UBP13_MOUSE
ID UBP13_MOUSE Reviewed; 858 AA.
AC Q5BKP2; D3YYG7;
DT 13-JUN-2012, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 13;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 13;
DE AltName: Full=Ubiquitin thioesterase 13;
DE AltName: Full=Ubiquitin-specific-processing protease 13;
GN Name=Usp13;
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=Heart;
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=Heart;
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).
CC -!- FUNCTION: Deubiquitinase that mediates deubiquitination of target
CC proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various
CC processes such as autophagy and endoplasmic reticulum-associated
CC degradation (ERAD). Component of a regulatory loop that controls
CC autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a
CC key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-
CC containing complexes. Also deubiquitinates USP10, an essential
CC regulator of p53/TP53 stability. In turn, PIK3C3/VPS34-containing
CC complexes regulate USP13 stability, suggesting the existence of a
CC regulatory system by which PIK3C3/VPS34-containing complexes regulate
CC p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1
CC and mediates deubiquitination of SKP2, thereby regulating endoplasmic
CC reticulum-associated degradation (ERAD). Also regulates ERAD through
CC the deubiquitination of UBL4A a component of the BAG6/BAT3 complex.
CC Mediates stabilization of SIAH2 independently of deubiquitinase
CC activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2
CC autoubiquitination. Has a weak deubiquitinase activity in vitro and
CC preferentially cleaves 'Lys-63'-linked polyubiquitin chains. In
CC contrast to USP5, it is not able to mediate unanchored polyubiquitin
CC disassembly. Able to cleave ISG15 in vitro; however, additional
CC experiments are required to confirm such data.
CC {ECO:0000250|UniProtKB:Q92995}.
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;
CC -!- ACTIVITY REGULATION: Specifically inhibited by spautin-1 (specific and
CC potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP13
CC and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-
CC containing complexes. The weak deubiquitinase activity in vitro
CC suggests the existence of some mechanism that activates the enzyme (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with UFD1. Interacts (via UBA domains) with SIAH2
CC (when ubiquitinated). Interacts with BAG6; the interaction is direct
CC and may mediate UBL4A deubiquitination. Interacts (via UBA 2 domain)
CC with AMFR; the interaction is direct. Interacts with UBL4A; may be
CC indirect via BAG6. {ECO:0000250|UniProtKB:Q92995}.
CC -!- DOMAIN: The UBP-type zinc finger has lost its ability to bind ubiquitin
CC and USP13 is not activated by unanchored ubiquitin. {ECO:0000250}.
CC -!- DOMAIN: The UBA domains mediate binding to ubiquitin. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR EMBL; AC111140; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466530; EDL35015.1; -; Genomic_DNA.
DR EMBL; BC090999; AAH90999.1; -; mRNA.
DR CCDS; CCDS17301.1; -.
DR RefSeq; NP_001013042.1; NM_001013024.2.
DR AlphaFoldDB; Q5BKP2; -.
DR SMR; Q5BKP2; -.
DR BioGRID; 215466; 2.
DR STRING; 10090.ENSMUSP00000072155; -.
DR MEROPS; C19.012; -.
DR iPTMnet; Q5BKP2; -.
DR PhosphoSitePlus; Q5BKP2; -.
DR MaxQB; Q5BKP2; -.
DR PaxDb; Q5BKP2; -.
DR PRIDE; Q5BKP2; -.
DR ProteomicsDB; 298090; -.
DR Antibodypedia; 1352; 321 antibodies from 35 providers.
DR DNASU; 72607; -.
DR Ensembl; ENSMUST00000072312; ENSMUSP00000072155; ENSMUSG00000056900.
DR GeneID; 72607; -.
DR KEGG; mmu:72607; -.
DR UCSC; uc008owr.1; mouse.
DR CTD; 8975; -.
DR MGI; MGI:1919857; Usp13.
DR VEuPathDB; HostDB:ENSMUSG00000056900; -.
DR eggNOG; KOG0944; Eukaryota.
DR GeneTree; ENSGT00940000157401; -.
DR InParanoid; Q5BKP2; -.
DR OMA; TMDMENN; -.
DR OrthoDB; 556111at2759; -.
DR PhylomeDB; Q5BKP2; -.
DR TreeFam; TF300576; -.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-8948751; Regulation of PTEN stability and activity.
DR BioGRID-ORCS; 72607; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Usp13; mouse.
DR PRO; PR:Q5BKP2; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q5BKP2; protein.
