[1]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. STRAIN=ATCC 204511 / S288c / AB972; PubMed=9169870 [NCBI, ExPASy, EBI, Israel, Japan] 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., Pearson D., Rajandream M.A., Rice P., Rowley N., Skelton J., Smith V., Walsh S.V., Whitehead S., Barrell B.G.; "The nucleotide sequence of Saccharomyces cerevisiae chromosome IX."; Nature 387:84-87(1997).
[2]	PROTEIN SEQUENCE OF 23-36; 103-114; 116-127; 181-192; 237-248; 309-318 AND 346-370, AND MASS SPECTROMETRY. Bienvenut W.V., Peters C.; Submitted (JUN-2005) to UniProtKB.
[3]	FUNCTION, AND CATALYTIC ACTIVITY. PubMed=4284830 [NCBI, ExPASy, EBI, Israel, Japan] Strassman M., Ceci L.N.; "Enzymatic formation of alpha-ketoadipic acid from homoisocitric acid."; J. Biol. Chem. 240:4357-4361(1965).
[4]	BIOPHYSICOCHEMICAL PROPERTIES. DOI=10.1016/0003-9861(70)90167-0; PubMed=4395693 [NCBI, ExPASy, EBI, Israel, Japan] Rowley B., Tucci A.F.; "Homoisocitric dehydrogenase from yeast."; Arch. Biochem. Biophys. 141:499-510(1970).
[5]	ENZYME REGULATION. DOI=10.1007/BF00421603; PubMed=3939712 [NCBI, ExPASy, EBI, Israel, Japan] Urrestarazu L.A., Borell C.W., Bhattacharjee J.K.; "General and specific controls of lysine biosynthesis in Saccharomyces cerevisiae."; Curr. Genet. 9:341-344(1985).
[6]	IDENTIFICATION BY MASS SPECTROMETRY. DOI=10.1073/pnas.93.25.14440; PubMed=8962070 [NCBI, ExPASy, EBI, Israel, Japan] Shevchenko A., Jensen O.N., Podtelejnikov A.V., Sagliocco F., Wilm M., Vorm O., Mortensen P., Shevchenko A., Boucherie H., Mann M.; "Linking genome and proteome by mass spectrometry: large-scale identification of yeast proteins from two dimensional gels."; Proc. Natl. Acad. Sci. U.S.A. 93:14440-14445(1996).
[7]	SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. DOI=10.1038/nature02026; PubMed=14562095 [NCBI, ExPASy, EBI, Israel, Japan] Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K.; "Global analysis of protein localization in budding yeast."; Nature 425:686-691(2003).
[8]	LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. DOI=10.1038/nature02046; PubMed=14562106 [NCBI, ExPASy, EBI, Israel, Japan] Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S.; "Global analysis of protein expression in yeast."; Nature 425:737-741(2003).
[9]	SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. DOI=10.1073/pnas.2135385100; PubMed=14576278 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "The proteome of Saccharomyces cerevisiae mitochondria."; Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003).
[10]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98; SER-107; SER-108; THR-146 AND SER-211, AND MASS SPECTROMETRY. DOI=10.1074/mcp.M700468-MCP200; PubMed=18407956 [NCBI, ExPASy, EBI, Israel, Japan] Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.; "A multidimensional chromatography technology for in-depth phosphoproteome analysis."; Mol. Cell. Proteomics 7:1389-1396(2008).

Comments

FUNCTION: Catalyzes the NAD(+)-dependent conversion of homoisocitrate to alpha-ketoadipate.
CATALYTIC ACTIVITY: (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD⁺ = 2-oxoadipate + CO₂ + NADH.
COFACTOR: Binds 1 magnesium or manganese ion per subunit (By similarity).
ENZYME REGULATION: Activity is repressed 4-fold by lysine.

