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Protein

NF-kappa-B inhibitor zeta

Gene

Nfkbiz

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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). Involved in the induction of T helper 17 cells (Th17) differentiation upon recognition of antigen by T cell antigen receptor (TCR) (PubMed:25282160).By similarity5 Publications

GO - Biological processi

  • inflammatory response Source: MGI
  • positive regulation of inflammatory response Source: Ensembl
  • positive regulation of T-helper 17 cell differentiation Source: UniProtKB
  • T cell receptor signaling pathway Source: UniProtKB

Keywordsi

Molecular functionActivator
Biological processTranscription, 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:Inap, Mail
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:1931595 Nfkbiz

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice have splenocytes with defective proliferation in response to LPS but not to anti-CD40, IL-4 and anti-IgM. Though mice grew normally after birth, some of them started to develop atopic dermatitis-like skin lesions with acanthosis and lichenoid changes at the age of 4-5 weeks. All mice developed the disease by the age of 10 weeks. 5-week-old mice show pathological changes in the conjunctiva, including a heavy lymphocyte infiltration into the submucosa and loss of goblet cells in the conjunctival epithelium.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi163K → A: Abolishes nuclear localization. 1 Publication1
Mutagenesisi164R → A: Abolishes nuclear localization. 1 Publication1
Mutagenesisi177K → A: Abolishes nuclear localization. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003235781 – 728NF-kappa-B inhibitor zetaAdd BLAST728

Proteomic databases

PaxDbiQ9EST8
PRIDEiQ9EST8

PTM databases

iPTMnetiQ9EST8
PhosphoSitePlusiQ9EST8

Expressioni

Tissue specificityi

Expressed in kidney, liver, lung and heart. Expressed at very low levels in skeletal muscle, spleen and brain.1 Publication

Inductioni

By IL-1, LPS, peptidoglycan, bacterial lipoprotein, flagellin, MALP-2, R-848 and CpG DNA, but not by TNF-alpha.4 Publications

Gene expression databases

BgeeiENSMUSG00000035356 Expressed in 262 organ(s), highest expression level in islet of Langerhans
GenevisibleiQ9EST8 MM

Interactioni

Subunit structurei

Interacts with NFKB1/p50. Interacts with RELA; the interaction was not detected in (PubMed:11356851) (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Akirin2B1AXD83EBI-10107924,EBI-10107866

Protein-protein interaction databases

BioGridi219820, 5 interactors
IntActiQ9EST8, 1 interactor
MINTiQ9EST8
STRINGi10090.ENSMUSP00000041173

Structurei

3D structure databases

ProteinModelPortaliQ9EST8
SMRiQ9EST8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati453 – 482ANK 1Add BLAST30
Repeati489 – 518ANK 2Add BLAST30
Repeati522 – 551ANK 3Add BLAST30
Repeati561 – 589ANK 4Add BLAST29
Repeati591 – 617ANK 5Add BLAST27
Repeati622 – 651ANK 6Add BLAST30
Repeati658 – 691ANK 7Add BLAST34

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni329 – 403Required for transcriptional activityAdd BLAST75
Regioni414 – 728Interaction with NFKB1/p50Add BLAST315

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi163 – 178Nuclear localization signalAdd BLAST16

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504 Eukaryota
COG0666 LUCA
GeneTreeiENSGT00550000074527
HOVERGENiHBG059690
InParanoidiQ9EST8
KOiK14242
OMAiLEYSPYS
OrthoDBiEOG091G06D9
PhylomeDBiQ9EST8
TreeFamiTF330224

Family and domain databases

CDDicd00204 ANK, 2 hits
Gene3Di1.25.40.20, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
PfamiView protein in Pfam
PF12796 Ank_2, 2 hits
PRINTSiPR01415 ANKYRIN
SMARTiView protein in SMART
SM00248 ANK, 6 hits
SUPFAMiSSF48403 SSF48403, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 3 hits

