ID   UBP10_YEAST             Reviewed;         792 AA.
AC   P53874; D6W101;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   21-SEP-2011, sequence version 2.
DT   27-MAR-2024, entry version 183.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 10;
DE            EC=3.4.19.12 {ECO:0000269|PubMed:10490600};
DE   AltName: Full=Deubiquitinating enzyme 10;
DE   AltName: Full=Disrupter of telomere silencing protein 4 {ECO:0000303|PubMed:9755194};
DE   AltName: Full=Ubiquitin thioesterase 10;
DE   AltName: Full=Ubiquitin-specific-processing protease 10;
GN   Name=UBP10; Synonyms=DOT4 {ECO:0000303|PubMed:9755194};
GN   OrderedLocusNames=YNL186W; ORFNames=N1619;
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 [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169873;
RA   Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA   Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA   Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA   Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA   Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA   Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA   Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA   Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA   Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA   Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA   Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA   Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA   Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA   Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA   Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA   Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA   Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT   evolutionary implications.";
RL   Nature 387:93-98(1997).
RN   [2]
RP   GENOME REANNOTATION, AND SEQUENCE REVISION TO 310.
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   [3]
RP   FUNCTION.
RX   PubMed=9755194; DOI=10.1093/genetics/150.2.613;
RA   Singer M.S., Kahana A., Wolf A.J., Meisinger L.L., Peterson S.E.,
RA   Goggin C., Mahowald M., Gottschling D.E.;
RT   "Identification of high-copy disruptors of telomeric silencing in
RT   Saccharomyces cerevisiae.";
RL   Genetics 150:613-632(1998).
RN   [4]
RP   FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, INTERACTION WITH
RP   SIR4, MUTAGENESIS OF CYS-371, AND CATALYTIC ACTIVITY.
RX   PubMed=10490600; DOI=10.1128/mcb.19.10.6608;
RA   Kahana A., Gottschling D.E.;
RT   "DOT4 links silencing and cell growth in Saccharomyces cerevisiae.";
RL   Mol. Cell. Biol. 19:6608-6620(1999).
RN   [5]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=11352638; DOI=10.1006/bbrc.2001.4669;
RA   Kahana A.;
RT   "The deubiquitinating enzyme Dot4p is involved in regulating nutrient
RT   uptake.";
RL   Biochem. Biophys. Res. Commun. 282:916-920(2001).
RN   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=14623890; DOI=10.1074/jbc.m306464200;
RA   Orlandi I., Bettiga M., Alberghina L., Vai M.;
RT   "Transcriptional profiling of ubp10 null mutant reveals altered
RT   subtelomeric gene expression and insurgence of oxidative stress response.";
RL   J. Biol. Chem. 279:6414-6425(2004).
RN   [7]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=15721261; DOI=10.1016/j.molcel.2005.01.007;
RA   Emre N.C., Ingvarsdottir K., Wyce A., Wood A., Krogan N.J., Henry K.W.,
RA   Li K., Marmorstein R., Greenblatt J.F., Shilatifard A., Berger S.L.;
RT   "Maintenance of low histone ubiquitylation by Ubp10 correlates with
RT   telomere-proximal Sir2 association and gene silencing.";
RL   Mol. Cell 17:585-594(2005).
RN   [8]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=15988024; DOI=10.1128/mcb.25.14.6123-6139.2005;
RA   Gardner R.G., Nelson Z.W., Gottschling D.E.;
RT   "Ubp10/Dot4p regulates the persistence of ubiquitinated histone H2B:
RT   distinct roles in telomeric silencing and general chromatin.";
RL   Mol. Cell. Biol. 25:6123-6139(2005).
RN   [9]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=17028327; DOI=10.1534/genetics.106.063099;
RA   Calzari L., Orlandi I., Alberghina L., Vai M.;
RT   "The histone deubiquitinating enzyme Ubp10 is involved in rDNA locus
RT   control in Saccharomyces cerevisiae by affecting Sir2p association.";
RL   Genetics 174:2249-2254(2006).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19779198; DOI=10.1126/science.1172867;
RA   Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT   "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT   into evolution.";
RL   Science 325:1682-1686(2009).
