Full text data of NFKBIB
NFKBIB
(IKBB, TRIP9)
[Confidence: low (only semi-automatic identification from reviews)]
NF-kappa-B inhibitor beta; NF-kappa-BIB (I-kappa-B-beta; IkB-B; IkB-beta; IkappaBbeta; Thyroid receptor-interacting protein 9; TR-interacting protein 9; TRIP-9)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
NF-kappa-B inhibitor beta; NF-kappa-BIB (I-kappa-B-beta; IkB-B; IkB-beta; IkappaBbeta; Thyroid receptor-interacting protein 9; TR-interacting protein 9; TRIP-9)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q15653
ID IKBB_HUMAN Reviewed; 356 AA.
AC Q15653; A8K3F4; Q96BJ7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 04-JAN-2005, sequence version 2.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=NF-kappa-B inhibitor beta;
DE Short=NF-kappa-BIB;
DE AltName: Full=I-kappa-B-beta;
DE Short=IkB-B;
DE Short=IkB-beta;
DE Short=IkappaBbeta;
DE AltName: Full=Thyroid receptor-interacting protein 9;
DE Short=TR-interacting protein 9;
DE Short=TRIP-9;
GN Name=NFKBIB; Synonyms=IKBB, TRIP9;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM
RP 2).
RC TISSUE=Cervix carcinoma;
RX PubMed=7776974; DOI=10.1210/me.9.2.243;
RA Lee J.W., Choi H.-S., Gyuris J., Brent R., Moore D.D.;
RT "Two classes of proteins dependent on either the presence or absence
RT of thyroid hormone for interaction with the thyroid hormone
RT receptor.";
RL Mol. Endocrinol. 9:243-254(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT TRP-339.
RG SeattleSNPs variation discovery resource;
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 100-338 (ISOFORM 2).
RC TISSUE=Pancreas, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP CHARACTERIZATION.
RX PubMed=8816457;
RA Suyang H., Phillips R.J., Douglas I., Ghosh S.;
RT "Role of unphosphorylated, newly synthesized IkappaB beta in
RT persistent activation of NF-kappaB.";
RL Mol. Cell. Biol. 16:5444-5449(1996).
RN [8]
RP INTERACTION WITH NKIRAS1 AND NKIRAS2.
RX PubMed=10657303; DOI=10.1126/science.287.5454.869;
RA Fenwick C., Na S.-Y., Voll R.E., Zhong H., Im S.-Y., Lee J.W.,
RA Ghosh S.;
RT "A subclass of Ras proteins that regulate the degradation of
RT IkappaB.";
RL Science 287:869-873(2000).
RN [9]
RP MUTAGENESIS OF SER-19 AND SER-23, AND PHOSPHORYLATION AT SER-19 AND
RP SER-23.
RX PubMed=8657102;
RA DiDonato J.A., Mercurio F., Rosette C., Wu-Li J., Suyang H., Ghosh S.,
RA Karin M.;
RT "Mapping of the inducible IkappaB phosphorylation sites that signal
RT its ubiquitination and degradation.";
RL Mol. Cell. Biol. 16:1295-1304(1996).
RN [10]
RP PHOSPHORYLATION AT SER-313 AND SER-315.
RX PubMed=8887627;
RA Chu Z.L., McKinsey T.A., Liu L., Qi X., Ballard D.W.;
RT "Basal phosphorylation of the PEST domain in the I(kappa)B(beta)
RT regulates its functional interaction with the c-rel proto-oncogene
RT product.";
RL Mol. Cell. Biol. 16:5974-5984(1996).
RN [11]
RP INTERACTION WITH NKIRAS1.
RX PubMed=12672800; DOI=10.1074/jbc.M301021200;
RA Chen Y., Wu J., Ghosh G.;
RT "KappaB-Ras binds to the unique insert within the ankyrin repeat
RT domain of IkappaBbeta and regulates cytoplasmic retention of
RT IkappaBbeta.NF-kappaB complexes.";
RL J. Biol. Chem. 278:23101-23106(2003).
RN [12]
RP INTERACTION WITH NKIRAS1.
RX PubMed=15024091; DOI=10.1128/MCB.24.7.3048-3056.2004;
RA Chen Y., Vallee S., Wu J., Vu D., Sondek J., Ghosh G.;
RT "Inhibition of NF-kappaB activity by IkappaBbeta in association with
RT kappaB-Ras.";
RL Mol. Cell. Biol. 24:3048-3056(2004).
RN [13]
RP INTERACTION WITH COMMD1.
RX PubMed=16573520; DOI=10.1042/BJ20051664;
RA de Bie P., van de Sluis B., Burstein E., Duran K.J., Berger R.,
RA Duckett C.S., Wijmenga C., Klomp L.W.;
RT "Characterization of COMMD protein-protein interactions in NF-kappaB
RT signalling.";
RL Biochem. J. 398:63-71(2006).
