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IKKB_MOUSE
ID   IKKB_MOUSE              Reviewed;         757 AA.
AC   O88351; Q9R1J6;
DT   01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   03-AUG-2022, entry version 195.
DE   RecName: Full=Inhibitor of nuclear factor kappa-B kinase subunit beta;
DE            Short=I-kappa-B-kinase beta;
DE            Short=IKK-B;
DE            Short=IKK-beta;
DE            Short=IkBKB;
DE            EC=2.7.11.10;
DE   AltName: Full=I-kappa-B kinase 2;
DE            Short=IKK2;
DE   AltName: Full=Nuclear factor NF-kappa-B inhibitor kinase beta;
DE            Short=NFKBIKB;
DE   AltName: Full=Serine/threonine protein kinase IKBKB;
DE            EC=2.7.11.1 {ECO:0000269|PubMed:25326420, ECO:0000269|PubMed:30988283};
GN   Name=Ikbkb; Synonyms=Ikkb;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PHOSPHORYLATION BY MEKK1.
RC   STRAIN=C57BL/6J; TISSUE=Spleen;
RX   PubMed=9520401; DOI=10.1073/pnas.95.7.3537;
RA   Nakano H., Shindo M., Sakon S., Nishinaka S., Mihara M., Yagita H.,
RA   Okumura K.;
RT   "Differential regulation of IkappaB kinase alpha and beta by two upstream
RT   kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK
RT   kinase kinase-1.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:3537-3542(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Hu M.C.-T., Wang Y.-P., Mikhail A., Qiu W.R.;
RT   "Murine IkB kinase-B, a developmentally regulated protein kinase that
RT   constitutively phosphorylates serine residues of IkB.";
RL   Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=10229185; DOI=10.1016/s1074-7613(00)80042-4;
RA   Tanaka M., Fuentes M.E., Yamaguchi K., Durnin M.H., Dalrymple S.A.,
RA   Hardy K.L., Goeddel D.V.;
RT   "Embryonic lethality, liver degeneration, and impaired NF-kappa B
RT   activation in IKK-beta-deficient mice.";
RL   Immunity 10:421-429(1999).
RN   [4]
RP   DEVELOPMENTAL STAGE.
RX   PubMed=10523828; DOI=10.1038/sj.onc.1202740;
RA   Hu M.C.-T., Wang Y.-P., Qiu W.R., Mikhail A., Meyer C.F., Tan T.-H.;
RT   "Hematopoietic progenitor kinase-1 (HPK1) stress response signaling pathway
RT   activates IkappaB kinases (IKK-alpha/beta) and IKK-beta is a
RT   developmentally regulated protein kinase.";
RL   Oncogene 18:5514-5524(1999).
RN   [5]
RP   IKK PHOSPHORYLATION.
RX   PubMed=9819420; DOI=10.1128/mcb.18.12.7336;
RA   Nemoto S., DiDonato J.A., Lin A.;
RT   "Coordinate regulation of IkappaB kinases by mitogen-activated protein
RT   kinase kinase kinase 1 and NF-kappaB-inducing kinase.";
RL   Mol. Cell. Biol. 18:7336-7343(1998).
RN   [6]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=10195897; DOI=10.1126/science.284.5412.321;
RA   Li Q., Van Antwerp D., Mercurio F., Lee K.F., Verma I.M.;
RT   "Severe liver degeneration in mice lacking the IkappaB kinase 2 gene.";
RL   Science 284:321-325(1999).
RN   [7]
RP   REVIEW.
RX   PubMed=10712233; DOI=10.1152/ajpcell.2000.278.3.c451;
RA   Jobin C., Sartor R.B.;
RT   "The I kappa B/NF-kappa B system: a key determinant of mucosal inflammation
RT   and protection.";
RL   Am. J. Physiol. 278:C451-C462(2000).
RN   [8]
RP   INTERACTION WITH EIF2AK2.
RX   PubMed=10848580; DOI=10.1128/mcb.20.13.4532-4542.2000;
RA   Bonnet M.C., Weil R., Dam E., Hovanessian A.G., Meurs E.F.;
RT   "PKR stimulates NF-kappaB irrespective of its kinase function by
RT   interacting with the IkappaB kinase complex.";
RL   Mol. Cell. Biol. 20:4532-4542(2000).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, Kidney, Lung, Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [10]
RP   INTERACTION WITH TERF2IP.
