ID UCHL5_MOUSE Reviewed; 329 AA.
AC Q9WUP7; Q9CVJ4; Q9CXZ3; Q9R107;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2001, sequence version 2.
DT 24-JAN-2024, entry version 182.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase isozyme L5;
DE Short=UCH-L5;
DE EC=3.4.19.12;
DE AltName: Full=Ubiquitin C-terminal hydrolase UCH37;
DE AltName: Full=Ubiquitin thioesterase L5;
GN Name=Uchl5; Synonyms=Uch37;
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 [MRNA] (ISOFORM 1).
RA Xu W., DeMartino G.N., Slaughter C.A., Cohen R.E.;
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Li T.W., Sun B., Mustafa F.B., Lee M.K., Teo T.S.;
RT "Identification of a novel mouse ubiquitin C-terminal hydrolase: cloning,
RT expression and functional characterization.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Embryonic liver, Pancreas, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=Czech II; TISSUE=Mammary gland;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, 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 ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-158, SUCCINYLATION [LARGE SCALE
RP ANALYSIS] AT LYS-47 AND LYS-289, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Protease that specifically cleaves 'Lys-48'-linked
CC polyubiquitin chains. Deubiquitinating enzyme associated with the 19S
CC regulatory subunit of the 26S proteasome. Putative regulatory component
CC of the INO80 complex; however is inactive in the INO80 complex and is
CC activated by a transient interaction of the INO80 complex with the
CC proteasome via ADRM1 (By similarity). {ECO:0000250}.
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: Activated by ADRM1. Inhibited by interaction with
CC NFRKB (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Component of the 19S (PA700) regulatory complex of the 26S
CC proteasome. Interacts with ADRM1 and NFRKB. Component of the INO80
CC complex; specifically part of a complex module associated with N-
CC terminus of INO80 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Associates with the proteasome 19S subunit in the cytoplasm.
CC Associates with the INO80 complex in the nucleus (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9WUP7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9WUP7-2; Sequence=VSP_005255;
CC -!- SIMILARITY: Belongs to the peptidase C12 family. {ECO:0000305}.
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DR EMBL; AF148447; AAD31534.1; -; mRNA.
DR EMBL; AF175903; AAD50311.1; -; mRNA.
DR EMBL; AK017925; BAB31005.1; -; mRNA.
DR EMBL; AK011117; BAB27412.1; -; mRNA.
DR EMBL; AK007860; BAB25312.1; -; mRNA.
DR EMBL; BC006891; AAH06891.1; -; mRNA.
DR CCDS; CCDS15346.1; -. [Q9WUP7-1]
DR CCDS; CCDS78699.1; -. [Q9WUP7-2]
DR RefSeq; NP_001153338.1; NM_001159866.1. [Q9WUP7-2]
DR RefSeq; NP_062508.2; NM_019562.2. [Q9WUP7-1]
DR PDB; 4WLQ; X-ray; 2.85 A; A=1-329.
DR PDB; 4WLR; X-ray; 2.00 A; A=1-329.
DR PDBsum; 4WLQ; -.
DR PDBsum; 4WLR; -.
DR AlphaFoldDB; Q9WUP7; -.
DR SMR; Q9WUP7; -.
DR BioGRID; 207842; 84.
DR ComplexPortal; CPX-878; INO80 chromatin remodeling complex.
DR IntAct; Q9WUP7; 3.
DR MINT; Q9WUP7; -.
DR STRING; 10090.ENSMUSP00000140106; -.
DR MEROPS; C12.005; -.
DR iPTMnet; Q9WUP7; -.
DR PhosphoSitePlus; Q9WUP7; -.
DR SwissPalm; Q9WUP7; -.
DR REPRODUCTION-2DPAGE; Q9WUP7; -.
DR EPD; Q9WUP7; -.
DR MaxQB; Q9WUP7; -.
DR PaxDb; 10090-ENSMUSP00000140106; -.
DR PeptideAtlas; Q9WUP7; -.