CC -!- FUNCTION: Inhibits NF-kappa-B by complexing with and trapping it
CC in the cytoplasm. However, the unphosphorylated form resynthesized
CC after cell stimulation is able to bind NF-kappa-B allowing its
CC transport to the nucleus and protecting it to further NFKBIA-
CC dependent inactivation. Association with inhibitor kappa B-
CC interacting NKIRAS1 and NKIRAS2 prevent its phosphorylation
CC rendering it more resistant to degradation, explaining its slower
CC degradation.
CC -!- SUBUNIT: Interacts with THRB (via ligand-binding domain).
CC Interacts with RELA and REL. Interacts with COMMD1 and inhibitor
CC kappa B-interacting Ras-like NKIRAS1 and NKIRAS2.
CC -!- INTERACTION:
CC Q04206:RELA; NbExp=6; IntAct=EBI-352889, EBI-73886;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By
CC similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15653-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15653-2; Sequence=VSP_012409, VSP_012410;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined.
CC -!- PTM: Phosphorylated by RPS6KA1; followed by degradation.
CC Interaction with NKIRAS1 and NKIRAS2 probably prevents
CC phosphorylation.
CC -!- SIMILARITY: Belongs to the NF-kappa-B inhibitor family.
CC -!- SIMILARITY: Contains 6 ANK repeats.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/nfkbib/";
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DR EMBL; L40407; AAC41742.1; -; Genomic_DNA.
DR EMBL; BT006743; AAP35389.1; -; mRNA.
DR EMBL; AY736284; AAU10088.1; -; Genomic_DNA.
DR EMBL; AK290569; BAF83258.1; -; mRNA.
DR EMBL; CH471126; EAW56843.1; -; Genomic_DNA.
DR EMBL; BC007197; AAH07197.1; -; mRNA.
DR EMBL; BC015528; AAH15528.1; -; mRNA.
DR RefSeq; NP_001230045.1; NM_001243116.1.
DR RefSeq; NP_002494.2; NM_002503.4.
DR UniGene; Hs.9731; -.
DR ProteinModelPortal; Q15653; -.
DR SMR; Q15653; 50-302.
DR DIP; DIP-27532N; -.
DR IntAct; Q15653; 5.
DR MINT; MINT-1131598; -.
DR STRING; 9606.ENSP00000312988; -.
DR BindingDB; Q15653; -.
DR PhosphoSite; Q15653; -.
DR DMDM; 57015399; -.
DR PaxDb; Q15653; -.
DR PRIDE; Q15653; -.
DR DNASU; 4793; -.
DR Ensembl; ENST00000313582; ENSP00000312988; ENSG00000104825.
DR Ensembl; ENST00000572515; ENSP00000459728; ENSG00000104825.
DR GeneID; 4793; -.
DR KEGG; hsa:4793; -.
DR UCSC; uc002ojw.3; human.
DR CTD; 4793; -.
DR GeneCards; GC19P039390; -.
DR HGNC; HGNC:7798; NFKBIB.
DR HPA; CAB010447; -.
DR MIM; 604495; gene.
DR neXtProt; NX_Q15653; -.
DR PharmGKB; PA31602; -.
DR eggNOG; NOG272177; -.
DR HOVERGEN; HBG019039; -.
DR KO; K02581; -.
DR OMA; DEWCDSG; -.
DR PhylomeDB; Q15653; -.
DR Reactome; REACT_6782; TRAF6 Mediated Induction of proinflammatory cytokines.
DR Reactome; REACT_6900; Immune System.
DR SABIO-RK; Q15653; -.
DR SignaLink; Q15653; -.
DR ChiTaRS; NFKBIB; human.
DR GeneWiki; NFKBIB; -.
DR GenomeRNAi; 4793; -.
DR NextBio; 18470; -.
DR PRO; PR:Q15653; -.
DR ArrayExpress; Q15653; -.
DR Bgee; Q15653; -.
DR CleanEx; HS_NFKBIB; -.
DR Genevestigator; Q15653; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004871; F:signal transducer activity; TAS:ProtInc.
DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:Reactome.
DR GO; GO:0032481; P:positive regulation of type I interferon production; TAS:Reactome.
DR GO; GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR GO; GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
DR GO; GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
DR GO; GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
DR GO; GO:0006351; P:transcription, DNA-dependent; TAS:ProtInc.
DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR Gene3D; 1.25.40.20; -; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR Pfam; PF00023; Ank; 3.
DR Pfam; PF12796; Ank_2; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 6.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Complete proteome; Cytoplasm;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat.
FT CHAIN 1 356 NF-kappa-B inhibitor beta.
FT /FTId=PRO_0000067004.
FT REPEAT 57 86 ANK 1.
FT REPEAT 93 122 ANK 2.
FT REPEAT 126 155 ANK 3.
FT REPEAT 206 235 ANK 4.