RX   PubMed=20622870; DOI=10.1038/ncb2080;
RA   Teo H., Ghosh S., Luesch H., Ghosh A., Wong E.T., Malik N., Orth A.,
RA   de Jesus P., Perry A.S., Oliver J.D., Tran N.L., Speiser L.J., Wong M.,
RA   Saez E., Schultz P., Chanda S.K., Verma I.M., Tergaonkar V.;
RT   "Telomere-independent Rap1 is an IKK adaptor and regulates NF-kappaB-
RT   dependent gene expression.";
RL   Nat. Cell Biol. 12:758-767(2010).
RN   [11]
RP   INTERACTION WITH ZC3H12A.
RX   PubMed=22037600; DOI=10.1038/ni.2137;
RA   Iwasaki H., Takeuchi O., Teraguchi S., Matsushita K., Uehata T.,
RA   Kuniyoshi K., Satoh T., Saitoh T., Matsushita M., Standley D.M., Akira S.;
RT   "The IkappaB kinase complex regulates the stability of cytokine-encoding
RT   mRNA induced by TLR-IL-1R by controlling degradation of regnase-1.";
RL   Nat. Immunol. 12:1167-1175(2011).
RN   [12]
RP   INTERACTION WITH AKAP13, IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=23090968; DOI=10.1128/mcb.00887-12;
RA   del Vescovo C.D., Cotecchia S., Diviani D.;
RT   "A-kinase-anchoring protein-Lbc anchors IkappaB kinase beta to support
RT   interleukin-6-mediated cardiomyocyte hypertrophy.";
RL   Mol. Cell. Biol. 33:14-27(2013).
RN   [13]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=25326420; DOI=10.1073/pnas.1418516111;
RA   Ren J., Chen X., Chen Z.J.;
RT   "IKKbeta is an IRF5 kinase that instigates inflammation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 111:17438-17443(2014).
RN   [14]
RP   FUNCTION.
RX   PubMed=30988283; DOI=10.1038/s41467-019-09690-0;
RA   Dondelinger Y., Delanghe T., Priem D., Wynosky-Dolfi M.A., Sorobetea D.,
RA   Rojas-Rivera D., Giansanti P., Roelandt R., Gropengiesser J.,
RA   Ruckdeschel K., Savvides S.N., Heck A.J.R., Vandenabeele P., Brodsky I.E.,
RA   Bertrand M.J.M.;
RT   "Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in
RT   models of infection and inflammation.";
RL   Nat. Commun. 10:1729-1729(2019).
CC   -!- FUNCTION: Serine kinase that plays an essential role in the NF-kappa-B
CC       signaling pathway which is activated by multiple stimuli such as
CC       inflammatory cytokines, bacterial or viral products, DNA damages or
CC       other cellular stresses. Acts as part of the canonical IKK complex in
CC       the conventional pathway of NF-kappa-B activation and phosphorylates
CC       inhibitors of NF-kappa-B on 2 critical serine residues. These
CC       modifications allow polyubiquitination of the inhibitors and subsequent
CC       degradation by the proteasome. In turn, free NF-kappa-B is translocated
CC       into the nucleus and activates the transcription of hundreds of genes
CC       involved in immune response, growth control, or protection against
CC       apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates
CC       several other components of the signaling pathway including NEMO/IKBKG,
CC       NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1
CC       and IKBKE. IKK-related kinase phosphorylations may prevent the
CC       overproduction of inflammatory mediators since they exert a negative
CC       regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-
CC       dependent inactivation of this pro-apoptotic transcription factor. Also
CC       phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within
CC       the nucleus, acts as an adapter protein for NFKBIA degradation in UV-
CC       induced NF-kappa-B activation (By similarity). Phosphorylates RIPK1 at
CC       'Ser-25' which represses its kinase activity and consequently prevents
CC       TNF-mediated RIPK1-dependent cell death (PubMed:30988283).
CC       Phosphorylates the C-terminus of IRF5, stimulating IRF5
CC       homodimerization and translocation into the nucleus (PubMed:25326420).
CC       {ECO:0000250|UniProtKB:O14920, ECO:0000269|PubMed:25326420,
CC       ECO:0000269|PubMed:30988283}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[I-kappa-B protein] = ADP + H(+) + O-phospho-L-
CC         seryl-[I-kappa-B protein]; Xref=Rhea:RHEA:19073, Rhea:RHEA-
CC         COMP:13698, Rhea:RHEA-COMP:13699, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421,
CC         ChEBI:CHEBI:456216; EC=2.7.11.10;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC         Evidence={ECO:0000269|PubMed:25326420, ECO:0000269|PubMed:30988283};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.1; Evidence={ECO:0000305};
CC   -!- SUBUNIT: Component of the I-kappa-B-kinase (IKK) core complex
CC       consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK-
CC       beta/IKBKB dimers are associated with four gamma/IKBKG subunits. The
CC       IKK core complex seems to associate with regulatory or adapter proteins
CC       to form a IKK-signalosome holo-complex (By similarity). The IKK complex
CC       associates with TERF2IP/RAP1, leading to promote IKK-mediated
CC       phosphorylation of RELA/p65 (PubMed:20622870). Part of a complex
CC       composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Part of a
CC       70-90 kDa complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA,
CC       RELA, ELP1 and MAP3K14. Found in a membrane raft complex, at least
CC       composed of BCL10, CARD11, DPP4 and IKBKB. Interacts with SQSTM1
CC       through PRKCZ or PRKCI. Forms an NGF-induced complex with IKBKB, PRKCI
CC       and TRAF6. May interact with MAVS/IPS1. Interacts with NALP2. Interacts
CC       with TICAM1. Interacts with FAF1; the interaction disrupts the IKK
CC       complex formation. Interacts with ATM. Part of a ternary complex
CC       consisting of TANK, IKBKB and IKBKG. Interacts with NIBP; the
CC       interaction is direct. Interacts with ARRB1 and ARRB2. Interacts with
CC       TRIM21. Interacts with NLRC5; prevents IKBKB phosphorylation and kinase
CC       activity. Interacts with PDPK1 (By similarity). Interacts with
CC       EIF2AK2/PKR (PubMed:10848580). The phosphorylated form interacts with
CC       PPM1A and PPM1B. Interacts with ZNF268 isoform 2; the interaction is
CC       further increased in a TNF-alpha-dependent manner. Interacts with
CC       IKBKE. Interacts with NAA10, leading to NAA10 degradation. Interacts
CC       with FOXO3 (By similarity). Interacts with ZC3H12A (PubMed:22037600).
CC       Interacts with AKAP13 (PubMed:23090968). Interacts with LRRC14;
CC       disrupts IKBKB-IKBKG interaction preventing I-kappa-B-kinase (IKK) core
CC       complex formation and leading to a decrease of IKBKB phosphorylation
CC       and NF-kappaB activation (By similarity). Interacts with SASH1 (By
CC       similarity). Interacts with ARFIP2 (By similarity). Interacts with
CC       FKBP5 (By similarity). {ECO:0000250|UniProtKB:O14920,
CC       ECO:0000269|PubMed:10848580, ECO:0000269|PubMed:20622870,
CC       ECO:0000269|PubMed:22037600}.
CC   -!- INTERACTION:
CC       O88351; Q60680: Chuk; NbExp=4; IntAct=EBI-447960, EBI-646245;
CC       O88351; O88522: Ikbkg; NbExp=8; IntAct=EBI-447960, EBI-998011;
CC       O88351; P68040: Rack1; NbExp=4; IntAct=EBI-447960, EBI-296749;
CC       O88351; Q14145: KEAP1; Xeno; NbExp=2; IntAct=EBI-447960, EBI-751001;
CC       O88351; P01375: TNF; Xeno; NbExp=3; IntAct=EBI-447960, EBI-359977;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O14920}. Nucleus
CC       {ECO:0000250|UniProtKB:O14920}. Membrane raft
CC       {ECO:0000250|UniProtKB:O14920}. Note=Colocalized with DPP4 in membrane
CC       rafts. {ECO:0000250|UniProtKB:O14920}.
CC   -!- TISSUE SPECIFICITY: Detected in heart (at protein level)
CC       (PubMed:23090968). Expressed in liver, kidney and spleen.
CC       {ECO:0000269|PubMed:23090968}.
CC   -!- DEVELOPMENTAL STAGE: While it is expressed ubiquitously throughout the
CC       mouse embryo, at 9.5 dpc its expression begins to be localized to the
CC       brain, neural ganglia, neural tube, and in liver at 12.5 dpc. At 15.5
CC       dpc, the expression is further restricted to specific tissues of the
CC       embryo. {ECO:0000269|PubMed:10523828}.
CC   -!- DOMAIN: The kinase domain is located in the N-terminal region. The
CC       leucine zipper is important to allow homo- and hetero-dimerization. At
CC       the C-terminal region is located the region responsible for the
CC       interaction with NEMO/IKBKG (By similarity). {ECO:0000250}.
