Homoisocitrate dehydrogenase, mitochondrial precursor - Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

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P40495 (LYS12_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 109. History...

Clusters with 100%, 90%, 50% identity |

Documents (4) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Homoisocitrate dehydrogenase, mitochondrial
Short name=HIcDH
EC=1.1.1.87

Gene names

Name:	LYS12
Synonyms:	LYS10, LYS11
Ordered Locus Names:	YIL094C
ORF Names:	YI9910.02C

Organism

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

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces ›

Protein attributes

Sequence length	371 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the NAD⁺-dependent conversion of homoisocitrate to alpha-ketoadipate. Ref.4
Catalytic activity	(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD⁺ = 2-oxoadipate + CO₂ + NADH. Ref.4 Ref.11 Ref.13
Cofactor	Binds 1 magnesium or manganese ion per subunit. Ref.11 Ref.13
Enzyme regulation	Inhibited by the reaction product NADH. Inhibited by oxalate; this is a non-competitive inhibitor. Ref.11
Pathway	Amino-acid biosynthesis; L-lysine biosynthesis via AAA pathway; L-alpha-aminoadipate from 2-oxoglutarate: step 4/5.
Subcellular location	Mitochondrion Ref.8 Ref.10.
Induction	Activity is repressed 4-fold by lysine. Ref.6 Ref.11
Miscellaneous	Present with 19079 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the isocitrate and isopropylmalate dehydrogenases family.
Biophysicochemical properties	Kinetic parameters: The KM for homoisocitrate is lower than 10 µM. K_M=1.5 mM for 2-oxoadipate Ref.5 K_M=330 µM for NAD⁺ K_M=65 µM for NADH pH dependence: Optimum pH is 8.3-8.8 for the forward reaction, and 7 for the reverse reaction.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Lysine biosynthesis
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	Magnesium Manganese Metal-binding NAD
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	lysine biosynthetic process via aminoadipic acid Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	mitochondrion Inferred from direct assay PubMed 11914276 Ref.10 PubMed 16823961. Source: SGD
Molecular_function	NAD binding Inferred from electronic annotation. Source: InterPro homoisocitrate dehydrogenase activity Inferred from direct assay Ref.11. Source: SGD magnesium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 22

Mitochondrion Potential

Chain

23 – 371

349

Homoisocitrate dehydrogenase, mitochondrial

PRO_0000043097

Sites

Metal binding

243

Magnesium or manganese By similarity

Metal binding

267

Magnesium or manganese By similarity

Metal binding

271

Magnesium or manganese By similarity

Binding site

114

Substrate By similarity

Binding site

124

Substrate By similarity

Binding site

143

Substrate By similarity

Binding site

243

Substrate By similarity

Site

150

Critical for catalysis

Site

206

Critical for catalysis

Amino acid modifications

Modified residue

Phosphoserine Ref.12

Modified residue

107

Phosphoserine Ref.12

Modified residue

108

Phosphoserine Ref.12

Modified residue

146

Phosphothreonine Ref.12

Modified residue

211

Phosphoserine Ref.12

Experimental info

Mutagenesis

150

Y → F: Strongly reduced enzyme activity. Ref.13

Mutagenesis

206

K → M: Strongly reduced enzyme activity. Ref.13

Sequences

Sequence

Length

Mass (Da)

Tools

P40495 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: 43CAFA86F75ED3C6
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FASTA

371

40,069

        10         20         30         40         50         60 
MFRSVATRLS ACRGLASNAA RKSLTIGLIP GDGIGKEVIP AGKQVLENLN SKHGLSFNFI 

        70         80         90        100        110        120 
DLYAGFQTFQ ETGKALPDET VKVLKEQCQG ALFGAVQSPT TKVEGYSSPI VALRREMGLF 

       130        140        150        160        170        180 
ANVRPVKSVE GEKGKPIDMV IVRENTEDLY IKIEKTYIDK ATGTRVADAT KRISEIATRR 

       190        200        210        220        230        240 
IATIALDIAL KRLQTRGQAT LTVTHKSNVL SQSDGLFREI CKEVYESNKD KYGQIKYNEQ 

       250        260        270        280        290        300 
IVDSMVYRLF REPQCFDVIV APNLYGDILS DGAAALVGSL GVVPSANVGP EIVIGEPCHG 

       310        320        330        340        350        360 
SAPDIAGKGI ANPIATIRST ALMLEFLGHN EAAQDIYKAV DANLREGSIK TPDLGGKAST 

