CYSD_YEAST
ID CYSD_YEAST Reviewed; 444 AA.
AC P06106; D6VYU6;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Homocysteine/cysteine synthase {ECO:0000305};
DE EC=2.5.1.47 {ECO:0000269|PubMed:4609980};
DE EC=2.5.1.49 {ECO:0000269|PubMed:4609980, ECO:0000269|PubMed:4947307};
DE AltName: Full=O-acetylserine/O-acetylhomoserine sulfhydrylase {ECO:0000303|PubMed:8511969};
DE Short=OAS-OAH SHLase {ECO:0000303|PubMed:8511969};
DE Short=OAS-OAH sulfhydrylase {ECO:0000303|PubMed:4609980};
GN Name=MET17 {ECO:0000303|PubMed:8511969};
GN Synonyms=MET15 {ECO:0000303|PubMed:1781681},
GN MET25 {ECO:0000303|PubMed:3022238};
GN OrderedLocusNames=YLR303W {ECO:0000312|SGD:S000004294}; ORFNames=L8003.1;
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].
RC STRAIN=ATCC 28383 / FL100 / VTT C-80102;
RX PubMed=3022238; DOI=10.1093/nar/14.20.7861;
RA Kerjan P., Cherest H., Surdin-Kerjan Y.;
RT "Nucleotide sequence of the Saccharomyces cerevisiae MET25 gene.";
RL Nucleic Acids Res. 14:7861-7871(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169871;
RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA Zollner A., Hani J., Hoheisel J.D.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL Nature 387:87-90(1997).
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 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 PROTEIN SEQUENCE OF 2-21, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND COFACTOR.
RX PubMed=7765825; DOI=10.1007/bf00170230;
RA Yamagata S., Isaji M., Nakamura K., Fujisaki S., Doi K., Bawden S.,
RA D'Andrea R.;
RT "Overexpression of the Saccharomyces cerevisiae MET17/MET25 gene in
RT Escherichia coli and comparative characterization of the product with O-
RT acetylserine.O-acetylhomoserine sulfhydrylase of the yeast.";
RL Appl. Microbiol. Biotechnol. 42:92-99(1994).
RN [6]
RP PROTEIN SEQUENCE OF 2-10.
RX PubMed=8511969; DOI=10.1002/yea.320090409;
RA Ono B., Ishii N., Naito K., Miyoshi S., Shinoda S., Yamamoto S., Ohmori S.;
RT "Cystathionine gamma-lyase of Saccharomyces cerevisiae: structural gene and
RT cystathionine gamma-synthase activity.";
RL Yeast 9:389-397(1993).
RN [7]
RP PROTEIN SEQUENCE OF 131-140 AND 351-362.
RC STRAIN=ATCC 38531 / Y41;
RX PubMed=8935650; DOI=10.1111/j.1574-6968.1996.tb08073.x;
RA Norbeck J., Blomberg A.;
RT "Protein expression during exponential growth in 0.7 M NaCl medium of
RT Saccharomyces cerevisiae.";
RL FEMS Microbiol. Lett. 137:1-8(1996).
RN [8]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RX PubMed=4947307; DOI=10.1093/oxfordjournals.jbchem.a129712;
RA Yamagata S.;
RT "Homocysteine synthesis in yeast. Partial purification and properties of O-
RT acetylhomoserine sulfhydrylase.";
RL J. Biochem. 70:1035-1045(1971).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RX PubMed=4609980; DOI=10.1093/oxfordjournals.jbchem.a130505;
RA Yamagata S., Takeshima K., Naiki N.;
RT "Evidence for the identity of O-acetylserine sulfhydrylase with O-
RT acetylhomoserine sulfhydrylase in yeast.";
RL J. Biochem. 75:1221-1229(1974).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=795806; DOI=10.1093/oxfordjournals.jbchem.a131338;
RA Yamagata S., Takeshima K.;
RT "O-acetylserine and O-acetylhomoserine sulfhydrylase of yeast. Further
RT purification and characterization as a pyridoxal enzyme.";
RL J. Biochem. 80:777-785(1976).
RN [11]
RP SUBUNIT.
RX PubMed=795807; DOI=10.1093/oxfordjournals.jbchem.a131339;
RA Yamagata S.;
RT "O-acetylserine and O-acetylhomoserine sulfhydrylase of yeast. Subunit
RT structure.";
RL J. Biochem. 80:787-797(1976).
RN [12]
RP FUNCTION.
RX PubMed=3299001; DOI=10.1007/bf00331505;
RA D'Andrea R., Surdin-Kerjan Y., Pure G., Cherest H.;
RT "Molecular genetics of met17 and met25 mutants of Saccharomyces cerevisiae:
RT intragenic complementation between mutations of a single structural gene.";
RL Mol. Gen. Genet. 207:165-170(1987).
