DUG1_YEAST
ID DUG1_YEAST Reviewed; 481 AA.
AC P43616; D6VTS7;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Cys-Gly metallodipeptidase DUG1;
DE EC=3.4.13.-;
DE AltName: Full=Deficient in utilization of glutathione protein 1;
DE AltName: Full=GSH degradosomal complex subunit DUG1;
GN Name=DUG1; OrderedLocusNames=YFR044C;
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=7670463; DOI=10.1038/ng0795-261;
RA Murakami Y., Naitou M., Hagiwara H., Shibata T., Ozawa M., Sasanuma S.,
RA Sasanuma M., Tsuchiya Y., Soeda E., Yokoyama K., Yamazaki M., Tashiro H.,
RA Eki T.;
RT "Analysis of the nucleotide sequence of chromosome VI from Saccharomyces
RT cerevisiae.";
RL Nat. Genet. 10:261-268(1995).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204511 / S288c / AB972;
RX PubMed=8686379;
RX DOI=10.1002/(sici)1097-0061(199602)12:2<149::aid-yea893>3.0.co;2-g;
RA Eki T., Naitou M., Hagiwara H., Ozawa M., Sasanuma S., Sasanuma M.,
RA Tsuchiya Y., Shibata T., Hanaoka F., Murakami Y.;
RT "Analysis of a 36.2 kb DNA sequence including the right telomere of
RT chromosome VI from Saccharomyces cerevisiae.";
RL Yeast 12:149-167(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=8962070; DOI=10.1073/pnas.93.25.14440;
RA Shevchenko A., Jensen O.N., Podtelejnikov A.V., Sagliocco F., Wilm M.,
RA Vorm O., Mortensen P., Shevchenko A., Boucherie H., Mann M.;
RT "Linking genome and proteome by mass spectrometry: large-scale
RT identification of yeast proteins from two dimensional gels.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:14440-14445(1996).
RN [6]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [7]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [8]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=16823961; DOI=10.1021/pr050477f;
RA Reinders J., Zahedi R.P., Pfanner N., Meisinger C., Sickmann A.;
RT "Toward the complete yeast mitochondrial proteome: multidimensional
RT separation techniques for mitochondrial proteomics.";
RL J. Proteome Res. 5:1543-1554(2006).
RN [9]
RP FUNCTION, IDENTIFICATION IN THE GSH DEGRADOSOMAL COMPLEX, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17179087; DOI=10.1534/genetics.106.066944;
RA Ganguli D., Kumar C., Bachhawat A.K.;
RT "The alternative pathway of glutathione degradation is mediated by a novel
RT protein complex involving three new genes in Saccharomyces cerevisiae.";
RL Genetics 175:1137-1151(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [11]
RP SUBUNIT, FUNCTION, COFACTOR, AND DISRUPTION PHENOTYPE.
RX PubMed=19346245; DOI=10.1074/jbc.m808952200;
RA Kaur H., Kumar C., Junot C., Toledano M.B., Bachhawat A.K.;
RT "Dug1p Is a Cys-Gly peptidase of the gamma-glutamyl cycle of Saccharomyces
RT cerevisiae and represents a novel family of Cys-Gly peptidases.";
RL J. Biol. Chem. 284:14493-14502(2009).
CC -!- FUNCTION: Catalytic component of the GSH degradosomal complex involved
CC in the degradation of glutathione (GSH) and other peptides containing a
CC gamma-glu-X bond. Functions also in a DUG2-DUG3-independent manner as a
CC dipeptidase with high specificity for Cys-Gly and no activity toward
CC tri- or tetrapeptides. {ECO:0000269|PubMed:17179087,
CC ECO:0000269|PubMed:19346245}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:19346245};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:19346245};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.4 mM for Cys-Gly (at pH 8.0 and in the presence of 20 uM
CC manganese ions);
CC KM=0.8 mM for Cys-Gly (at pH 8.0 and in the presence of 200 uM zinc
CC ions);
CC -!- SUBUNIT: Homodimer. Component of the GSH degradosomal complex composed
CC of at least DUG1, DUG2 and DUG3. {ECO:0000269|PubMed:17179087,
CC ECO:0000269|PubMed:19346245}.
CC -!- INTERACTION:
CC P43616; P43616: DUG1; NbExp=2; IntAct=EBI-5137, EBI-5137;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:17179087}. Mitochondrion
CC {ECO:0000269|PubMed:16823961}.
CC -!- DISRUPTION PHENOTYPE: Accumulation of Cys-Gly dipeptide and enhanced
CC GSH toxicity. {ECO:0000269|PubMed:19346245}.
CC -!- MISCELLANEOUS: Present with 22300 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the peptidase M20A family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D50617; BAA09283.1; -; Genomic_DNA.
DR EMBL; AY692702; AAT92721.1; -; Genomic_DNA.
DR EMBL; BK006940; DAA12487.1; -; Genomic_DNA.
DR PIR; S56299; S56299.
DR RefSeq; NP_116702.1; NM_001180009.1.
DR PDB; 4G1P; X-ray; 2.55 A; A=1-481.
