LYS12_YEAST
ID LYS12_YEAST Reviewed; 371 AA.
AC P40495; D6VVJ3;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Homoisocitrate dehydrogenase, mitochondrial;
DE Short=HIcDH;
DE EC=1.1.1.87;
DE Flags: Precursor;
GN Name=LYS12; Synonyms=LYS10, LYS11; OrderedLocusNames=YIL094C;
GN ORFNames=YI9910.02C;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169870;
RA Churcher C.M., Bowman S., Badcock K., Bankier A.T., Brown D.,
RA Chillingworth T., Connor R., Devlin K., Gentles S., Hamlin N., Harris D.E.,
RA Horsnell T., Hunt S., Jagels K., Jones M., Lye G., Moule S., Odell C.,
RA Pearson D., Rajandream M.A., Rice P., Rowley N., Skelton J., Smith V.,
RA Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IX.";
RL Nature 387:84-87(1997).
RN [2]
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 [3]
RP PROTEIN SEQUENCE OF 23-36; 103-114; 116-127; 181-192; 237-248; 309-318 AND
RP 346-370, AND IDENTIFICATION BY MASS SPECTROMETRY.
RA Bienvenut W.V., Peters C.;
RL Submitted (JUN-2005) to UniProtKB.
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=4284830; DOI=10.1016/s0021-9258(18)97069-9;
RA Strassman M., Ceci L.N.;
RT "Enzymatic formation of alpha-ketoadipic acid from homoisocitric acid.";
RL J. Biol. Chem. 240:4357-4361(1965).
RN [5]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=4395693; DOI=10.1016/0003-9861(70)90167-0;
RA Rowley B., Tucci A.F.;
RT "Homoisocitric dehydrogenase from yeast.";
RL Arch. Biochem. Biophys. 141:499-510(1970).
RN [6]
RP INDUCTION.
RX PubMed=3939712; DOI=10.1007/bf00421603;
RA Urrestarazu L.A., Borell C.W., Bhattacharjee J.K.;
RT "General and specific controls of lysine biosynthesis in Saccharomyces
RT cerevisiae.";
RL Curr. Genet. 9:341-344(1985).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=8962070; DOI=10.1073/pnas.93.25.14440;
RA Shevchenko A., Jensen O.N., Podtelejnikov A.V., Sagliocco F., Wilm M.,
RA Vorm O., Mortensen P., Shevchenko A., Boucherie H., Mann M.;
RT "Linking genome and proteome by mass spectrometry: large-scale
RT identification of yeast proteins from two dimensional gels.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:14440-14445(1996).
RN [8]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [9]
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 [10]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 76625 / YPH499;
RX PubMed=14576278; DOI=10.1073/pnas.2135385100;
RA Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E.,
RA Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P.,
RA Pfanner N., Meisinger C.;
RT "The proteome of Saccharomyces cerevisiae mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003).
RN [11]
RP CATALYTIC ACTIVITY, COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=17223711; DOI=10.1021/bi062067q;
RA Lin Y., Alguindigue S.S., Volkman J., Nicholas K.M., West A.H., Cook P.F.;
RT "Complete kinetic mechanism of homoisocitrate dehydrogenase from
RT Saccharomyces cerevisiae.";
RL Biochemistry 46:890-898(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98, AND IDENTIFICATION BY
RP 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 [13]
RP CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF TYR-150 AND LYS-206.
RX PubMed=19530703; DOI=10.1021/bi900175z;
RA Lin Y., West A.H., Cook P.F.;
RT "Site-directed mutagenesis as a probe of the acid-base catalytic mechanism
RT of homoisocitrate dehydrogenase from Saccharomyces cerevisiae.";
RL Biochemistry 48:7305-7312(2009).
CC -!- FUNCTION: Catalyzes the NAD(+)-dependent conversion of homoisocitrate
CC to alpha-ketoadipate. {ECO:0000269|PubMed:4284830}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3S)-homoisocitrate + NAD(+) = 2-oxoadipate + CO2 + NADH;
CC Xref=Rhea:RHEA:11900, ChEBI:CHEBI:15404, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57499, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.87;
CC Evidence={ECO:0000269|PubMed:17223711, ECO:0000269|PubMed:19530703,
CC ECO:0000269|PubMed:4284830};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:17223711, ECO:0000269|PubMed:19530703};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:17223711,
CC ECO:0000269|PubMed:19530703};
CC -!- ACTIVITY REGULATION: Inhibited by the reaction product NADH. Inhibited
CC by oxalate; this is a non-competitive inhibitor.