RN [13]
RP GENE NAME.
RX PubMed=1781681; DOI=10.1128/aem.57.11.3183-3186.1991;
RA Ono B., Ishii N., Fujino S., Aoyama I.;
RT "Role of hydrosulfide ions (HS-) in methylmercury resistance in
RT Saccharomyces cerevisiae.";
RL Appl. Environ. Microbiol. 57:3183-3186(1991).
RN [14]
RP PATHWAY.
RX PubMed=1732168; DOI=10.1093/genetics/130.1.51;
RA Cherest H., Surdin-Kerjan Y.;
RT "Genetic analysis of a new mutation conferring cysteine auxotrophy in
RT Saccharomyces cerevisiae: updating of the sulfur metabolism pathway.";
RL Genetics 130:51-58(1992).
RN [15]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=11914276; DOI=10.1101/gad.970902;
RA Kumar A., Agarwal S., Heyman J.A., Matson S., Heidtman M., Piccirillo S.,
RA Umansky L., Drawid A., Jansen R., Liu Y., Cheung K.-H., Miller P.,
RA Gerstein M., Roeder G.S., Snyder M.;
RT "Subcellular localization of the yeast proteome.";
RL Genes Dev. 16:707-719(2002).
RN [16]
RP PATHWAY.
RX PubMed=12586406; DOI=10.1111/j.1574-6968.2003.tb11531.x;
RA Takagi H., Yoshioka K., Awano N., Nakamori S., Ono B.;
RT "Role of Saccharomyces cerevisiae serine O-acetyltransferase in cysteine
RT biosynthesis.";
RL FEMS Microbiol. Lett. 218:291-297(2003).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44, 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 [19]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-160, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22106047; DOI=10.1002/pmic.201100166;
RA Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL Proteomics 12:236-240(2012).
CC -!- FUNCTION: Catalyzes the conversion of O-acetyl-L-homoserine (OAH) into
CC homocysteine in the methionine biosynthesis pathway. Also catalyzes the
CC conversion of O-acetylserine (OAS) into cysteine, the last step in the
CC cysteine biosynthesis pathway (PubMed:7765825, PubMed:4609980,
CC PubMed:795806). However, it seems that in S.cerevisiae cysteine
CC biosynthesis occurs exclusively through the cystathionine pathway and
CC not via direct incorporation of sulfur into OAS (PubMed:1732168). It
CC therefore has no metabolic role in cysteine biosynthesis and may only
CC have a regulatory role controlling OAS levels (PubMed:12586406).
CC {ECO:0000269|PubMed:4609980, ECO:0000269|PubMed:7765825,
CC ECO:0000269|PubMed:795806, ECO:0000305|PubMed:12586406,
CC ECO:0000305|PubMed:1732168}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=methanethiol + O-acetyl-L-homoserine = acetate + H(+) + L-
CC methionine; Xref=Rhea:RHEA:10048, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16007, ChEBI:CHEBI:30089, ChEBI:CHEBI:57716,
CC ChEBI:CHEBI:57844; EC=2.5.1.49; Evidence={ECO:0000269|PubMed:4609980,
CC ECO:0000269|PubMed:4947307, ECO:0000269|PubMed:7765825,
CC ECO:0000269|PubMed:795806};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hydrogen sulfide + O-acetyl-L-serine = acetate + L-cysteine;
CC Xref=Rhea:RHEA:14829, ChEBI:CHEBI:29919, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:35235, ChEBI:CHEBI:58340; EC=2.5.1.47;
CC Evidence={ECO:0000269|PubMed:4609980, ECO:0000269|PubMed:7765825,
CC ECO:0000269|PubMed:795806};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:4609980, ECO:0000269|PubMed:4947307,
CC ECO:0000269|PubMed:7765825, ECO:0000269|PubMed:795806};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.7 mM for O-acetyl-L-homoserine {ECO:0000269|PubMed:7765825};
CC KM=6.67 mM for O-acetyl-L-homoserine (at pH 7.8 in Tris-HCl buffer)
CC {ECO:0000269|PubMed:4609980};
CC KM=5.12 mM for O-acetyl-L-serine (at pH 7.8 in potassium phosphate
CC buffer) {ECO:0000269|PubMed:4609980};
CC pH dependence:
CC Optimum pH is 7.8 (for O-acetylhomoserine sulfhydrylase activity in
CC Tris-HCl buffer) and 8.4 (for both O-acetylhomoserine sulfhydrylase
CC and O-acetylserine sulfhydrylase activities in barbital-HCl buffer).