BIOPHYSICOCHEMICAL PROPERTIES:

Kinetic parameters:	K_M=1.5 mM for 2-oxoadipate;
	K_M=330 µM for NAD⁺;
	K_M=65 µM for NADH;
	Note=The K_M for homoisocitrate is lower than 10 µM;
pH dependence:	Optimum pH is 8.3-8.8 for the forward reaction, and 7 for the reverse reaction;

PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via AAA pathway; L-alpha-aminoadipate from 2-oxoglutarate: step 3/4 .
SUBCELLULAR LOCATION: Mitochondrion.
MISCELLANEOUS: Present with 19079 molecules/cell in log phase SD medium.
SIMILARITY: Belongs to the isocitrate and isopropylmalate dehydrogenases family.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

Z46728; CAA86700.1; -; Genomic_DNA.

[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

S49786; S49786.

RefSeq

NP_012172.1; -.

3D structure databases

HSSP

P12010; 2AYQ. [HSSP ENTRY / PDB]

ModBase

P40495.

Protein-protein interaction databases

DIP

DIP:4162N; -.

IntAct

P40495; -.

Organism-specific databases

YIL094c; -.

S000001356; LYS12.

Gene expression databases

GermOnline

YIL094C; Saccharomyces cerevisiae.

Ontologies

GO:0005739;	Cellular component: mitochondrion (inferred from electronic annotation from UniProtKB-KW).
GO:0047046;	Molecular function: homoisocitrate dehydrogenase activity (inferred from electronic annotation from EC).
GO:0000287;	Molecular function: magnesium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0030145;	Molecular function: manganese ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0009085;	Biological process: lysine biosynthetic process (inferred from electronic annotation from UniProtKB-KW).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR001804; IsoCit_IM_DHase.
Graphical view of domain structure.

Gene3D

G3DSA:3.40.718.10; IDH_IMDH; 1.

PANTHER

PTHR11835; IDH_IMDH_dimeric; 1.

Pfam

PF00180; Iso_dh; 1.
Pfam graphical view of domain structure.

PROSITE

PS00470; IDH_IMDH; 1.

ProtoNet

P40495.

Proteomic databases

PeptideAtlas

P40495; -.

Genome annotation databases

Ensembl

YIL094C; Saccharomyces cerevisiae. [Contig view]

854714; -.

Z47047_GR; YIL094C.

sce:YIL094C; -.

fig|4932.3.peg.1699; -.

Phylogenomic databases

HOGENOM

P40495; -.

Other

LinkHub

P40495; -.

NextBio

977383; -.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Amino-acid biosynthesis; Complete proteome; Direct protein sequencing; Lysine biosynthesis; Magnesium; Manganese; Metal-binding; Mitochondrion; NAD; Oxidoreductase; Phosphoprotein; Transit peptide.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`TRANSIT`	`1 22`	`22`	`Mitochondrion (Potential).`
`CHAIN`	`23 371`	`349`	`Homoisocitrate dehydrogenase, mitochondrial.`	`PRO_0000043097`
`METAL`	`243 243`		`Magnesium or manganese (By similarity).`
`METAL`	`267 267`		`Magnesium or manganese (By similarity).`
`METAL`	`271 271`		`Magnesium or manganese (By similarity).`
`BINDING`	`114 114`		`Substrate (By similarity).`
`BINDING`	`124 124`		`Substrate (By similarity).`
`BINDING`	`143 143`		`Substrate (By similarity).`
`BINDING`	`243 243`		`Substrate (By similarity).`
`SITE`	`150 150`	`1`	`Critical for catalysis (By similarity).`
`SITE`	`206 206`	`1`	`Critical for catalysis (By similarity).`
`MOD_RES`	`98 98`		`Phosphoserine.`
`MOD_RES`	`107 107`		`Phosphoserine.`
`MOD_RES`	`108 108`		`Phosphoserine.`
`MOD_RES`	`146 146`		`Phosphothreonine.`
`MOD_RES`	`211 211`		`Phosphoserine.`

Sequence information

Length: 371 AA [This is the length of the unprocessed precursor]

Molecular weight: 40069 Da [This is the MW of the unprocessed precursor]

CRC64: 43CAFA86F75ED3C6 [This is a checksum on the sequence]

        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

P40495 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools