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Protein

NF-kappa-B inhibitor zeta

Gene

NFKBIZ

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in regulation of NF-kappa-B transcription factor complexes. Inhibits NF-kappa-B activity without affecting its nuclear translocation upon stimulation. Inhibits DNA-binding of RELA and NFKB1/p50, and of the NF-kappa-B p65-p50 heterodimer and the NF-kappa-B p50-p50 homodimer. Seems also to activate NF-kappa-B-mediated transcription. In vitro, upon association with NFKB1/p50 has transcriptional activation activity and, together with NFKB1/p50 and RELA, is recruited to LCN2 promoters. Promotes transcription of LCN2 and DEFB4. Is recruited to IL-6 promoters and activates IL-6 but decreases TNF-alpha production in response to LPS. Seems to be involved in the induction of inflammatory genes activated through TLR/IL-1 receptor signaling. May promote apoptosis (By similarity).By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
NF-kappa-B inhibitor zeta
Alternative name(s):
I-kappa-B-zeta
Short name:
IkB-zeta
Short name:
IkappaBzeta
IL-1 inducible nuclear ankyrin-repeat protein
Short name:
INAP
Molecule possessing ankyrin repeats induced by lipopolysaccharide
Short name:
MAIL
Gene namesi
Name:NFKBIZ
Synonyms:IKBZ, INAP, MAIL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:29805. NFKBIZ.

Subcellular locationi

  • Nucleus 1 Publication

  • Note: Aggregated in dot-like structures. Colocalizes with NCOR2.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134990505.

Polymorphism and mutation databases

BioMutaiNFKBIZ.
DMDMi74752456.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 718718NF-kappa-B inhibitor zetaPRO_0000323577Add
BLAST

Proteomic databases

MaxQBiQ9BYH8.
PaxDbiQ9BYH8.
PRIDEiQ9BYH8.

PTM databases

iPTMnetiQ9BYH8.
PhosphoSiteiQ9BYH8.

Expressioni

Tissue specificityi

Expressed at high levels in peripheral blood leukocytes and lung, at moderate levels in liver, placenta, and at low levels in spleen, kidney, skeletal muscle and heart.1 Publication

Inductioni

By TNF, IL1/interleukin-1 and bacterial lipopolysaccharides (LPS).1 Publication

Gene expression databases

BgeeiQ9BYH8.
CleanExiHS_NFKBIZ.
ExpressionAtlasiQ9BYH8. baseline and differential.
GenevisibleiQ9BYH8. HS.

Organism-specific databases

HPAiHPA010547.

Interactioni

Subunit structurei

Interacts with NFKB1/p50. Interacts with RELA.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Akirin2B1AXD83EBI-3939694,EBI-10107866From a different organism.

Protein-protein interaction databases

BioGridi122139. 3 interactions.
IntActiQ9BYH8. 4 interactions.
STRINGi9606.ENSP00000325663.

Structurei

3D structure databases

ProteinModelPortaliQ9BYH8.
SMRiQ9BYH8. Positions 384-707.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati443 – 47230ANK 1Add
BLAST
Repeati479 – 50830ANK 2Add
BLAST
Repeati512 – 54130ANK 3Add
BLAST
Repeati551 – 58030ANK 4Add
BLAST
Repeati582 – 60726ANK 5Add
BLAST
Repeati612 – 64130ANK 6Add
BLAST
Repeati648 – 68134ANK 7Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni321 – 39474Required for transcriptional activityBy similarityAdd
BLAST
Regioni404 – 718315Interaction with NFKB1/p50By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi164 – 17916Nuclear localization signalBy similarityAdd
BLAST

Sequence similaritiesi

Contains 7 ANK repeats.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00550000074527.
HOGENOMiHOG000113023.
HOVERGENiHBG059690.
InParanoidiQ9BYH8.
KOiK14242.
OMAiYEPNLFD.
PhylomeDBiQ9BYH8.
TreeFamiTF330224.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
PfamiPF12796. Ank_2. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 6 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 2 hits.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 3 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BYH8-1) [UniParc]FASTAAdd to basket