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q9EST8-1) [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 RGGEGLLDAA GDCGLMTSPL NLAYFYGASP PSAPGAGDTG
60 70 80 90 100
YLSAVPSAPG SPGSDSSDFS STSSVSSCGA VESRPRGGAR AERPQVEPHM
110 120 130 140 150
GVGRQQRGPF QGVRVKNSVK ELLLHIRSNK QKASGQPVDE FKTQSVNIEQ
160 170 180 190 200
LTDLKSAVSA VGKRKGPDPL SDGPVCKRPA LLPSHFVTSP QTPTPGESME
210 220 230 240 250
DVRHSESKLD SSAALLQNII NIKNECNPVS LNTVQVSWMS PTVPQNSPRD
260 270 280 290 300
QCQDFHGGQA FSPPQKYQPF QVSGSPQMMD QASMYQYSPQ TQNMQQPPPL
310 320 330 340 350
PPQQQHQQNY PHNSPLQFSP YSRMSQSPKY DSNLFDTHEP QFCTGQSFVS
360 370 380 390 400
LLTGPGEPES LAVPVPAPTS IPPQTETQLQ TFSLMPSNAC EAVVGVHDVG
410 420 430 440 450
SHSLGTSLSL QNIMGSPMNT TQLGKSFFQW QVEQEESKLA NIPQDQFLAR
460 470 480 490 500
DGDGDTFLHI AVAQGRRALS YVLARKMNAL HMLDIKEHNG QSAFQVAVAA
510 520 530 540 550
NQHLIVQDLV NLGAQVNTTD CWGRTPLHVC AEKGHSQVLQ AIQKGAVRSN
560 570 580 590 600
QFVDLEATNY DGLTPLHCAV VAHNAVVHEL QRNRQSHSPE VQDLLLRNKS
610 620 630 640 650
LVDTIKCLIQ MGAAVEAKDR KSGRTALHLA AEEANLELIR LFLELPSCLS
660 670 680 690 700
FVNAKAYNGN TALHVAASLQ YRVTQLDAVR LLMRKGADPS TRNLENEQPV
710 720
HLVPDGPVGE QIRRILKGKS IQQRAPPY
Note: Major.
Length:728
Mass (Da):79,007
Last modified:March 1, 2001 - v1
Checksum:iE2CAB725295A08B7
GO
Isoform 2 (identifier: Q9EST8-2) [UniParc]FASTAAdd to basket
Also known as: MAIL-S

The sequence of this isoform differs from the canonical sequence as follows:
     1-99: Missing.

Show »
Length:629
Mass (Da):69,179
Checksum:i8F87AA6147324534
GO
Isoform 3 (identifier: Q9EST8-3) [UniParc]FASTAAdd to basket
Also known as: D

The sequence of this isoform differs from the canonical sequence as follows:
     236-429: Missing.

Show »
Length:534
Mass (Da):57,666
Checksum:iCC42F49D3E2E5995
GO

Sequence cautioni

The sequence BAE24648 differs from that shown. Reason: Frameshift at positions 216 and 227.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti31N → K in BAE30878 (PubMed:16141072).Curated1
Sequence conflicti87G → D in BAE35257 (PubMed:16141072).Curated1
Sequence conflicti87G → D in BAE34809 (PubMed:16141072).Curated1
Sequence conflicti142K → E in BAE35257 (PubMed:16141072).Curated1
Sequence conflicti142K → E in BAE34809 (PubMed:16141072).Curated1
Sequence conflicti208K → E in BAE29631 (PubMed:16141072).Curated1
Sequence conflicti223K → R in BAE35601 (PubMed:16141072).Curated1
Sequence conflicti239M → I in BAE24648 (PubMed:11278262).Curated1
Sequence conflicti273S → G in BAE29631 (PubMed:16141072).Curated1
Sequence conflicti461A → V in BAE35257 (PubMed:16141072).Curated1
Sequence conflicti461A → V in BAE34809 (PubMed:16141072).Curated1
Sequence conflicti475R → K in BAE35257 (PubMed:16141072).Curated1
Sequence conflicti475R → K in BAE34809 (PubMed:16141072).Curated1
Sequence conflicti600S → G in BAE23017 (PubMed:11278262).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0320241 – 99Missing in isoform 2. 1 PublicationAdd BLAST99
Alternative sequenceiVSP_032025236 – 429Missing in isoform 3. 1 PublicationAdd BLAST194

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020974 mRNA Translation: BAB18302.1
AB040458 Genomic DNA Translation: BAB85809.1
AB026551 mRNA Translation: BAA95161.2
AB047549 mRNA Translation: BAB32782.1
AK082908 mRNA Translation: BAC38681.1
AK136509 mRNA Translation: BAE23017.1
AK141318 mRNA Translation: BAE24648.1 Frameshift.
AK150519 mRNA Translation: BAE29631.1
AK152016 mRNA Translation: BAE30878.1
AK159093 mRNA Translation: BAE34809.1
AK159171 mRNA Translation: BAE34871.1
AK159459 mRNA Translation: BAE35101.1
AK159645 mRNA Translation: BAE35257.1
AK159917 mRNA Translation: BAE35480.1
AK160065 mRNA Translation: BAE35601.1
BC058188 mRNA Translation: AAH58188.1
AB196497 mRNA Translation: BAD82955.1
CCDSiCCDS28216.1 [Q9EST8-1]
CCDS49869.1 [Q9EST8-2]
RefSeqiNP_001152866.1, NM_001159394.1 [Q9EST8-1]
NP_001152867.1, NM_001159395.1 [Q9EST8-2]
NP_085115.1, NM_030612.3 [Q9EST8-1]
UniGeneiMm.247272