CC {ECO:0000269|PubMed:17223711}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.5 mM for 2-oxoadipate {ECO:0000269|PubMed:4395693};
CC KM=330 uM for NAD(+) {ECO:0000269|PubMed:4395693};
CC KM=65 uM for NADH {ECO:0000269|PubMed:4395693};
CC Note=The KM for homoisocitrate is lower than 10 uM.;
CC pH dependence:
CC Optimum pH is 8.3-8.8 for the forward reaction, and 7 for the reverse
CC reaction. {ECO:0000269|PubMed:4395693};
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via AAA
CC pathway; L-alpha-aminoadipate from 2-oxoglutarate: step 4/5.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:14576278}.
CC -!- INDUCTION: Activity is repressed 4-fold by lysine.
CC {ECO:0000269|PubMed:3939712}.
CC -!- MISCELLANEOUS: Present with 19079 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Z46728; CAA86700.1; -; Genomic_DNA.
DR EMBL; BK006942; DAA08459.1; -; Genomic_DNA.
DR PIR; S49786; S49786.
DR RefSeq; NP_012172.1; NM_001179442.1.
DR AlphaFoldDB; P40495; -.
DR SMR; P40495; -.
DR BioGRID; 34898; 108.
DR DIP; DIP-4162N; -.
DR IntAct; P40495; 101.
DR MINT; P40495; -.
DR STRING; 4932.YIL094C; -.
DR BindingDB; P40495; -.
DR ChEMBL; CHEMBL1075252; -.
DR iPTMnet; P40495; -.
DR MaxQB; P40495; -.
DR PaxDb; P40495; -.
DR PRIDE; P40495; -.
DR EnsemblFungi; YIL094C_mRNA; YIL094C; YIL094C.
DR GeneID; 854714; -.
DR KEGG; sce:YIL094C; -.
DR SGD; S000001356; LYS12.
DR VEuPathDB; FungiDB:YIL094C; -.
DR eggNOG; KOG0785; Eukaryota.
DR GeneTree; ENSGT00950000182989; -.
DR HOGENOM; CLU_031953_0_1_1; -.
DR InParanoid; P40495; -.
DR OMA; KLFRQPS; -.
DR BioCyc; YEAST:YIL094C-MON; -.
DR BRENDA; 1.1.1.87; 984.
DR UniPathway; UPA00033; UER00030.
DR ChiTaRS; LYS12; yeast.
DR PRO; PR:P40495; -.
DR Proteomes; UP000002311; Chromosome IX.
DR RNAct; P40495; protein.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0047046; F:homoisocitrate dehydrogenase activity; IDA:SGD.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0009085; P:lysine biosynthetic process; IBA:GO_Central.
DR GO; GO:0019878; P:lysine biosynthetic process via aminoadipic acid; IEA:UniProtKB-UniPathway.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
DR PROSITE; PS00470; IDH_IMDH; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Direct protein sequencing; Lysine biosynthesis;
KW Magnesium; Metal-binding; Mitochondrion; NAD; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..22
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 23..371
FT /note="Homoisocitrate dehydrogenase, mitochondrial"
FT /id="PRO_0000043097"
FT BINDING 96..98
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 98
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 114
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 124
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 143
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 150
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 206
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 208
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 208
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 243
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 267
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 271
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 300..304
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 312
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT SITE 150
FT /note="Critical for catalysis"
FT SITE 206
FT /note="Critical for catalysis"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MUTAGEN 150
FT /note="Y->F: Strongly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:19530703"
FT MUTAGEN 206
FT /note="K->M: Strongly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:19530703"
SQ SEQUENCE 371 AA; 40069 MW; 43CAFA86F75ED3C6 CRC64;
MFRSVATRLS ACRGLASNAA RKSLTIGLIP GDGIGKEVIP AGKQVLENLN SKHGLSFNFI
DLYAGFQTFQ ETGKALPDET VKVLKEQCQG ALFGAVQSPT TKVEGYSSPI VALRREMGLF
ANVRPVKSVE GEKGKPIDMV IVRENTEDLY IKIEKTYIDK ATGTRVADAT KRISEIATRR
IATIALDIAL KRLQTRGQAT LTVTHKSNVL SQSDGLFREI CKEVYESNKD KYGQIKYNEQ
IVDSMVYRLF REPQCFDVIV APNLYGDILS DGAAALVGSL GVVPSANVGP EIVIGEPCHG
SAPDIAGKGI ANPIATIRST ALMLEFLGHN EAAQDIYKAV DANLREGSIK TPDLGGKAST
QQVVDDVLSR L