CC   -!- PTM: Upon cytokine stimulation, phosphorylated on Ser-177 and Ser-181
CC       by MEKK1 and/or MAP3K14/NIK as well as TBK1 and PRKCZ; which enhances
CC       activity. Once activated, autophosphorylates on the C-terminal serine
CC       cluster; which decreases activity and prevents prolonged activation of
CC       the inflammatory response. Phosphorylated by the IKK-related kinases
CC       TBK1 and IKBKE, which is associated with reduced CHUK/IKKA and IKBKB
CC       activity and NF-kappa-B-dependent gene transcription. Dephosphorylated
CC       at Ser-177 and Ser-181 by PPM1A and PPM1B.
CC       {ECO:0000250|UniProtKB:O14920}.
CC   -!- PTM: Ubiquitinated. Monoubiquitination involves TRIM21 that leads to
CC       inhibition of Tax-induced NF-kappa-B signaling. 'Ser-163' may not serve
CC       as a monoubiquitination site. Ubiquitination on 'Ser-163' may modulate
CC       phosphorylation on C-terminal serine residues.
CC       {ECO:0000250|UniProtKB:O14920}.
CC   -!- PTM: Hydroxylated by PHD1/EGLN2, loss of hydroxylation under hypoxic
CC       conditions results in activation of NF-kappa-B.
CC       {ECO:0000250|UniProtKB:O14920}.
CC   -!- DISRUPTION PHENOTYPE: Mice present extensive liver damage from
CC       apoptosis and die as embryos. They show a marked reduction in TNF-alpha
CC       and IL1-alpha-induced NF-kappa-B activity.
CC       {ECO:0000269|PubMed:10195897, ECO:0000269|PubMed:10229185}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC       kinase family. I-kappa-B kinase subfamily. {ECO:0000255|PROSITE-
CC       ProRule:PRU00159}.
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DR   EMBL; AF026524; AAC23557.1; -; mRNA.
DR   EMBL; AF088910; AAD52095.1; -; mRNA.
DR   CCDS; CCDS52522.1; -.
DR   RefSeq; NP_034676.1; NM_010546.2.
DR   AlphaFoldDB; O88351; -.
DR   SMR; O88351; -.
DR   BioGRID; 200601; 31.
DR   ComplexPortal; CPX-3270; IkappaB kinase complex.
DR   CORUM; O88351; -.
DR   DIP; DIP-29813N; -.
DR   IntAct; O88351; 27.
DR   MINT; O88351; -.
DR   STRING; 10090.ENSMUSP00000033939; -.
DR   BindingDB; O88351; -.
DR   ChEMBL; CHEMBL6012; -.
DR   iPTMnet; O88351; -.
DR   PhosphoSitePlus; O88351; -.
DR   EPD; O88351; -.
DR   jPOST; O88351; -.
DR   MaxQB; O88351; -.
DR   PaxDb; O88351; -.
DR   PeptideAtlas; O88351; -.
DR   PRIDE; O88351; -.
DR   ProteomicsDB; 266962; -.
DR   DNASU; 16150; -.
DR   GeneID; 16150; -.
DR   KEGG; mmu:16150; -.
DR   CTD; 3551; -.
DR   MGI; MGI:1338071; Ikbkb.
DR   eggNOG; KOG4250; Eukaryota.
DR   InParanoid; O88351; -.
DR   PhylomeDB; O88351; -.
DR   BRENDA; 2.7.11.10; 3474.
DR   Reactome; R-MMU-1169091; Activation of NF-kappaB in B cells.
DR   Reactome; R-MMU-1810476; RIP-mediated NFkB activation via ZBP1.
DR   Reactome; R-MMU-202424; Downstream TCR signaling.
DR   Reactome; R-MMU-209543; p75NTR recruits signalling complexes.
DR   Reactome; R-MMU-209560; NF-kB is activated and signals survival.
DR   Reactome; R-MMU-2871837; FCERI mediated NF-kB activation.
DR   Reactome; R-MMU-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR   Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR   Reactome; R-MMU-5357956; TNFR1-induced NFkappaB signaling pathway.
DR   Reactome; R-MMU-5607764; CLEC7A (Dectin-1) signaling.
DR   Reactome; R-MMU-5684264; MAP3K8 (TPL2)-dependent MAPK1/3 activation.
DR   Reactome; R-MMU-9020702; Interleukin-1 signaling.
DR   Reactome; R-MMU-933542; TRAF6 mediated NF-kB activation.
DR   Reactome; R-MMU-937039; IRAK1 recruits IKK complex.
DR   Reactome; R-MMU-937041; IKK complex recruitment mediated by RIP1.
DR   Reactome; R-MMU-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
DR   BioGRID-ORCS; 16150; 18 hits in 78 CRISPR screens.
DR   ChiTaRS; Ikbkb; mouse.
DR   PRO; PR:O88351; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; O88351; protein.
