ID   DHOM_YEAST              Reviewed;         359 AA.
AC   P31116; D6VWV8;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   27-MAR-2024, entry version 189.
DE   RecName: Full=Homoserine dehydrogenase;
DE            Short=HDH;
DE            EC=1.1.1.3;
GN   Name=HOM6; OrderedLocusNames=YJR139C; ORFNames=J2132;
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 26786 / X2180-1A;
RX   PubMed=8500624; DOI=10.1016/0014-5793(93)81359-8;
RA   Thomas D., Barbey R., Surdin-Kerjan Y.;
RT   "Evolutionary relationships between yeast and bacterial homoserine
RT   dehydrogenases.";
RL   FEBS Lett. 323:289-293(1993).
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   PROTEIN SEQUENCE OF 129-158 AND 327-354.
RX   PubMed=1897932; DOI=10.1016/0003-9861(91)90359-q;
RA   Yumoto N., Kawata Y., Noda S., Tokushige M.;
RT   "Rapid purification and characterization of homoserine dehydrogenase from
RT   Saccharomyces cerevisiae.";
RL   Arch. Biochem. Biophys. 285:270-275(1991).
RN   [5]
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   [6]
RP   IDENTIFICATION BY 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   [7]
RP   IDENTIFICATION BY 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   [8]
RP   UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-290, 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).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 2-359 IN COMPLEX WITH NAD AND
RP   SUBSTRATE, AND MUTAGENESIS OF GLU-208; ASP-219 AND LYS-223.
RX   PubMed=10700284; DOI=10.1038/73359;
RA   DeLaBarre B., Thompson P.R., Wright G.D., Berghuis A.M.;
RT   "Crystal structures of homoserine dehydrogenase suggest a novel catalytic
RT   mechanism for oxidoreductases.";
RL   Nat. Struct. Biol. 7:238-244(2000).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG.
RX   PubMed=14583265; DOI=10.1016/j.chembiol.2003.09.015;
RA   Jacques S.L., Mirza I.A., Ejim L., Koteva K., Hughes D.W., Green K.,
RA   Kinach R., Honek J.F., Lai H.K., Berghuis A.M., Wright G.D.;
RT   "Enzyme-assisted suicide: molecular basis for the antifungal activity of 5-
RT   hydroxy-4-oxonorvaline by potent inhibition of homoserine dehydrogenase.";
RL   Chem. Biol. 10:989-995(2003).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 2-359 IN COMPLEX WITH INHIBITORS.
RX   PubMed=15210149; DOI=10.1016/j.bmc.2004.05.009;
RA   Ejim L., Mirza I.A., Capone C., Nazi I., Jenkins S., Chee G.-L.,
RA   Berghuis A.M., Wright G.D.;
RT   "New phenolic inhibitors of yeast homoserine dehydrogenase.";
RL   Bioorg. Med. Chem. 12:3825-3830(2004).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-homoserine + NADP(+) = H(+) + L-aspartate 4-semialdehyde +
CC         NADPH; Xref=Rhea:RHEA:15761, ChEBI:CHEBI:15378, ChEBI:CHEBI:57476,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:537519; EC=1.1.1.3;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-homoserine + NAD(+) = H(+) + L-aspartate 4-semialdehyde +
CC         NADH; Xref=Rhea:RHEA:15757, ChEBI:CHEBI:15378, ChEBI:CHEBI:57476,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:537519; EC=1.1.1.3;
CC   -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC       pathway; L-homoserine from L-aspartate: step 3/3.
CC   -!- PATHWAY: Amino-acid biosynthesis; L-threonine biosynthesis; L-threonine
CC       from L-aspartate: step 3/5.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10700284,
CC       ECO:0000269|PubMed:14583265, ECO:0000269|PubMed:15210149}.
CC   -!- MISCELLANEOUS: Present with 48900 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the homoserine dehydrogenase family.
CC       {ECO:0000305}.
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DR   EMBL; X64457; CAA45787.1; -; Genomic_DNA.
