P31116 (DHOM_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homoserine dehydrogenase
Short name=HDH
EC=1.1.1.3

Gene names

Name:	HOM6
Ordered Locus Names:	YJR139C
ORF Names:	J2132

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	359 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H.
Pathway	Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-homoserine from L-aspartate: step 3/3. Amino-acid biosynthesis; L-threonine biosynthesis; L-threonine from L-aspartate: step 3/5.
Subunit structure	Homodimer.
Miscellaneous	Present with 48900 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the homoserine dehydrogenase family.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Branched-chain amino acid biosynthesis Isoleucine biosynthesis Methionine biosynthesis Threonine biosynthesis
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	homoserine biosynthetic process Inferred from mutant phenotype PubMed 4380684. Source: SGD isoleucine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW methionine biosynthetic process Inferred from mutant phenotype PubMed 4380684. Source: SGD threonine biosynthetic process Inferred from mutant phenotype PubMed 4380684. Source: SGD
Cellular_component	cytoplasm Inferred from direct assay PubMed 14562095. Source: SGD nucleus Inferred from direct assay PubMed 14562095. Source: SGD
Molecular_function	NADP binding Inferred from electronic annotation. Source: InterPro homoserine dehydrogenase activity Inferred from direct assay PubMed 11341915. Source: SGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 359

359

Homoserine dehydrogenase

PRO_0000066707

Regions

Nucleotide binding

11 – 18

8

NADP

Sites

Active site

223

1

Proton donor Potential

Binding site

93

1

NADP

Binding site

117

1

NADP

Binding site

208

1

Substrate

Amino acid modifications

Modified residue

237

1

Phosphoserine Ref.6 Ref.7

Modified residue

239

1

Phosphothreonine Ref.6

Modified residue

344

1

Phosphothreonine Ref.7

Experimental info

Mutagenesis

117

1

K → A: Loss of activity.

Mutagenesis

208

1

E → D: Increases KM for aspartate-semialdehyde 48-fold and reduces Kcat by 50%. Ref.8

Mutagenesis

208

1

E → L or Q: Loss of activity. Ref.8

Mutagenesis

219

1

D → L: Reduces Kcat 150-fold. Ref.8

Mutagenesis

223

1

K → V: Loss of activity. Ref.8

Sequence conflict

134

1

K → L AA sequence Ref.4

Sequence conflict

152

1

Missing AA sequence Ref.4

Sequence conflict

327

1

R → V AA sequence Ref.4

Sequence conflict

333

1

Missing AA sequence Ref.4

Secondary structure

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359

Helix Strand Turn

Details...

