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Protein

OTU domain-containing protein 7B

Gene

Otud7b

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses. In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B. Negatively regulates mucosal immunity against infections. Mediates deubiquitination of EGFR. Has deubiquitinating activity toward 'Lys-11', 'Lys-48' or 'Lys-63'-linked polyubiquitin chains. In vitro, has preference for 'Lys-11'-linked polyubiquitin chains; however such data are unsure in vivo. Hydrolyzes both linear and branched forms of polyubiquitin.1 Publication

Catalytic activityi

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).

Enzyme regulationi

Deubiquitinase activity is inhibited following interactin with PARK7.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei191 – 1911By similarity
Active sitei194 – 1941NucleophileCurated
Active sitei358 – 3581Proton acceptorCurated

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri793 – 82836A20-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • cysteine-type peptidase activity Source: UniProtKB
  • DNA binding Source: InterPro
  • K63-linked polyubiquitin binding Source: BHF-UCL
  • Lys48-specific deubiquitinase activity Source: MGI
  • ubiquitin-specific protease activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • mucosal immune response Source: UniProtKB
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • negative regulation of interleukin-8 production Source: MGI
  • negative regulation of protein localization to nucleus Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: ParkinsonsUK-UCL
  • protein deubiquitination Source: MGI
  • protein K11-linked deubiquitination Source: UniProtKB
  • protein K48-linked deubiquitination Source: UniProtKB
  • protein K63-linked deubiquitination Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Immunity, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Protein family/group databases

MEROPSiC64.002.

Names & Taxonomyi

Protein namesi
Recommended name:
OTU domain-containing protein 7B (EC:3.4.19.12)
Alternative name(s):
Cellular zinc finger anti-NF-kappa-B protein
Zinc finger A20 domain-containing protein 1
Zinc finger protein Cezanne
Gene namesi
Name:Otud7b
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:2654703. Otud7b.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Shuttles be cytoplasm and the nucleus in a XPO1/CRM1-dependent manner.

GO - Cellular componenti

  • cytoplasm Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice do not show obvious defects in survival, except a moderately reduced body weight. They however display hyperactivation of non-canonical NF-kappa-B without affecting canonical NF-kappa-B activation. Mice show B-cell hyper-responsiveness to antigens, lymphoid follicular hyperplasia in the intestinal mucosa and elevated host-defense ability against an intestinal bacterial pathogen, Citrobacter rodentium.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi194 – 1941C → S: Loss of deubiquitinating activity; when associated with R-358. 1 Publication
Mutagenesisi358 – 3581H → R: Loss of deubiquitinating activity; when associated with S-194. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 840840OTU domain-containing protein 7BPRO_0000421819Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei100 – 1001PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated by EGFR.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiB2RUR8.
PaxDbiB2RUR8.
PRIDEiB2RUR8.

Expressioni

Gene expression databases

ExpressionAtlasiB2RUR8. baseline and differential.
GenevisibleiB2RUR8. MM.

Interactioni

Subunit structurei

Interacts with TRAF6. Interacts with PARK7, leading to inhibit deubiquitinase activity. Interacts with EGFR, ITCH and NEDD4 (By similarity). Interacts with TRAF3.By similarity1 Publication

Protein-protein interaction databases

BioGridi230871. 5 interactions.
DIPiDIP-60128N.
IntActiB2RUR8. 1 interaction.
STRINGi10090.ENSMUSP00000046413.

Structurei

3D structure databases

ProteinModelPortaliB2RUR8.
SMRiB2RUR8. Positions 1-59, 147-395.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini183 – 365183OTUPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni152 – 401250TRAF-bindingBy similarityAdd
BLAST
Regioni167 – 440274CatalyticBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi483 – 49816Nuclear localization signalSequence AnalysisAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase C64 family.Curated
Contains 1 A20-type zinc finger.PROSITE-ProRule annotation
Contains 1 OTU domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri793 – 82836A20-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG282016.
GeneTreeiENSGT00530000062989.
HOGENOMiHOG000048103.
HOVERGENiHBG050904.
InParanoidiB2RUR8.
KOiK11860.
OMAiYPHQDSI.
OrthoDBiEOG7JHM57.
PhylomeDBiB2RUR8.
TreeFamiTF323312.

