ID   UBL1_YEAST              Reviewed;         236 AA.
AC   P35127; D6VWR8;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1994, sequence version 1.
DT   27-MAR-2024, entry version 187.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase YUH1;
DE            Short=UCH;
DE            EC=3.4.19.12;
DE   AltName: Full=Ubiquitin thioesterase;
GN   Name=YUH1; OrderedLocusNames=YJR099W; ORFNames=J1941;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   DOI=10.1038/nbt0789-698;
RA   Miller H.I., Henzel W.J., Ridgway J.B., Kuang W.-J., Chisholm V.,
RA   Liu C.-C.;
RT   "Cloning and expression of a yeast ubiquitin-protein cleaving activity in
RT   Escherichia coli.";
RL   Biotechnology (N.Y.) 7:698-704(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA   Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA   Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA   Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA   Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA   Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA   Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA   Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA   Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA   To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA   von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT   "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL   EMBO J. 15:2031-2049(1996).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [4]
RP   FUNCTION.
RX   PubMed=2555355; DOI=10.1016/s0021-9258(19)47067-1;
RA   Liu C.C., Miller H.I., Kohr W.J., Silber J.I.;
RT   "Purification of a ubiquitin protein peptidase from yeast with efficient in
RT   vitro assays.";
RL   J. Biol. Chem. 264:20331-20338(1989).
RN   [5]
RP   CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX   PubMed=10527495; DOI=10.1006/abio.1999.4234;
RA   Layfield R., Franklin K., Landon M., Walker G., Wang P., Ramage R.,
RA   Brown A., Love S., Urquhart K., Muir T., Baker R., Mayer R.J.;
RT   "Chemically synthesized ubiquitin extension proteins detect distinct
RT   catalytic capacities of deubiquitinating enzymes.";
RL   Anal. Biochem. 274:40-49(1999).
RN   [6]
RP   FUNCTION IN RUB1 PROCESSING.
RX   PubMed=12455997; DOI=10.1128/ec.1.3.491-494.2002;
RA   Linghu B., Callis J., Goebl M.G.;
RT   "Rub1p processing by Yuh1p is required for wild-type levels of Rub1p
RT   conjugation to Cdc53p.";
RL   Eukaryot. Cell 1:491-494(2002).
RN   [7]
RP   FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=17709260; DOI=10.1016/j.pep.2007.07.005;
RA   Yu H.A., Kim S.G., Kim E.J., Lee W.J., Kim D.O., Park K., Park Y.C.,
RA   Seo J.H.;
RT   "Characterization of ubiquitin C-terminal hydrolase 1 (YUH1) from
RT   Saccharomyces cerevisiae expressed in recombinant Escherichia coli.";
RL   Protein Expr. Purif. 56:20-26(2007).
RN   [8]
RP   FUNCTION IN UBB(+1) HYDROLYSIS.
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   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH UBIQUITIN, AND
RP   ACTIVE SITE.
RX   PubMed=10406793; DOI=10.1093/emboj/18.14.3877;
RA   Johnston S.C., Riddle S.M., Cohen R.E., Hill C.P.;
RT   "Structural basis for the specificity of ubiquitin C-terminal hydrolases.";
RL   EMBO J. 18:3877-3887(1999).
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 RUB1.
CC       Preferentially cleaves ubiquitin from peptides and small adducts.
CC       {ECO:0000269|PubMed:12455997, ECO:0000269|PubMed:17709260,
CC       ECO:0000269|PubMed:21762696, ECO:0000269|PubMed:2555355}.
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:10527495};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 8.5. Inactive at a pH below 6.5.
CC         {ECO:0000269|PubMed:17709260};
CC       Temperature dependence:
CC         Optimum temperature is 27 degrees Celsius.
CC         {ECO:0000269|PubMed:17709260};
CC   -!- MISCELLANEOUS: Can hydrolyze human UBB(+1), a mutated form of ubiquitin
CC       which is not effectively degraded by the proteasome and is associated
CC       with neurogenerative disorders. It can do so despite of the fact that
CC       the C-terminal 'Gly-76' of ubiquitin has been substituted for a
CC       tyrosine in UBB(+1).
CC   -!- SIMILARITY: Belongs to the peptidase C12 family. {ECO:0000305}.
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DR   EMBL; Z49599; CAA89629.1; -; Genomic_DNA.
DR   EMBL; BK006943; DAA08884.1; -; Genomic_DNA.
DR   PIR; S51332; S51332.
DR   RefSeq; NP_012633.1; NM_001181757.1.
DR   PDB; 1CMX; X-ray; 2.25 A; A/C=1-235.
DR   PDB; 7EN4; NMR; -; A=1-236.
DR   PDBsum; 1CMX; -.
DR   PDBsum; 7EN4; -.
DR   AlphaFoldDB; P35127; -.
DR   SMR; P35127; -.
DR   BioGRID; 33854; 128.
DR   DIP; DIP-5052N; -.
DR   IntAct; P35127; 1.
DR   STRING; 4932.YJR099W; -.
DR   MEROPS; C12.002; -.
DR   iPTMnet; P35127; -.
DR   MaxQB; P35127; -.
DR   PaxDb; 4932-YJR099W; -.
DR   PeptideAtlas; P35127; -.
DR   EnsemblFungi; YJR099W_mRNA; YJR099W; YJR099W.
DR   GeneID; 853562; -.
DR   KEGG; sce:YJR099W; -.
DR   AGR; SGD:S000003860; -.
DR   SGD; S000003860; YUH1.
DR   VEuPathDB; FungiDB:YJR099W; -.
DR   eggNOG; KOG1415; Eukaryota.
DR   GeneTree; ENSGT00940000172624; -.
DR   HOGENOM; CLU_054406_0_2_1; -.
DR   InParanoid; P35127; -.
DR   OMA; EFTADHQ; -.
DR   OrthoDB; 179179at2759; -.
DR   BioCyc; YEAST:G3O-31727-MONOMER; -.
DR   BRENDA; 3.4.19.12; 984.
DR   Reactome; R-SCE-5689603; UCH proteinases.
DR   Reactome; R-SCE-8951664; Neddylation.
DR   BioGRID-ORCS; 853562; 0 hits in 10 CRISPR screens.
DR   EvolutionaryTrace; P35127; -.
DR   PRO; PR:P35127; -.
DR   Proteomes; UP000002311; Chromosome X.
DR   RNAct; P35127; Protein.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:SGD.
DR   GO; GO:0010992; P:ubiquitin recycling; IC:SGD.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR   Gene3D; 3.40.532.10; Peptidase C12, ubiquitin carboxyl-terminal hydrolase; 1.
DR   IDEAL; IID50315; -.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR001578; Peptidase_C12_UCH.
DR   InterPro; IPR036959; Peptidase_C12_UCH_sf.
DR   PANTHER; PTHR10589; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR10589:SF17; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   Pfam; PF01088; Peptidase_C12; 1.
DR   PRINTS; PR00707; UBCTHYDRLASE.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS00140; UCH_1; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Hydrolase; Protease; Reference proteome; Thiol protease;
KW   Ubl conjugation pathway.
FT   CHAIN           1..236
FT                   /note="Ubiquitin carboxyl-terminal hydrolase YUH1"
FT                   /id="PRO_0000211073"
FT   REGION          10..15
FT                   /note="Interaction with ubiquitin"
FT   REGION          149..157
FT                   /note="Interaction with ubiquitin"
FT   REGION          219..228
FT                   /note="Interaction with ubiquitin"
FT   ACT_SITE        90
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10091"
FT   ACT_SITE        166
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10091"
FT   SITE            84
FT                   /note="Transition state stabilizer"
FT   SITE            181
FT                   /note="Important for enzyme activity"
FT                   /evidence="ECO:0000250"
FT   HELIX           15..25
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   STRAND          31..36
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   STRAND          39..41
FT                   /evidence="ECO:0007829|PDB:7EN4"
FT   HELIX           44..46
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   STRAND          54..60
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   STRAND          75..79
FT                   /evidence="ECO:0007829|PDB:7EN4"
FT   HELIX           90..100
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   HELIX           103..105
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   HELIX           111..122
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   STRAND          126..129
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   HELIX           132..143
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   HELIX           146..150
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   STRAND          152..154
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   STRAND          158..160
FT                   /evidence="ECO:0007829|PDB:7EN4"
FT   STRAND          164..172
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   STRAND          174..180
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   STRAND          189..193
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   HELIX           201..203
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   HELIX           205..221
FT                   /evidence="ECO:0007829|PDB:1CMX"
FT   STRAND          223..225
FT                   /evidence="ECO:0007829|PDB:7EN4"
FT   STRAND          227..233
FT                   /evidence="ECO:0007829|PDB:1CMX"
SQ   SEQUENCE   236 AA;  26385 MW;  D239FEE25798B395 CRC64;
     MSGENRAVVP IESNPEVFTN FAHKLGLKNE WAYFDIYSLT EPELLAFLPR PVKAIVLLFP
     INEDRKSSTS QQITSSYDVI WFKQSVKNAC GLYAILHSLS NNQSLLEPGS DLDNFLKSQS
     DTSSSKNRFD DVTTDQFVLN VIKENVQTFS TGQSEAPEAT ADTNLHYITY VEENGGIFEL
     DGRNLSGPLY LGKSDPTATD LIEQELVRVR VASYMENANE EDVLNFAMLG LGPNWE
//