DR Bgee; ENSMUSG00000056900; Expressed in interventricular septum and 195 other tissues.
DR ExpressionAtlas; Q5BKP2; baseline and differential.
DR Genevisible; Q5BKP2; MM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:1904288; F:BAT3 complex binding; ISO:MGI.
DR GO; GO:0051087; F:chaperone binding; ISO:MGI.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; ISO:MGI.
DR GO; GO:0070628; F:proteasome binding; ISO:MGI.
DR GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR GO; GO:1904378; P:maintenance of unfolded protein involved in ERAD pathway; ISO:MGI.
DR GO; GO:1904294; P:positive regulation of ERAD pathway; ISO:MGI.
DR GO; GO:0016579; P:protein deubiquitination; IBA:GO_Central.
DR GO; GO:0035523; P:protein K29-linked deubiquitination; ISO:MGI.
DR GO; GO:0044313; P:protein K6-linked deubiquitination; ISO:MGI.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.30.40.10; -; 2.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR016652; Ubiquitinyl_hydrolase.
DR InterPro; IPR041432; UBP13_Znf-UBP_var.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR Pfam; PF00627; UBA; 2.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02148; zf-UBP; 1.
DR Pfam; PF17807; zf-UBP_var; 1.
DR PIRSF; PIRSF016308; UBP; 1.
DR SMART; SM00165; UBA; 2.
DR SMART; SM00290; ZnF_UBP; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50030; UBA; 2.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 1: Evidence at protein level;
KW Autophagy; Hydrolase; Isopeptide bond; Metal-binding; Phosphoprotein;
KW Protease; Reference proteome; Repeat; Thiol protease; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..858
FT /note="Ubiquitin carboxyl-terminal hydrolase 13"
FT /id="PRO_0000418011"
FT DOMAIN 334..856
FT /note="USP"
FT DOMAIN 650..691
FT /note="UBA 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 722..762
FT /note="UBA 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT ZN_FING 185..293
FT /note="UBP-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT ACT_SITE 343
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 818
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT BINDING 209
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 212
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 229
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 242
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT MOD_RES 112
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92995"
FT CROSSLNK 309
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q92995"
FT CROSSLNK 403
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q92995"
SQ SEQUENCE 858 AA; 96723 MW; 04989BACB784192C CRC64;
MQRRGALFSV PGGGGKMAAG DLGELLVPHM PTIRVPRSGD RVYKNECAFS YDSPNSEGGL
YVCMNTFLAF GREHVERHFR KTGQSVYMHL KRHMREKVRG ASGGALPKRR NSKIFLDLDM
DDDLNSDDYE YEDEAKLVIF PDHYEIALPN IEELPALVTI ACDAVLSSKS PYRKQDPDTW
ENEVPVSKYA NNLVQLDNGV RIPPSGWKCA RCDLRENLWL NLTDGSVLCG KWFFDSSGGN
GHALEHYRDM GYPLAVKLGT ITPDGADVYS FQEEGPVSDP HLAKHLAHFG IDMLHTQGTE
NGLRDNDIKP RVSEWEVIQE SGTKLKPMYG PGYTGLKNLG NSCYLSSVMQ AIFSIPEFQR
AYVGNLPRIF DYSPLDPTQD FNTQMTKLGH GLLSGQYSKP PVKSELIEQV MKEEHKPQQN
GISPRMFKAF VSKSHPEFSS NRQQDAQEFF LHLVNLVERN RIGSENPSDV FRFLVEERIQ
CCQTRKVRYT ERVDYLMQLP VAMEAATNKD ELITYELMRR EAEANRRPLP ELVRAKIPFS
ACLQAFAEPD NVDDFWSSAL QAKSAGVKTS RFASFPEYLV VQIKKFTFGL DWVPRKFDVS
IDMPDLLDIS HLRARGLQPG EEELPDISPP IVIPDDSKDR LMNQLIDPSD IDESSVMQLA
EMGFPLEACR KAVYFTGNTG AEVAFNWIIV HMEEPDFAEP LAIPGYGGAG ASVFGATGLD
NQPPEEIVAI ITSMGFQRNQ AVQALQATNH NLERALDWIF SHPEFEEDSD FVIEMENNAN
ANIVSEAKPE GPRVKDGSGM YELFAFISHM GTSTMSGHYV CHIKKEGRWV IYNDHKVCAS
ERPPKDLGYM YFYRRIPS