DR ProteomicsDB; 298115; -. [Q9WUP7-1]
DR ProteomicsDB; 298116; -. [Q9WUP7-2]
DR Pumba; Q9WUP7; -.
DR Antibodypedia; 1573; 367 antibodies from 30 providers.
DR DNASU; 56207; -.
DR Ensembl; ENSMUST00000018333.13; ENSMUSP00000018333.8; ENSMUSG00000018189.13. [Q9WUP7-2]
DR Ensembl; ENSMUST00000189936.7; ENSMUSP00000140106.2; ENSMUSG00000018189.13. [Q9WUP7-1]
DR GeneID; 56207; -.
DR KEGG; mmu:56207; -.
DR UCSC; uc007cxe.2; mouse. [Q9WUP7-1]
DR UCSC; uc007cxf.2; mouse. [Q9WUP7-2]
DR AGR; MGI:1914848; -.
DR CTD; 51377; -.
DR MGI; MGI:1914848; Uchl5.
DR VEuPathDB; HostDB:ENSMUSG00000018189; -.
DR eggNOG; KOG2778; Eukaryota.
DR GeneTree; ENSGT00940000155195; -.
DR HOGENOM; CLU_018316_0_0_1; -.
DR InParanoid; Q9WUP7; -.
DR OMA; YIQYEIQ; -.
DR OrthoDB; 276003at2759; -.
DR PhylomeDB; Q9WUP7; -.
DR TreeFam; TF313976; -.
DR Reactome; R-MMU-5689603; UCH proteinases.
DR BioGRID-ORCS; 56207; 9 hits in 118 CRISPR screens.
DR ChiTaRS; Uchl5; mouse.
DR PRO; PR:Q9WUP7; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9WUP7; Protein.
DR Bgee; ENSMUSG00000018189; Expressed in blastoderm cell in morula and 284 other cell types or tissues.
DR ExpressionAtlas; Q9WUP7; baseline and differential.
DR Genevisible; Q9WUP7; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0031597; C:cytosolic proteasome complex; ISO:MGI.
DR GO; GO:0031011; C:Ino80 complex; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; ISO:MGI.
DR GO; GO:0070628; F:proteasome binding; ISO:MGI.
DR GO; GO:0006338; P:chromatin remodeling; ISO:MGI.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0048853; P:forebrain morphogenesis; IMP:BHF-UCL.
DR GO; GO:0021670; P:lateral ventricle development; IMP:BHF-UCL.
DR GO; GO:0030901; P:midbrain development; IMP:BHF-UCL.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0045739; P:positive regulation of DNA repair; IDA:ComplexPortal.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:MGI.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; ISO:MGI.
DR GO; GO:1904507; P:positive regulation of telomere maintenance in response to DNA damage; IMP:ComplexPortal.
DR GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:MGI.
DR GO; GO:0033044; P:regulation of chromosome organization; ISO:MGI.
DR GO; GO:0006282; P:regulation of DNA repair; IDA:ComplexPortal.
DR GO; GO:0006275; P:regulation of DNA replication; ISO:MGI.
DR GO; GO:0060382; P:regulation of DNA strand elongation; ISO:MGI.
DR GO; GO:0045995; P:regulation of embryonic development; IMP:ComplexPortal.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; ISO:MGI.
DR GO; GO:0000723; P:telomere maintenance; IMP:ComplexPortal.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR CDD; cd02255; Peptidase_C12; 1.
DR DisProt; DP01190; -. [Q9WUP7-2]
DR Gene3D; 1.20.58.860; -; 1.
DR Gene3D; 3.40.532.10; Peptidase C12, ubiquitin carboxyl-terminal hydrolase; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001578; Peptidase_C12_UCH.
DR InterPro; IPR036959; Peptidase_C12_UCH_sf.
DR InterPro; IPR017390; Ubiquitinyl_hydrolase_UCH37.
DR InterPro; IPR033837; UCH37.
DR InterPro; IPR041507; UCH_C.
DR PANTHER; PTHR10589; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR PANTHER; PTHR10589:SF16; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE ISOZYME L5; 1.
