UCHL3_HUMAN
ID UCHL3_HUMAN Reviewed; 230 AA.
AC P15374; B2R970; Q5TBK8; Q6IBE9;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase isozyme L3;
DE Short=UCH-L3;
DE EC=3.4.19.12 {ECO:0000269|PubMed:15157086, ECO:0000269|PubMed:15531586, ECO:0000269|PubMed:19047059, ECO:0000269|PubMed:20380862, ECO:0000269|PubMed:2530630, ECO:0000269|PubMed:9790970};
DE AltName: Full=Ubiquitin thioesterase L3;
GN Name=UCHL3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=2530630; DOI=10.1126/science.2530630;
RA Wilkinson K.D., Lee K., Deshpande S., Duerksen-Hughes P., Boss J.M.,
RA Pohl J.;
RT "The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal
RT hydrolase.";
RL Science 246:670-673(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [8]
RP FUNCTION, ENZYME ACTIVITY, TISSUE SPECIFICITY, AND MUTAGENESIS OF CYS-95.
RX PubMed=9790970; DOI=10.1006/bbrc.1998.9532;
RA Wada H., Kito K., Caskey L.S., Yeh E.T.H., Kamitani T.;
RT "Cleavage of the C-terminus of NEDD8 by UCH-L3.";
RL Biochem. Biophys. Res. Commun. 251:688-692(1998).
RN [9]
RP IDENTIFICATION AS TUMOR-ASSOCIATED ANTIGEN BY MASS SPECTROMETRY.
RX PubMed=14595809; DOI=10.1002/pmic.200300594;
RA Nam M.J., Madoz-Gurpide J., Wang H., Lescure P., Schmalbach C.E., Zhao R.,
RA Misek D.E., Kuick R., Brenner D.E., Hanash S.M.;
RT "Molecular profiling of the immune response in colon cancer using protein
RT microarrays: occurrence of autoantibodies to ubiquitin C-terminal hydrolase
RT L3.";
RL Proteomics 3:2108-2115(2003).
RN [10]
RP CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX PubMed=15157086; DOI=10.1021/bi049722j;
RA Mason D.E., Ek J., Peters E.C., Harris J.L.;
RT "Substrate profiling of deubiquitin hydrolases with a positional scanning
RT library and mass spectrometry.";
RL Biochemistry 43:6535-6544(2004).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP CATALYTIC ACTIVITY.
RX PubMed=19047059; DOI=10.1074/jbc.m807172200;
RA Popp M.W., Artavanis-Tsakonas K., Ploegh H.L.;
RT "Substrate filtering by the active site crossover loop in UCHL3 revealed by
RT sortagging and gain-of-function mutations.";
RL J. Biol. Chem. 284:3593-3602(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH UBIQUITIN, FUNCTION,
RP ACTIVITY REGULATION, AND MUTAGENESIS OF ASP-33 AND CYS-95.
RX PubMed=19154770; DOI=10.1016/j.neuint.2008.12.013;
RA Setsuie R., Sakurai M., Sakaguchi Y., Wada K.;
RT "Ubiquitin dimers control the hydrolase activity of UCH-L3.";
RL Neurochem. Int. 54:314-321(2009).
RN [15]
RP ENZYME ACTIVITY, AND MUTAGENESIS OF ASP-33 AND CYS-95.
RX PubMed=20380862; DOI=10.1016/j.neuint.2010.03.021;
RA Setsuie R., Suzuki M., Tsuchiya Y., Wada K.;
RT "Skeletal muscles of Uchl3 knockout mice show polyubiquitinated protein
RT accumulation and stress responses.";
RL Neurochem. Int. 56:911-918(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP FUNCTION.
RX PubMed=21762696; DOI=10.1016/j.febslet.2011.06.037;
RA Dennissen F.J., Kholod N., Hermes D.J., Kemmerling N., Steinbusch H.W.,
RA Dantuma N.P., van Leeuwen F.W.;
RT "Mutant ubiquitin (UBB(+1)) associated with neurodegenerative disorders is
RT hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3).";
RL FEBS Lett. 585:2568-2574(2011).
RN [18]
RP FUNCTION, AND LINKAGE SPECIFICITY.
RX PubMed=22689415; DOI=10.1002/cbic.201200261;
RA Iphofer A., Kummer A., Nimtz M., Ritter A., Arnold T., Frank R.,
RA van den Heuvel J., Kessler B.M., Jansch L., Franke R.;
RT "Profiling ubiquitin linkage specificities of deubiquitinating enzymes with
RT branched ubiquitin isopeptide probes.";
RL ChemBioChem 13:1416-1420(2012).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
RX PubMed=9233788; DOI=10.1093/emboj/16.13.3787;
RA Johnston S.C., Larsen C.N., Cook W.J., Wilkinson K.D., Hill C.P.;
RT "Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8-A
RT resolution.";
RL EMBO J. 16:3787-3796(1997).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) IN COMPLEX WITH UBIQUITIN
RP VINYLMETHYLESTER, AND ENZYME ACTIVITY.
RX PubMed=15531586; DOI=10.1074/jbc.m410770200;
RA Misaghi S., Galardy P.J., Meester W.J.N., Ovaa H., Ploegh H.L., Gaudet R.;
RT "Structure of the ubiquitin hydrolase UCH-L3 complexed with a suicide
RT substrate.";
RL J. Biol. Chem. 280:1512-1520(2005).
CC -!- FUNCTION: Deubiquitinating enzyme (DUB) that controls levels of
CC cellular ubiquitin through processing of ubiquitin precursors and
CC ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a
CC peptide bond at the C-terminal glycine of either ubiquitin or NEDD8.
CC Has a 10-fold preference for Arg and Lys at position P3'', and exhibits
CC a preference towards 'Lys-48'-linked ubiquitin chains. Deubiquitinates
CC ENAC in apical compartments, thereby regulating apical membrane
CC recycling. Indirectly increases the phosphorylation of IGFIR, AKT and
CC FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis.
CC Required for stress-response retinal, skeletal muscle and germ cell
CC maintenance. May be involved in working memory. Can hydrolyze UBB(+1),
CC a mutated form of ubiquitin which is not effectively degraded by the
CC proteasome and is associated with neurogenerative disorders.
CC {ECO:0000269|PubMed:19154770, ECO:0000269|PubMed:21762696,
CC ECO:0000269|PubMed:22689415, ECO:0000269|PubMed:2530630,
CC ECO:0000269|PubMed:9790970}.
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:15157086,
CC ECO:0000269|PubMed:15531586, ECO:0000269|PubMed:19047059,
CC ECO:0000269|PubMed:20380862, ECO:0000269|PubMed:2530630,
CC ECO:0000269|PubMed:9790970};
CC -!- ACTIVITY REGULATION: Inhibited by monoubiquitin and diubiquitin.
CC {ECO:0000269|PubMed:19154770}.
CC -!- SUBUNIT: Preferentially binds diubiquitin; the interaction does not
CC hydrolyze diubiquitin but, in vitro, inhibits the hydrolyzing activity
CC on other substrates. {ECO:0000269|PubMed:15531586}.
CC -!- INTERACTION:
CC P15374; G5E9A7: DMWD; NbExp=3; IntAct=EBI-954554, EBI-10976677;
CC P15374; Q15797: SMAD1; NbExp=2; IntAct=EBI-954554, EBI-1567153;
CC P15374; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-954554, EBI-5235340;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle, and
CC testis. {ECO:0000269|PubMed:9790970}.
CC -!- MISCELLANEOUS: Identified as a tumor-specific antigen in colon cancer.
CC -!- SIMILARITY: Belongs to the peptidase C12 family. {ECO:0000305}.
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DR EMBL; M30496; AAA36791.1; -; mRNA.
DR EMBL; BT019359; AAV38166.1; -; mRNA.
DR EMBL; CR456855; CAG33136.1; -; mRNA.
DR EMBL; AK313665; BAG36417.1; -; mRNA.
DR EMBL; AL137244; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471093; EAW80542.1; -; Genomic_DNA.
DR EMBL; BC018125; AAH18125.1; -; mRNA.
DR CCDS; CCDS9453.1; -.
DR PIR; A40085; A40085.
DR RefSeq; NP_001257881.1; NM_001270952.1.
DR RefSeq; NP_005993.1; NM_006002.4.
