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 24-JAN-2024, entry version 212. 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 CCDS; CCDS92612.1; -. [Q15653-2] 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; 87. DR CORUM; Q15653; -. DR DIP; DIP-27532N; -. DR ELM; Q15653; -. DR IntAct; Q15653; 39. 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; 9606-ENSP00000312988; -. DR PeptideAtlas; Q15653; -. DR ProteomicsDB; 60694; -. [Q15653-1] DR ProteomicsDB; 60695; -. [Q15653-2] DR Pumba; Q15653; -. DR Antibodypedia; 4179; 891 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 AGR; HGNC:7798; -. 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; 621606at2759; -. 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; 27 hits in 1162 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 101 other cell types or tissues. DR ExpressionAtlas; Q15653; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. 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:0006351; P:DNA-templated transcription; TAS:ProtInc. DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl. DR GO; GO:0043122; P:regulation of canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR036770; Ankyrin_rpt-contain_sf. DR PANTHER; PTHR47303; -; 1. DR PANTHER; PTHR47303:SF1; NF-KAPPA-B INHIBITOR BETA; 1. DR Pfam; PF00023; Ank; 1. DR Pfam; PF12796; Ank_2; 1. DR Pfam; PF13637; Ank_4; 1. DR PRINTS; PR01415; ANKYRIN. DR SMART; SM00248; ANK; 6. DR SUPFAM; SSF48403; Ankyrin repeat; 1. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 4. DR Genevisible; Q15653; HS. 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 //