UBP10_YEAST
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 03-AUG-2022, entry version 177.
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; 236.
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; P53874; -.
DR PRIDE; P53874; -.
DR EnsemblFungi; YNL186W_mRNA; YNL186W; YNL186W.
DR GeneID; 855535; -.
DR KEGG; sce:YNL186W; -.
DR SGD; S000005130; UBP10.
DR VEuPathDB; FungiDB:YNL186W; -.
DR eggNOG; KOG1870; Eukaryota.
DR HOGENOM; CLU_016013_1_1_1; -.
DR InParanoid; P53874; -.
DR OMA; ELSKRMW; -.
DR BioCyc; YEAST:G3O-33197-MON; -.
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:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0016578; P:histone deubiquitination; IMP:SGD.
DR GO; GO:0016579; P:protein deubiquitination; IDA:SGD.
DR GO; GO:2001020; P:regulation of response to DNA damage stimulus; IMP:SGD.
DR GO; GO:0031509; P:subtelomeric heterochromatin assembly; IMP:SGD.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR DisProt; DP01189; -.
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 Pfam; PF00443; UCH; 1.
DR SUPFAM; SSF54001; SSF54001; 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