       370 
QQVVDDVLSR L

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome IX." Churcher C.M., Bowman S., Badcock K., Bankier A.T., Brown D., Chillingworth T., Connor R., Devlin K., Gentles S., Hamlin N., Harris D.E., Horsnell T., Hunt S., Jagels K., Jones M., Lye G., Moule S., Odell C. Barrell B.G. Nature 387:84-87(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[2]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[3]	Bienvenut W.V., Peters C. Submitted (JUN-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 23-36; 103-114; 116-127; 181-192; 237-248; 309-318 AND 346-370, MASS SPECTROMETRY.
[4]	"Enzymatic formation of alpha-ketoadipic acid from homoisocitric acid." Strassman M., Ceci L.N. J. Biol. Chem. 240:4357-4361(1965) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY.
[5]	"Homoisocitric dehydrogenase from yeast." Rowley B., Tucci A.F. Arch. Biochem. Biophys. 141:499-510(1970) [PubMed] [Europe PMC] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[6]	"General and specific controls of lysine biosynthesis in Saccharomyces cerevisiae." Urrestarazu L.A., Borell C.W., Bhattacharjee J.K. Curr. Genet. 9:341-344(1985) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[7]	"Linking genome and proteome by mass spectrometry: large-scale identification of yeast proteins from two dimensional gels." Shevchenko A., Jensen O.N., Podtelejnikov A.V., Sagliocco F., Wilm M., Vorm O., Mortensen P., Shevchenko A., Boucherie H., Mann M. Proc. Natl. Acad. Sci. U.S.A. 93:14440-14445(1996) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY.
[8]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[9]	"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].
[10]	"The proteome of Saccharomyces cerevisiae mitochondria." Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E., Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P., Pfanner N., Meisinger C. Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Strain: ATCC 76625 / YPH499.
[11]	"Complete kinetic mechanism of homoisocitrate dehydrogenase from Saccharomyces cerevisiae." Lin Y., Alguindigue S.S., Volkman J., Nicholas K.M., West A.H., Cook P.F. Biochemistry 46:890-898(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, COFACTOR, ENZYME REGULATION.
[12]	"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-98; SER-107; SER-108; THR-146 AND SER-211, MASS SPECTROMETRY.
[13]	"Site-directed mutagenesis as a probe of the acid-base catalytic mechanism of homoisocitrate dehydrogenase from Saccharomyces cerevisiae." Lin Y., West A.H., Cook P.F. Biochemistry 48:7305-7312(2009) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, COFACTOR, MUTAGENESIS OF TYR-150 AND LYS-206.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z46728 Genomic DNA. Translation: CAA86700.1. BK006942 Genomic DNA. Translation: DAA08459.1.
PIR	S49786.
RefSeq	NP_012172.1. NM_001179442.1.
3D structure databases
ProteinModelPortal	P40495.
SMR	P40495. Positions 22-371.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-4162N.
IntAct	P40495. 93 interactions.
MINT	MINT-491742.
STRING	4932.YIL094C.
Proteomic databases
PaxDb	P40495.
PeptideAtlas	P40495.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YIL094C; YIL094C; YIL094C.
GeneID	854714.
KEGG	sce:YIL094C.
Organism-specific databases
CYGD	YIL094c.
SGD	S000001356. LYS12.
Phylogenomic databases
eggNOG	COG0473.
GeneTree	ENSGT00550000076087.
HOGENOM	HOG000021111.
KO	K05824.
OMA	NVRPINN.
OrthoDB	EOG4350FP.
Enzyme and pathway databases
UniPathway	UPA00033; UER00030.
Gene expression databases
Genevestigator	P40495.
GermOnline	YIL094C. Saccharomyces cerevisiae.
Family and domain databases
Gene3D	3.40.718.10. 1 hit.
InterPro	IPR019818. IsoCit/isopropylmalate_DH_CS. IPR001804. Isocitrate/isopropylmalate_DH. IPR024084. IsoPropMal-DH-like_dom. [Graphical view]
PANTHER	PTHR11835. PTHR11835. 1 hit.
Pfam	PF00180. Iso_dh. 1 hit. [Graphical view]
PROSITE	PS00470. IDH_IMDH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P40495.
ChEMBL	CHEMBL1075252.
NextBio	977383.

Entry information

Entry name

LYS12_YEAST

Accession

Primary (citable) accession number: P40495
Secondary accession number(s): D6VVJ3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	May 1, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program

Relevant documents

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

Yeast chromosome IX

Yeast (Saccharomyces cerevisiae) chromosome IX: entries and gene names

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents