U17LC_MOUSE
ID U17LC_MOUSE Reviewed; 545 AA.
AC G5E8I7; O55190; O55191;
DT 31-JAN-2018, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 17-like protein C {ECO:0000312|MGI:MGI:107698};
DE EC=3.4.19.12 {ECO:0000269|PubMed:11443643, ECO:0000269|PubMed:8995226};
DE AltName: Full=Deubiquitinating enzyme 2 {ECO:0000305|PubMed:8995226};
GN Name=Usp17lc {ECO:0000312|MGI:MGI:107698};
GN Synonyms=DUB-2 {ECO:0000303|PubMed:8995226},
GN Dub2 {ECO:0000312|MGI:MGI:107698}, Usp17l5 {ECO:0000312|MGI:MGI:107698};
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 {ECO:0000312|Proteomes:UP000000589};
RN [1] {ECO:0000312|EMBL:AAB95194.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP TISSUE SPECIFICITY, INDUCTION, ACTIVE SITE, AND MUTAGENESIS OF CYS-60.
RC STRAIN=129/Sv {ECO:0000312|EMBL:AAB95194.1};
RX PubMed=8995226; DOI=10.1074/jbc.272.1.51;
RA Zhu Y., Lambert K., Corless C., Copeland N.G., Gilbert D.J., Jenkins N.A.,
RA D'Andrea A.D.;
RT "DUB-2 is a member of a novel family of cytokine-inducible deubiquitinating
RT enzymes.";
RL J. Biol. Chem. 272:51-57(1997).
RN [2] {ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Proteomes:UP000000589};
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 [3] {ECO:0000312|EMBL:EDL16660.1}
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 [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF CYS-60;
RP ASP-133; HIS-298 AND HIS-307.
RX PubMed=11443643; DOI=10.1002/ajh.1130;
RA Lee J.H., Kim Y.S., Kim M., Baek K.H.;
RT "Critical regions for deubiquitinating activity of DUB-2 expressed in T-
RT lymphocytes.";
RL Am. J. Hematol. 67:270-272(2001).
RN [5] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22984479; DOI=10.1371/journal.pone.0044223;
RA Baek K.H., Lee H., Yang S., Lim S.B., Lee W., Lee J.E., Lim J.J., Jun K.,
RA Lee D.R., Chung Y.;
RT "Embryonic demise caused by targeted disruption of a cysteine protease Dub-
RT 2.";
RL PLoS ONE 7:E44223-E44223(2012).
CC -!- FUNCTION: Deubiquitinating enzyme that removes conjugated ubiquitin
CC from specific proteins to regulate different cellular processes
CC (PubMed:8995226, PubMed:11443643). Important for preimplantation stage
CC embryonic development (PubMed:22984479). {ECO:0000269|PubMed:11443643,
CC ECO:0000269|PubMed:22984479, ECO:0000269|PubMed:8995226}.
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:11443643,
CC ECO:0000269|PubMed:8995226};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q6R6M4}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:Q6R6M4}.
CC -!- TISSUE SPECIFICITY: Expressed in T cells. {ECO:0000269|PubMed:8995226}.
CC -!- INDUCTION: Rapidly up-regulated in response to the cytokine IL2.
CC {ECO:0000269|PubMed:8995226}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal, with no survival beyond
CC embryonic stage E5.5. Blastocysts fail to hatch and there is
CC significant apoptosis of the trophectoderm. Cell proliferation may also
CC be impaired. Blastocysts at stage E3.5 appear to have normal
CC morphology. {ECO:0000269|PubMed:22984479}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP17 subfamily.
CC {ECO:0000305}.
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DR EMBL; U70368; AAB95194.1; -; Genomic_DNA.
DR EMBL; U70369; AAB94636.1; -; mRNA.
DR EMBL; AC162877; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466531; EDL16660.1; -; Genomic_DNA.
DR CCDS; CCDS21572.1; -.
DR RefSeq; NP_034219.3; NM_010089.3.
DR AlphaFoldDB; G5E8I7; -.
DR SMR; G5E8I7; -.
DR STRING; 10090.ENSMUSP00000102505; -.
DR MEROPS; C19.032; -.
DR iPTMnet; G5E8I7; -.
DR PhosphoSitePlus; G5E8I7; -.
