IDH2_YEAST
ID IDH2_YEAST Reviewed; 369 AA.
AC P28241; D6W2J3;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Isocitrate dehydrogenase [NAD] subunit 2, mitochondrial;
DE EC=1.1.1.41;
DE AltName: Full=Isocitric dehydrogenase;
DE AltName: Full=NAD(+)-specific ICDH;
DE Flags: Precursor;
GN Name=IDH2; OrderedLocusNames=YOR136W; ORFNames=O3326, YOR3326W;
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 [GENOMIC DNA].
RX PubMed=1939242; DOI=10.1016/s0021-9258(18)54554-3;
RA Cupp J.R., McAlister-Henn L.;
RT "NAD(+)-dependent isocitrate dehydrogenase. Cloning, nucleotide sequence,
RT and disruption of the IDH2 gene from Saccharomyces cerevisiae.";
RL J. Biol. Chem. 266:22199-22205(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=8904341;
RX DOI=10.1002/(sici)1097-0061(19960315)12:3<281::aid-yea904>3.0.co;2-o;
RA Wiemann S., Rechmann S., Benes V., Voss H., Schwager C., Vlcek C.,
RA Stegemann J., Zimmermann J., Erfle H., Paces V., Ansorge W.;
RT "Sequencing and analysis of 51 kb on the right arm of chromosome XV from
RT Saccharomyces cerevisiae reveals 30 open reading frames.";
RL Yeast 12:281-288(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9200815;
RX DOI=10.1002/(sici)1097-0061(19970615)13:7<655::aid-yea120>3.0.co;2-i;
RA Voss H., Benes V., Andrade M.A., Valencia A., Rechmann S., Teodoru C.,
RA Schwager C., Paces V., Sander C., Ansorge W.;
RT "DNA sequencing and analysis of 130 kb from yeast chromosome XV.";
RL Yeast 13:655-672(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169874;
RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL Nature 387:98-102(1997).
RN [5]
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 [6]
RP PROTEIN SEQUENCE OF 16-26.
RC STRAIN=SG7;
RX PubMed=2198251; DOI=10.1128/jb.172.8.4280-4287.1990;
RA Keys D.A., McAlister-Henn L.;
RT "Subunit structure, expression, and function of NAD(H)-specific isocitrate
RT dehydrogenase in Saccharomyces cerevisiae.";
RL J. Bacteriol. 172:4280-4287(1990).
RN [7]
RP RNA-BINDING, AND PROTEIN SEQUENCE OF 16-34.
RX PubMed=7505425; DOI=10.1093/nar/21.23.5328;
RA Elzinga S.D.J., Bednarz A.L., van Oosterum K., Dekker P.J.T., Grivell L.A.;
RT "Yeast mitochondrial NAD(+)-dependent isocitrate dehydrogenase is an RNA-
RT binding protein.";
RL Nucleic Acids Res. 21:5328-5331(1993).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=11502169; DOI=10.1021/bi010277r;
RA Grandier-Vazeille X., Bathany K., Chaignepain S., Camougrand N., Manon S.,
RA Schmitter J.-M.;
RT "Yeast mitochondrial dehydrogenases are associated in a supramolecular
RT complex.";
RL Biochemistry 40:9758-9769(2001).
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-349, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 76625 / YPH499;
RX PubMed=17761666; DOI=10.1074/mcp.m700098-mcp200;
RA Reinders J., Wagner K., Zahedi R.P., Stojanovski D., Eyrich B.,
RA van der Laan M., Rehling P., Sickmann A., Pfanner N., Meisinger C.;
RT "Profiling phosphoproteins of yeast mitochondria reveals a role of
RT phosphorylation in assembly of the ATP synthase.";
RL Mol. Cell. Proteomics 6:1896-1906(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-105 AND THR-153, AND
RP IDENTIFICATION BY 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-153 AND THR-327, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
CC -!- FUNCTION: Performs an essential role in the oxidative function of the
CC citric acid cycle. Also binds RNA; specifically to the 5'-untranslated
CC leaders of mitochondrial mRNAs.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-threo-isocitrate + NAD(+) = 2-oxoglutarate + CO2 + NADH;
CC Xref=Rhea:RHEA:23632, ChEBI:CHEBI:15562, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.41;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Allosterically regulated by several compounds
CC including AMP, NAD(+), and citrate.
CC -!- SUBUNIT: Octamer of two non-identical subunits IDH1 and IDH2.
CC -!- INTERACTION:
CC P28241; P28834: IDH1; NbExp=6; IntAct=EBI-8883, EBI-8878;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:11502169}.
CC -!- MISCELLANEOUS: Present with 43100 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}.
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DR EMBL; M74131; AAA34702.1; -; Genomic_DNA.
DR EMBL; X94335; CAA64054.1; -; Genomic_DNA.
DR EMBL; Z75043; CAA99335.1; -; Genomic_DNA.
DR EMBL; X90518; CAA62110.1; -; Genomic_DNA.
DR EMBL; BK006948; DAA10909.1; -; Genomic_DNA.
DR PIR; A39309; A39309.
DR RefSeq; NP_014779.1; NM_001183555.1.
DR PDB; 3BLV; X-ray; 3.20 A; B/D/F/H=16-369.
DR PDB; 3BLW; X-ray; 4.30 A; B/D/F/H/J/L/N/P=16-369.
DR PDB; 3BLX; X-ray; 2.70 A; B/D/F/H/J/L/N/P=16-369.
DR PDBsum; 3BLV; -.
DR PDBsum; 3BLW; -.
DR PDBsum; 3BLX; -.
DR AlphaFoldDB; P28241; -.
DR SMR; P28241; -.
DR BioGRID; 34531; 335.
DR ComplexPortal; CPX-558; Mitochondrial isocitrate dehydrogenase complex (NAD+).
DR DIP; DIP-4296N; -.
DR IntAct; P28241; 46.
DR MINT; P28241; -.
DR STRING; 4932.YOR136W; -.
DR MoonProt; P28241; -.
DR iPTMnet; P28241; -.
DR MaxQB; P28241; -.
DR PaxDb; P28241; -.
DR PRIDE; P28241; -.
DR EnsemblFungi; YOR136W_mRNA; YOR136W; YOR136W.
DR GeneID; 854303; -.
DR KEGG; sce:YOR136W; -.
DR SGD; S000005662; IDH2.
DR VEuPathDB; FungiDB:YOR136W; -.
DR eggNOG; KOG0785; Eukaryota.
DR GeneTree; ENSGT00950000182989; -.
DR HOGENOM; CLU_031953_0_1_1; -.
DR InParanoid; P28241; -.
DR OMA; CVRPCRY; -.
DR BioCyc; MetaCyc:YOR136W-MON; -.
DR BioCyc; YEAST:YOR136W-MON; -.
DR BRENDA; 1.1.1.41; 984.
DR Reactome; R-SCE-71403; Citric acid cycle (TCA cycle).
DR EvolutionaryTrace; P28241; -.
DR PRO; PR:P28241; -.
DR Proteomes; UP000002311; Chromosome XV.
DR RNAct; P28241; protein.
DR GO; GO:0005962; C:mitochondrial isocitrate dehydrogenase complex (NAD+); IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0004449; F:isocitrate dehydrogenase (NAD+) activity; IEA:UniProtKB-EC.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006537; P:glutamate biosynthetic process; TAS:SGD.
DR GO; GO:0006102; P:isocitrate metabolic process; IDA:SGD.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IDA:ComplexPortal.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR004434; Isocitrate_DH_NAD.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
DR TIGRFAMs; TIGR00175; mito_nad_idh; 1.
DR PROSITE; PS00470; IDH_IMDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Direct protein sequencing; Magnesium;
KW Manganese; Metal-binding; Mitochondrion; NAD; Oxidoreductase;
KW Phosphoprotein; Reference proteome; RNA-binding; Transit peptide;
KW Tricarboxylic acid cycle.
FT TRANSIT 1..15
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:2198251,
FT ECO:0000269|PubMed:7505425"
FT CHAIN 16..369
FT /note="Isocitrate dehydrogenase [NAD] subunit 2,
FT mitochondrial"
FT /id="PRO_0000014434"
FT BINDING 119
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 129
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 150
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 237
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 237
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 263
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 267
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT SITE 157
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250"
FT SITE 204
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 105
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 153
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 327
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 349
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17761666"
FT CONFLICT 25
FT /note="R -> G (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:3BLV"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 48..60
FT /evidence="ECO:0007829|PDB:3BLX"
FT TURN 61..63
FT /evidence="ECO:0007829|PDB:3BLX"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:3BLX"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:3BLX"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 86..95
FT /evidence="ECO:0007829|PDB:3BLX"
FT STRAND 96..100
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 114..122
FT /evidence="ECO:0007829|PDB:3BLX"
FT STRAND 124..132
FT /evidence="ECO:0007829|PDB:3BLX"
FT STRAND 145..151
FT /evidence="ECO:0007829|PDB:3BLX"
FT STRAND 153..163
FT /evidence="ECO:0007829|PDB:3BLX"
FT STRAND 168..176
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 177..193
FT /evidence="ECO:0007829|PDB:3BLX"
FT STRAND 197..204
FT /evidence="ECO:0007829|PDB:3BLX"
FT TURN 206..208
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 210..223
FT /evidence="ECO:0007829|PDB:3BLX"
FT STRAND 229..235
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 236..245
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 247..250
FT /evidence="ECO:0007829|PDB:3BLX"
FT STRAND 253..257
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 259..273
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:3BLX"
FT STRAND 281..288
FT /evidence="ECO:0007829|PDB:3BLX"
FT STRAND 290..294
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 300..302
FT /evidence="ECO:0007829|PDB:3BLX"
FT TURN 303..306
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 311..324
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 327..335
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 337..341
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:3BLX"
FT HELIX 358..367
FT /evidence="ECO:0007829|PDB:3BLX"
SQ SEQUENCE 369 AA; 39739 MW; 3A48C999776CE373 CRC64;
MLRNTFFRNT SRRFLATVKQ PSIGRYTGKP NPSTGKYTVS FIEGDGIGPE ISKSVKKIFS
AANVPIEWES CDVSPIFVNG LTTIPDPAVQ SITKNLVALK GPLATPIGKG HRSLNLTLRK
TFGLFANVRP AKSIEGFKTT YENVDLVLIR ENTEGEYSGI EHIVCPGVVQ SIKLITRDAS
ERVIRYAFEY ARAIGRPRVI VVHKSTIQRL ADGLFVNVAK ELSKEYPDLT LETELIDNSV
LKVVTNPSAY TDAVSVCPNL YGDILSDLNS GLSAGSLGLT PSANIGHKIS IFEAVHGSAP
DIAGQDKANP TALLLSSVMM LNHMGLTNHA DQIQNAVLST IASGPENRTG DLAGTATTSS
FTEAVIKRL
