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Protein

OTU domain-containing protein 7B

Gene

Otud7b

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 (PubMed:23334419). Negatively regulates mucosal immunity against infections (PubMed:23334419). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B (PubMed:26903241). Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (PubMed:26903241). Mediates deubiquitination of EGFR (By similarity). Has deubiquitinating activity toward 'Lys-11', 'Lys-48' and 'Lys-63'-linked polyubiquitin chains. Has a much higher catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro); however the physiological significance of these data are unsure. Hydrolyzes both linear and branched forms of polyubiquitin (By similarity).By similarity2 Publications

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).1 Publication

Activity regulationi

Deubiquitinase activity is inhibited following interaction with PARK7.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei191By similarity1
Active sitei194Nucleophile1 Publication1
Sitei197Stabilizes the conformation of the regulatory loopBy similarity1
Active sitei358Proton acceptor1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri793 – 828A20-typePROSITE-ProRule annotationAdd BLAST36

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processAdaptive immunity, Immunity, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-5357786 TNFR1-induced proapoptotic signaling
R-MMU-5357905 Regulation of TNFR1 signaling
R-MMU-5357956 TNFR1-induced NFkappaB signaling pathway
R-MMU-5689896 Ovarian tumor domain proteases

Protein family/group databases

MEROPSiC64.001

Names & Taxonomyi

Protein namesi
Recommended name:
OTU domain-containing protein 7B (EC:3.4.19.121 Publication)
Alternative name(s):
Cellular zinc finger anti-NF-kappa-B protein
Zinc finger A20 domain-containing protein 1
Zinc finger protein CezanneCurated
Gene namesi
Name:Otud7b
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:2654703 Otud7b

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

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

No visible phenotype in neonates (PubMed:26903241). Mice do not show obvious defects in survival, except a moderately reduced body weight (PubMed:23334419). 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 (PubMed:23334419). At 12 months after birth, mutant mice display impaired T cell homeostasis with increased numbers of naive T cells and reduced numbers of Th1 memory-like T cells (PubMed:26903241). Young adults that have no overt change in T cell homeostasis still show impaired production of effector T cells in response to repeated stimulation with an antigen and an impaired defense against infection by L.monocytogenes (PubMed:26903241). Conversely, mutant mice are less susceptible to experimentally induced autoimmune encephalitis (PubMed:26903241).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi194C → S: Loss of deubiquitinating activity; when associated with R-358. 1 Publication1
Mutagenesisi358H → R: Loss of deubiquitinating activity; when associated with S-194. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004218191 – 840OTU domain-containing protein 7BAdd BLAST840

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei100PhosphoserineCombined sources1
Modified residuei464PhosphoserineCombined sources1
Modified residuei467PhosphoserineCombined sources1
Modified residuei471PhosphoserineCombined sources1
Modified residuei730PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated by EGFR.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiB2RUR8
MaxQBiB2RUR8
PaxDbiB2RUR8
PeptideAtlasiB2RUR8
PRIDEiB2RUR8

PTM databases

iPTMnetiB2RUR8
PhosphoSitePlusiB2RUR8

Expressioni

Gene expression databases

BgeeiENSMUSG00000038495 Expressed in 262 organ(s), highest expression level in blood
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 (PubMed:23334419). Interacts with ZAP70 in activated T cells, but not in resting T cells (PubMed:26903241).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CD40P259422EBI-3454264,EBI-525714From Homo sapiens.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi230871, 6 interactors
DIPiDIP-60128N
IntActiB2RUR8, 5 interactors
STRINGi10090.ENSMUSP00000046413

Structurei

3D structure databases

ProteinModelPortaliB2RUR8
SMRiB2RUR8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini183 – 365OTUPROSITE-ProRule annotationAdd BLAST183

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni152 – 401TRAF-bindingBy similarityAdd BLAST250
Regioni167 – 440CatalyticBy similarityAdd BLAST274
Regioni187 – 193Regulatory loopBy similarity7

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi483 – 498Nuclear localization signalSequence analysisAdd BLAST16

Domaini

The protein undergoes a significant conformation change upon binding to ubiquitinated substrates. The loop that precedes the active site is in an autoinhibitory conformation in the apoprotein. Ubiquitin binding leads to a conformation change; the loop is stabilized in a catalytically competent conformation with the result that the active site Cys can form the reaction state intermediate.By similarity

Sequence similaritiesi

Belongs to the peptidase C64 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri793 – 828A20-typePROSITE-ProRule annotationAdd BLAST36

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4345 Eukaryota
ENOG410XT8E LUCA
GeneTreeiENSGT00530000062989
HOGENOMiHOG000048103
HOVERGENiHBG050904
InParanoidiB2RUR8
KOiK11860
OMAiYATFPRQ
OrthoDBiEOG091G03R0
PhylomeDBiB2RUR8
TreeFamiTF323312

Family and domain databases

InterProiView protein in InterPro
IPR003323 OTU_dom
IPR002653 Znf_A20
PfamiView protein in Pfam
PF02338 OTU, 1 hit
PF01754 zf-A20, 1 hit
SMARTiView protein in SMART
SM00259 ZnF_A20, 1 hit
PROSITEiView protein in PROSITE
PS50802 OTU, 1 hit
PS51036 ZF_A20, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D3Z210D3Z210_MOUSE
OTU domain-containing protein 7B
Otud7b
195Annotation score:
D3YYZ8D3YYZ8_MOUSE
OTU domain-containing protein 7B
Otud7b
101Annotation score:

Sequence cautioni

The sequence AAH37040 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_006501385.3
XP_006501449.1, XM_006501386.3
XP_006501452.1, XM_006501389.3
XP_017175035.1, XM_017319546.1
XP_017175036.1, XM_017319547.1
UniGeneiMm.272336
Mm.487453

Genome annotation databases

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

Similar proteinsi

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_006501385.3
XP_006501449.1, XM_006501386.3
XP_006501452.1, XM_006501389.3
XP_017175035.1, XM_017319546.1
XP_017175036.1, XM_017319547.1
UniGeneiMm.272336
Mm.487453

3D structure databases

ProteinModelPortaliB2RUR8
SMRiB2RUR8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi230871, 6 interactors
DIPiDIP-60128N
IntActiB2RUR8, 5 interactors
STRINGi10090.ENSMUSP00000046413

Protein family/group databases

MEROPSiC64.001

PTM databases

iPTMnetiB2RUR8
PhosphoSitePlusiB2RUR8

Proteomic databases

EPDiB2RUR8
MaxQBiB2RUR8
PaxDbiB2RUR8
PeptideAtlasiB2RUR8
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

eggNOGiKOG4345 Eukaryota
ENOG410XT8E LUCA
GeneTreeiENSGT00530000062989
HOGENOMiHOG000048103
HOVERGENiHBG050904
InParanoidiB2RUR8
KOiK11860
OMAiYATFPRQ
OrthoDBiEOG091G03R0
PhylomeDBiB2RUR8
TreeFamiTF323312

Enzyme and pathway databases

ReactomeiR-MMU-5357786 TNFR1-induced proapoptotic signaling
R-MMU-5357905 Regulation of TNFR1 signaling
R-MMU-5357956 TNFR1-induced NFkappaB signaling pathway
R-MMU-5689896 Ovarian tumor domain proteases

Miscellaneous databases

ChiTaRSiOtud7b mouse
PROiPR:B2RUR8
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038495 Expressed in 262 organ(s), highest expression level in blood
ExpressionAtlasiB2RUR8 baseline and differential
GenevisibleiB2RUR8 MM

Family and domain databases

InterProiView protein in InterPro
IPR003323 OTU_dom
IPR002653 Znf_A20
PfamiView protein in Pfam
PF02338 OTU, 1 hit
PF01754 zf-A20, 1 hit
SMARTiView protein in SMART
SM00259 ZnF_A20, 1 hit
PROSITEiView protein in PROSITE
PS50802 OTU, 1 hit
PS51036 ZF_A20, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiOTU7B_MOUSE
AccessioniPrimary (citable) accession number: B2RUR8
Secondary accession number(s): Q8CFS0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 6, 2013
Last sequence update: July 1, 2008
Last modified: September 12, 2018
This is version 92 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. SIMILARITY comments
    Index of protein domains and families
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. 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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