DR Pfam; PF01088; Peptidase_C12; 1.
DR Pfam; PF18031; UCH_C; 1.
DR PIRSF; PIRSF038120; Ubiquitinyl_hydrolase_UCH37; 1.
DR PRINTS; PR00707; UBCTHYDRLASE.
DR SUPFAM; SSF54001; Cysteine proteinases; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; DNA damage;
KW DNA recombination; DNA repair; Hydrolase; Nucleus; Protease; Proteasome;
KW Reference proteome; Thiol protease; Transcription;
KW Transcription regulation; Ubl conjugation pathway.
FT CHAIN 1..329
FT /note="Ubiquitin carboxyl-terminal hydrolase isozyme L5"
FT /id="PRO_0000211067"
FT REGION 313..329
FT /note="Interaction with ADRM1"
FT /evidence="ECO:0000250"
FT ACT_SITE 88
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 164
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT SITE 179
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000250"
FT MOD_RES 47
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 158
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 289
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT VAR_SEQ 246
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|Ref.2"
FT /id="VSP_005255"
FT CONFLICT 20
FT /note="E -> K (in Ref. 1; AAD31534)"
FT /evidence="ECO:0000305"
FT CONFLICT 24
FT /note="G -> R (in Ref. 1; AAD31534)"
FT /evidence="ECO:0000305"
FT CONFLICT 104
FT /note="D -> E (in Ref. 1; BAB25312)"
FT /evidence="ECO:0000305"
FT HELIX 15..24
FT /evidence="ECO:0007829|PDB:4WLR"
FT STRAND 28..34
FT /evidence="ECO:0007829|PDB:4WLR"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:4WLR"
FT STRAND 48..57
FT /evidence="ECO:0007829|PDB:4WLR"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:4WLR"
FT HELIX 72..75
FT /evidence="ECO:0007829|PDB:4WLR"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:4WLQ"
FT HELIX 88..97
FT /evidence="ECO:0007829|PDB:4WLR"
FT HELIX 108..118
FT /evidence="ECO:0007829|PDB:4WLR"
FT HELIX 123..131
FT /evidence="ECO:0007829|PDB:4WLR"
FT HELIX 134..142
FT /evidence="ECO:0007829|PDB:4WLR"
FT STRAND 163..171
FT /evidence="ECO:0007829|PDB:4WLR"
FT STRAND 174..178
FT /evidence="ECO:0007829|PDB:4WLR"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:4WLR"
FT STRAND 186..190
FT /evidence="ECO:0007829|PDB:4WLR"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:4WLQ"
FT HELIX 197..209
FT /evidence="ECO:0007829|PDB:4WLR"
FT STRAND 219..225
FT /evidence="ECO:0007829|PDB:4WLR"
FT HELIX 227..244
FT /evidence="ECO:0007829|PDB:4WLR"
FT HELIX 256..289
FT /evidence="ECO:0007829|PDB:4WLR"
FT HELIX 293..305
FT /evidence="ECO:0007829|PDB:4WLR"
FT HELIX 309..318
FT /evidence="ECO:0007829|PDB:4WLR"
SQ SEQUENCE 329 AA; 37617 MW; 1EAB5223FB707917 CRC64;
MSSNAGEWCL MESDPGVFTE LIKGFGCRGA QVEEIWSLEP ESFEKLKPVH GLIFLFKWQP
GEEPAGSVVQ DSRLETIFFA KQVINNACAT QAIVSVLLNC THQDVHLGET LSEFKEFSQS
FDAAMKGLAL SNSDVIRQVH NSFARQQMFE FDTKTPAKEE DAFHFVSYVP VNGRLYELDG
LREGPIDLGA CNQDDWITAV RPVIEKRIQK YSEGEIRFNL MAIVSDRKMI YEQKIAELQR
QLAEEEPMDT DQGSTVLSAI QSEVARNQML IEEEVQKLKR YKIENIRRKH NYLPFIMELL
KTLAEHQQLI PLVEKAKEKQ NAKKAQETK
//
