OTU7B_MOUSE
ID OTU7B_MOUSE Reviewed; 840 AA.
AC B2RUR8; Q8CFS0;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=OTU domain-containing protein 7B;
DE EC=3.4.19.12 {ECO:0000269|PubMed:23334419};
DE AltName: Full=Cellular zinc finger anti-NF-kappa-B protein;
DE AltName: Full=Zinc finger A20 domain-containing protein 1;
DE AltName: Full=Zinc finger protein Cezanne {ECO:0000305};
GN Name=Otud7b;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-100; SER-464; SER-467;
RP SER-471 AND THR-730, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, INTERACTION WITH TRAF3,
RP MUTAGENESIS OF CYS-194 AND HIS-358, AND ACTIVE SITE.
RX PubMed=23334419; DOI=10.1038/nature11831;
RA Hu H., Brittain G.C., Chang J.H., Puebla-Osorio N., Jin J., Zal A.,
RA Xiao Y., Cheng X., Chang M., Fu Y.X., Zal T., Zhu C., Sun S.C.;
RT "OTUD7B controls non-canonical NF-kappaB activation through
RT deubiquitination of TRAF3.";
RL Nature 494:371-374(2013).
RN [7]
RP DISRUPTION PHENOTYPE, FUNCTION, AND INTERACTION WITH ZAP70.
RX PubMed=26903241; DOI=10.1084/jem.20151426;
RA Hu H., Wang H., Xiao Y., Jin J., Chang J.H., Zou Q., Xie X., Cheng X.,
RA Sun S.C.;
RT "Otud7b facilitates T cell activation and inflammatory responses by
RT regulating Zap70 ubiquitination.";
RL J. Exp. Med. 213:399-414(2016).
CC -!- FUNCTION: Negative regulator of the non-canonical NF-kappa-B pathway
CC that acts by mediating deubiquitination of TRAF3, an inhibitor of the
CC NF-kappa-B pathway, thereby acting as a negative regulator of B-cell
CC responses. In response to non-canonical NF-kappa-B stimuli,
CC deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3,
CC preventing TRAF3 proteolysis and over-activation of non-canonical NF-
CC kappa-B (PubMed:23334419). Negatively regulates mucosal immunity
CC against infections (PubMed:23334419). Deubiquitinates ZAP70, and
CC thereby regulates T cell receptor (TCR) signaling that leads to the
CC activation of NF-kappa-B (PubMed:26903241). Plays a role in T cell
CC homeostasis and is required for normal T cell responses, including
CC production of IFNG and IL2 (PubMed:26903241). Mediates deubiquitination
CC of EGFR (By similarity). Has deubiquitinating activity toward 'Lys-11',
CC 'Lys-48' and 'Lys-63'-linked polyubiquitin chains. Has a much higher
CC catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro);
CC however the physiological significance of these data are unsure.
CC Hydrolyzes both linear and branched forms of polyubiquitin (By
CC similarity). {ECO:0000250|UniProtKB:Q6GQQ9,
CC ECO:0000269|PubMed:23334419, ECO:0000269|PubMed:26903241}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:23334419};
CC -!- ACTIVITY REGULATION: Deubiquitinase activity is inhibited following
CC interaction with PARK7. {ECO:0000250|UniProtKB:Q6GQQ9}.
CC -!- SUBUNIT: Interacts with TRAF6. Interacts with PARK7, leading to inhibit
CC deubiquitinase activity. Interacts with EGFR, ITCH and NEDD4 (By
CC similarity). Interacts with TRAF3 (PubMed:23334419). Interacts with
CC ZAP70 in activated T cells, but not in resting T cells
CC (PubMed:26903241). {ECO:0000250|UniProtKB:Q6GQQ9,
CC ECO:0000269|PubMed:23334419, ECO:0000269|PubMed:26903241}.
CC -!- INTERACTION:
CC B2RUR8; P25942: CD40; Xeno; NbExp=2; IntAct=EBI-3454264, EBI-525714;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q6GQQ9}. Nucleus
CC {ECO:0000250|UniProtKB:Q6GQQ9}. Note=Shuttles be cytoplasm and the
CC nucleus in a XPO1/CRM1-dependent manner.
CC {ECO:0000250|UniProtKB:Q6GQQ9}.
CC -!- DOMAIN: The protein undergoes a significant conformation change upon
CC binding to ubiquitinated substrates. The loop that precedes the active
CC site is in an autoinhibitory conformation in the apoprotein. Ubiquitin
CC binding leads to a conformation change; the loop is stabilized in a
CC catalytically competent conformation with the result that the active
CC site Cys can form the reaction state intermediate.