DR PDB; 1UCH; X-ray; 1.80 A; A=1-230.
DR PDB; 1XD3; X-ray; 1.45 A; A/C=1-230.
DR PDB; 6ISU; X-ray; 1.87 A; A=1-230.
DR PDB; 6QML; X-ray; 2.10 A; A/D=4-230.
DR PDBsum; 1UCH; -.
DR PDBsum; 1XD3; -.
DR PDBsum; 6ISU; -.
DR PDBsum; 6QML; -.
DR AlphaFoldDB; P15374; -.
DR BMRB; P15374; -.
DR SMR; P15374; -.
DR BioGRID; 113194; 169.
DR DIP; DIP-29135N; -.
DR IntAct; P15374; 19.
DR MINT; P15374; -.
DR STRING; 9606.ENSP00000366819; -.
DR BindingDB; P15374; -.
DR ChEMBL; CHEMBL6195; -.
DR DrugCentral; P15374; -.
DR GuidetoPHARMACOLOGY; 2427; -.
DR MEROPS; C12.003; -.
DR GlyGen; P15374; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P15374; -.
DR MetOSite; P15374; -.
DR PhosphoSitePlus; P15374; -.
DR BioMuta; UCHL3; -.
DR DMDM; 136682; -.
DR OGP; P15374; -.
DR REPRODUCTION-2DPAGE; IPI00011250; -.
DR EPD; P15374; -.
DR jPOST; P15374; -.
DR MassIVE; P15374; -.
DR MaxQB; P15374; -.
DR PaxDb; P15374; -.
DR PeptideAtlas; P15374; -.
DR PRIDE; P15374; -.
DR ProteomicsDB; 53133; -.
DR Antibodypedia; 10104; 441 antibodies from 40 providers.
DR DNASU; 7347; -.
DR Ensembl; ENST00000377595.8; ENSP00000366819.3; ENSG00000118939.18.
DR GeneID; 7347; -.
DR KEGG; hsa:7347; -.
DR MANE-Select; ENST00000377595.8; ENSP00000366819.3; NM_006002.5; NP_005993.1.
DR UCSC; uc001vjq.5; human.
DR CTD; 7347; -.
DR DisGeNET; 7347; -.
DR GeneCards; UCHL3; -.
DR HGNC; HGNC:12515; UCHL3.
DR HPA; ENSG00000118939; Low tissue specificity.
DR MIM; 603090; gene.
DR neXtProt; NX_P15374; -.
DR OpenTargets; ENSG00000118939; -.
DR PharmGKB; PA37162; -.
DR VEuPathDB; HostDB:ENSG00000118939; -.
DR eggNOG; KOG1415; Eukaryota.
DR GeneTree; ENSGT00940000154925; -.
DR HOGENOM; CLU_054406_1_1_1; -.
DR InParanoid; P15374; -.
DR OMA; YVCFVKG; -.
DR OrthoDB; 1013351at2759; -.
DR PhylomeDB; P15374; -.
DR TreeFam; TF316166; -.
DR BRENDA; 3.4.19.12; 2681.
DR PathwayCommons; P15374; -.
DR Reactome; R-HSA-5689603; UCH proteinases.
DR Reactome; R-HSA-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR Reactome; R-HSA-8951664; Neddylation.
DR SABIO-RK; P15374; -.
DR SignaLink; P15374; -.
DR BioGRID-ORCS; 7347; 7 hits in 1124 CRISPR screens.
DR ChiTaRS; UCHL3; human.
DR EvolutionaryTrace; P15374; -.
DR GeneWiki; UCHL3; -.
DR GenomeRNAi; 7347; -.
DR Pharos; P15374; Tchem.
DR PRO; PR:P15374; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; P15374; protein.
DR Bgee; ENSG00000118939; Expressed in right adrenal gland and 114 other tissues.
DR ExpressionAtlas; P15374; baseline and differential.
DR Genevisible; P15374; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0019784; F:deNEDDylase activity; TAS:Reactome.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0030163; P:protein catabolic process; IDA:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; TAS:Reactome.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.40.532.10; -; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001578; Peptidase_C12_UCH.
DR InterPro; IPR036959; Peptidase_C12_UCH_sf.