Also known as: MAIL-L

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MIVDKLLDDS RGGEGLRDAA GGCGLMTSPL NLSYFYGASP PAAAPGACDA
60 70 80 90 100
SCSVLGPSAP GSPGSDSSDF SSASSVSSCG AVESRSRGGA RAERQPVEPH
110 120 130 140 150
MGVGRQQRGP FQGVRVKNSV KELLLHIRSH KQKASGQAVD DFKTQGVNIE
160 170 180 190 200
QFRELKNTVS YSGKRKGPDS LSDGPACKRP ALLHSQFLTP PQTPTPGESM
210 220 230 240 250
EDVHLNEPKQ ESSADLLQNI INIKNECSPV SLNTVQVSWL NPVVVPQSSP
260 270 280 290 300
AEQCQDFHGG QVFSPPQKCQ PFQVRGSQQM IDQASLYQYS PQNQHVEQQP
310 320 330 340 350
HYTHKPTLEY SPFPIPPQSP AYEPNLFDGP ESQFCPNQSL VSLLGDQRES
360 370 380 390 400
ENIANPMQTS SSVQQQNDAH LHSFSMMPSS ACEAMVGHEM ASDSSNTSLP
410 420 430 440 450
FSNMGNPMNT TQLGKSLFQW QVEQEESKLA NISQDQFLSK DADGDTFLHI
460 470 480 490 500
AVAQGRRALS YVLARKMNAL HMLDIKEHNG QSAFQVAVAA NQHLIVQDLV
510 520 530 540 550
NIGAQVNTTD CWGRTPLHVC AEKGHSQVLQ AIQKGAVGSN QFVDLEATNY
560 570 580 590 600
DGLTPLHCAV IAHNAVVHEL QRNQQPHSPE VQELLLKNKS LVDTIKCLIQ
610 620 630 640 650
MGAAVEAKDR KSGRTALHLA AEEANLELIR LFLELPSCLS FVNAKAYNGN
660 670 680 690 700
TALHVAASLQ YRLTQLDAVR LLMRKGADPS TRNLENEQPV HLVPDGPVGE
710
QIRRILKGKS IQQRAPPY
Length:718
Mass (Da):78,061
Last modified:June 1, 2001 - v1
Checksum:i5656E00F2507DC7C
GO
Isoform 2 (identifier: Q9BYH8-2) [UniParc]FASTAAdd to basket

Also known as: MAIL-S, Transcription variant 3

The sequence of this isoform differs from the canonical sequence as follows:
     1-100: Missing.

Show »
Length:618
Mass (Da):68,245
Checksum:i483EE108DC96AA52
GO
Isoform 3 (identifier: Q9BYH8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     237-358: Missing.

Show »
Length:596
Mass (Da):64,298
Checksum:iFB69A4BAF8B33318
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti567 – 5671V → F in BAC03746 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti307 – 3071T → S.
Corresponds to variant rs3821727 [ dbSNP | Ensembl ].
VAR_039547

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 100100Missing in isoform 2. 3 PublicationsVSP_032022Add
BLAST
Alternative sequencei237 – 358122Missing in isoform 3. 1 PublicationVSP_032023Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037925 mRNA. Translation: BAB40337.1.
AF548362 mRNA. Translation: AAN40698.1.
DQ224339 mRNA. Translation: ABB02425.1.
AK054787 mRNA. Translation: BAG51424.1.
AK091782 mRNA. Translation: BAC03746.1.
CH471052 Genomic DNA. Translation: EAW79771.1.
CH471052 Genomic DNA. Translation: EAW79772.1.
BC060800 mRNA. Translation: AAH60800.1.
CCDSiCCDS2946.1. [Q9BYH8-1]
CCDS43123.1. [Q9BYH8-2]
RefSeqiNP_001005474.1. NM_001005474.2. [Q9BYH8-2]
NP_113607.1. NM_031419.3. [Q9BYH8-1]
UniGeneiHs.319171.

