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P40495 (LYS12_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length371 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

KM=1.5 mM for 2-oxoadipate Ref.5

KM=330 µM for NAD+

KM=65 µM for NADH

pH dependence:

Optimum pH is 8.3-8.8 for the forward reaction, and 7 for the reverse reaction.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2222Mitochondrion Potential
Chain23 – 371349Homoisocitrate dehydrogenase, mitochondrial
PRO_0000043097

Sites

Metal binding2431Magnesium or manganese By similarity
Metal binding2671Magnesium or manganese By similarity
Metal binding2711Magnesium or manganese By similarity
Binding site1141Substrate By similarity
Binding site1241Substrate By similarity
Binding site1431Substrate By similarity
Binding site2431Substrate By similarity
Site1501Critical for catalysis
Site2061Critical for catalysis

Amino acid modifications

Modified residue981Phosphoserine Ref.12

Experimental info

Mutagenesis1501Y → F: Strongly reduced enzyme activity. Ref.13
Mutagenesis2061K → M: Strongly reduced enzyme activity. Ref.13

Sequences

Sequence LengthMass (Da)Tools
P40495 [UniParc].

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

FASTA37140,069
        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' 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. expand/collapse author list , Pearson D., Rajandream M.A., Rice P., Rowley N., Skelton J., Smith V., Walsh S.V., Whitehead S., Barrell B.G.
Nature 387:84-87(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 204508 / S288c.
[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, IDENTIFICATION BY 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].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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.
PIRS49786.
RefSeqNP_012172.1. NM_001179442.1.

3D structure databases

ProteinModelPortalP40495.
SMRP40495. Positions 22-371.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid34898. 68 interactions.
DIPDIP-4162N.
IntActP40495. 90 interactions.
MINTMINT-491742.
STRING4932.YIL094C.

Chemistry

BindingDBP40495.
ChEMBLCHEMBL1075252.

Proteomic databases

PaxDbP40495.
PeptideAtlasP40495.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblFungiYIL094C; YIL094C; YIL094C.
GeneID854714.
KEGGsce:YIL094C.

Organism-specific databases

CYGDYIL094c.
SGDS000001356. LYS12.

Phylogenomic databases

eggNOGCOG0473.
GeneTreeENSGT00550000076087.
HOGENOMHOG000021111.
KOK05824.
OMAVTIIHKS.
OrthoDBEOG7R83BB.

Enzyme and pathway databases

BioCycYEAST:YIL094C-MONOMER.
UniPathwayUPA00033; UER00030.

Gene expression databases

GenevestigatorP40495.

Family and domain databases

Gene3D3.40.718.10. 1 hit.
InterProIPR019818. IsoCit/isopropylmalate_DH_CS.
IPR001804. Isocitrate/isopropylmalate_DH.
IPR024084. IsoPropMal-DH-like_dom.
[Graphical view]
PANTHERPTHR11835. PTHR11835. 1 hit.
PfamPF00180. Iso_dh. 1 hit.
[Graphical view]
PROSITEPS00470. IDH_IMDH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio977383.

Entry information

Entry nameLYS12_YEAST
AccessionPrimary (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: April 16, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome IX

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

Yeast

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

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways