DHOM_YEAST
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 03-AUG-2022, entry version 183.
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; 518.
DR DIP; DIP-6315N; -.
DR IntAct; P31116; 11.
DR MINT; P31116; -.
DR STRING; 4932.YJR139C; -.
DR iPTMnet; P31116; -.
DR MaxQB; P31116; -.
DR PaxDb; P31116; -.
DR PRIDE; P31116; -.
DR TopDownProteomics; P31116; -.
DR EnsemblFungi; YJR139C_mRNA; YJR139C; YJR139C.
DR GeneID; 853604; -.
DR KEGG; sce:YJR139C; -.
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; FNEFSTT; -.
DR BioCyc; YEAST:YJR139C-MON; -.
DR BRENDA; 1.1.1.3; 984.
DR SABIO-RK; P31116; -.
DR UniPathway; UPA00050; UER00063.
DR UniPathway; UPA00051; UER00465.
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 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; PTHR43070; 1.
DR Pfam; PF00742; Homoserine_dh; 1.
DR Pfam; PF03447; NAD_binding_3; 1.
DR PIRSF; PIRSF036497; HDH_short; 1.
DR SUPFAM; SSF51735; SSF51735; 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 48-
FT 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