Genome annotation databases

EnsembliENST00000326151; ENSP00000325593; ENSG00000144802. [Q9BYH8-3]
ENST00000326172; ENSP00000325663; ENSG00000144802. [Q9BYH8-1]
ENST00000394054; ENSP00000377618; ENSG00000144802. [Q9BYH8-2]
GeneIDi64332.
KEGGihsa:64332.
UCSCiuc003dvo.4. human. [Q9BYH8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037925 mRNA. Translation: BAB40337.1.
AF548362 mRNA. Translation: AAN40698.1.
DQ224339 mRNA. Translation: ABB02425.1.
AK054787 mRNA. Translation: BAG51424.1.
AK091782 mRNA. Translation: BAC03746.1.
CH471052 Genomic DNA. Translation: EAW79771.1.
CH471052 Genomic DNA. Translation: EAW79772.1.
BC060800 mRNA. Translation: AAH60800.1.
CCDSiCCDS2946.1. [Q9BYH8-1]
CCDS43123.1. [Q9BYH8-2]
RefSeqiNP_001005474.1. NM_001005474.2. [Q9BYH8-2]
NP_113607.1. NM_031419.3. [Q9BYH8-1]
UniGeneiHs.319171.

3D structure databases

ProteinModelPortaliQ9BYH8.
SMRiQ9BYH8. Positions 384-707.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122139. 3 interactions.
IntActiQ9BYH8. 4 interactions.
STRINGi9606.ENSP00000325663.

PTM databases

iPTMnetiQ9BYH8.
PhosphoSiteiQ9BYH8.

Polymorphism and mutation databases

BioMutaiNFKBIZ.
DMDMi74752456.

Proteomic databases

MaxQBiQ9BYH8.
PaxDbiQ9BYH8.
PRIDEiQ9BYH8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000326151; ENSP00000325593; ENSG00000144802. [Q9BYH8-3]
ENST00000326172; ENSP00000325663; ENSG00000144802. [Q9BYH8-1]
ENST00000394054; ENSP00000377618; ENSG00000144802. [Q9BYH8-2]
GeneIDi64332.
KEGGihsa:64332.
UCSCiuc003dvo.4. human. [Q9BYH8-1]

Organism-specific databases

CTDi64332.
GeneCardsiNFKBIZ.
HGNCiHGNC:29805. NFKBIZ.
HPAiHPA010547.
MIMi608004. gene.
neXtProtiNX_Q9BYH8.
PharmGKBiPA134990505.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00550000074527.
HOGENOMiHOG000113023.
HOVERGENiHBG059690.
InParanoidiQ9BYH8.
KOiK14242.
OMAiYEPNLFD.
PhylomeDBiQ9BYH8.
TreeFamiTF330224.

Miscellaneous databases

ChiTaRSiNFKBIZ. human.
GeneWikiiNFKBIZ.
GenomeRNAii64332.
PROiQ9BYH8.
SOURCEiSearch...

Gene expression databases

BgeeiQ9BYH8.
CleanExiHS_NFKBIZ.
ExpressionAtlasiQ9BYH8. baseline and differential.
GenevisibleiQ9BYH8. HS.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
PfamiPF12796. Ank_2. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 6 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 2 hits.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 3 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Human MAIL: an inflammation-associated gene that is induced by lipopolysaccharide in leukocytes."
    Ochiai K., Morimatsu M., Kitamura H., Shiina T., Syuto B.
    Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Peripheral blood.
  2. "MAIL a novel IkB family member is induced by lipopolysaccharide in human monocytes and binds proIL-1beta."
    Parker-Barnes J.M., Yee J.F., Hart J.M., Doseff A.I., Wewers M.D.
    Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Monocyte.
  3. "A novel member of the IkappaB family, human IkappaB-zeta, inhibits transactivation of p65 and its DNA binding."
    Totzke G., Essmann F., Pohlmann S., Lindenblatt C., Janicke R.U., Schulze-Osthoff K.
    J. Biol. Chem. 281:12645-12654(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION IN NF-KAPPA-B INHIBITION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH RELA AND NFKB1, INDUCTION.
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
    Tissue: Cerebellum and Lung.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Placenta.
  7. "IL-1beta-specific up-regulation of neutrophil gelatinase-associated lipocalin is controlled by IkappaB-zeta."
    Cowland J.B., Muta T., Borregaard N.
    J. Immunol. 176:5559-5566(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN NF-KAPPA-B ACTIVATION.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiIKBZ_HUMAN
AccessioniPrimary (citable) accession number: Q9BYH8
Secondary accession number(s): B3KNR2
, D3DN54, Q8IUL4, Q8NAZ8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: June 1, 2001
Last modified: June 8, 2016
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.