IKBB_HUMAN
ID IKBB_HUMAN Reviewed; 356 AA.
AC Q15653; A8K3F4; Q96BJ7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 2.
DT 03-AUG-2022, entry version 204.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 2), AND
RP INTERACTION WITH THRB.
RC TISSUE=Cervix carcinoma;
RX PubMed=7776974; DOI=10.1210/mend.9.2.7776974;
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 of
RT thyroid hormone for interaction with the thyroid hormone 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 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 SEQUENCE
RP [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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP CHARACTERIZATION.
RX PubMed=8816457; DOI=10.1128/mcb.16.10.5444;
RA Suyang H., Phillips R.J., Douglas I., Ghosh S.;
RT "Role of unphosphorylated, newly synthesized IkappaB beta in persistent
RT 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., Ghosh S.;
RT "A subclass of Ras proteins that regulate the degradation of IkappaB.";
RL Science 287:869-873(2000).
RN [9]
RP MUTAGENESIS OF SER-19 AND SER-23, AND PHOSPHORYLATION AT SER-19 AND SER-23.
RX PubMed=8657102; DOI=10.1128/mcb.16.4.1295;
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 its
RT ubiquitination and degradation.";
RL Mol. Cell. Biol. 16:1295-1304(1996).
RN [10]
RP PHOSPHORYLATION AT SER-313 AND SER-315.
RX PubMed=8887627; DOI=10.1128/mcb.16.11.5974;
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) regulates
RT its functional interaction with the c-rel proto-oncogene 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 domain of
RT IkappaBbeta and regulates cytoplasmic retention of IkappaBbeta.NF-kappaB
RT 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).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Inhibits NF-kappa-B by complexing with and trapping it in the
CC cytoplasm. However, the unphosphorylated form resynthesized after cell
CC stimulation is able to bind NF-kappa-B allowing its transport to the
CC nucleus and protecting it to further NFKBIA-dependent inactivation.
CC Association with inhibitor kappa B-interacting NKIRAS1 and NKIRAS2
CC prevent its phosphorylation rendering it more resistant to degradation,
CC explaining its slower degradation.
CC -!- SUBUNIT: Interacts with THRB (via ligand-binding domain)
CC (PubMed:7776974). Interacts with RELA and REL (By similarity).
CC Interacts with COMMD1 (PubMed:16573520). Interacts with inhibitor kappa
CC B-interacting Ras-like NKIRAS1 and NKIRAS2 (PubMed:10657303,
CC PubMed:12672800, PubMed:15024091). {ECO:0000250,
CC ECO:0000269|PubMed:10657303, ECO:0000269|PubMed:12672800,
CC ECO:0000269|PubMed:15024091, ECO:0000269|PubMed:16573520,
CC ECO:0000269|PubMed:7776974}.
CC -!- INTERACTION:
CC Q15653; Q96KE9-2: BTBD6; NbExp=3; IntAct=EBI-352889, EBI-12012762;
CC Q15653; P17568: NDUFB7; NbExp=3; IntAct=EBI-352889, EBI-1246238;
CC Q15653; P19838: NFKB1; NbExp=3; IntAct=EBI-352889, EBI-300010;
CC Q15653; Q04206: RELA; NbExp=6; IntAct=EBI-352889, EBI-73886;
CC Q15653; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-352889, EBI-5235340;
CC Q15653; Q8N1B4: VPS52; NbExp=3; IntAct=EBI-352889, EBI-2799833;
CC Q15653; P14340; Xeno; NbExp=2; IntAct=EBI-352889, EBI-465733;
CC Q15653; PRO_0000037965 [P14340]; Xeno; NbExp=2; IntAct=EBI-352889, EBI-9825968;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
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. Interaction
CC with NKIRAS1 and NKIRAS2 probably prevents phosphorylation.
CC {ECO:0000269|PubMed:8657102, ECO:0000269|PubMed:8887627}.
CC -!- SIMILARITY: Belongs to the NF-kappa-B inhibitor family. {ECO:0000305}.
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 CCDS; CCDS12524.1; -. [Q15653-1]
DR RefSeq; NP_001230045.1; NM_001243116.1.
DR RefSeq; NP_002494.2; NM_002503.4. [Q15653-1]
DR AlphaFoldDB; Q15653; -.
DR SMR; Q15653; -.
DR BioGRID; 110860; 63.
DR CORUM; Q15653; -.
DR DIP; DIP-27532N; -.
DR ELM; Q15653; -.
DR IntAct; Q15653; 38.
DR STRING; 9606.ENSP00000312988; -.
DR iPTMnet; Q15653; -.
DR PhosphoSitePlus; Q15653; -.
DR BioMuta; NFKBIB; -.
DR DMDM; 57015399; -.
DR EPD; Q15653; -.
DR jPOST; Q15653; -.
DR MassIVE; Q15653; -.
DR MaxQB; Q15653; -.
DR PaxDb; Q15653; -.
DR PeptideAtlas; Q15653; -.
DR PRIDE; Q15653; -.
DR ProteomicsDB; 60694; -. [Q15653-1]
DR ProteomicsDB; 60695; -. [Q15653-2]
DR Antibodypedia; 4179; 808 antibodies from 45 providers.
DR DNASU; 4793; -.
DR Ensembl; ENST00000313582.6; ENSP00000312988.5; ENSG00000104825.17. [Q15653-1]
DR Ensembl; ENST00000572515.5; ENSP00000459728.1; ENSG00000104825.17. [Q15653-2]
DR Ensembl; ENST00000634647.1; ENSP00000489145.1; ENSG00000282905.2. [Q15653-2]
DR Ensembl; ENST00000635517.2; ENSP00000489138.1; ENSG00000282905.2. [Q15653-1]
DR GeneID; 4793; -.
DR KEGG; hsa:4793; -.
DR MANE-Select; ENST00000313582.6; ENSP00000312988.5; NM_002503.5; NP_002494.2.
DR UCSC; uc002ojw.4; human. [Q15653-1]
DR CTD; 4793; -.
DR DisGeNET; 4793; -.
DR GeneCards; NFKBIB; -.
DR HGNC; HGNC:7798; NFKBIB.
DR HPA; ENSG00000104825; Tissue enhanced (testis).
DR MIM; 604495; gene.
DR neXtProt; NX_Q15653; -.
DR OpenTargets; ENSG00000104825; -.
DR PharmGKB; PA31602; -.
DR VEuPathDB; HostDB:ENSG00000104825; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000161595; -.
DR HOGENOM; CLU_000134_6_0_1; -.
DR InParanoid; Q15653; -.
DR OMA; AEADEWC; -.
DR OrthoDB; 1341288at2759; -.
DR PhylomeDB; Q15653; -.
DR TreeFam; TF320166; -.
DR PathwayCommons; Q15653; -.
DR Reactome; R-HSA-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-HSA-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-HSA-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
DR SABIO-RK; Q15653; -.
DR SignaLink; Q15653; -.
DR SIGNOR; Q15653; -.
DR BioGRID-ORCS; 4793; 24 hits in 1085 CRISPR screens.
DR ChiTaRS; NFKBIB; human.
DR GeneWiki; NFKBIB; -.
DR GenomeRNAi; 4793; -.
DR Pharos; Q15653; Tbio.
DR PRO; PR:Q15653; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q15653; protein.
DR Bgee; ENSG00000104825; Expressed in left testis and 99 other tissues.
DR ExpressionAtlas; Q15653; baseline and differential.
DR Genevisible; Q15653; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IBA:GO_Central.
DR GO; GO:0007253; P:cytoplasmic sequestering of NF-kappaB; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0006351; P:transcription, DNA-templated; TAS:ProtInc.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF13637; Ank_4; 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; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..356
FT /note="NF-kappa-B inhibitor beta"
FT /id="PRO_0000067004"
FT REPEAT 57..86
FT /note="ANK 1"
FT REPEAT 93..122
FT /note="ANK 2"
FT REPEAT 126..155
FT /note="ANK 3"
FT REPEAT 206..235
FT /note="ANK 4"
FT REPEAT 240..269
FT /note="ANK 5"
FT REPEAT 273..302
FT /note="ANK 6"
FT REGION 149..193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 298..356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 19
FT /note="Phosphoserine; by RPS6KA1"
FT /evidence="ECO:0000269|PubMed:8657102"
FT MOD_RES 23
FT /note="Phosphoserine; by RPS6KA1"
FT /evidence="ECO:0000269|PubMed:8657102"
FT MOD_RES 183
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 313
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:8887627"
FT MOD_RES 315
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:8887627"
FT VAR_SEQ 324..338
FT /note="DEYDDIVVHSSRSQT -> VSQEERQGSPAGGSG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_012409"
FT VAR_SEQ 339..356
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_012410"
FT VARIANT 339
FT /note="R -> W (in dbSNP:rs17886215)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_020771"
FT MUTAGEN 19
FT /note="S->A: No degradation; when associated with A-23."
FT /evidence="ECO:0000269|PubMed:8657102"
FT MUTAGEN 23
FT /note="S->A: No degradation; when associated with A-19."
FT /evidence="ECO:0000269|PubMed:8657102"
FT CONFLICT 19
FT /note="S -> T (in Ref. 1; AAC41742)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="S -> G (in Ref. 1; AAC41742)"
FT /evidence="ECO:0000305"
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