CC {ECO:0000250|UniProtKB:Q6GQQ9}.
CC -!- PTM: Phosphorylated by EGFR. {ECO:0000250|UniProtKB:Q6GQQ9}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype in neonates
CC (PubMed:26903241). Mice do not show obvious defects in survival, except
CC a moderately reduced body weight (PubMed:23334419). They however
CC display hyperactivation of non-canonical NF-kappa-B without affecting
CC canonical NF-kappa-B activation. Mice show B-cell hyper-responsiveness
CC to antigens, lymphoid follicular hyperplasia in the intestinal mucosa
CC and elevated host-defense ability against an intestinal bacterial
CC pathogen, Citrobacter rodentium (PubMed:23334419). At 12 months after
CC birth, mutant mice display impaired T cell homeostasis with increased
CC numbers of naive T cells and reduced numbers of Th1 memory-like T cells
CC (PubMed:26903241). Young adults that have no overt change in T cell
CC homeostasis still show impaired production of effector T cells in
CC response to repeated stimulation with an antigen and an impaired
CC defense against infection by L.monocytogenes (PubMed:26903241).
CC Conversely, mutant mice are less susceptible to experimentally induced
CC autoimmune encephalitis (PubMed:26903241).
CC {ECO:0000269|PubMed:23334419, ECO:0000269|PubMed:26903241}.
CC -!- SIMILARITY: Belongs to the peptidase C64 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH37040.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; AC092094; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466620; EDL38862.1; -; Genomic_DNA.
DR EMBL; BC141397; AAI41398.1; -; mRNA.
DR EMBL; BC037040; AAH37040.1; ALT_SEQ; mRNA.
DR EMBL; BC141398; AAI41399.1; -; mRNA.
DR CCDS; CCDS17629.1; -.
DR RefSeq; NP_001020784.1; NM_001025613.1.
DR RefSeq; NP_001020785.1; NM_001025614.1.
DR RefSeq; XP_006501448.1; XM_006501385.3.
DR RefSeq; XP_006501449.1; XM_006501386.3.
DR RefSeq; XP_006501452.1; XM_006501389.3.
DR RefSeq; XP_017175035.1; XM_017319546.1.
DR RefSeq; XP_017175036.1; XM_017319547.1.
DR AlphaFoldDB; B2RUR8; -.
DR SMR; B2RUR8; -.
DR BioGRID; 230871; 7.
DR DIP; DIP-60128N; -.
DR IntAct; B2RUR8; 5.
DR STRING; 10090.ENSMUSP00000088291; -.
DR MEROPS; C64.001; -.
DR iPTMnet; B2RUR8; -.
DR PhosphoSitePlus; B2RUR8; -.
DR EPD; B2RUR8; -.
DR jPOST; B2RUR8; -.
DR MaxQB; B2RUR8; -.
DR PaxDb; B2RUR8; -.
DR PeptideAtlas; B2RUR8; -.
DR PRIDE; B2RUR8; -.
DR ProteomicsDB; 294404; -.
DR Antibodypedia; 72463; 239 antibodies from 30 providers.
DR DNASU; 229603; -.
DR Ensembl; ENSMUST00000035519; ENSMUSP00000046413; ENSMUSG00000038495.
DR Ensembl; ENSMUST00000090785; ENSMUSP00000088291; ENSMUSG00000038495.
DR Ensembl; ENSMUST00000098849; ENSMUSP00000096449; ENSMUSG00000038495.
DR GeneID; 229603; -.
DR KEGG; mmu:229603; -.
DR UCSC; uc008qma.1; mouse.
DR CTD; 56957; -.
DR MGI; MGI:2654703; Otud7b.
DR VEuPathDB; HostDB:ENSMUSG00000038495; -.
DR eggNOG; KOG4345; Eukaryota.
DR GeneTree; ENSGT00940000159172; -.
DR HOGENOM; CLU_013263_0_0_1; -.
DR InParanoid; B2RUR8; -.
DR OMA; LSIMRIT; -.
DR OrthoDB; 728724at2759; -.
DR PhylomeDB; B2RUR8; -.
DR TreeFam; TF323312; -.
DR Reactome; R-MMU-5357786; TNFR1-induced proapoptotic signaling.
DR Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-MMU-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases.
DR BioGRID-ORCS; 229603; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Otud7b; mouse.
DR PRO; PR:B2RUR8; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; B2RUR8; protein.
DR Bgee; ENSMUSG00000038495; Expressed in blood and 242 other tissues.