FT REPEAT 240 269 ANK 5.
FT REPEAT 273 302 ANK 6.
FT COMPBIAS 186 195 Asp/Glu-rich (acidic).
FT MOD_RES 19 19 Phosphoserine; by RPS6KA1.
FT MOD_RES 23 23 Phosphoserine; by RPS6KA1.
FT MOD_RES 313 313 Phosphoserine; by CK2.
FT MOD_RES 315 315 Phosphoserine; by CK2.
FT VAR_SEQ 324 338 DEYDDIVVHSSRSQT -> VSQEERQGSPAGGSG (in
FT isoform 2).
FT /FTId=VSP_012409.
FT VAR_SEQ 339 356 Missing (in isoform 2).
FT /FTId=VSP_012410.
FT VARIANT 339 339 R -> W (in dbSNP:rs17886215).
FT /FTId=VAR_020771.
FT MUTAGEN 19 19 S->A: No degradation; when associated
FT with A-23.
FT MUTAGEN 23 23 S->A: No degradation; when associated
FT with A-19.
FT CONFLICT 19 19 S -> T (in Ref. 1; AAC41742).
FT CONFLICT 319 319 S -> G (in Ref. 1; AAC41742).
SQ SEQUENCE 356 AA; 37771 MW; E84575971B6F81CC CRC64;
MAGVACLGKA ADADEWCDSG LGSLGPDAAA PGGPGLGAEL GPGLSWAPLV FGYVTEDGDT
ALHLAVIHQH EPFLDFLLGF SAGTEYMDLQ NDLGQTALHL AAILGETSTV EKLYAAGAGL
CVAERRGHTA LHLACRVGAH ACARALLQPR PRRPREAPDT YLAQGPDRTP DTNHTPVALY
PDSDLEKEEE ESEEDWKLQL EAENYEGHTP LHVAVIHKDV EMVRLLRDAG ADLDKPEPTC
GRSPLHLAVE AQAADVLELL LRAGANPAAR MYGGRTPLGS AMLRPNPILA RLLRAHGAPE
PEGEDEKSGP CSSSSDSDSG DEGDEYDDIV VHSSRSQTRL PPTPASKPLP DDPRPV
//
ID IKBB_HUMAN Reviewed; 356 AA.
AC Q15653; A8K3F4; Q96BJ7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 04-JAN-2005, sequence version 2.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=NF-kappa-B inhibitor beta;
DE Short=NF-kappa-BIB;
DE AltName: Full=I-kappa-B-beta;
DE Short=IkB-B;
DE Short=IkB-beta;
DE Short=IkappaBbeta;
DE AltName: Full=Thyroid receptor-interacting protein 9;
DE Short=TR-interacting protein 9;
DE Short=TRIP-9;
GN Name=NFKBIB; Synonyms=IKBB, TRIP9;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM
RP 2).
RC TISSUE=Cervix carcinoma;
RX PubMed=7776974; DOI=10.1210/me.9.2.243;
RA Lee J.W., Choi H.-S., Gyuris J., Brent R., Moore D.D.;
RT "Two classes of proteins dependent on either the presence or absence
RT of thyroid hormone for interaction with the thyroid hormone
RT receptor.";
RL Mol. Endocrinol. 9:243-254(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT TRP-339.
RG SeattleSNPs variation discovery resource;
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 100-338 (ISOFORM 2).
RC TISSUE=Pancreas, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP CHARACTERIZATION.
RX PubMed=8816457;
RA Suyang H., Phillips R.J., Douglas I., Ghosh S.;
RT "Role of unphosphorylated, newly synthesized IkappaB beta in
RT persistent activation of NF-kappaB.";
RL Mol. Cell. Biol. 16:5444-5449(1996).
RN [8]
RP INTERACTION WITH NKIRAS1 AND NKIRAS2.
RX PubMed=10657303; DOI=10.1126/science.287.5454.869;
RA Fenwick C., Na S.-Y., Voll R.E., Zhong H., Im S.-Y., Lee J.W.,
RA Ghosh S.;
RT "A subclass of Ras proteins that regulate the degradation of
RT IkappaB.";
RL Science 287:869-873(2000).
RN [9]
RP MUTAGENESIS OF SER-19 AND SER-23, AND PHOSPHORYLATION AT SER-19 AND
RP SER-23.
RX PubMed=8657102;
RA DiDonato J.A., Mercurio F., Rosette C., Wu-Li J., Suyang H., Ghosh S.,
RA Karin M.;
RT "Mapping of the inducible IkappaB phosphorylation sites that signal
RT its ubiquitination and degradation.";
RL Mol. Cell. Biol. 16:1295-1304(1996).
RN [10]
RP PHOSPHORYLATION AT SER-313 AND SER-315.
