to the
brain, neural ganglia, neural tube, and in liver at 12.5 dpc. At 15.5
dpc, the expression is further restricted to specific tissues of the
embryo. {ECO:0000269|PubMed:10523828}.
-!- 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). {ECO:0000250}.
-!- PTM: 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.
{ECO:0000250|UniProtKB:O14920}.
-!- PTM: 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.
{ECO:0000250|UniProtKB:O14920}.
-!- PTM: Hydroxylated by PHD1/EGLN2, loss of hydroxylation under hypoxic
conditions results in activation of NF-kappa-B.
{ECO:0000250|UniProtKB:O14920}.
-!- DISRUPTION PHENOTYPE: Mice present extensive liver damage from
apoptosis and die as embryos. They show a marked reduction in TNF-alpha
and IL1-alpha-induced NF-kappa-B activity.
{ECO:0000269|PubMed:10195897, ECO:0000269|PubMed:10229185}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
kinase family. I-kappa-B kinase subfamily. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
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EMBL; AF026524; AAC23557.1; -; mRNA.
EMBL; AF088910; AAD52095.1; -; mRNA.
CCDS; CCDS52522.1; -.
RefSeq; NP_034676.1; NM_010546.2.
SMR; O88351; -.
BioGRID; 200601; 26.
ComplexPortal; CPX-3270; IkappaB kinase complex.
CORUM; O88351; -.
DIP; DIP-29813N; -.
IntAct; O88351; 26.
MINT; O88351; -.
STRING; 10090.ENSMUSP00000033939; -.
BindingDB; O88351; -.
ChEMBL; CHEMBL6012; -.
iPTMnet; O88351; -.
PhosphoSitePlus; O88351; -.
EPD; O88351; -.
MaxQB; O88351; -.
PaxDb; O88351; -.
PeptideAtlas; O88351; -.
PRIDE; O88351; -.
GeneID; 16150; -.
KEGG; mmu:16150; -.
CTD; 3551; -.
MGI; MGI:1338071; Ikbkb.
eggNOG; KOG4250; Eukaryota.
eggNOG; ENOG410XRMU; LUCA.
InParanoid; O88351; -.
KO; K07209; -.
PhylomeDB; O88351; -.
BRENDA; 2.7.11.10; 3474.
Reactome; R-MMU-1169091; Activation of NF-kappaB in B cells.
Reactome; R-MMU-168638; NOD1/2 Signaling Pathway.
Reactome; R-MMU-1810476; RIP-mediated NFkB activation via ZBP1.
Reactome; R-MMU-202424; Downstream TCR signaling.
Reactome; R-MMU-209543; p75NTR recruits signalling complexes.
Reactome; R-MMU-209560; NF-kB is activated and signals survival.
Reactome; R-MMU-2871837; FCERI mediated NF-kB activation.
Reactome; R-MMU-445989; TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
Reactome; R-MMU-5357956; TNFR1-induced NFkappaB signaling pathway.
Reactome; R-MMU-5607764; CLEC7A (Dectin-1) signaling.
Reactome; R-MMU-5684264; MAP3K8 (TPL2)-dependent MAPK1/3 activation.
Reactome; R-MMU-9020702; Interleukin-1 signaling.
Reactome; R-MMU-933542; TRAF6 mediated NF-kB activation.
Reactome; R-MMU-937039; IRAK1 recruits IKK complex.
Reactome; R-MMU-937041; IKK complex recruitment mediated by RIP1.
Reactome; R-MMU-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
BioGRID-ORCS; 16150; 4 hits in 13 CRISPR screens.
ChiTaRS; Ikbkb; mouse.
PRO; PR:O88351; -.
Proteomes; UP000000589; Unplaced.
RNAct; O88351; protein.
GO; GO:0035631; C:CD40 receptor complex; IDA:BHF-UCL.
GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:BHF-UCL.
GO; GO:0005829; C:cytosol; ISO:MGI.
GO; GO:0008385; C:IkappaB kinase complex; ISO:MGI.
GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
GO; GO:0005524; F:ATP binding; ISO:MGI.
GO; GO:0042802; F:identical protein binding; ISO:MGI.
GO; GO:0008384; F:IkappaB kinase activity; IDA:MGI.
GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
GO; GO:0004672; F:protein kinase activity; IDA:MGI.
GO; GO:0019901; F:protein kinase binding; ISO:MGI.
GO; GO:0019903; F:protein phosphatase binding; IPI:ARUK-UCL.
GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
GO; GO:1990459; F:transferrin receptor binding; ISO:MGI.
GO; GO:0001782; P:B cell homeostasis; IMP:MGI.
GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
GO; GO:0030866; P:cortical actin cytoskeleton organization; ISO:MGI.
GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
GO; GO:0007252; P:I-kappaB phosphorylation; TAS:MGI.
GO; GO:0070498; P:interleukin-1-mediated signaling pathway; ISO:MGI.
GO; GO:1903347; P:negative regulation of bicellular tight junction assembly; ISO:MGI.
GO; GO:0035509; P:negative regulation of myosin-light-chain-phosphatase activity; ISO:MGI.
GO; GO:0031175; P:neuron projection development; ISO:MGI.
GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:MGI.
GO; GO:2001259; P:positive regulation of cation channel activity; IGI:MGI.
GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
GO; GO:1901216; P:positive regulation of neuron death; ISO:MGI.
GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
GO; GO:0010765; P:positive regulation of sodium ion transport; IGI:MGI.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
GO; GO:1903140; P:regulation of establishment of endothelial barrier; ISO:MGI.
GO; GO:0042325; P:regulation of phosphorylation; ISO:MGI.
GO; GO:0061847; P:response to cholecystokinin; ISO:MGI.
GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB.
InterPro; IPR041185; IKBKB_SDD.
InterPro; IPR022007; IKKbetaNEMObind.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR008271; Ser/Thr_kinase_AS.
Pfam; PF18397; IKBKB_SDD; 1.
Pfam; PF12179; IKKbetaNEMObind; 1.
Pfam; PF00069; Pkinase; 1.
SMART; SM01239; IKKbetaNEMObind; 1.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
1: Evidence at protein level;
ATP-binding; Cytoplasm; Hydroxylation; Isopeptide bond; Kinase; Membrane;
Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
S-nitrosylation; Serine/threonine-protein kinase; Transferase;
Ubl conjugation.
CHAIN 1..757
/note="Inhibitor of nuclear factor kappa-B kinase subunit
beta"
/id="PRO_0000086014"
DOMAIN 15..300
/note="Protein kinase"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
NP_BIND 21..29
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
REGION 458..479
/note="Leucine-zipper"
REGION 737..742
/note="NEMO-binding"
ACT_SITE 145
/note="Proton acceptor"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
ECO:0000255|PROSITE-ProRule:PRU10027"
BINDING 44
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
MOD_RES 177
/note="Phosphoserine; by TBK1 and PKC/PRKCZ"
/evidence="ECO:0000250|UniProtKB:O14920"
MOD_RES 179
/note="S-nitrosocysteine"
/evidence="ECO:0000250|UniProtKB:O14920"
MOD_RES 181
/note="Phosphoserine; by TBK1, PKC/PRKCZ and PDPK1"
/evidence="ECO:0000250|UniProtKB:O14920"
MOD_RES 191
/note="Hydroxyproline"
/evidence="ECO:0000250"
MOD_RES 670
/note="Phosphoserine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:O14920"
MOD_RES 672
/note="Phosphoserine"
/evidence="ECO:0000244|PubMed:21183079"
MOD_RES 675
/note="Phosphoserine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:O14920"
MOD_RES 682
/note="Phosphoserine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:O14920"
MOD_RES 689
/note="Phosphoserine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:O14920"
MOD_RES 692
/note="Phosphoserine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:O14920"