DR   GO; GO:0035631; C:CD40 receptor complex; IDA:BHF-UCL.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:BHF-UCL.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0008385; C:IkappaB kinase complex; ISO:MGI.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR   GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; ISO:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0008384; F:IkappaB kinase activity; IDA:MGI.
DR   GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR   GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR   GO; GO:0019903; F:protein phosphatase binding; IPI:ARUK-UCL.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR   GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
DR   GO; GO:1990459; F:transferrin receptor binding; ISO:MGI.
DR   GO; GO:0001782; P:B cell homeostasis; IMP:MGI.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
DR   GO; GO:0030866; P:cortical actin cytoskeleton organization; ISO:MGI.
DR   GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR   GO; GO:0007252; P:I-kappaB phosphorylation; TAS:MGI.
DR   GO; GO:0070498; P:interleukin-1-mediated signaling pathway; ISO:MGI.
DR   GO; GO:1903347; P:negative regulation of bicellular tight junction assembly; ISO:MGI.
DR   GO; GO:0035509; P:negative regulation of myosin-light-chain-phosphatase activity; ISO:MGI.
DR   GO; GO:0031175; P:neuron projection development; ISO:MGI.
DR   GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR   GO; GO:2001259; P:positive regulation of cation channel activity; IGI:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR   GO; GO:1901216; P:positive regulation of neuron death; ISO:MGI.
DR   GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR   GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR   GO; GO:0010765; P:positive regulation of sodium ion transport; IGI:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
DR   GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR   GO; GO:1903140; P:regulation of establishment of endothelial barrier; ISO:MGI.
DR   GO; GO:0042325; P:regulation of phosphorylation; ISO:MGI.
DR   GO; GO:0061847; P:response to cholecystokinin; ISO:MGI.
DR   GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB.
DR   Gene3D; 1.20.1270.250; -; 1.
DR   InterPro; IPR041185; IKBKB_SDD.
DR   InterPro; IPR046375; IKBKB_SDD_sf.
DR   InterPro; IPR022007; IKKbetaNEMObind.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   Pfam; PF18397; IKBKB_SDD; 1.
DR   Pfam; PF12179; IKKbetaNEMObind; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM01239; IKKbetaNEMObind; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; SSF56112; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Cytoplasm; Hydroxylation; Isopeptide bond; Kinase; Membrane;
KW   Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW   S-nitrosylation; Serine/threonine-protein kinase; Transferase;
KW   Ubl conjugation.
FT   CHAIN           1..757
FT                   /note="Inhibitor of nuclear factor kappa-B kinase subunit
FT                   beta"
FT                   /id="PRO_0000086014"
FT   DOMAIN          15..300
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          458..479
FT                   /note="Leucine-zipper"
FT   REGION          683..703
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          737..742
FT                   /note="NEMO-binding"
FT   COMPBIAS        683..698
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        145
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         21..29
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         44
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         177
FT                   /note="Phosphoserine; by TBK1 and PKC/PRKCZ"
FT                   /evidence="ECO:0000250|UniProtKB:O14920"
FT   MOD_RES         179
FT                   /note="S-nitrosocysteine"
FT                   /evidence="ECO:0000250|UniProtKB:O14920"
FT   MOD_RES         181
FT                   /note="Phosphoserine; by TBK1, PKC/PRKCZ and PDPK1"
FT                   /evidence="ECO:0000250|UniProtKB:O14920"
FT   MOD_RES         191
FT                   /note="Hydroxyproline"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         670
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:O14920"
FT   MOD_RES         672
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         675
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:O14920"
FT   MOD_RES         682
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:O14920"
FT   MOD_RES         689
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:O14920"
FT   MOD_RES         692
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:O14920"
FT   MOD_RES         697
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:O14920"
FT   MOD_RES         705
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:O14920"
FT   MOD_RES         733
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:O14920"
FT   MOD_RES         740
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:O14920"
FT   CROSSLNK        163
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:O14920"
FT   CONFLICT        56
FT                   /note="N -> D (in Ref. 2; AAD52095)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        343
FT                   /note="N -> D (in Ref. 2; AAD52095)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        356
FT                   /note="K -> E (in Ref. 2; AAD52095)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        390
FT                   /note="L -> F (in Ref. 2; AAD52095)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        406
FT                   /note="P -> Q (in Ref. 2; AAD52095)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        573
FT                   /note="K -> R (in Ref. 2; AAD52095)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        736..757
FT                   /note="TLDWSWLQMEDEERCSLEQACD -> VTA (in Ref. 2)"
FT                   /evidence="ECO:0000305"
SQ   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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