RX PubMed=8887627;
RA Chu Z.L., McKinsey T.A., Liu L., Qi X., Ballard D.W.;
RT "Basal phosphorylation of the PEST domain in the I(kappa)B(beta)
RT regulates its functional interaction with the c-rel proto-oncogene
RT product.";
RL Mol. Cell. Biol. 16:5974-5984(1996).
RN [11]
RP INTERACTION WITH NKIRAS1.
RX PubMed=12672800; DOI=10.1074/jbc.M301021200;
RA Chen Y., Wu J., Ghosh G.;
RT "KappaB-Ras binds to the unique insert within the ankyrin repeat
RT domain of IkappaBbeta and regulates cytoplasmic retention of
RT IkappaBbeta.NF-kappaB complexes.";
RL J. Biol. Chem. 278:23101-23106(2003).
RN [12]
RP INTERACTION WITH NKIRAS1.
RX PubMed=15024091; DOI=10.1128/MCB.24.7.3048-3056.2004;
RA Chen Y., Vallee S., Wu J., Vu D., Sondek J., Ghosh G.;
RT "Inhibition of NF-kappaB activity by IkappaBbeta in association with
RT kappaB-Ras.";
RL Mol. Cell. Biol. 24:3048-3056(2004).
RN [13]
RP INTERACTION WITH COMMD1.
RX PubMed=16573520; DOI=10.1042/BJ20051664;
RA de Bie P., van de Sluis B., Burstein E., Duran K.J., Berger R.,
RA Duckett C.S., Wijmenga C., Klomp L.W.;
RT "Characterization of COMMD protein-protein interactions in NF-kappaB
RT signalling.";
RL Biochem. J. 398:63-71(2006).
CC -!- FUNCTION: Inhibits NF-kappa-B by complexing with and trapping it
CC in the cytoplasm. However, the unphosphorylated form resynthesized
CC after cell stimulation is able to bind NF-kappa-B allowing its
CC transport to the nucleus and protecting it to further NFKBIA-
CC dependent inactivation. Association with inhibitor kappa B-
CC interacting NKIRAS1 and NKIRAS2 prevent its phosphorylation
CC rendering it more resistant to degradation, explaining its slower
CC degradation.
CC -!- SUBUNIT: Interacts with THRB (via ligand-binding domain).
CC Interacts with RELA and REL. Interacts with COMMD1 and inhibitor
CC kappa B-interacting Ras-like NKIRAS1 and NKIRAS2.
CC -!- INTERACTION:
CC Q04206:RELA; NbExp=6; IntAct=EBI-352889, EBI-73886;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By
CC similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15653-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15653-2; Sequence=VSP_012409, VSP_012410;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined.
CC -!- PTM: Phosphorylated by RPS6KA1; followed by degradation.
CC Interaction with NKIRAS1 and NKIRAS2 probably prevents
CC phosphorylation.
CC -!- SIMILARITY: Belongs to the NF-kappa-B inhibitor family.
CC -!- SIMILARITY: Contains 6 ANK repeats.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/nfkbib/";
CC -----------------------------------------------------------------------
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DR EMBL; L40407; AAC41742.1; -; Genomic_DNA.
DR EMBL; BT006743; AAP35389.1; -; mRNA.
DR EMBL; AY736284; AAU10088.1; -; Genomic_DNA.
DR EMBL; AK290569; BAF83258.1; -; mRNA.
DR EMBL; CH471126; EAW56843.1; -; Genomic_DNA.
DR EMBL; BC007197; AAH07197.1; -; mRNA.
DR EMBL; BC015528; AAH15528.1; -; mRNA.
DR RefSeq; NP_001230045.1; NM_001243116.1.
DR RefSeq; NP_002494.2; NM_002503.4.
DR UniGene; Hs.9731; -.
DR ProteinModelPortal; Q15653; -.
DR SMR; Q15653; 50-302.
DR DIP; DIP-27532N; -.
DR IntAct; Q15653; 5.
DR MINT; MINT-1131598; -.
DR STRING; 9606.ENSP00000312988; -.
DR BindingDB; Q15653; -.
DR PhosphoSite; Q15653; -.
DR DMDM; 57015399; -.
DR PaxDb; Q15653; -.
DR PRIDE; Q15653; -.
DR DNASU; 4793; -.
DR Ensembl; ENST00000313582; ENSP00000312988; ENSG00000104825.
DR Ensembl; ENST00000572515; ENSP00000459728; ENSG00000104825.
DR GeneID; 4793; -.
DR KEGG; hsa:4793; -.
DR UCSC; uc002ojw.3; human.
DR CTD; 4793; -.
DR GeneCards; GC19P039390; -.
DR HGNC; HGNC:7798; NFKBIB.
DR HPA; CAB010447; -.
DR MIM; 604495; gene.
DR neXtProt; NX_Q15653; -.
DR PharmGKB; PA31602; -.
DR eggNOG; NOG272177; -.
DR HOVERGEN; HBG019039; -.
DR KO; K02581; -.