Beta strand

4 – 11

8

Helix

15 – 26

12

Beta strand

30 – 39

10

Beta strand

41 – 46

6

Turn

54 – 57

4

Helix

59 – 64

6

Helix

73 – 80

8

Beta strand

87 – 91

5

Helix

96 – 99

4

Helix

102 – 107

6

Beta strand

111 – 113

3

Helix

118 – 120

3

Helix

124 – 130

7

Beta strand

135 – 137

3

Helix

143 – 145

3

Turn

146 – 149

4

Beta strand

150 – 152

3

Helix

153 – 162

10

Beta strand

166 – 172

7

Helix

175 – 184

10

Helix

194 – 204

11

Helix

212 – 215

4

Helix

218 – 230

13

Helix

249 – 251

3

Beta strand

255 – 257

3

Helix

258 – 264

7

Helix

265 – 267

3

Helix

268 – 278

11

Turn

279 – 282

4

Beta strand

283 – 292

10

Turn

293 – 296

4

Beta strand

297 – 309

13

Helix

310 – 313

4

Beta strand

319 – 327

9

Beta strand

332 – 336

5

Helix

341 – 358

18

Sequences

	Sequence		Length	Mass (Da)
	P31116 [UniParc]. Last modified July 1, 1993. Version 1. Checksum: 6C106F9EB0BD0CC5	FASTA	359	38,502
	10 20 30 40 50 60 MSTKVVNVAV IGAGVVGSAF LDQLLAMKST ITYNLVLLAE AERSLISKDF SPLNVGSDWK 70 80 90 100 110 120 AALAASTTKT LPLDDLIAHL KTSPKPVILV DNTSSAYIAG FYTKFVENGI SIATPNKKAF 130 140 150 160 170 180 SSDLATWKAL FSNKPTNGFV YHEATVGAGL PIISFLREII QTGDEVEKIE GIFSGTLSYI 190 200 210 220 230 240 FNEFSTSQAN DVKFSDVVKV AKKLGYTEPD PRDDLNGLDV ARKVTIVGRI SGVEVESPTS 250 260 270 280 290 300 FPVQSLIPKP LESVKSADEF LEKLSDYDKD LTQLKKEAAT ENKVLRFIGK VDVATKSVSV 310 320 330 340 350 GIEKYDYSHP FASLKGSDNV ISIKTKRYTN PVVIQGAGAG AAVTAAGVLG DVIKIAQRL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Evolutionary relationships between yeast and bacterial homoserine dehydrogenases." Thomas D., Barbey R., Surdin-Kerjan Y. FEBS Lett. 323:289-293(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 26786 / X2180-1A.
[2]	"Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X." Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C., Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D., Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J., Heumann K. , Hilger F., Hollenberg C.P., Huang M.-E., Jacq C., Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E., Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T., Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B., Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R., Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N., To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H., von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L. EMBO J. 15:2031-2049(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[3]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[4]	"Rapid purification and characterization of homoserine dehydrogenase from Saccharomyces cerevisiae." Yumoto N., Kawata Y., Noda S., Tokushige M. Arch. Biochem. Biophys. 285:270-275(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 129-158 AND 327-354.
[5]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[6]	"Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases." Smolka M.B., Albuquerque C.P., Chen S.H., Zhou H. Proc. Natl. Acad. Sci. U.S.A. 104:10364-10369(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-237 AND THR-239, MASS SPECTROMETRY.
[7]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-237 AND THR-344, MASS SPECTROMETRY.
[8]	"Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases." DeLaBarre B., Thompson P.R., Wright G.D., Berghuis A.M. Nat. Struct. Biol. 7:238-244(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 2-359 IN COMPLEX WITH NAD AND SUBSTRATE, MUTAGENESIS OF GLU-208; ASP-219 AND LYS-223.
[9]	"Enzyme-assisted suicide: molecular basis for the antifungal activity of 5-hydroxy-4-oxonorvaline by potent inhibition of homoserine dehydrogenase." Jacques S.L., Mirza I.A., Ejim L., Koteva K., Hughes D.W., Green K., Kinach R., Honek J.F., Lai H.K., Berghuis A.M., Wright G.D. Chem. Biol. 10:989-995(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG.
[10]	"New phenolic inhibitors of yeast homoserine dehydrogenase." Ejim L., Mirza I.A., Capone C., Nazi I., Jenkins S., Chee G.-L., Berghuis A.M., Wright G.D. Bioorg. Med. Chem. 12:3825-3830(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 2-359 IN COMPLEX WITH INHIBITORS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X64457 Genomic DNA. Translation: CAA45787.1.
Z49639 Genomic DNA. Translation: CAA89671.1.
BK006943 Genomic DNA. Translation: DAA08924.1.

PIR

S33317.

RefSeq

NP_012673.3. NM_001181797.3.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EBF	X-ray	2.30	A/B	2-359	[»]
1EBU	X-ray	2.60	A/B/C/D	2-359	[»]
1Q7G	X-ray	2.60	A/B	1-359	[»]
1TVE	X-ray	3.00	A/B	2-359	[»]

ProteinModelPortal

P31116.

SMR

P31116. Positions 2-359.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6315N.

IntAct

P31116. 7 interactions.

MINT

MINT-2731902.

Proteomic databases

PaxDb

P31116.

PeptideAtlas

P31116.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YJR139C; YJR139C; YJR139C.

GeneID

853604.

KEGG

sce:YJR139C.
sce:YJR142W.

Organism-specific databases

CYGD

YJR139c.

SGD

S000003900. HOM6.

Phylogenomic databases

eggNOG

COG0460.

HOGENOM

HOG000024037.

KO

K00003.

OMA

KLIARVW.

OrthoDB

EOG4X6GJ2.

Enzyme and pathway databases

UniPathway

UPA00050; UER00063.
UPA00051; UER00465.

Gene expression databases

ArrayExpress

P31116.

Genevestigator

P31116.

GermOnline

YJR139C. Saccharomyces cerevisiae.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

InterPro

IPR005106. Asp/hSer_DH_NAD-bd.
IPR001342. HDH_cat.
IPR019811. HDH_CS.
IPR022697. HDH_short.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

Pfam

PF00742. Homoserine_dh. 1 hit.
PF03447. NAD_binding_3. 1 hit.
[Graphical view]

PIRSF

PIRSF036497. HDH_short. 1 hit.

PROSITE

PS01042. HOMOSER_DHGENASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P31116.

NextBio

974436.

Entry information

Entry name

DHOM_YEAST

Accession

Primary (citable) accession number: P31116
Secondary accession number(s): D6VWV8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	July 1, 1993
Last modified:	April 3, 2013
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program