CC {ECO:0000269|PubMed:4609980, ECO:0000269|PubMed:4947307};
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; L-homocysteine from O-acetyl-L-homoserine.
CC {ECO:0000305|PubMed:12586406, ECO:0000305|PubMed:1732168}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:795807}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11914276}.
CC -!- SIMILARITY: Belongs to the trans-sulfuration enzymes family.
CC {ECO:0000305}.
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DR EMBL; X04493; CAA28181.1; -; Genomic_DNA.
DR EMBL; U17243; AAB67347.1; -; Genomic_DNA.
DR EMBL; AY723848; AAU09765.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09612.1; -; Genomic_DNA.
DR PIR; A25539; A25539.
DR RefSeq; NP_013406.1; NM_001182191.1.
DR AlphaFoldDB; P06106; -.
DR SMR; P06106; -.
DR BioGRID; 31567; 110.
DR DIP; DIP-1664N; -.
DR IntAct; P06106; 5.
DR MINT; P06106; -.
DR STRING; 4932.YLR303W; -.
DR CarbonylDB; P06106; -.
DR iPTMnet; P06106; -.
DR PaxDb; P06106; -.
DR PRIDE; P06106; -.
DR EnsemblFungi; YLR303W_mRNA; YLR303W; YLR303W.
DR GeneID; 851010; -.
DR KEGG; sce:YLR303W; -.
DR SGD; S000004294; MET17.
DR VEuPathDB; FungiDB:YLR303W; -.
DR eggNOG; KOG0053; Eukaryota.
DR HOGENOM; CLU_018986_4_0_1; -.
DR InParanoid; P06106; -.
DR OMA; TYTLFAH; -.
DR BioCyc; MetaCyc:YLR303W-MON; -.
DR BioCyc; YEAST:YLR303W-MON; -.
DR ChiTaRS; MET17; yeast.
DR PRO; PR:P06106; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; P06106; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005886; C:plasma membrane; HDA:SGD.
DR GO; GO:0004124; F:cysteine synthase activity; IDA:SGD.
DR GO; GO:0003961; F:O-acetylhomoserine aminocarboxypropyltransferase activity; IDA:SGD.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0019344; P:cysteine biosynthetic process; TAS:SGD.
DR GO; GO:0006555; P:methionine metabolic process; IMP:SGD.
DR GO; GO:0019346; P:transsulfuration; IEA:InterPro.
DR CDD; cd00614; CGS_like; 1.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR000277; Cys/Met-Metab_PyrdxlP-dep_enz.
DR InterPro; IPR006235; OAc-hSer/O-AcSer_sulfhydrylase.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR Pfam; PF01053; Cys_Met_Meta_PP; 1.
DR PIRSF; PIRSF001434; CGS; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR TIGRFAMs; TIGR01326; OAH_OAS_sulfhy; 1.
DR PROSITE; PS00868; CYS_MET_METAB_PP; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Cysteine biosynthesis; Cytoplasm;
KW Direct protein sequencing; Isopeptide bond; Methionine biosynthesis;
KW Multifunctional enzyme; Phosphoprotein; Pyridoxal phosphate;
KW Reference proteome; Transferase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:7765825,
FT ECO:0000269|PubMed:8511969"
FT CHAIN 2..444
FT /note="Homocysteine/cysteine synthase"
FT /id="PRO_0000114776"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:18407956"
FT MOD_RES 209
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P06721"
FT CROSSLNK 160
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
SQ SEQUENCE 444 AA; 48672 MW; F84224625C921B35 CRC64;
MPSHFDTVQL HAGQENPGDN AHRSRAVPIY ATTSYVFENS KHGSQLFGLE VPGYVYSRFQ
NPTSNVLEER IAALEGGAAA LAVSSGQAAQ TLAIQGLAHT GDNIVSTSYL YGGTYNQFKI
SFKRFGIEAR FVEGDNPEEF EKVFDERTKA VYLETIGNPK YNVPDFEKIV AIAHKHGIPV
VVDNTFGAGG YFCQPIKYGA DIVTHSATKW IGGHGTTIGG IIVDSGKFPW KDYPEKFPQF
SQPAEGYHGT IYNEAYGNLA YIVHVRTELL RDLGPLMNPF ASFLLLQGVE TLSLRAERHG
ENALKLAKWL EQSPYVSWVS YPGLASHSHH ENAKKYLSNG FGGVLSFGVK DLPNADKETD
PFKLSGAQVV DNLKLASNLA NVGDAKTLVI APYFTTHKQL NDKEKLASGV TKDLIRVSVG
IEFIDDIIAD FQQSFETVFA GQKP