DR OMA; DEWCDSG; -.
DR PhylomeDB; Q15653; -.
DR Reactome; REACT_6782; TRAF6 Mediated Induction of proinflammatory cytokines.
DR Reactome; REACT_6900; Immune System.
DR SABIO-RK; Q15653; -.
DR SignaLink; Q15653; -.
DR ChiTaRS; NFKBIB; human.
DR GeneWiki; NFKBIB; -.
DR GenomeRNAi; 4793; -.
DR NextBio; 18470; -.
DR PRO; PR:Q15653; -.
DR ArrayExpress; Q15653; -.
DR Bgee; Q15653; -.
DR CleanEx; HS_NFKBIB; -.
DR Genevestigator; Q15653; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004871; F:signal transducer activity; TAS:ProtInc.
DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:Reactome.
DR GO; GO:0032481; P:positive regulation of type I interferon production; TAS:Reactome.
DR GO; GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR GO; GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
DR GO; GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
DR GO; GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
DR GO; GO:0006351; P:transcription, DNA-dependent; TAS:ProtInc.
DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR Gene3D; 1.25.40.20; -; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR Pfam; PF00023; Ank; 3.
DR Pfam; PF12796; Ank_2; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 6.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Complete proteome; Cytoplasm;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat.
FT CHAIN 1 356 NF-kappa-B inhibitor beta.
FT /FTId=PRO_0000067004.
FT REPEAT 57 86 ANK 1.
FT REPEAT 93 122 ANK 2.
FT REPEAT 126 155 ANK 3.
FT REPEAT 206 235 ANK 4.
FT REPEAT 240 269 ANK 5.
FT REPEAT 273 302 ANK 6.
FT COMPBIAS 186 195 Asp/Glu-rich (acidic).
FT MOD_RES 19 19 Phosphoserine; by RPS6KA1.
FT MOD_RES 23 23 Phosphoserine; by RPS6KA1.
FT MOD_RES 313 313 Phosphoserine; by CK2.
FT MOD_RES 315 315 Phosphoserine; by CK2.
FT VAR_SEQ 324 338 DEYDDIVVHSSRSQT -> VSQEERQGSPAGGSG (in
FT isoform 2).
FT /FTId=VSP_012409.
FT VAR_SEQ 339 356 Missing (in isoform 2).
FT /FTId=VSP_012410.
FT VARIANT 339 339 R -> W (in dbSNP:rs17886215).
FT /FTId=VAR_020771.
FT MUTAGEN 19 19 S->A: No degradation; when associated
FT with A-23.
FT MUTAGEN 23 23 S->A: No degradation; when associated
FT with A-19.
FT CONFLICT 19 19 S -> T (in Ref. 1; AAC41742).
FT CONFLICT 319 319 S -> G (in Ref. 1; AAC41742).
SQ SEQUENCE 356 AA; 37771 MW; E84575971B6F81CC CRC64;
MAGVACLGKA ADADEWCDSG LGSLGPDAAA PGGPGLGAEL GPGLSWAPLV FGYVTEDGDT
ALHLAVIHQH EPFLDFLLGF SAGTEYMDLQ NDLGQTALHL AAILGETSTV EKLYAAGAGL
CVAERRGHTA LHLACRVGAH ACARALLQPR PRRPREAPDT YLAQGPDRTP DTNHTPVALY
PDSDLEKEEE ESEEDWKLQL EAENYEGHTP LHVAVIHKDV EMVRLLRDAG ADLDKPEPTC
GRSPLHLAVE AQAADVLELL LRAGANPAAR MYGGRTPLGS AMLRPNPILA RLLRAHGAPE
PEGEDEKSGP CSSSSDSDSG DEGDEYDDIV VHSSRSQTRL PPTPASKPLP DDPRPV
//
MIM
604495
*RECORD*
*FIELD* NO
604495
*FIELD* TI
*604495 NUCLEAR FACTOR OF KAPPA LIGHT CHAIN GENE ENHANCER IN B CELLS INHIBITOR,
BETA; NFKBIB
read more;;INHIBITOR OF KAPPA LIGHT CHAIN GENE ENHANCER IN B CELLS, BETA;;
I-KAPPA-B-BETA; IKBB;;
THYROID HORMONE RECEPTOR INTERACTOR 9; TRIP9
*FIELD* TX
DESCRIPTION
NFKB1 (164011) or NFKB2 (164012) is bound to REL (164910), RELA
(164014), or RELB (604758) to form the NFKB complex. The NFKB complex is
inhibited by I-kappa-B proteins (NFKBIA, 164008, or NFKBIB), which
inactivate NF-kappa-B by trapping it in the cytoplasm. Phosphorylation
of serine residues on the I-kappa-B proteins by kinases (IKBKA, 600664
or IKBKB, 603258) marks them for destruction via the ubiquitination
pathway, thereby allowing activation of the NF-kappa-B complex.