MOD_RES 697
/note="Phosphoserine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:O14920"
MOD_RES 705
/note="Phosphoserine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:O14920"
MOD_RES 733
/note="Phosphoserine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:O14920"
MOD_RES 740
/note="Phosphoserine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:O14920"
CROSSLNK 163
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in ubiquitin)"
/evidence="ECO:0000250|UniProtKB:O14920"
CONFLICT 56
/note="N -> D (in Ref. 2; AAD52095)"
/evidence="ECO:0000305"
CONFLICT 343
/note="N -> D (in Ref. 2; AAD52095)"
/evidence="ECO:0000305"
CONFLICT 356
/note="K -> E (in Ref. 2; AAD52095)"
/evidence="ECO:0000305"
CONFLICT 390
/note="L -> F (in Ref. 2; AAD52095)"
/evidence="ECO:0000305"
CONFLICT 406
/note="P -> Q (in Ref. 2; AAD52095)"
/evidence="ECO:0000305"
CONFLICT 573
/note="K -> R (in Ref. 2; AAD52095)"
/evidence="ECO:0000305"
CONFLICT 736..757
/note="TLDWSWLQMEDEERCSLEQACD -> VTA (in Ref. 2)"
/evidence="ECO:0000305"
SEQUENCE 757 AA; 86690 MW; FED962F095449C5E CRC64;
MSWSPSLPTQ TCGAWEMKER LGTGGFGNVI RWHNQATGEQ IAIKQCRQEL SPKNRNRWCL
EIQIMRRLNH PNVVAARDVP EGMQNLAPND LPLLAMEYCQ GGDLRRYLNQ FENCCGLREG
AVLTLLSDIA SALRYLHENR IIHRDLKPEN IVLQQGEKRL IHKIIDLGYA KELDQGSLCT
SFVGTLQYLA PELLEQQKYT VTVDYWSFGT LAFECITGFR PFLPNWQPVQ WHSKVRQKSE
VDIVVSEDLN GAVKFSSSLP FPNNLNSVLA ERLEKWLQLM LMWHPRQRGT DPQYGPNGCF
RALDDILNLK LVHVLNMVTG TVHTYPVTED ESLQSLKTRI QENTGILETD QELLQKAGLV
LLPDKPATQC ISDSKTNEGL TLDMDLVFLL DNSKINYETQ ITPRPPPESV SCILQEPKRN
LSFFQLRKVW GQVWHSIQTL KEDCNRLQQG QRAAMMSLLR NNSCLSKMKN AMASTAQQLK
AKLDFFKTSI QIDLEKYKEQ TEFGITSDKL LLAWREMEQA VEQCGRENDV KHLVERMMAL
QTDIVDLQRS PMGRKQGGTL DDLEEQAREL YRKLREKPRD QRTEGDSQEM VRLLLQAIQS
FEKKVRVIYT QLSKTVVCKQ KALELLPKVE EVVSLMNEDE RTVVRLQEKR QKELWNLLKI
ACSKVRGPVS GSPDSMNVSR LSHPGQLMSQ PSSACDSLPE SDKKSEELVA EAHALCSRLE
SALQDTVKEQ DRSFTTLDWS WLQMEDEERC SLEQACD


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E1953h ELISA kit Homo sapiens,Human,I-kappa-B kinase 2,I-kappa-B-kinase beta,IkBKB,IKBKB,IKK2,IKKB,IKK-B,IKK-beta,Inhibitor of nuclear factor kappa-B kinase subunit beta,NFKBIKB,Nuclear factor NF-kappa-B in 96T
U1953b CLIA Bos taurus,Bovine,I-kappa-B kinase 2,I-kappa-B-kinase beta,IkBKB,IKBKB,IKK2,IKK-B,IKK-beta,Inhibitor of nuclear factor kappa-B kinase subunit beta,NFKBIKB,Nuclear factor NF-kappa-B inhibitor kina 96T
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U1953b CLIA kit Bos taurus,Bovine,I-kappa-B kinase 2,I-kappa-B-kinase beta,IkBKB,IKBKB,IKK2,IKK-B,IKK-beta,Inhibitor of nuclear factor kappa-B kinase subunit beta,NFKBIKB,Nuclear factor NF-kappa-B inhibitor 96T
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Pathways :
WP32: Translation Factors
WP1571: EBV LMP1 signaling
WP1224: EBV LMP1 signaling
WP262: EBV LMP1 signaling
WP866: EBV LMP1 signaling
WP1328: EBV LMP1 signaling
WP1102: EBV LMP1 signaling
WP758: EBV LMP1 signaling
WP1278: EBV LMP1 signaling
WP1209: EBV LMP1 signaling
WP1655: Geraniol degradation
WP1243: EBV LMP1 signaling
WP1566: Citrate cycle (TCA cycle)
WP1614: 1- and 2-Methylnaphthalene degradation
WP1628: beta-Alanine metabolism
WP3: Keap1-Nrf2 Pathway
WP1207: Fatty Acid Beta Oxidation
WP812: TGF Beta Signaling Pathway
WP237: Glucocorticoid & Mineralcorticoid Metabolism
WP763: Mitochondrial LC-Fatty Acid Beta-Oxidation