RN   [11]
RP   FUNCTION.
RX   PubMed=22056669; DOI=10.1101/gad.177220.111;
RA   Schulze J.M., Hentrich T., Nakanishi S., Gupta A., Emberly E.,
RA   Shilatifard A., Kobor M.S.;
RT   "Splitting the task: Ubp8 and Ubp10 deubiquitinate different cellular pools
RT   of H2BK123.";
RL   Genes Dev. 25:2242-2247(2011).
RN   [12]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH PCNA/POL30.
RX   PubMed=22829782; DOI=10.1371/journal.pgen.1002826;
RA   Gallego-Sanchez A., Andres S., Conde F., San-Segundo P.A., Bueno A.;
RT   "Reversal of PCNA ubiquitylation by Ubp10 in Saccharomyces cerevisiae.";
RL   PLoS Genet. 8:E1002826-E1002826(2012).
RN   [13]
RP   FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP   DHR2 AND UTP22.
RX   PubMed=22902402; DOI=10.1016/j.celrep.2012.07.009;
RA   Richardson L.A., Reed B.J., Charette J.M., Freed E.F., Fredrickson E.K.,
RA   Locke M.N., Baserga S.J., Gardner R.G.;
RT   "A conserved deubiquitinating enzyme controls cell growth by regulating RNA
RT   polymerase I stability.";
RL   Cell Rep. 2:372-385(2012).
RN   [14]
RP   DOMAIN, AND INTERACTION WITH DHR2; SIR4 AND UTP22.
RX   PubMed=26149687; DOI=10.1074/jbc.m115.650952;
RA   Reed B.J., Locke M.N., Gardner R.G.;
RT   "A conserved deubiquitinating enzyme uses intrinsically disordered regions
RT   to scaffold multiple protein interaction sites.";
RL   J. Biol. Chem. 290:20601-20612(2015).
CC   -!- FUNCTION: Deubiquitinating enzyme involved in telomere and HM loci
CC       silencing, which is the repression of chromatin structure which leads
CC       to a stop in the transcription of nearby genes (PubMed:9755194,
CC       PubMed:10490600, PubMed:14623890). Targets histone H2B for
CC       deubiquitination, thus helping to localize SIR2 to the telomere
CC       (PubMed:15721261, PubMed:17028327, PubMed:22056669). At silent
CC       chromatin, including telomeres and the rDNA locus, not only maintains
CC       low H2B 'Lys-123' ubiquitination (H2BK123Ub), but also low H3 'Lys-4'
CC       and 'Lys-79' methylation (H3K4me and H3K79me, respectively)
CC       (PubMed:15721261, PubMed:15988024). Controls the proliferating-cell
CC       nuclear antigen PCNA/POL30 deubiquitination which is crucial for
CC       keeping TLS polymerases in check as well as for down-regulating the
CC       error-free bypass (PubMed:22829782). Deubiquitinates and stabilizes
CC       RPA190, the largest subunit of RNA polymerase I, to achieve optimal
CC       levels of ribosomes and cell growth (PubMed:22902402). Protects also
CC       nutrient transporters such as GAP1 from ubiquitin-dependent endocytosis
CC       (PubMed:11352638). {ECO:0000269|PubMed:10490600,
CC       ECO:0000269|PubMed:11352638, ECO:0000269|PubMed:14623890,
CC       ECO:0000269|PubMed:15721261, ECO:0000269|PubMed:15988024,
CC       ECO:0000269|PubMed:17028327, ECO:0000269|PubMed:22056669,
CC       ECO:0000269|PubMed:22829782, ECO:0000269|PubMed:22902402,
CC       ECO:0000269|PubMed:9755194}.
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:10490600};
CC   -!- SUBUNIT: Interacts with SIR4 (PubMed:10490600, PubMed:26149687).
CC       Interacts with the proliferating-cell nuclear antigen PCNA/POL30
CC       (PubMed:22829782). Interacts with DHR2 and UTP22 (PubMed:22902402,
CC       PubMed:26149687). {ECO:0000269|PubMed:10490600,
CC       ECO:0000269|PubMed:22829782, ECO:0000269|PubMed:26149687}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10490600}.
