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B2RUR8

- OTU7B_MOUSE

UniProt

B2RUR8 - OTU7B_MOUSE

Protein

OTU domain-containing protein 7B

Gene

Otud7b

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 60 (01 Oct 2014)
      Sequence version 1 (01 Jul 2008)
      Previous versions | rss
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    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

    1. cysteine-type peptidase activity Source: UniProtKB
    2. DNA binding Source: InterPro
    3. K63-linked polyubiquitin binding Source: BHF-UCL
    4. protein binding Source: UniProtKB
    5. ubiquitin-specific protease activity Source: UniProtKB
    6. ubiquitin thiolesterase activity Source: UniProtKB
    7. zinc ion binding Source: InterPro

    GO - Biological processi

    1. mucosal immune response Source: UniProtKB
    2. negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
    3. negative regulation of transcription from RNA polymerase II promoter Source: ParkinsonsUK-UCL
    4. protein deubiquitination Source: MGI
    5. protein K11-linked deubiquitination Source: UniProtKB
    6. protein K48-linked deubiquitination Source: UniProtKB
    7. protein K63-linked deubiquitination Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Immunity, Ubl conjugation pathway

    Keywords - Ligandi

    Metal-binding, Zinc

    Protein family/group databases

    MEROPSiC64.001.

    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: 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

    1. cytoplasm Source: MGI
    2. microtubule cytoskeleton Source: Ensembl
    3. nucleus Source: UniProtKB-SubCell

    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

    ArrayExpressiB2RUR8.
    GenevestigatoriB2RUR8.

    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

    DIPiDIP-60128N.
    IntActiB2RUR8. 1 interaction.
    STRINGi10090.ENSMUSP00000088291.

    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.
    OMAiYATFPRQ.
    OrthoDBiEOG7JHM57.
    PhylomeDBiB2RUR8.
    TreeFamiTF323312.

    Family and domain databases

    InterProiIPR003323. OTU.
    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

    MTLDMDAVLS DFVRSTGAEP GLARDLLEGK NWDVSAALSD FEQLRQVHAG    50
    NLSPPFSGGS TCPKTPEKGG SDREPTRPSR PILQRQDDVI QEKRLSRGIS 100
    HASSSIVSLA RSHVSSNGGG GGSSEHPLEM PICAFQLPDL TVYKEDFRSF 150
    IERDLIEQSM LVALEQAGRL NWWVSMDSTC QRLLPLATTG DGNCLLHAAS 200
    LGMWGFHDRD LVLRKALYAL MEKGVEKEAL RRRWRWQQTQ QNKESGLVYT 250
    EDEWQKEWNE LIKLASSEPR MHLGSNGASG GGVESSEEPV YESLEEFHVF 300
    VLAHVLKRPI VVVADTMLRD SGGEAFAPIP FGGIYLPLEV PASQCHRSPL 350
    VLAYDQAHFS ALVSMEQKES AKEQAVIPLT DSEHKLLPLH FAVDPGKGWE 400
    WGKDDNDNVR LASIILSLEV KLHLLHSYMN VKWIPLSSDS QAPLAQPESP 450
    TASAGDEPRS TPESGESDKE SVGSSSLGNE GSRRKEKSKR DREKDKKRAD 500
    SVANKLGSFG KTLGSKLKKN MGGLMHSKGP KPGGLGSGSG ISSGTETLEK 550
    KKKNNTLKSW KGGKEEAAGD GPVSEKPPSE SVGNGGSKYS QEVMQSLSTM 600
    RIAMQGEGKY IFVGTLKMGH RHQYQEEMIQ RYLADAEERF LAEQKQKEVE 650
    RKIMNGGLVS GPPPAKKPEP DGGEDQPSDS PAEPKAMAFS TAYPGGFTIP 700
    RPSGGGVHCQ EPRRQLAGGP CVGGLPSYAT FPRQYPGRPY PHQDNIPALE 750
    PGKDGVHRGA LLPPQFRVAD SYSNGYREPP EPDGWAGAPR GLPPTQTKCK 800
    QPNCSFYGHP ETNNLCSCCY REELRRRERE PGGELLAHRF 840
    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. Reason: Contaminating sequence. Potential poly-A sequence.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_006501447.1. XM_006501384.1.
    XP_006501448.1. XM_006501385.1.
    XP_006501449.1. XM_006501386.1.
    XP_006501450.1. XM_006501387.1.
    XP_006501451.1. XM_006501388.1.
    XP_006501452.1. XM_006501389.1.
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS17629.1.
    RefSeqi NP_001020784.1. NM_001025613.1.
    NP_001020785.1. NM_001025614.1.
    XP_006501447.1. XM_006501384.1.
    XP_006501448.1. XM_006501385.1.
    XP_006501449.1. XM_006501386.1.
    XP_006501450.1. XM_006501387.1.
    XP_006501451.1. XM_006501388.1.
    XP_006501452.1. XM_006501389.1.
    UniGenei Mm.272336.
    Mm.487453.

    3D structure databases

    ProteinModelPortali B2RUR8.
    SMRi B2RUR8. Positions 1-59, 147-395.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-60128N.
    IntActi B2RUR8. 1 interaction.
    STRINGi 10090.ENSMUSP00000088291.

    Protein family/group databases

    MEROPSi C64.001.

    Proteomic databases

    MaxQBi B2RUR8.
    PaxDbi B2RUR8.
    PRIDEi B2RUR8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000035519 ; ENSMUSP00000046413 ; ENSMUSG00000038495 .
    ENSMUST00000090785 ; ENSMUSP00000088291 ; ENSMUSG00000038495 .
    ENSMUST00000098849 ; ENSMUSP00000096449 ; ENSMUSG00000038495 .
    GeneIDi 229603.
    KEGGi mmu:229603.
    UCSCi uc008qma.1. mouse.

    Organism-specific databases

    CTDi 56957.
    MGIi MGI:2654703. Otud7b.

    Phylogenomic databases

    eggNOGi NOG282016.
    GeneTreei ENSGT00530000062989.
    HOGENOMi HOG000048103.
    HOVERGENi HBG050904.
    InParanoidi B2RUR8.
    KOi K11860.
    OMAi YATFPRQ.
    OrthoDBi EOG7JHM57.
    PhylomeDBi B2RUR8.
    TreeFami TF323312.

    Miscellaneous databases

    NextBioi 379553.
    PROi B2RUR8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi B2RUR8.
    Genevestigatori B2RUR8.

    Family and domain databases

    InterProi IPR003323. OTU.
    IPR002653. Znf_A20.
    [Graphical view ]
    Pfami PF02338. OTU. 1 hit.
    [Graphical view ]
    PROSITEi PS50802. OTU. 1 hit.
    PS51036. ZF_A20. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 60 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