WP443: Beta Oxidation Meta MAPP
WP1653: Galactose metabolism
WP1225: estrogen signalling
WP2152: BDNF
WP366: TGF beta Signaling Pathway

Related Genes :
[IKBKB IKKB] Inhibitor of nuclear factor kappa-B kinase subunit beta (I-kappa-B-kinase beta) (IKK-B) (IKK-beta) (IkBKB) (EC 2.7.11.10) (I-kappa-B kinase 2) (IKK2) (Nuclear factor NF-kappa-B inhibitor kinase beta) (NFKBIKB)
[Ikbkb Ikkb] Inhibitor of nuclear factor kappa-B kinase subunit beta (I-kappa-B-kinase beta) (IKK-B) (IKK-beta) (IkBKB) (EC 2.7.11.10) (I-kappa-B kinase 2) (IKK2) (Nuclear factor NF-kappa-B inhibitor kinase beta) (NFKBIKB)
[Ikbkb Ikkb] Inhibitor of nuclear factor kappa-B kinase subunit beta (I-kappa-B-kinase beta) (IKK-B) (IKK-beta) (IkBKB) (EC 2.7.11.10) (I-kappa-B kinase 2) (IKK2) (Nuclear factor NF-kappa-B inhibitor kinase beta) (NFKBIKB)
[IKBKB] Inhibitor of nuclear factor kappa-B kinase subunit beta (I-kappa-B-kinase beta) (IKK-B) (IKK-beta) (IkBKB) (EC 2.7.11.10) (I-kappa-B kinase 2) (IKK2) (Nuclear factor NF-kappa-B inhibitor kinase beta) (NFKBIKB)
[CHUK IKKA TCF16] Inhibitor of nuclear factor kappa-B kinase subunit alpha (I-kappa-B kinase alpha) (IKK-A) (IKK-alpha) (IkBKA) (IkappaB kinase) (EC 2.7.11.10) (Conserved helix-loop-helix ubiquitous kinase) (I-kappa-B kinase 1) (IKK1) (Nuclear factor NF-kappa-B inhibitor kinase alpha) (NFKBIKA) (Transcription factor 16) (TCF-16)
[Chuk Ikka] Inhibitor of nuclear factor kappa-B kinase subunit alpha (I-kappa-B kinase alpha) (IKK-A) (IKK-alpha) (IkBKA) (IkappaB kinase) (EC 2.7.11.10) (Conserved helix-loop-helix ubiquitous kinase) (I-kappa-B kinase 1) (IKK1) (Nuclear factor NF-kappa-B inhibitor kinase alpha) (NFKBIKA)
[CHUK IKKA] Inhibitor of nuclear factor kappa-B kinase subunit alpha (I-kappa-B kinase alpha) (IKK-A) (IKK-alpha) (IkBKA) (EC 2.7.11.10) (I-kappa-B kinase 1) (IKK1) (Nuclear factor NF-kappa-B inhibitor kinase alpha) (NFKBIKA)
[chuk ikk1 zgc:56539] Inhibitor of nuclear factor kappa-B kinase subunit alpha (I kappa-B kinase alpha) (IKK-A) (IKK-alpha) (IkBKA) (IkappaB kinase) (EC 2.7.11.10) (Conserved helix-loop-helix ubiquitous kinase) (I-kappa-B kinase 1) (IKK1) (Nuclear factor NF-kappa-B inhibitor kinase alpha) (NFKBIKA)
[IKBKE IKKE IKKI KIAA0151] Inhibitor of nuclear factor kappa-B kinase subunit epsilon (I-kappa-B kinase epsilon) (IKK-E) (IKK-epsilon) (IkBKE) (EC 2.7.11.10) (Inducible I kappa-B kinase) (IKK-i)
[Ikbke Ikke Ikki] Inhibitor of nuclear factor kappa-B kinase subunit epsilon (I-kappa-B kinase epsilon) (IKK-E) (IKK-epsilon) (IkBKE) (EC 2.7.11.10) (Inducible I kappa-B kinase) (IKK-i)
[IKBKG FIP3 NEMO] NF-kappa-B essential modulator (NEMO) (FIP-3) (IkB kinase-associated protein 1) (IKKAP1) (Inhibitor of nuclear factor kappa-B kinase subunit gamma) (I-kappa-B kinase subunit gamma) (IKK-gamma) (IKKG) (IkB kinase subunit gamma) (NF-kappa-B essential modifier)
[Ikbkg Nemo] NF-kappa-B essential modulator (NEMO) (IkB kinase-associated protein 1) (IKKAP1) (mFIP-3) (Inhibitor of nuclear factor kappa-B kinase subunit gamma) (I-kappa-B kinase subunit gamma) (IKK-gamma) (IKKG) (IkB kinase subunit gamma) (NF-kappa-B essential modifier)
[IKBKG] NF-kappa-B essential modulator (NEMO) (FIP-3) (IkB kinase-associated protein 1) (IKKAP1) (Inhibitor of nuclear factor kappa-B kinase subunit gamma) (I-kappa-B kinase subunit gamma) (IKK-gamma) (IKKG) (IkB kinase subunit gamma) (NF-kappa-B essential modifier)
