IKBD_MOUSE
ID IKBD_MOUSE Reviewed; 327 AA.
AC Q2TB02; Q3TJP0; Q8CIW1;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2008, sequence version 2.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=NF-kappa-B inhibitor delta;
DE AltName: Full=I-kappa-B-delta;
DE Short=IkB-delta;
DE Short=IkappaBdelta;
DE AltName: Full=IkappaBNS;
GN Name=Nfkbid; Synonyms=Ikbns;
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], FUNCTION, INTERACTION WITH NFKB1; RELA AND
RP RELB, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=11931770; DOI=10.1016/s1097-2765(02)00469-0;
RA Fiorini E., Schmitz I., Marissen W.E., Osborn S.L., Touma M., Sasada T.,
RA Reche P.A., Tibaldi E.V., Hussey R.E., Kruisbeek A.M., Reinherz E.L.,
RA Clayton L.K.;
RT "Peptide-induced negative selection of thymocytes activates transcription
RT of an NF-kappa B inhibitor.";
RL Mol. Cell 9:637-648(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP FUNCTION, AND INDUCTION BY IL-10 AND LPS.
RX PubMed=15749903; DOI=10.4049/jimmunol.174.6.3650;
RA Hirotani T., Lee P.Y., Kuwata H., Yamamoto M., Matsumoto M., Kawase I.,
RA Akira S., Takeda K.;
RT "The nuclear IkappaB protein IkappaBNS selectively inhibits
RT lipopolysaccharide-induced IL-6 production in macrophages of the colonic
RT lamina propria.";
RL J. Immunol. 174:3650-3657(2005).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16410444; DOI=10.1182/blood-2005-10-4190;
RA Fujita S., Seino K., Sato K., Sato Y., Eizumi K., Yamashita N.,
RA Taniguchi M., Sato K.;
RT "Regulatory dendritic cells act as regulators of acute lethal systemic
RT inflammatory response.";
RL Blood 107:3656-3664(2006).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16413922; DOI=10.1016/j.immuni.2005.11.004;
RA Kuwata H., Matsumoto M., Atarashi K., Morishita H., Hirotani T., Koga R.,
RA Takeda K.;
RT "IkappaBNS inhibits induction of a subset of Toll-like receptor-dependent
RT genes and limits inflammation.";
RL Immunity 24:41-51(2006).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17641034; DOI=10.4049/jimmunol.179.3.1681;
RA Touma M., Antonini V., Kumar M., Osborn S.L., Bobenchik A.M., Keskin D.B.,
RA Connolly J.E., Grusby M.J., Reinherz E.L., Clayton L.K.;
RT "Functional role for I kappa BNS in T cell cytokine regulation as revealed
RT by targeted gene disruption.";
RL J. Immunol. 179:1681-1692(2007).
RN [8]
RP FUNCTION.
RX PubMed=25282160; DOI=10.1038/ni.3008;
RA Jeltsch K.M., Hu D., Brenner S., Zoeller J., Heinz G.A., Nagel D.,
RA Vogel K.U., Rehage N., Warth S.C., Edelmann S.L., Gloury R., Martin N.,
RA Lohs C., Lech M., Stehklein J.E., Geerlof A., Kremmer E., Weber A.,
RA Anders H.J., Schmitz I., Schmidt-Supprian M., Fu M., Holtmann H.,
RA Krappmann D., Ruland J., Kallies A., Heikenwalder M., Heissmeyer V.;
RT "Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their
RT cooperatively repressed targets to promote T(H)17 differentiation.";
RL Nat. Immunol. 15:1079-1089(2014).
CC -!- FUNCTION: Regulates the expression of IL-2, IL-6, and other cytokines
CC through regulation on NF-kappa-B activity. Functions in the regulation
CC of inflammatory responses (PubMed:11931770, PubMed:15749903,
CC PubMed:16410444, PubMed:16413922, PubMed:17641034). Involved in the
CC induction of T helper 17 cells (Th17) differentiation upon recognition
CC of antigen by T cell antigen receptor (TCR) (PubMed:25282160).
CC According to PubMed:11931770, it may also regulate TCR-induced negative
CC selection of thymocytes (PubMed:11931770).
CC {ECO:0000269|PubMed:11931770, ECO:0000269|PubMed:15749903,
CC ECO:0000269|PubMed:16410444, ECO:0000269|PubMed:16413922,
CC ECO:0000269|PubMed:17641034, ECO:0000269|PubMed:25282160}.
CC -!- SUBUNIT: Interacts with NFKB1, RELA and RELB; in the nucleus.
CC {ECO:0000269|PubMed:11931770}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11931770}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in spleen and at low levels
CC in thymus. Expressed in a population of antigen-presenting dendritic
CC cells which may act as regulators of systemic inflammatory response.
CC {ECO:0000269|PubMed:11931770, ECO:0000269|PubMed:16410444}.
CC -!- INDUCTION: Up-regulated in thymocytes upon TCR-triggered cell death (at
CC protein level). Up-regulated by IL-10 or LPS.
CC {ECO:0000269|PubMed:11931770, ECO:0000269|PubMed:15749903}.
CC -!- DISRUPTION PHENOTYPE: Mice are highly sensitive to LPS-induced
CC endotoxin shock and susceptible to intestinal inflammation caused by
CC exposure to microflora. They display no overt T-cell selection
CC phenotype but an impaired proliferation of T-cells. Thymocytes and T-
CC cells seem to produce less IL-2 and IFNG. {ECO:0000269|PubMed:16413922,
CC ECO:0000269|PubMed:17641034}.
CC -!- SIMILARITY: Belongs to the NF-kappa-B inhibitor family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE39455.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY078069; AAL79957.1; -; mRNA.
DR EMBL; AK167356; BAE39455.1; ALT_FRAME; mRNA.
DR EMBL; BC110633; AAI10634.1; -; mRNA.
DR CCDS; CCDS21091.1; -.
DR RefSeq; NP_742154.1; NM_172142.3.
DR RefSeq; XP_006540016.1; XM_006539953.3.
DR AlphaFoldDB; Q2TB02; -.
DR SMR; Q2TB02; -.
DR IntAct; Q2TB02; 1.
DR STRING; 10090.ENSMUSP00000042317; -.
DR iPTMnet; Q2TB02; -.
DR PhosphoSitePlus; Q2TB02; -.
DR EPD; Q2TB02; -.
DR PaxDb; Q2TB02; -.
DR PRIDE; Q2TB02; -.
DR ProteomicsDB; 269387; -.
DR Antibodypedia; 48023; 153 antibodies from 18 providers.
DR Ensembl; ENSMUST00000046177; ENSMUSP00000042317; ENSMUSG00000036931.
DR Ensembl; ENSMUST00000108175; ENSMUSP00000103810; ENSMUSG00000036931.
DR GeneID; 243910; -.
DR KEGG; mmu:243910; -.
DR UCSC; uc009gei.1; mouse.
DR CTD; 84807; -.
DR MGI; MGI:3041243; Nfkbid.
DR VEuPathDB; HostDB:ENSMUSG00000036931; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000153695; -.
DR HOGENOM; CLU_046801_0_0_1; -.
DR InParanoid; Q2TB02; -.
DR OrthoDB; 964992at2759; -.
DR PhylomeDB; Q2TB02; -.
DR TreeFam; TF330224; -.
DR BioGRID-ORCS; 243910; 2 hits in 73 CRISPR screens.
DR PRO; PR:Q2TB02; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q2TB02; protein.
DR Bgee; ENSMUSG00000036931; Expressed in granulocyte and 66 other tissues.
DR ExpressionAtlas; Q2TB02; baseline and differential.
DR Genevisible; Q2TB02; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0051059; F:NF-kappaB binding; IPI:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:MGI.
DR GO; GO:0033085; P:negative regulation of T cell differentiation in thymus; IDA:MGI.
DR GO; GO:2000321; P:positive regulation of T-helper 17 cell differentiation; IMP:UniProtKB.
DR GO; GO:0070245; P:positive regulation of thymocyte apoptotic process; IDA:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0033077; P:T cell differentiation in thymus; IDA:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0070242; P:thymocyte apoptotic process; IDA:MGI.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR Pfam; PF00023; Ank; 1.
DR Pfam; PF12796; Ank_2; 1.
DR SMART; SM00248; ANK; 5.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 3.
PE 1: Evidence at protein level;
KW ANK repeat; Inflammatory response; Nucleus; Reference proteome; Repeat.
FT CHAIN 1..327
FT /note="NF-kappa-B inhibitor delta"
FT /id="PRO_0000331115"
FT REPEAT 62..97
FT /note="ANK 1"
FT REPEAT 98..127
FT /note="ANK 2"
FT REPEAT 131..160
FT /note="ANK 3"
FT REPEAT 166..215
FT /note="ANK 4"
FT REPEAT 220..250
FT /note="ANK 5"
FT REPEAT 257..290
FT /note="ANK 6"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 293..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 10..39
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 249
FT /note="R -> W (in Ref. 3; AAI10634)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 327 AA; 34942 MW; 0EF48A8E2592A6E6 CRC64;
MEDSLDTRLY PEPSLSQVGS WRVSSLPSGS PQLPSPTGPS LETARAHILA LGPQQLLAQD
EEGDTLLHLF AARGLRWAAY AAAEVLQMYR QLDIREHKGK TPLLVAAAAN QPLIVEDLLS
LGAEPNATDH QGRSVLHVAA TYGLPGVLSA VFKSGIQVDL EARDFEGLTP LHTAVLALNA
AMLPASVCPR MQNSQARDRL TCVQMLLQMG ASHTSQEIKS NKTILHLAVQ AANPTLVQLL
LGLPRGDLRA FVNMKAHGNT ALHMAAALPP GPPQEAIVRH LLAAGADPTL RNLENEQPVH
LLRPGPGPEG LRQLLKRSRT APPGLSS