DR   EMBL; Z49639; CAA89671.1; -; Genomic_DNA.
DR   EMBL; BK006943; DAA08924.1; -; Genomic_DNA.
DR   PIR; S33317; S33317.
DR   RefSeq; NP_012673.3; NM_001181797.3.
DR   PDB; 1EBF; X-ray; 2.30 A; A/B=2-359.
DR   PDB; 1EBU; X-ray; 2.60 A; A/B/C/D=2-359.
DR   PDB; 1Q7G; X-ray; 2.60 A; A/B=1-359.
DR   PDB; 1TVE; X-ray; 3.00 A; A/B=2-359.
DR   PDBsum; 1EBF; -.
DR   PDBsum; 1EBU; -.
DR   PDBsum; 1Q7G; -.
DR   PDBsum; 1TVE; -.
DR   AlphaFoldDB; P31116; -.
DR   SMR; P31116; -.
DR   BioGRID; 33895; 536.
DR   DIP; DIP-6315N; -.
DR   IntAct; P31116; 11.
DR   MINT; P31116; -.
DR   STRING; 4932.YJR139C; -.
DR   iPTMnet; P31116; -.
DR   MaxQB; P31116; -.
DR   PaxDb; 4932-YJR139C; -.
DR   PeptideAtlas; P31116; -.
DR   TopDownProteomics; P31116; -.
DR   EnsemblFungi; YJR139C_mRNA; YJR139C; YJR139C.
DR   GeneID; 853604; -.
DR   KEGG; sce:YJR139C; -.
DR   AGR; SGD:S000003900; -.
DR   SGD; S000003900; HOM6.
DR   VEuPathDB; FungiDB:YJR139C; -.
DR   eggNOG; KOG0455; Eukaryota.
DR   GeneTree; ENSGT00940000176517; -.
DR   HOGENOM; CLU_009116_0_1_1; -.
DR   InParanoid; P31116; -.
DR   OMA; DWQSAFS; -.
DR   OrthoDB; 5487989at2759; -.
DR   BioCyc; YEAST:YJR139C-MONOMER; -.
DR   BRENDA; 1.1.1.3; 984.
DR   SABIO-RK; P31116; -.
DR   UniPathway; UPA00050; UER00063.
DR   UniPathway; UPA00051; UER00465.
DR   BioGRID-ORCS; 853604; 2 hits in 10 CRISPR screens.
DR   EvolutionaryTrace; P31116; -.
DR   PRO; PR:P31116; -.
DR   Proteomes; UP000002311; Chromosome X.
DR   RNAct; P31116; Protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0005634; C:nucleus; HDA:SGD.
DR   GO; GO:0004072; F:aspartate kinase activity; IEA:InterPro.
DR   GO; GO:0004412; F:homoserine dehydrogenase activity; IDA:SGD.
DR   GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR   GO; GO:0009067; P:aspartate family amino acid biosynthetic process; IBA:GO_Central.
DR   GO; GO:0009090; P:homoserine biosynthetic process; IMP:SGD.
DR   GO; GO:0009097; P:isoleucine biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0009086; P:methionine biosynthetic process; IMP:SGD.
DR   GO; GO:0009088; P:threonine biosynthetic process; IMP:SGD.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   InterPro; IPR005106; Asp/hSer_DH_NAD-bd.
DR   InterPro; IPR011147; Bifunc_aspartokin/hSer_DH.
DR   InterPro; IPR001342; HDH_cat.
DR   InterPro; IPR019811; HDH_CS.
DR   InterPro; IPR022697; HDH_short.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   PANTHER; PTHR43070; -; 1.
DR   PANTHER; PTHR43070:SF5; HOMOSERINE DEHYDROGENASE; 1.
DR   Pfam; PF00742; Homoserine_dh; 1.
DR   Pfam; PF03447; NAD_binding_3; 1.
DR   PIRSF; PIRSF036497; HDH_short; 1.