CC       Chromosome, telomere {ECO:0000269|PubMed:15721261}. Nucleus, nucleolus
CC       {ECO:0000269|PubMed:22902402}. Note=Preferentially localizes to silent
CC       chromatin (PubMed:15988024). {ECO:0000269|PubMed:15988024}.
CC   -!- DOMAIN: Residues 2-27 within the N-terminal intrinsically disordered
CC       regions (IDR) constitute the binding module for DHR2 which is required
CC       to coordinate the UBP10-DHR2 interaction (PubMed:26149687).
CC       {ECO:0000269|PubMed:26149687}.
CC   -!- DOMAIN: Residues 109-145 within the N-terminal intrinsically disordered
CC       regions (IDR) constitute the binding module for SIR4 which required to
CC       coordinate the UBP10-SIR4 interaction, but also to direct UBP10's
CC       functional role in telomere chromatin silencing (PubMed:26149687).
CC       {ECO:0000269|PubMed:26149687}.
CC   -!- DOMAIN: Residues 167-208 within the N-terminal intrinsically disordered
CC       regions (IDR) constitute the binding module for UTP22 which is required
CC       to coordinate the UBP10-UTP22 interaction (PubMed:26149687).
CC       {ECO:0000269|PubMed:26149687}.
CC   -!- DISRUPTION PHENOTYPE: Exhibits reduced silencing and a corresponding
CC       decrease in the level of SIR4 (PubMed:10490600). Reduces also the level
CC       of the low-affinity, high-capacity transporter of amino acids GAP1
CC       (PubMed:11352638). Leads to alterations in expression of subtelomeric
CC       genes together with a broad change in the whole transcriptional
CC       profile, closely parallel to that induced by oxidative stress
CC       (PubMed:14623890). Results also in extrachromosomal rDNA circles (ERCs)
CC       accumulation (PubMed:17028327). Accumulates also mono- and di-
CC       ubiquitinated PCNA/POL30 in response to DNA damage and replicative
CC       stress (PubMed:22829782). Leads to reduced pre-rRNAs, mature rRNAs, and
CC       translating ribosomes (PubMed:22902402). {ECO:0000269|PubMed:10490600,
CC       ECO:0000269|PubMed:11352638, ECO:0000269|PubMed:14623890,
CC       ECO:0000269|PubMed:17028327, ECO:0000269|PubMed:22829782,
CC       ECO:0000269|PubMed:22902402}.
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR   EMBL; Z71462; CAA96080.1; -; Genomic_DNA.
DR   EMBL; BK006947; DAA10367.2; -; Genomic_DNA.
DR   PIR; S63141; S63141.
DR   RefSeq; NP_014213.2; NM_001183024.2.
DR   PDB; 6RR0; X-ray; 2.18 A; H/I/J/K/L/M/N=117-128.
DR   PDBsum; 6RR0; -.
DR   AlphaFoldDB; P53874; -.
DR   SMR; P53874; -.
DR   BioGRID; 35647; 254.
DR   DIP; DIP-6664N; -.
DR   IntAct; P53874; 22.
DR   MINT; P53874; -.
DR   STRING; 4932.YNL186W; -.
DR   MEROPS; C19.088; -.
DR   iPTMnet; P53874; -.
DR   MaxQB; P53874; -.
DR   PaxDb; 4932-YNL186W; -.
DR   PeptideAtlas; P53874; -.
DR   EnsemblFungi; YNL186W_mRNA; YNL186W; YNL186W.
DR   GeneID; 855535; -.
DR   KEGG; sce:YNL186W; -.
DR   AGR; SGD:S000005130; -.
DR   SGD; S000005130; UBP10.
DR   VEuPathDB; FungiDB:YNL186W; -.
DR   eggNOG; KOG1870; Eukaryota.
DR   HOGENOM; CLU_016013_1_1_1; -.
DR   InParanoid; P53874; -.
DR   OMA; HCLQPDG; -.
DR   OrthoDB; 74526at2759; -.
DR   BioCyc; YEAST:G3O-33197-MONOMER; -.