Family and domain databases

InterProiIPR003323. OTU_dom.
IPR002653. Znf_A20.
[Graphical view]
PfamiPF02338. OTU. 1 hit.
[Graphical view]
PROSITEiPS50802. OTU. 1 hit.
PS51036. ZF_A20. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

B2RUR8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTLDMDAVLS DFVRSTGAEP GLARDLLEGK NWDVSAALSD FEQLRQVHAG
60 70 80 90 100
NLSPPFSGGS TCPKTPEKGG SDREPTRPSR PILQRQDDVI QEKRLSRGIS
110 120 130 140 150
HASSSIVSLA RSHVSSNGGG GGSSEHPLEM PICAFQLPDL TVYKEDFRSF
160 170 180 190 200
IERDLIEQSM LVALEQAGRL NWWVSMDSTC QRLLPLATTG DGNCLLHAAS
210 220 230 240 250
LGMWGFHDRD LVLRKALYAL MEKGVEKEAL RRRWRWQQTQ QNKESGLVYT
260 270 280 290 300
EDEWQKEWNE LIKLASSEPR MHLGSNGASG GGVESSEEPV YESLEEFHVF
310 320 330 340 350
VLAHVLKRPI VVVADTMLRD SGGEAFAPIP FGGIYLPLEV PASQCHRSPL
360 370 380 390 400
VLAYDQAHFS ALVSMEQKES AKEQAVIPLT DSEHKLLPLH FAVDPGKGWE
410 420 430 440 450
WGKDDNDNVR LASIILSLEV KLHLLHSYMN VKWIPLSSDS QAPLAQPESP
460 470 480 490 500
TASAGDEPRS TPESGESDKE SVGSSSLGNE GSRRKEKSKR DREKDKKRAD
510 520 530 540 550
SVANKLGSFG KTLGSKLKKN MGGLMHSKGP KPGGLGSGSG ISSGTETLEK
560 570 580 590 600
KKKNNTLKSW KGGKEEAAGD GPVSEKPPSE SVGNGGSKYS QEVMQSLSTM
610 620 630 640 650
RIAMQGEGKY IFVGTLKMGH RHQYQEEMIQ RYLADAEERF LAEQKQKEVE
660 670 680 690 700
RKIMNGGLVS GPPPAKKPEP DGGEDQPSDS PAEPKAMAFS TAYPGGFTIP
710 720 730 740 750
RPSGGGVHCQ EPRRQLAGGP CVGGLPSYAT FPRQYPGRPY PHQDNIPALE
760 770 780 790 800
PGKDGVHRGA LLPPQFRVAD SYSNGYREPP EPDGWAGAPR GLPPTQTKCK
810 820 830 840
QPNCSFYGHP ETNNLCSCCY REELRRRERE PGGELLAHRF
Length:840
Mass (Da):91,983
Last modified:July 1, 2008 - v1
Checksum:iB63C06B656CC02EE
GO

Sequence cautioni

The sequence AAH37040.1 differs from that shown.Contaminating sequence. Potential poly-A sequence.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC092094 Genomic DNA. No translation available.
CH466620 Genomic DNA. Translation: EDL38862.1.
BC141397 mRNA. Translation: AAI41398.1.
BC037040 mRNA. Translation: AAH37040.1. Sequence problems.
BC141398 mRNA. Translation: AAI41399.1.
CCDSiCCDS17629.1.
RefSeqiNP_001020784.1. NM_001025613.1.
NP_001020785.1. NM_001025614.1.
XP_006501448.1. XM_006501385.2.
XP_006501449.1. XM_006501386.2.
XP_006501452.1. XM_006501389.2.
XP_011238399.1. XM_011240097.1.
XP_011238400.1. XM_011240098.1.
XP_011238401.1. XM_011240099.1.
UniGeneiMm.272336.
Mm.487453.