[IKBKG NEMO] NF-kappa-B essential modulator (NEMO) (IkB kinase-associated protein 1) (IKKAP1) (Inhibitor of nuclear factor kappa-B kinase subunit gamma) (I-kappa-B kinase subunit gamma) (IKK-gamma) (IKKG) (IkB kinase subunit gamma) (NF-kappa-B essential modifier)
[Ikbkg Nemo] NF-kappa-B essential modulator (NEMO) (IkB kinase-associated protein 1) (IKKAP1) (Inhibitor of nuclear factor kappa-B kinase subunit gamma) (I-kappa-B kinase subunit gamma) (IKK-gamma) (IKKG) (IkB kinase subunit gamma) (NF-kappa-B essential modifier)
[chuk ikka TEgg047h13.1] Inhibitor of nuclear factor kappa-B kinase subunit alpha (I kappa-B kinase alpha) (IKK-A) (IKK-alpha) (IkBKA) (IkappaB kinase) (EC 2.7.11.10) (Conserved helix-loop-helix ubiquitous kinase) (Nuclear factor NF-kappa-B inhibitor kinase alpha) (NFKBIKA)
[TBK1 NAK] Serine/threonine-protein kinase TBK1 (EC 2.7.11.1) (NF-kappa-B-activating kinase) (T2K) (TANK-binding kinase 1)
[IKBIP IKIP] Inhibitor of nuclear factor kappa-B kinase-interacting protein (I kappa-B kinase-interacting protein) (IKBKB-interacting protein) (IKK-interacting protein)
[TRAF3IP2 C6orf2 C6orf4 C6orf5 C6orf6] Adapter protein CIKS (Connection to IKK and SAPK/JNK) (Nuclear factor NF-kappa-B activator 1) (ACT1) (TRAF3-interacting protein 2)
[RELA NFKB3] Transcription factor p65 (Nuclear factor NF-kappa-B p65 subunit) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3)
[NFKB2 LYT10] Nuclear factor NF-kappa-B p100 subunit (DNA-binding factor KBF2) (H2TF1) (Lymphocyte translocation chromosome 10 protein) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2) (Oncogene Lyt-10) (Lyt10) [Cleaved into: Nuclear factor NF-kappa-B p52 subunit]
[Rel CG11992] Nuclear factor NF-kappa-B p110 subunit (Rel-p110) (Relish protein) [Cleaved into: Nuclear factor NF-kappa-B p68 subunit (Rel-p68); Nuclear factor NF-kappa-B p49 subunit (Rel-p49)]
[NFKB1] Nuclear factor NF-kappa-B p105 subunit (DNA-binding factor KBF1) (EBP-1) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) [Cleaved into: Nuclear factor NF-kappa-B p50 subunit]
[Nfkb1] Nuclear factor NF-kappa-B p105 subunit (DNA-binding factor KBF1) (EBP-1) (NF-kappa-B1 p84/NF-kappa-B1 p98) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) [Cleaved into: Nuclear factor NF-kappa-B p50 subunit]
[TONSL IKBR NFKBIL2] Tonsoku-like protein (Inhibitor of kappa B-related protein) (I-kappa-B-related protein) (IkappaBR) (NF-kappa-B inhibitor-like protein 2) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 2)
[Nfkb2] Nuclear factor NF-kappa-B p100 subunit (DNA-binding factor KBF2) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2) [Cleaved into: Nuclear factor NF-kappa-B p52 subunit]
[Nfkb1] Nuclear factor NF-kappa-B p105 subunit (DNA-binding factor KBF1) (EBP-1) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) [Cleaved into: Nuclear factor NF-kappa-B p50 subunit] (Fragment)
[Rela Nfkb3] Transcription factor p65 (Nuclear factor NF-kappa-B p65 subunit) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3)
[NFKBIA IKBA MAD3 NFKBI] NF-kappa-B inhibitor alpha (I-kappa-B-alpha) (IkB-alpha) (IkappaBalpha) (Major histocompatibility complex enhancer-binding protein MAD3)
[NFKB1] Nuclear factor NF-kappa-B p105 subunit (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) [Cleaved into: Nuclear factor NF-kappa-B p50 subunit]

Bibliography :