DR ExpressionAtlas; B2RUR8; baseline and differential.
DR Genevisible; B2RUR8; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:MGI.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IMP:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IDA:BHF-UCL.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0002385; P:mucosal immune response; IMP:UniProtKB.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0032717; P:negative regulation of interleukin-8 production; ISO:MGI.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016579; P:protein deubiquitination; IDA:MGI.
DR GO; GO:0071947; P:protein deubiquitination involved in ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0035871; P:protein K11-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; IMP:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB.
DR InterPro; IPR003323; OTU_dom.
DR InterPro; IPR002653; Znf_A20.
DR Pfam; PF02338; OTU; 1.
DR Pfam; PF01754; zf-A20; 1.
DR SMART; SM00259; ZnF_A20; 1.
DR PROSITE; PS50802; OTU; 1.
DR PROSITE; PS51036; ZF_A20; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Cytoplasm; Hydrolase; Immunity; Metal-binding; Nucleus;
KW Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..840
FT /note="OTU domain-containing protein 7B"
FT /id="PRO_0000421819"
FT DOMAIN 183..365
FT /note="OTU"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT ZN_FING 793..828
FT /note="A20-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT REGION 49..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 152..401
FT /note="TRAF-binding"
FT /evidence="ECO:0000250"
FT REGION 167..440
FT /note="Catalytic"
FT /evidence="ECO:0000250"
FT REGION 187..193
FT /note="Regulatory loop"
FT /evidence="ECO:0000250|UniProtKB:Q6GQQ9"
FT REGION 440..592
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 653..710
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 483..498
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 67..88
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 440..460
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 480..502
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 546..571
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 191
FT /evidence="ECO:0000250"
FT ACT_SITE 194
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:23334419"
FT ACT_SITE 358
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:23334419"
FT BINDING 799
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 804
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 816
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 819
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT SITE 197
FT /note="Stabilizes the conformation of the regulatory loop"
FT /evidence="ECO:0000250|UniProtKB:Q6GQQ9"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 464
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 730
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 194
FT /note="C->S: Loss of deubiquitinating activity; when
FT associated with R-358."
FT /evidence="ECO:0000269|PubMed:23334419"
FT MUTAGEN 358
FT /note="H->R: Loss of deubiquitinating activity; when
FT associated with S-194."
FT /evidence="ECO:0000269|PubMed:23334419"
SQ SEQUENCE 840 AA; 91983 MW; B63C06B656CC02EE CRC64;
MTLDMDAVLS DFVRSTGAEP GLARDLLEGK NWDVSAALSD FEQLRQVHAG NLSPPFSGGS
TCPKTPEKGG SDREPTRPSR PILQRQDDVI QEKRLSRGIS HASSSIVSLA RSHVSSNGGG
GGSSEHPLEM PICAFQLPDL TVYKEDFRSF IERDLIEQSM LVALEQAGRL NWWVSMDSTC
QRLLPLATTG DGNCLLHAAS LGMWGFHDRD LVLRKALYAL MEKGVEKEAL RRRWRWQQTQ
QNKESGLVYT EDEWQKEWNE LIKLASSEPR MHLGSNGASG GGVESSEEPV YESLEEFHVF
VLAHVLKRPI VVVADTMLRD SGGEAFAPIP FGGIYLPLEV PASQCHRSPL VLAYDQAHFS
ALVSMEQKES AKEQAVIPLT DSEHKLLPLH FAVDPGKGWE WGKDDNDNVR LASIILSLEV
KLHLLHSYMN VKWIPLSSDS QAPLAQPESP TASAGDEPRS TPESGESDKE SVGSSSLGNE
GSRRKEKSKR DREKDKKRAD SVANKLGSFG KTLGSKLKKN MGGLMHSKGP KPGGLGSGSG
ISSGTETLEK KKKNNTLKSW KGGKEEAAGD GPVSEKPPSE SVGNGGSKYS QEVMQSLSTM
RIAMQGEGKY IFVGTLKMGH RHQYQEEMIQ RYLADAEERF LAEQKQKEVE RKIMNGGLVS
GPPPAKKPEP DGGEDQPSDS PAEPKAMAFS TAYPGGFTIP RPSGGGVHCQ EPRRQLAGGP
CVGGLPSYAT FPRQYPGRPY PHQDNIPALE PGKDGVHRGA LLPPQFRVAD SYSNGYREPP
EPDGWAGAPR GLPPTQTKCK QPNCSFYGHP ETNNLCSCCY REELRRRERE PGGELLAHRF
