IKBZ_HUMAN
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 03-AUG-2022, entry version 166.
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}.
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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 MINT; Q9BYH8; -.
DR STRING; 9606.ENSP00000325663; -.
DR iPTMnet; Q9BYH8; -.
DR PhosphoSitePlus; Q9BYH8; -.
DR BioMuta; NFKBIZ; -.
DR DMDM; 74752456; -.
DR MassIVE; Q9BYH8; -.
DR MaxQB; Q9BYH8; -.
DR PaxDb; Q9BYH8; -.
DR PeptideAtlas; Q9BYH8; -.
DR PRIDE; Q9BYH8; -.
DR ProteomicsDB; 79649; -. [Q9BYH8-1]
DR ProteomicsDB; 79650; -. [Q9BYH8-2]
DR ProteomicsDB; 79651; -. [Q9BYH8-3]
DR Antibodypedia; 2134; 202 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 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; 867160at2759; -.
DR PhylomeDB; Q9BYH8; -.
DR TreeFam; TF330224; -.
DR PathwayCommons; Q9BYH8; -.
DR SignaLink; Q9BYH8; -.
DR SIGNOR; Q9BYH8; -.
DR BioGRID-ORCS; 64332; 6 hits in 1081 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 179 other tissues.
DR ExpressionAtlas; Q9BYH8; baseline and differential.
DR Genevisible; Q9BYH8; HS.
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:0006954; P:inflammatory response; 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:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISS:UniProtKB.
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 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; 3.
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 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