Activated NFKB complex translocates into the nucleus and binds DNA at
kappa-B-binding motifs such as 5-prime GGGRNNYYCC 3-prime or 5-prime
HGGARNYYCC 3-prime (where H is A, C, or T; R is an A or G purine; and Y
is a C or T pyrimidine).
CLONING
Lee et al. (1995) identified NFKBIB, also known as NF-kappa-BIB, as a
protein, which they designated TRIP9 for 'thyroid hormone receptor
interacting protein-9,' that specifically interacted with the
ligand-binding domain of thyroid hormone receptor-beta (190160). TRIP9
interaction with the thyroid hormone receptor was dependent upon the
presence of thyroid hormone. TRIP9 contains 3 ankyrin repeats and is
most closely related to BCL3 (109560). Northern blot analysis revealed
that TRIP9 was expressed as 2.8- and 1.8-kb transcripts in all tissues
examined.
Using a yeast 2-hybrid screen with p65 (164014) as bait, Okamoto et al.
(1998) isolated a full-length NFKBIB cDNA clone from a human placenta
Matchmaker cDNA library. The NFKBIB cDNA is 1,940 bp.
GENE FUNCTION
Fenwick et al. (2000) identified 2 proteins, KBRAS1 (604496) and KBRAS2
(604497), which interacted with the PEST domains of I-kappa-B-alpha and
I-kappa-B-beta and decreased their rate of degradation. In cells, KBRAS
proteins associated only with NF-kappa-B:I-kappa-B complexes; the
authors suggested that therefore this may provide an explanation for the
slower rate of degradation of I-kappa-B-beta compared with that of
I-kappa-B-alpha.
Using electrophoretic mobility shift analysis (EMSA), Hoffmann et al.
(2002) showed that persistent stimulation of T cells, monocytes, or
fibroblasts with TNFA (191160) resulted in the coordinated degradation,
synthesis, and localization of IKBA, IKBB, and IKBE (604548) necessary
to generate the characteristic NFKB activation profile.
Rao et al. (2010) reported that in vivo, I-kappa-B-beta serves both to
inhibit and to facilitate the inflammatory response. I-kappa-B-beta
degradation releases NF-kappa-B dimers, which upregulate proinflammatory
target genes such as TNF-alpha. Surprisingly, absence of I-kappa-B-beta
results in a dramatic reduction of TNF-alpha in response to
lipopolysaccharide, even though activation of NF-kappa-B is normal. The
inhibition of TNF-alpha mRNA expression correlates with the absence of
nuclear, hypophosphorylated I-kappa-B-beta bound to p65 (164014):c-Rel
(164910) heterodimers at a specific kappa-B site on the TNF-alpha
promoter. Therefore, I-kappa-B-beta acts through p65:c-Rel dimers to
maintain prolonged expression of TNF-alpha. As a result,
I-kappa-B-beta-null mice are resistant to lipopolysaccharide-induced
septic shock and collagen-induced arthritis.
MAPPING
By fluorescence in situ hybridization, Okamoto et al. (1998) mapped the
NFKBIB gene to 19q13.1, in close proximity to the BCL3 gene. They
suggested the likelihood that the 2 genes share the same ancestral
origin and that they were generated by localized gene duplication.
ANIMAL MODEL
Hoffmann et al. (2002) generated mice deficient in Ikbb and Ikbe by
homologous recombination and intercrossed them with Ikba-deficient mice
to yield embryonic fibroblasts containing only 1 Ikb isoform. TNFA
stimulation of the Ikba fibroblasts resulted in a highly oscillatory
Nfkb response, whereas in Ikbb and Ikbe fibroblasts nuclear Nfkb
increased monotonically. Hoffmann et al. (2002) concluded that IKBA
mediates rapid NFKB activation and strong negative feedback regulation,
while IKBB and IKBE respond more slowly to IKK activation and act to
dampen long-term oscillations of the NFKB response. Computational and
EMSA analyses revealed bimodal signal-processing characteristics with
respect to the duration of the stimulus, enabling the generation of
specificity in gene expression of IP10 (CXCL10; 147310) and RANTES
(CCL5; 187011). In a commentary, Ting and Endy (2002) compared the
duration of signaling to the creation of an audible tone by pressing a
piano key, which causes a hammer to hit a string. How hard the string is
hit, and whether or not string vibration is sustained after the key is
released, can be modified by depressing a foot pedal, much as signal
transduction pathways are activated and modified by information in the
environment.
*FIELD* RF
1. Fenwick, C.; Na, S.-Y.; Voll, R. E.; Zhong, H.; Im, S.-Y.; Lee,
J. W.; Ghosh, S.: A subclass of Ras proteins that regulate the degradation
of I-kappa-B. Science 287: 869-873, 2000.