DR PANTHER; PTHR10589; PTHR10589; 1.
DR Pfam; PF01088; Peptidase_C12; 1.
DR PRINTS; PR00707; UBCTHYDRLASE.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00140; UCH_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Hydrolase; Phosphoprotein; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..230
FT /note="Ubiquitin carboxyl-terminal hydrolase isozyme L3"
FT /id="PRO_0000211061"
FT REGION 8..13
FT /note="Interaction with ubiquitin"
FT /evidence="ECO:0000269|PubMed:15531586"
FT REGION 152..159
FT /note="Interaction with ubiquitin. Crossover loop which
FT restricts access of large ubiquitin adducts to the active
FT site"
FT /evidence="ECO:0000269|PubMed:15531586,
FT ECO:0000269|PubMed:19047059"
FT REGION 219..224
FT /note="Interaction with ubiquitin"
FT /evidence="ECO:0000269|PubMed:15531586"
FT ACT_SITE 95
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:19154770,
FT ECO:0000269|PubMed:20380862, ECO:0000269|PubMed:9790970"
FT ACT_SITE 169
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P09936"
FT SITE 184
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:P09936"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MUTAGEN 33
FT /note="D->A: Decreased interaction with diubiquitin. No
FT accumulation of free diubiquitin. Decreased levels of
FT polyubiquitinated lysozyme."
FT /evidence="ECO:0000269|PubMed:19154770,
FT ECO:0000269|PubMed:20380862"
FT MUTAGEN 95
FT /note="C->A: Increased interaction with diubiquitin."
FT /evidence="ECO:0000269|PubMed:19154770,
FT ECO:0000269|PubMed:20380862, ECO:0000269|PubMed:9790970"
FT MUTAGEN 95
FT /note="C->S: Abolishes enzymatic activity. Increased
FT interaction with diubiquitin."
FT /evidence="ECO:0000269|PubMed:19154770,
FT ECO:0000269|PubMed:20380862, ECO:0000269|PubMed:9790970"
FT STRAND 9..11
FT /evidence="ECO:0007829|PDB:6QML"
FT HELIX 13..22
FT /evidence="ECO:0007829|PDB:1XD3"
FT STRAND 29..33
FT /evidence="ECO:0007829|PDB:1XD3"
FT HELIX 39..42
FT /evidence="ECO:0007829|PDB:1XD3"
FT STRAND 49..57
FT /evidence="ECO:0007829|PDB:1XD3"
FT HELIX 60..76
FT /evidence="ECO:0007829|PDB:1XD3"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:1UCH"
FT HELIX 95..105
FT /evidence="ECO:0007829|PDB:1XD3"
FT HELIX 106..110
FT /evidence="ECO:0007829|PDB:1XD3"
FT HELIX 118..126
FT /evidence="ECO:0007829|PDB:1XD3"
FT HELIX 131..139
FT /evidence="ECO:0007829|PDB:1XD3"
FT HELIX 142..152
FT /evidence="ECO:0007829|PDB:1XD3"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:1XD3"
FT STRAND 168..176
FT /evidence="ECO:0007829|PDB:1XD3"
FT STRAND 179..183
FT /evidence="ECO:0007829|PDB:1XD3"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:1XD3"
FT STRAND 191..195
FT /evidence="ECO:0007829|PDB:1XD3"
FT TURN 198..200
FT /evidence="ECO:0007829|PDB:1XD3"
FT HELIX 201..215
FT /evidence="ECO:0007829|PDB:1XD3"
FT STRAND 223..229
FT /evidence="ECO:0007829|PDB:1XD3"
SQ SEQUENCE 230 AA; 26183 MW; 8ACACE6E1D86FD55 CRC64;
MEGQRWLPLE ANPEVTNQFL KQLGLHPNWQ FVDVYGMDPE LLSMVPRPVC AVLLLFPITE
KYEVFRTEEE EKIKSQGQDV TSSVYFMKQT ISNACGTIGL IHAIANNKDK MHFESGSTLK
KFLEESVSMS PEERARYLEN YDAIRVTHET SAHEGQTEAP SIDEKVDLHF IALVHVDGHL
YELDGRKPFP INHGETSDET LLEDAIEVCK KFMERDPDEL RFNAIALSAA