DR   SUPFAM; SSF55347; Glyceraldehyde-3-phosphate dehydrogenase-like, C-terminal domain; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   PROSITE; PS01042; HOMOSER_DHGENASE; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Amino-acid biosynthesis;
KW   Branched-chain amino acid biosynthesis; Direct protein sequencing;
KW   Isoleucine biosynthesis; Isopeptide bond; Methionine biosynthesis; NADP;
KW   Oxidoreductase; Reference proteome; Threonine biosynthesis;
KW   Ubl conjugation.
FT   CHAIN           1..359
FT                   /note="Homoserine dehydrogenase"
FT                   /id="PRO_0000066707"
FT   ACT_SITE        223
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255"
FT   BINDING         11..18
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000269|PubMed:10700284"
FT   BINDING         93
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000269|PubMed:10700284"
FT   BINDING         117
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000269|PubMed:10700284"
FT   BINDING         208
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:10700284"
FT   CROSSLNK        290
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0007744|PubMed:22106047"
FT   MUTAGEN         117
FT                   /note="K->A: Loss of activity."
FT   MUTAGEN         208
FT                   /note="E->D: Increases KM for aspartate-semialdehyde
FT                   48-fold and reduces kcat by 50%."
FT                   /evidence="ECO:0000269|PubMed:10700284"
FT   MUTAGEN         208
FT                   /note="E->L,Q: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:10700284"
FT   MUTAGEN         219
FT                   /note="D->L: Reduces kcat 150-fold."
FT                   /evidence="ECO:0000269|PubMed:10700284"
FT   MUTAGEN         223
FT                   /note="K->V: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:10700284"
FT   CONFLICT        134
FT                   /note="K -> L (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        152
FT                   /note="Missing (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        327
FT                   /note="R -> V (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        333
FT                   /note="Missing (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   STRAND          4..11
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           15..26
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   STRAND          30..39
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   STRAND          41..46
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   TURN            54..57
FT                   /evidence="ECO:0007829|PDB:1EBU"
FT   HELIX           59..64
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           73..80
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   STRAND          87..91
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           96..99
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           102..107
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   STRAND          111..113
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           118..120
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           124..130
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   STRAND          135..137
FT                   /evidence="ECO:0007829|PDB:1EBU"
FT   HELIX           143..145
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   TURN            146..149
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   STRAND          150..152
FT                   /evidence="ECO:0007829|PDB:1EBU"
FT   HELIX           153..162
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   STRAND          166..172
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           175..184
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           194..204
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           212..215
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           218..230
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           249..251
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   STRAND          255..257
FT                   /evidence="ECO:0007829|PDB:1TVE"
FT   HELIX           258..264
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           265..267
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           268..278
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   TURN            279..282
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   STRAND          283..292
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   TURN            293..296
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   STRAND          297..309
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           310..313
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   STRAND          319..327
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   STRAND          332..336
FT                   /evidence="ECO:0007829|PDB:1EBF"
FT   HELIX           341..358
FT                   /evidence="ECO:0007829|PDB:1EBF"
SQ   SEQUENCE   359 AA;  38502 MW;  6C106F9EB0BD0CC5 CRC64;
     MSTKVVNVAV IGAGVVGSAF LDQLLAMKST ITYNLVLLAE AERSLISKDF SPLNVGSDWK
     AALAASTTKT LPLDDLIAHL KTSPKPVILV DNTSSAYIAG FYTKFVENGI SIATPNKKAF
     SSDLATWKAL FSNKPTNGFV YHEATVGAGL PIISFLREII QTGDEVEKIE GIFSGTLSYI
     FNEFSTSQAN DVKFSDVVKV AKKLGYTEPD PRDDLNGLDV ARKVTIVGRI SGVEVESPTS
     FPVQSLIPKP LESVKSADEF LEKLSDYDKD LTQLKKEAAT ENKVLRFIGK VDVATKSVSV
     GIEKYDYSHP FASLKGSDNV ISIKTKRYTN PVVIQGAGAG AAVTAAGVLG DVIKIAQRL
//