2. Hoffmann, A.; Levchenko, A.; Scott, M. L.; Baltimore, D.: The
I-kappa-B-NF-kappa-B signaling module: temporal control and selective
gene activation. Science 298: 1241-1245, 2002. Erratum: Science
318: 1550 only, 2007.
3. Lee, J. W.; Choi, H.-S.; Gyuris, J.; Brent, R.; Moore, D. D.:
Two classes of proteins dependent on either the presence or absence
of thyroid hormone for interaction with the thyroid hormone receptor. Molec.
Endocr. 9: 243-254, 1995.
4. Okamoto, T.; Ono, T.; Hori, M.; Yang, J.-P.; Tetsuka, T.; Kawabe,
T.; Sonta, S.: Assignment of the I-kappa-B-beta gene NFKBIB to human
chromosome band 19q13.1 by in situ hybridization. Cytogenet. Cell
Genet. 82: 105-106, 1998.
5. Rao, P.; Hayden, M. S.; Long, M.; Scott, M. L.; West, A. P.; Zhang,
D.; Oeckinghaus, A.; Lynch, C.; Hoffmann, A.; Baltimore, D.; Ghosh,
S.: I-kappa-B-beta acts to inhibit and activate gene expression during
the inflammatory response. Nature 466: 1115-1119, 2010.
6. Ting, A. Y.; Endy, D.: Decoding NF-kappa-B signaling. Science 298:
1189-1190, 2002.
*FIELD* CN
Ada Hamosh - updated: 9/14/2010
Ada Hamosh - updated: 4/24/2008
Paul J. Converse - updated: 11/14/2002
Paul J. Converse - updated: 2/16/2000
*FIELD* CD
Ada Hamosh: 2/3/2000
*FIELD* ED
alopez: 09/14/2010
terry: 9/14/2010
terry: 4/24/2008
mgross: 11/14/2002
alopez: 8/17/2000
alopez: 4/14/2000
carol: 2/16/2000
alopez: 2/4/2000
alopez: 2/3/2000
*RECORD*
*FIELD* NO
604495
*FIELD* TI
*604495 NUCLEAR FACTOR OF KAPPA LIGHT CHAIN GENE ENHANCER IN B CELLS INHIBITOR,
BETA; NFKBIB
read more;;INHIBITOR OF KAPPA LIGHT CHAIN GENE ENHANCER IN B CELLS, BETA;;
I-KAPPA-B-BETA; IKBB;;
THYROID HORMONE RECEPTOR INTERACTOR 9; TRIP9
*FIELD* TX
DESCRIPTION
NFKB1 (164011) or NFKB2 (164012) is bound to REL (164910), RELA
(164014), or RELB (604758) to form the NFKB complex. The NFKB complex is
inhibited by I-kappa-B proteins (NFKBIA, 164008, or NFKBIB), which
inactivate NF-kappa-B by trapping it in the cytoplasm. Phosphorylation
of serine residues on the I-kappa-B proteins by kinases (IKBKA, 600664
or IKBKB, 603258) marks them for destruction via the ubiquitination
pathway, thereby allowing activation of the NF-kappa-B complex.
Activated NFKB complex translocates into the nucleus and binds DNA at
kappa-B-binding motifs such as 5-prime GGGRNNYYCC 3-prime or 5-prime
HGGARNYYCC 3-prime (where H is A, C, or T; R is an A or G purine; and Y
is a C or T pyrimidine).
CLONING
Lee et al. (1995) identified NFKBIB, also known as NF-kappa-BIB, as a
protein, which they designated TRIP9 for 'thyroid hormone receptor
interacting protein-9,' that specifically interacted with the
ligand-binding domain of thyroid hormone receptor-beta (190160). TRIP9
interaction with the thyroid hormone receptor was dependent upon the
presence of thyroid hormone. TRIP9 contains 3 ankyrin repeats and is
most closely related to BCL3 (109560). Northern blot analysis revealed
that TRIP9 was expressed as 2.8- and 1.8-kb transcripts in all tissues
examined.
Using a yeast 2-hybrid screen with p65 (164014) as bait, Okamoto et al.
(1998) isolated a full-length NFKBIB cDNA clone from a human placenta
Matchmaker cDNA library. The NFKBIB cDNA is 1,940 bp.
GENE FUNCTION
Fenwick et al. (2000) identified 2 proteins, KBRAS1 (604496) and KBRAS2
(604497), which interacted with the PEST domains of I-kappa-B-alpha and
I-kappa-B-beta and decreased their rate of degradation. In cells, KBRAS
proteins associated only with NF-kappa-B:I-kappa-B complexes; the
authors suggested that therefore this may provide an explanation for the
slower rate of degradation of I-kappa-B-beta compared with that of
I-kappa-B-alpha.
Using electrophoretic mobility shift analysis (EMSA), Hoffmann et al.
(2002) showed that persistent stimulation of T cells, monocytes, or
fibroblasts with TNFA (191160) resulted in the coordinated degradation,
synthesis, and localization of IKBA, IKBB, and IKBE (604548) necessary
to generate the characteristic NFKB activation profile.
