ID IKBZ_HUMAN Reviewed; 718 AA. AC Q9BYH8; B3KNR2; D3DN54; Q8IUL4; Q8NAZ8; DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 24-JUL-2024, entry version 176. DE RecName: Full=NF-kappa-B inhibitor zeta; DE AltName: Full=I-kappa-B-zeta; DE Short=IkB-zeta; DE Short=IkappaBzeta; DE AltName: Full=IL-1 inducible nuclear ankyrin-repeat protein; DE Short=INAP; DE AltName: Full=Molecule possessing ankyrin repeats induced by lipopolysaccharide {ECO:0000303|Ref.1}; DE Short=MAIL {ECO:0000303|Ref.1}; GN Name=NFKBIZ; Synonyms=IKBZ, INAP, MAIL {ECO:0000303|Ref.1}; 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 [MRNA] (ISOFORM 1). RC TISSUE=Peripheral blood; RA Ochiai K., Morimatsu M., Kitamura H., Shiina T., Syuto B.; RT "Human MAIL: an inflammation-associated gene that is induced by RT lipopolysaccharide in leukocytes."; RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Monocyte; RA Parker-Barnes J.M., Yee J.F., Hart J.M., Doseff A.I., Wewers M.D.; RT "MAIL a novel IkB family member is induced by lipopolysaccharide in human RT monocytes and binds proIL-1beta."; RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION IN NF-KAPPA-B INHIBITION, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH RELA AND NFKB1, RP AND INDUCTION. RX PubMed=16513645; DOI=10.1074/jbc.m511956200; RA Totzke G., Essmann F., Pohlmann S., Lindenblatt C., Janicke R.U., RA Schulze-Osthoff K.; RT "A novel member of the IkappaB family, human IkappaB-zeta, inhibits RT transactivation of p65 and its DNA binding."; RL J. Biol. Chem. 281:12645-12654(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Cerebellum, and 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; 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 FUNCTION IN NF-KAPPA-B ACTIVATION. RX PubMed=16622025; DOI=10.4049/jimmunol.176.9.5559; RA Cowland J.B., Muta T., Borregaard N.; RT "IL-1beta-specific up-regulation of neutrophil gelatinase-associated RT lipocalin is controlled by IkappaB-zeta."; RL J. Immunol. 176:5559-5566(2006). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). CC -!- FUNCTION: Involved in regulation of NF-kappa-B transcription factor CC complexes (PubMed:16513645, PubMed:16622025). Inhibits NF-kappa-B CC activity without affecting its nuclear translocation upon stimulation CC (PubMed:16513645). Inhibits DNA-binding of RELA and NFKB1/p50, and of CC the NF-kappa-B p65-p50 heterodimer and the NF-kappa-B p50-p50 homodimer CC (PubMed:16513645). Seems also to activate NF-kappa-B-mediated CC transcription (PubMed:16622025). In vitro, upon association with CC NFKB1/p50 has transcriptional activation activity and, together with CC NFKB1/p50 and RELA, is recruited to LCN2 promoters (PubMed:16622025). CC Promotes transcription of LCN2 and DEFB4 (PubMed:16622025). Is CC recruited to IL-6 promoters and activates IL-6 but decreases TNF-alpha CC production in response to LPS (By similarity). Seems to be involved in CC the induction of inflammatory genes activated through TLR/IL-1 receptor CC signaling (By similarity). Involved in the induction of T helper 17 CC cells (Th17) differentiation upon recognition of antigen by T cell CC antigen receptor (TCR) (By similarity). {ECO:0000250|UniProtKB:Q9EST8, CC ECO:0000269|PubMed:16513645, ECO:0000269|PubMed:16622025}. CC -!- SUBUNIT: Interacts with NFKB1/p50 (PubMed:16513645). Interacts with CC RELA (PubMed:16513645). Interacts with AKIRIN2 (By similarity). CC {ECO:0000250|UniProtKB:Q9EST8, ECO:0000269|PubMed:16513645}. CC -!- INTERACTION: CC Q9BYH8; B1AXD8: Akirin2; Xeno; NbExp=3; IntAct=EBI-3939694, EBI-10107866; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16513645}. CC Note=Aggregated in dot-like structures (PubMed:16513645). Colocalizes CC with NCOR2 (PubMed:16513645). {ECO:0000269|PubMed:16513645}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=MAIL-L; CC IsoId=Q9BYH8-1; Sequence=Displayed; CC Name=2; Synonyms=MAIL-S, Transcription variant 3; CC IsoId=Q9BYH8-2; Sequence=VSP_032022; CC Name=3; CC IsoId=Q9BYH8-3; Sequence=VSP_032023; CC -!- TISSUE SPECIFICITY: Expressed at high levels in peripheral blood CC leukocytes and lung, at moderate levels in liver, placenta, and at low CC levels in spleen, kidney, skeletal muscle and heart. CC {ECO:0000269|PubMed:16513645}. CC -!- INDUCTION: By TNF, IL1/interleukin-1 and bacterial lipopolysaccharides CC (LPS). {ECO:0000269|PubMed:16513645}. 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; AB037925; BAB40337.1; -; mRNA. DR EMBL; AF548362; AAN40698.1; -; mRNA. DR EMBL; DQ224339; ABB02425.1; -; mRNA. DR EMBL; AK054787; BAG51424.1; -; mRNA. DR EMBL; AK091782; BAC03746.1; -; mRNA. DR EMBL; CH471052; EAW79771.1; -; Genomic_DNA. DR EMBL; CH471052; EAW79772.1; -; Genomic_DNA. DR EMBL; BC060800; AAH60800.1; -; mRNA. DR CCDS; CCDS2946.1; -. [Q9BYH8-1] DR CCDS; CCDS43123.1; -. [Q9BYH8-2] DR RefSeq; NP_001005474.1; NM_001005474.2. [Q9BYH8-2] DR RefSeq; NP_113607.1; NM_031419.3. [Q9BYH8-1] DR AlphaFoldDB; Q9BYH8; -. DR SMR; Q9BYH8; -. DR BioGRID; 122139; 11. DR IntAct; Q9BYH8; 6. DR STRING; 9606.ENSP00000325663; -. DR iPTMnet; Q9BYH8; -. DR PhosphoSitePlus; Q9BYH8; -. DR BioMuta; NFKBIZ; -. DR DMDM; 74752456; -. DR MassIVE; Q9BYH8; -. DR PaxDb; 9606-ENSP00000325663; -. DR PeptideAtlas; Q9BYH8; -. DR ProteomicsDB; 79649; -. [Q9BYH8-1] DR ProteomicsDB; 79650; -. [Q9BYH8-2] DR ProteomicsDB; 79651; -. [Q9BYH8-3] DR Antibodypedia; 2134; 211 antibodies from 25 providers. DR DNASU; 64332; -. DR Ensembl; ENST00000326151.9; ENSP00000325593.5; ENSG00000144802.11. [Q9BYH8-3] DR Ensembl; ENST00000326172.9; ENSP00000325663.5; ENSG00000144802.11. [Q9BYH8-1] DR Ensembl; ENST00000394054.6; ENSP00000377618.2; ENSG00000144802.11. [Q9BYH8-2] DR GeneID; 64332; -. DR KEGG; hsa:64332; -. DR MANE-Select; ENST00000326172.9; ENSP00000325663.5; NM_031419.4; NP_113607.1. DR UCSC; uc003dvo.4; human. [Q9BYH8-1] DR AGR; HGNC:29805; -. DR CTD; 64332; -. DR DisGeNET; 64332; -. DR GeneCards; NFKBIZ; -. DR HGNC; HGNC:29805; NFKBIZ. DR HPA; ENSG00000144802; Tissue enriched (bone). DR MIM; 608004; gene. DR neXtProt; NX_Q9BYH8; -. DR OpenTargets; ENSG00000144802; -. DR PharmGKB; PA134990505; -. DR VEuPathDB; HostDB:ENSG00000144802; -. DR eggNOG; KOG0504; Eukaryota. DR GeneTree; ENSGT00940000153695; -. DR HOGENOM; CLU_030240_0_0_1; -. DR InParanoid; Q9BYH8; -. DR OMA; LQRNQQH; -. DR OrthoDB; 5406967at2759; -. DR PhylomeDB; Q9BYH8; -. DR TreeFam; TF330224; -. DR PathwayCommons; Q9BYH8; -. DR SignaLink; Q9BYH8; -. DR SIGNOR; Q9BYH8; -. DR BioGRID-ORCS; 64332; 6 hits in 1159 CRISPR screens. DR ChiTaRS; NFKBIZ; human. DR GeneWiki; NFKBIZ; -. DR GenomeRNAi; 64332; -. DR Pharos; Q9BYH8; Tbio. DR PRO; PR:Q9BYH8; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q9BYH8; Protein. DR Bgee; ENSG00000144802; Expressed in epithelial cell of pancreas and 181 other cell types or tissues. DR ExpressionAtlas; Q9BYH8; baseline and differential. DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0070974; F:POU domain binding; IEA:InterPro. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0003712; F:transcription coregulator activity; IEA:Ensembl. DR GO; GO:0042100; P:B cell proliferation; IEA:Ensembl. DR GO; GO:1990117; P:B cell receptor apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0097398; P:cellular response to interleukin-17; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl. DR GO; GO:0006338; P:chromatin remodeling; IEA:Ensembl. DR GO; GO:0002544; P:chronic inflammatory response; IEA:Ensembl. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IEA:Ensembl. DR GO; GO:1904019; P:epithelial cell apoptotic process; IEA:Ensembl. DR GO; GO:0061436; P:establishment of skin barrier; IEA:Ensembl. DR GO; GO:0097194; P:execution phase of apoptosis; IEA:Ensembl. DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl. DR GO; GO:0090594; P:inflammatory response to wounding; IEA:Ensembl. DR GO; GO:0045190; P:isotype switching; IEA:Ensembl. DR GO; GO:0032980; P:keratinocyte activation; IEA:Ensembl. DR GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl. DR GO; GO:0043616; P:keratinocyte proliferation; IEA:Ensembl. DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0002317; P:plasma cell differentiation; IEA:Ensembl. DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:ARUK-UCL. DR GO; GO:2000321; P:positive regulation of T-helper 17 cell differentiation; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central. DR GO; GO:0072718; P:response to cisplatin; IEA:Ensembl. DR GO; GO:0051593; P:response to folic acid; IEA:Ensembl. DR GO; GO:0140459; P:response to Gram-positive bacterium; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0048536; P:spleen development; IEA:Ensembl. DR GO; GO:0002456; P:T cell mediated immunity; IEA:Ensembl. DR GO; GO:0050852; P:T cell receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0045063; P:T-helper 1 cell differentiation; IEA:Ensembl. DR GO; GO:0072539; P:T-helper 17 cell differentiation; IEA:Ensembl. DR GO; GO:0002224; P:toll-like receptor signaling pathway; IEA:Ensembl. DR GO; GO:0070897; P:transcription preinitiation complex assembly; IEA:Ensembl. DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR036770; Ankyrin_rpt-contain_sf. DR InterPro; IPR047571; OCA. DR PANTHER; PTHR24124; ANKYRIN REPEAT FAMILY A; 1. DR PANTHER; PTHR24124:SF5; NF-KAPPA-B INHIBITOR ZETA; 1. DR Pfam; PF12796; Ank_2; 2. 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; 3. DR PROSITE; PS52003; OCA; 1. PE 1: Evidence at protein level; KW Activator; Alternative splicing; ANK repeat; Nucleus; Reference proteome; KW Repeat; Repressor; Transcription; Transcription regulation. FT CHAIN 1..718 FT /note="NF-kappa-B inhibitor zeta" FT /id="PRO_0000323577" FT DOMAIN 108..130 FT /note="OCA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01347" FT REPEAT 443..472 FT /note="ANK 1" FT REPEAT 479..508 FT /note="ANK 2" FT REPEAT 512..541 FT /note="ANK 3" FT REPEAT 551..580 FT /note="ANK 4" FT REPEAT 582..607 FT /note="ANK 5" FT REPEAT 612..641 FT /note="ANK 6" FT REPEAT 648..681 FT /note="ANK 7" FT REGION 1..20 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 58..108 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 186..211 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 321..394 FT /note="Required for transcriptional activity" FT /evidence="ECO:0000250" FT REGION 404..718 FT /note="Interaction with NFKB1/p50" FT /evidence="ECO:0000250" FT MOTIF 164..179 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250" FT COMPBIAS 1..15 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 58..82 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 1..100 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:16513645, ECO:0000303|Ref.2" FT /id="VSP_032022" FT VAR_SEQ 237..358 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_032023" FT VARIANT 307 FT /note="T -> S (in dbSNP:rs3821727)" FT /id="VAR_039547" FT CONFLICT 567 FT /note="V -> F (in Ref. 4; BAC03746)" FT /evidence="ECO:0000305" SQ SEQUENCE 718 AA; 78061 MW; 5656E00F2507DC7C CRC64; MIVDKLLDDS RGGEGLRDAA GGCGLMTSPL NLSYFYGASP PAAAPGACDA SCSVLGPSAP GSPGSDSSDF SSASSVSSCG AVESRSRGGA RAERQPVEPH MGVGRQQRGP FQGVRVKNSV KELLLHIRSH KQKASGQAVD DFKTQGVNIE QFRELKNTVS YSGKRKGPDS LSDGPACKRP ALLHSQFLTP PQTPTPGESM EDVHLNEPKQ ESSADLLQNI INIKNECSPV SLNTVQVSWL NPVVVPQSSP AEQCQDFHGG QVFSPPQKCQ PFQVRGSQQM IDQASLYQYS PQNQHVEQQP HYTHKPTLEY SPFPIPPQSP AYEPNLFDGP ESQFCPNQSL VSLLGDQRES ENIANPMQTS SSVQQQNDAH LHSFSMMPSS ACEAMVGHEM ASDSSNTSLP FSNMGNPMNT TQLGKSLFQW QVEQEESKLA NISQDQFLSK DADGDTFLHI AVAQGRRALS YVLARKMNAL HMLDIKEHNG QSAFQVAVAA NQHLIVQDLV NIGAQVNTTD CWGRTPLHVC AEKGHSQVLQ AIQKGAVGSN QFVDLEATNY DGLTPLHCAV IAHNAVVHEL QRNQQPHSPE VQELLLKNKS LVDTIKCLIQ MGAAVEAKDR KSGRTALHLA AEEANLELIR LFLELPSCLS FVNAKAYNGN TALHVAASLQ YRLTQLDAVR LLMRKGADPS TRNLENEQPV HLVPDGPVGE QIRRILKGKS IQQRAPPY //