Genome annotation databases

EnsembliENSMUST00000036273; ENSMUSP00000041173; ENSMUSG00000035356 [Q9EST8-1]
ENSMUST00000096026; ENSMUSP00000093726; ENSMUSG00000035356 [Q9EST8-2]
ENSMUST00000114457; ENSMUSP00000110101; ENSMUSG00000035356 [Q9EST8-2]
ENSMUST00000114458; ENSMUSP00000110102; ENSMUSG00000035356 [Q9EST8-1]
GeneIDi80859
KEGGimmu:80859
UCSCiuc007zlm.2 mouse [Q9EST8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020974 mRNA Translation: BAB18302.1
AB040458 Genomic DNA Translation: BAB85809.1
AB026551 mRNA Translation: BAA95161.2
AB047549 mRNA Translation: BAB32782.1
AK082908 mRNA Translation: BAC38681.1
AK136509 mRNA Translation: BAE23017.1
AK141318 mRNA Translation: BAE24648.1 Frameshift.
AK150519 mRNA Translation: BAE29631.1
AK152016 mRNA Translation: BAE30878.1
AK159093 mRNA Translation: BAE34809.1
AK159171 mRNA Translation: BAE34871.1
AK159459 mRNA Translation: BAE35101.1
AK159645 mRNA Translation: BAE35257.1
AK159917 mRNA Translation: BAE35480.1
AK160065 mRNA Translation: BAE35601.1
BC058188 mRNA Translation: AAH58188.1
AB196497 mRNA Translation: BAD82955.1
CCDSiCCDS28216.1 [Q9EST8-1]
CCDS49869.1 [Q9EST8-2]
RefSeqiNP_001152866.1, NM_001159394.1 [Q9EST8-1]
NP_001152867.1, NM_001159395.1 [Q9EST8-2]
NP_085115.1, NM_030612.3 [Q9EST8-1]
UniGeneiMm.247272

3D structure databases

ProteinModelPortaliQ9EST8
SMRiQ9EST8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi219820, 5 interactors
IntActiQ9EST8, 1 interactor
MINTiQ9EST8
STRINGi10090.ENSMUSP00000041173

PTM databases

iPTMnetiQ9EST8
PhosphoSitePlusiQ9EST8

Proteomic databases

PaxDbiQ9EST8
PRIDEiQ9EST8

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000036273; ENSMUSP00000041173; ENSMUSG00000035356 [Q9EST8-1]
ENSMUST00000096026; ENSMUSP00000093726; ENSMUSG00000035356 [Q9EST8-2]
ENSMUST00000114457; ENSMUSP00000110101; ENSMUSG00000035356 [Q9EST8-2]
ENSMUST00000114458; ENSMUSP00000110102; ENSMUSG00000035356 [Q9EST8-1]
GeneIDi80859
KEGGimmu:80859
UCSCiuc007zlm.2 mouse [Q9EST8-1]

Organism-specific databases

CTDi64332
MGIiMGI:1931595 Nfkbiz

Phylogenomic databases

eggNOGiKOG0504 Eukaryota
COG0666 LUCA
GeneTreeiENSGT00550000074527
HOVERGENiHBG059690
InParanoidiQ9EST8
KOiK14242
OMAiLEYSPYS
OrthoDBiEOG091G06D9
PhylomeDBiQ9EST8
TreeFamiTF330224

Miscellaneous databases

ChiTaRSiNfkbiz mouse
PROiPR:Q9EST8
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000035356 Expressed in 262 organ(s), highest expression level in islet of Langerhans
GenevisibleiQ9EST8 MM

Family and domain databases

CDDicd00204 ANK, 2 hits
Gene3Di1.25.40.20, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
PfamiView protein in Pfam
PF12796 Ank_2, 2 hits
PRINTSiPR01415 ANKYRIN
SMARTiView protein in SMART
SM00248 ANK, 6 hits
SUPFAMiSSF48403 SSF48403, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 3 hits
ProtoNetiSearch...

Entry informationi

Entry nameiIKBZ_MOUSE
AccessioniPrimary (citable) accession number: Q9EST8
Secondary accession number(s): Q3TVL7
, Q3TWK9, Q3U8Y9, Q3UCI2, Q3URP0, Q3UW99, Q5NT97, Q99NA4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 1, 2001
Last modified: November 7, 2018
This is version 149 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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