DR   BioGRID-ORCS; 855535; 6 hits in 10 CRISPR screens.
DR   PRO; PR:P53874; -.
DR   Proteomes; UP000002311; Chromosome XIV.
DR   RNAct; P53874; Protein.
DR   GO; GO:0000781; C:chromosome, telomeric region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0043596; C:nuclear replication fork; IDA:SGD.
DR   GO; GO:0005730; C:nucleolus; IDA:SGD.
DR   GO; GO:0005634; C:nucleus; IDA:SGD.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:SGD.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0031509; P:subtelomeric heterochromatin formation; IMP:SGD.
DR   DisProt; DP01189; -.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
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   PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   Pfam; PF00443; UCH; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS00973; USP_2; 1.
DR   PROSITE; PS50235; USP_3; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Chromosome; Hydrolase; Nucleus; Protease; Reference proteome;
KW   Telomere; Thiol protease; Ubl conjugation pathway.
FT   CHAIN           1..792
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 10"
FT                   /id="PRO_0000080595"
FT   DOMAIN          362..733
FT                   /note="USP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT   REGION          2..27
FT                   /note="DHR2-binding module"
FT                   /evidence="ECO:0000269|PubMed:26149687"
FT   REGION          64..87
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          103..320
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          109..145
FT                   /note="SIR4-binding module"
FT                   /evidence="ECO:0000269|PubMed:26149687"
FT   REGION          167..208
FT                   /note="UTP22-binding module"
FT                   /evidence="ECO:0000269|PubMed:26149687"
FT   REGION          526..563
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          749..792
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        115..129
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        130..172
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        173..192
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        208..225
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        226..253
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        254..271
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        272..295
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        296..316
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        531..563
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        749..772
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        773..792
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        371
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT   ACT_SITE        691
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT   MUTAGEN         371
FT                   /note="C->A,S: Abolishes deubiquitinating activity."
FT                   /evidence="ECO:0000269|PubMed:10490600"
FT   CONFLICT        310
FT                   /note="E -> D (in Ref. 1; CAA96080)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   792 AA;  88531 MW;  AA2DE6DB0C560E37 CRC64;
     MTTQESIKPL VDRILSNPLQ FNAAMISNKS NNNDTSAAPE NSSYIVIGKQ HNNNSNSTAI
     AATAESKQIK ENNLIDRPNG KKTNTVPKSM AEALLLYTSK NDKDAADATG AKKSAELSTE
     LSTEPPSSSS EDDKVGKEEE EEGEIFHEAR DYVEPRKASL KERDNADKGD GEDIGEDIGE
     DIGEDIGEDI GEDIGENLGS PLATIDDSSN ENEKEKRKEL STSISSDDEI EDDEDEDDMD
     YDSSAMEKEL PEEEENDSSS KISEGEKKSL YQDLMENSTV EVNRYEPVNN TKENGNRNPK
     GEEEEEEEEE LKHKSRSITP PVTISNLSNF YQFNENINDR GSLNSTRIVK NWGDKFTNLK
     PRGLLNHGVT CYTNAAVQAM LHIPSIQHYL FDILMGKYDS TISKNSVSYT LAETSKKMWL
     PVSKNPRKNV SASYINPKHL ISRLDDINCM MSEWQQEDSH EYFMSLMSRL QEDSVPKGHK
     LIESIIYDIF GGLLKQIVTC KSCGSISKTE QPFYDLSLHL KGKKKLDPNS DLSSDSINGT
     SATTSTTTSN AATKPSLSSS SSVNLNNGSP FAAASDLSSA NRRFSIEKSI KDFFNPELIK
     VDKEQKGYVC EKCHKTTNAV KHSSILRAPE TLLVHLKKFR FNGTSSSKMK QAVSYPMFLD
     LTEYCESKEL PVKYQLLSVV VHEGRSLSSG HYIAHCKQPD GSWATYDDEY INIISERDVL
     KEPNAYYLLY TRLTPKSVPL PLAKSAMATG NVTSKSKQEQ AVNEPNNRPL KINSKKNNRK
     KWKKNKKRKF TK
//