DR MaxQB; G5E8I7; -.
DR PaxDb; G5E8I7; -.
DR PRIDE; G5E8I7; -.
DR DNASU; 13532; -.
DR Ensembl; ENSMUST00000079348; ENSMUSP00000078323; ENSMUSG00000058976.
DR Ensembl; ENSMUST00000106892; ENSMUSP00000102505; ENSMUSG00000058976.
DR GeneID; 13532; -.
DR KEGG; mmu:13532; -.
DR UCSC; uc009itr.1; mouse.
DR CTD; 13532; -.
DR MGI; MGI:107698; Usp17lc.
DR VEuPathDB; HostDB:ENSMUSG00000058976; -.
DR eggNOG; KOG1865; Eukaryota.
DR GeneTree; ENSGT00940000162665; -.
DR HOGENOM; CLU_008279_10_0_1; -.
DR InParanoid; G5E8I7; -.
DR OMA; ENAYHCN; -.
DR OrthoDB; 561804at2759; -.
DR PhylomeDB; G5E8I7; -.
DR TreeFam; TF315281; -.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-9648002; RAS processing.
DR BioGRID-ORCS; 13532; 2 hits in 51 CRISPR screens.
DR PRO; PR:G5E8I7; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; G5E8I7; protein.
DR Bgee; ENSMUSG00000058976; Expressed in animal zygote and 2 other tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:MGI.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0043009; P:chordate embryonic development; IMP:CACAO.
DR GO; GO:0016579; P:protein deubiquitination; IDA:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF00443; UCH; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Hydrolase; Nucleus; Protease; Reference proteome;
KW Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..545
FT /note="Ubiquitin carboxyl-terminal hydrolase 17-like
FT protein C"
FT /id="PRO_0000442982"
FT DOMAIN 51..348
FT /note="USP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT REGION 368..442
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 489..539
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 385..442
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 503..518
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 60
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035,
FT ECO:0000305|PubMed:11443643, ECO:0000305|PubMed:8995226"
FT ACT_SITE 307
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035,
FT ECO:0000305|PubMed:11443643"
FT MUTAGEN 60
FT /note="C->S: Abolishes deubiquitinating activity."
FT /evidence="ECO:0000269|PubMed:8995226"
FT MUTAGEN 133
FT /note="D->N: Abolishes deubiquitinating activity."
FT /evidence="ECO:0000269|PubMed:8995226"
FT MUTAGEN 298
FT /note="H->Q: Abolishes deubiquitinating activity."
FT /evidence="ECO:0000269|PubMed:8995226"
FT MUTAGEN 307
FT /note="H->Q: Abolishes deubiquitinating activity."
FT /evidence="ECO:0000269|PubMed:8995226"
FT CONFLICT 10
FT /note="A -> Q (in Ref. 1; AAB94636)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 545 AA; 61483 MW; F2E15EBB759F2203 CRC64;
MVVSLSFPEA DPALSSPGAQ QLHQDEAQVV VELTANDKPS LSWECPQGPG CGLQNTGNSC
YLNAALQCLT HTPPLADYML SQEYSQTCCS PEGCKMCAME AHVTQSLLHS HSGDVMKPSQ
ILTSAFHKHQ QEDAHEFLMF TLETMHESCL QVHRQSEPTS EDSSPIHDIF GGLWRSQIKC
LHCQGTSDTY DRFLDVPLDI SSAQSVNQAL WDTEKSEELR GENAYYCGRC RQKMPASKTL
HIHSAPKVLL LVLKRFSAFM GNKLDRKVSY PEFLDLKPYL SQPTGGPLPY ALYAVLVHEG
ATCHSGHYFS YVKARHGAWY KMDDTKVTSC DVTSVLNENA YVLFYVQQTD LKQVSIDMPE
GRVHEVLDPE YQLKKSRRKK HKKKSPCTED AGEPCKNREK RATKETSLGE GKVLQEKNHK
KAGQKHENTK LVPQEQNHQK LGQKHRINEI LPQEQNHQKA GQSLRNTEGE LDLPADAIVI
HLLRSTENWG RDAPDKENQP WHNADRLLTS QDPVNTGQLC RQEGRRRSKK GKNKNKQGQR
LLLVC