Rao et al. (2010) reported that in vivo, I-kappa-B-beta serves both to
inhibit and to facilitate the inflammatory response. I-kappa-B-beta
degradation releases NF-kappa-B dimers, which upregulate proinflammatory
target genes such as TNF-alpha. Surprisingly, absence of I-kappa-B-beta
results in a dramatic reduction of TNF-alpha in response to
lipopolysaccharide, even though activation of NF-kappa-B is normal. The
inhibition of TNF-alpha mRNA expression correlates with the absence of
nuclear, hypophosphorylated I-kappa-B-beta bound to p65 (164014):c-Rel
(164910) heterodimers at a specific kappa-B site on the TNF-alpha
promoter. Therefore, I-kappa-B-beta acts through p65:c-Rel dimers to
maintain prolonged expression of TNF-alpha. As a result,
I-kappa-B-beta-null mice are resistant to lipopolysaccharide-induced
septic shock and collagen-induced arthritis.
MAPPING
By fluorescence in situ hybridization, Okamoto et al. (1998) mapped the
NFKBIB gene to 19q13.1, in close proximity to the BCL3 gene. They
suggested the likelihood that the 2 genes share the same ancestral
origin and that they were generated by localized gene duplication.
ANIMAL MODEL
Hoffmann et al. (2002) generated mice deficient in Ikbb and Ikbe by
homologous recombination and intercrossed them with Ikba-deficient mice
to yield embryonic fibroblasts containing only 1 Ikb isoform. TNFA
stimulation of the Ikba fibroblasts resulted in a highly oscillatory
Nfkb response, whereas in Ikbb and Ikbe fibroblasts nuclear Nfkb
increased monotonically. Hoffmann et al. (2002) concluded that IKBA
mediates rapid NFKB activation and strong negative feedback regulation,
while IKBB and IKBE respond more slowly to IKK activation and act to
dampen long-term oscillations of the NFKB response. Computational and
EMSA analyses revealed bimodal signal-processing characteristics with
respect to the duration of the stimulus, enabling the generation of
specificity in gene expression of IP10 (CXCL10; 147310) and RANTES
(CCL5; 187011). In a commentary, Ting and Endy (2002) compared the
duration of signaling to the creation of an audible tone by pressing a
piano key, which causes a hammer to hit a string. How hard the string is
hit, and whether or not string vibration is sustained after the key is
released, can be modified by depressing a foot pedal, much as signal
transduction pathways are activated and modified by information in the
environment.
*FIELD* RF
1. Fenwick, C.; Na, S.-Y.; Voll, R. E.; Zhong, H.; Im, S.-Y.; Lee,
J. W.; Ghosh, S.: A subclass of Ras proteins that regulate the degradation
of I-kappa-B. Science 287: 869-873, 2000.
2. Hoffmann, A.; Levchenko, A.; Scott, M. L.; Baltimore, D.: The
I-kappa-B-NF-kappa-B signaling module: temporal control and selective
gene activation. Science 298: 1241-1245, 2002. Erratum: Science
318: 1550 only, 2007.
3. Lee, J. W.; Choi, H.-S.; Gyuris, J.; Brent, R.; Moore, D. D.:
Two classes of proteins dependent on either the presence or absence
of thyroid hormone for interaction with the thyroid hormone receptor. Molec.
Endocr. 9: 243-254, 1995.
4. Okamoto, T.; Ono, T.; Hori, M.; Yang, J.-P.; Tetsuka, T.; Kawabe,
T.; Sonta, S.: Assignment of the I-kappa-B-beta gene NFKBIB to human
chromosome band 19q13.1 by in situ hybridization. Cytogenet. Cell
Genet. 82: 105-106, 1998.
5. Rao, P.; Hayden, M. S.; Long, M.; Scott, M. L.; West, A. P.; Zhang,
D.; Oeckinghaus, A.; Lynch, C.; Hoffmann, A.; Baltimore, D.; Ghosh,
S.: I-kappa-B-beta acts to inhibit and activate gene expression during
the inflammatory response. Nature 466: 1115-1119, 2010.
6. Ting, A. Y.; Endy, D.: Decoding NF-kappa-B signaling. Science 298:
1189-1190, 2002.
*FIELD* CN
Ada Hamosh - updated: 9/14/2010
Ada Hamosh - updated: 4/24/2008
Paul J. Converse - updated: 11/14/2002
Paul J. Converse - updated: 2/16/2000
*FIELD* CD
Ada Hamosh: 2/3/2000
*FIELD* ED
alopez: 09/14/2010
terry: 9/14/2010
terry: 4/24/2008
mgross: 11/14/2002
alopez: 8/17/2000
alopez: 4/14/2000
carol: 2/16/2000
alopez: 2/4/2000
alopez: 2/3/2000