DR PDBsum; 4G1P; -.
DR AlphaFoldDB; P43616; -.
DR SMR; P43616; -.
DR BioGRID; 31202; 50.
DR DIP; DIP-6492N; -.
DR IntAct; P43616; 4.
DR MINT; P43616; -.
DR STRING; 4932.YFR044C; -.
DR MEROPS; M20.017; -.
DR iPTMnet; P43616; -.
DR MaxQB; P43616; -.
DR PaxDb; P43616; -.
DR PRIDE; P43616; -.
DR EnsemblFungi; YFR044C_mRNA; YFR044C; YFR044C.
DR GeneID; 850605; -.
DR KEGG; sce:YFR044C; -.
DR SGD; S000001940; DUG1.
DR VEuPathDB; FungiDB:YFR044C; -.
DR eggNOG; KOG2276; Eukaryota.
DR GeneTree; ENSGT00940000174652; -.
DR HOGENOM; CLU_029469_3_0_1; -.
DR InParanoid; P43616; -.
DR OMA; HITIPGF; -.
DR BioCyc; MetaCyc:MON3O-4; -.
DR BioCyc; YEAST:MON3O-4; -.
DR Reactome; R-SCE-174403; Glutathione synthesis and recycling.
DR Reactome; R-SCE-9753281; Paracetamol ADME.
DR SABIO-RK; P43616; -.
DR PRO; PR:P43616; -.
DR Proteomes; UP000002311; Chromosome VI.
DR RNAct; P43616; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070573; F:metallodipeptidase activity; IDA:SGD.
DR GO; GO:0008242; F:omega peptidase activity; IGI:SGD.
DR GO; GO:0008233; F:peptidase activity; IBA:GO_Central.
DR GO; GO:0006751; P:glutathione catabolic process; IMP:SGD.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR InterPro; IPR017153; CNDP/DUG1.
DR InterPro; IPR002933; Peptidase_M20.
DR InterPro; IPR011650; Peptidase_M20_dimer.
DR Pfam; PF07687; M20_dimer; 1.
DR Pfam; PF01546; Peptidase_M20; 1.
DR PIRSF; PIRSF037242; CNDP_dipeptidase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Dipeptidase; Hydrolase; Manganese; Metal-binding;
KW Metalloprotease; Mitochondrion; Phosphoprotein; Protease;
KW Reference proteome; Zinc.
FT CHAIN 1..481
FT /note="Cys-Gly metallodipeptidase DUG1"
FT /id="PRO_0000185275"
FT ACT_SITE 104
FT /evidence="ECO:0000250"
FT ACT_SITE 171
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 102
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 137
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 137
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 172
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 200
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 450
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT MOD_RES 451
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT HELIX 5..14
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 16..28
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 39..55
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:4G1P"
FT TURN 125..128
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:4G1P"
FT TURN 133..138
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 139..154
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 161..169
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:4G1P"
FT TURN 174..177
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 178..185
FT /evidence="ECO:0007829|PDB:4G1P"
FT TURN 186..192
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 195..198
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 204..208
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 210..215
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 217..226
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 228..230
FT /evidence="ECO:0007829|PDB:4G1P"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:4G1P"
FT TURN 238..240
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 244..252
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 267..270
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 276..281
FT /evidence="ECO:0007829|PDB:4G1P"
FT TURN 282..284
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 289..296
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 306..314
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 318..327
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 330..332
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 339..349
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 355..371
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 376..387
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 397..410
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 415..421
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 426..433
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 437..439
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 451..453
FT /evidence="ECO:0007829|PDB:4G1P"
FT STRAND 455..457
FT /evidence="ECO:0007829|PDB:4G1P"
FT HELIX 458..477
FT /evidence="ECO:0007829|PDB:4G1P"
SQ SEQUENCE 481 AA; 52871 MW; 3E53773A945F5EBC CRC64;
MSHSLTSVFQ KIDSLKPQFF SRLTKAIQIP AVSSDESLRS KVFDKAKFIS EQLSQSGFHD
IKMVDLGIQP PPISTPNLSL PPVILSRFGS DPSKKTVLVY GHYDVQPAQL EDGWDTEPFK
LVIDEAKGIM KGRGVTDDTG PLLSWINVVD AFKASGQEFP VNLVTCFEGM EESGSLKLDE
LIKKEANGYF KGVDAVCISD NYWLGTKKPV LTYGLRGCNY YQTIIEGPSA DLHSGIFGGV
VAEPMIDLMQ VLGSLVDSKG KILIDGIDEM VAPLTEKEKA LYKDIEFSVE ELNAATGSKT
SLYDKKEDIL MHRWRYPSLS IHGVEGAFSA QGAKTVIPAK VFGKFSIRTV PDMDSEKLTS
LVQKHCDAKF KSLNSPNKCR TELIHDGAYW VSDPFNAQFT AAKKATKLVY GVDPDFTREG
GSIPITLTFQ DALNTSVLLL PMGRGDDGAH SINEKLDISN FVGGMKTMAA YLQYYSESPE
N
