UBL1_YEAST
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 03-AUG-2022, entry version 179.
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 PDBsum; 1CMX; -.
DR AlphaFoldDB; P35127; -.
DR SMR; P35127; -.
DR BioGRID; 33854; 127.
DR DIP; DIP-5052N; -.
DR IntAct; P35127; 1.
DR STRING; 4932.YJR099W; -.
DR MEROPS; C12.002; -.
DR iPTMnet; P35127; -.
DR MaxQB; P35127; -.
DR PaxDb; P35127; -.
DR PRIDE; P35127; -.
DR EnsemblFungi; YJR099W_mRNA; YJR099W; YJR099W.
DR GeneID; 853562; -.
DR KEGG; sce:YJR099W; -.
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; YVCFVKG; -.
DR BioCyc; YEAST:G3O-31727-MON; -.
DR BRENDA; 3.4.19.12; 984.
DR Reactome; R-SCE-5689603; UCH proteinases.
DR Reactome; R-SCE-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR Reactome; R-SCE-8951664; Neddylation.
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:0016579; P:protein deubiquitination; IBA:GO_Central.
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; -; 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; 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 HELIX 44..46
FT /evidence="ECO:0007829|PDB:1CMX"
FT STRAND 54..60
FT /evidence="ECO:0007829|PDB:1CMX"
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 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 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