Genome annotation databases

EnsembliENSMUST00000035519; ENSMUSP00000046413; ENSMUSG00000038495.
ENSMUST00000090785; ENSMUSP00000088291; ENSMUSG00000038495.
ENSMUST00000098849; ENSMUSP00000096449; ENSMUSG00000038495.
GeneIDi229603.
KEGGimmu:229603.
UCSCiuc008qma.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC092094 Genomic DNA. No translation available.
CH466620 Genomic DNA. Translation: EDL38862.1.
BC141397 mRNA. Translation: AAI41398.1.
BC037040 mRNA. Translation: AAH37040.1. Sequence problems.
BC141398 mRNA. Translation: AAI41399.1.
CCDSiCCDS17629.1.
RefSeqiNP_001020784.1. NM_001025613.1.
NP_001020785.1. NM_001025614.1.
XP_006501448.1. XM_006501385.2.
XP_006501449.1. XM_006501386.2.
XP_006501452.1. XM_006501389.2.
XP_011238399.1. XM_011240097.1.
XP_011238400.1. XM_011240098.1.
XP_011238401.1. XM_011240099.1.
UniGeneiMm.272336.
Mm.487453.

3D structure databases

ProteinModelPortaliB2RUR8.
SMRiB2RUR8. Positions 1-59, 147-395.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi230871. 5 interactions.
DIPiDIP-60128N.
IntActiB2RUR8. 1 interaction.
STRINGi10090.ENSMUSP00000046413.

Protein family/group databases

MEROPSiC64.002.

Proteomic databases

MaxQBiB2RUR8.
PaxDbiB2RUR8.
PRIDEiB2RUR8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000035519; ENSMUSP00000046413; ENSMUSG00000038495.
ENSMUST00000090785; ENSMUSP00000088291; ENSMUSG00000038495.
ENSMUST00000098849; ENSMUSP00000096449; ENSMUSG00000038495.
GeneIDi229603.
KEGGimmu:229603.
UCSCiuc008qma.1. mouse.

Organism-specific databases

CTDi56957.
MGIiMGI:2654703. Otud7b.

Phylogenomic databases

eggNOGiNOG282016.
GeneTreeiENSGT00530000062989.
HOGENOMiHOG000048103.
HOVERGENiHBG050904.
InParanoidiB2RUR8.
KOiK11860.
OMAiYPHQDSI.
OrthoDBiEOG7JHM57.
PhylomeDBiB2RUR8.
TreeFamiTF323312.

Miscellaneous databases

ChiTaRSiOtud7b. mouse.
NextBioi379553.
PROiB2RUR8.
SOURCEiSearch...

Gene expression databases

ExpressionAtlasiB2RUR8. baseline and differential.
GenevisibleiB2RUR8. MM.

Family and domain databases

InterProiIPR003323. OTU_dom.
IPR002653. Znf_A20.
[Graphical view]
PfamiPF02338. OTU. 1 hit.
[Graphical view]
PROSITEiPS50802. OTU. 1 hit.
PS51036. ZF_A20. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "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].
    Tissue: Brain and Eye.
  4. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  5. "OTUD7B controls non-canonical NF-kappaB activation through deubiquitination of TRAF3."
    Hu H., Brittain G.C., Chang J.H., Puebla-Osorio N., Jin J., Zal A., Xiao Y., Cheng X., Chang M., Fu Y.X., Zal T., Zhu C., Sun S.C.
    Nature 494:371-374(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH TRAF3, MUTAGENESIS OF CYS-194 AND HIS-358.

Entry informationi

Entry nameiOTU7B_MOUSE
AccessioniPrimary (citable) accession number: B2RUR8
Secondary accession number(s): Q8CFS0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 6, 2013
Last sequence update: July 1, 2008
Last modified: July 22, 2015
This is version 68 of the entry and version 1 of the sequence. [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
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.