ID   IDH_SYNY3               Reviewed;         475 AA.
AC   P80046; P72820;
DT   01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 2.
DT   04-NOV-2026, entry version 149.
DE   RecName: Full=Isocitrate dehydrogenase [NADP] {ECO:0000303|PubMed:1730247};
DE            Short=IDH {ECO:0000303|PubMed:1730247};
DE            EC=1.1.1.42 {ECO:0000269|PubMed:1730247};
DE   AltName: Full=IDP;
DE   AltName: Full=NADP isocitrate dehydrogenase {ECO:0000303|PubMed:1730247};
DE            Short=NADP-IDH {ECO:0000303|PubMed:8763933};
DE   AltName: Full=NADP(+)-specific ICDH;
DE   AltName: Full=Oxalosuccinate decarboxylase;
GN   Name=icd {ECO:0000303|PubMed:8763933}; OrderedLocusNames=slr1289;
OS   Synechocystis sp. (strain ATCC 27184 / PCC 6803 / Kazusa).
OC   Bacteria; Bacillati; Cyanobacteriota; Cyanophyceae; Synechococcales;
OC   Merismopediaceae; Synechocystis.
OX   NCBI_TaxID=1111708;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, AND DISRUPTION PHENOTYPE.
RC   STRAIN=ATCC 27184 / PCC 6803 / Kazusa;
RX   PubMed=8763933; DOI=10.1128/jb.178.14.4070-4076.1996;
RA   Muro-Pastor M.I., Reyes J.C., Florencio F.J.;
RT   "The NADP+-isocitrate dehydrogenase gene (icd) is nitrogen regulated in
RT   cyanobacteria.";
RL   J. Bacteriol. 178:4070-4076(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 27184 / PCC 6803 / Kazusa;
RX   PubMed=8905231; DOI=10.1093/dnares/3.3.109;
RA   Kaneko T., Sato S., Kotani H., Tanaka A., Asamizu E., Nakamura Y.,
RA   Miyajima N., Hirosawa M., Sugiura M., Sasamoto S., Kimura T., Hosouchi T.,
RA   Matsuno A., Muraki A., Nakazaki N., Naruo K., Okumura S., Shimpo S.,
RA   Takeuchi C., Wada T., Watanabe A., Yamada M., Yasuda M., Tabata S.;
RT   "Sequence analysis of the genome of the unicellular cyanobacterium
RT   Synechocystis sp. strain PCC6803. II. Sequence determination of the entire
RT   genome and assignment of potential protein-coding regions.";
RL   DNA Res. 3:109-136(1996).
RN   [3]
RP   PROTEIN SEQUENCE OF 1-20, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY
RP   REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC   STRAIN=ATCC 27184 / PCC 6803 / Kazusa;
RX   PubMed=1730247; DOI=10.1111/j.1432-1033.1992.tb19833.x;
RA   Muro-Pastor M.I., Florencio F.J.;
RT   "Purification and properties of NADP-isocitrate dehydrogenase from the
RT   unicellular cyanobacterium Synechocystis sp. PCC 6803.";
RL   Eur. J. Biochem. 203:99-105(1992).
CC   -!- FUNCTION: Catalyzes the oxidative decarboxylation of isocitrate to 2-
CC       oxoglutarate and carbon dioxide with the concomitant reduction of
CC       NADP(+) (PubMed:1730247). Is specific for NADP(+), cannot use NAD(+)
CC       (PubMed:1730247). {ECO:0000269|PubMed:1730247}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH;
CC         Xref=Rhea:RHEA:19629, ChEBI:CHEBI:15562, ChEBI:CHEBI:16526,
CC         ChEBI:CHEBI:16810, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.42;
CC         Evidence={ECO:0000269|PubMed:1730247};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:1730247};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000269|PubMed:1730247};
CC       Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit (By similarity). Can use
CC       Mn(2+) or Mg(2+), but the activity is twofold higher in vitro with
CC       Mn(2+) (PubMed:1730247). {ECO:0000250|UniProtKB:P08200,
CC       ECO:0000269|PubMed:1730247};
CC   -!- ACTIVITY REGULATION: Inhibited non-competitively by ADP and 2-
CC       oxoglutarate, with respect to isocitrate and in a competitive manner by
CC       NADPH. {ECO:0000269|PubMed:1730247}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=59 uM for D,L-isocitrate (in the presence of Mg(2+))
CC         {ECO:0000269|PubMed:1730247};
CC         KM=5.7 uM for D,L-isocitrate (in the presence of Mn(2+))
CC         {ECO:0000269|PubMed:1730247};
CC         KM=12 uM for NADP(+) (in the presence of Mg(2+))
CC         {ECO:0000269|PubMed:1730247};
CC         KM=6 uM for NADP(+) (in the presence of Mn(2+))
CC         {ECO:0000269|PubMed:1730247};
CC         KM=125 uM for Mg(2+) {ECO:0000269|PubMed:1730247};
CC         KM=4 uM for Mn(2+) {ECO:0000269|PubMed:1730247};
CC       pH dependence:
CC         Optimum pH is 9.0 (PubMed:1730247). Active over a relatively broad pH
CC         range (7.5-10.0) (PubMed:1730247). {ECO:0000269|PubMed:1730247};
CC       Temperature dependence:
CC         Activity increases with temperature up to 70 degrees Celsius,
CC         although activity declines after a few minutes at this temperature.
CC         {ECO:0000269|PubMed:1730247};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:1730247}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- INDUCTION: Induced by nitrogen starvation (PubMed:8763933). Expression
CC       is regulated by the transcription factor NtcA, a positive regulator of
CC       genes subjected to nitrogen control in cyanobacteria (PubMed:8763933).
CC       {ECO:0000269|PubMed:8763933}.
CC   -!- DISRUPTION PHENOTYPE: Essential, it cannot be deleted.
CC       {ECO:0000269|PubMed:8763933}.
CC   -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC       dehydrogenases family. {ECO:0000305}.
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DR   EMBL; X83563; CAA58549.1; -; Genomic_DNA.
DR   EMBL; BA000022; BAA16835.1; -; Genomic_DNA.
DR   PIR; S74684; S74684.
DR   AlphaFoldDB; P80046; -.
DR   SMR; P80046; -.
DR   FunCoup; P80046; 312.
DR   IntAct; P80046; 2.
DR   STRING; 1148.gene:10497693; -.
DR   PaxDb; 1148-gene:10497693; -.
DR   EnsemblBacteria; BAA16835; BAA16835; BAA16835.
DR   KEGG; syn:slr1289; -.
DR   eggNOG; COG0538; Bacteria.
DR   InParanoid; P80046; -.
DR   OMA; AAIIKFV; -.
DR   PhylomeDB; P80046; -.
DR   Proteomes; UP000001425; Chromosome.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0004450; F:isocitrate dehydrogenase (NADP+) activity; EXP:UniProtKB.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR   GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR   Gene3D; 3.40.718.10; Isopropylmalate Dehydrogenase; 2.
DR   InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR   InterPro; IPR004439; Isocitrate_DH_NADP_dimer_prok.
DR   InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR   NCBIfam; NF005425; icd; 1.
DR   NCBIfam; NF005610; PRK07362.1; 1.
DR   NCBIfam; TIGR00183; prok_nadp_idh; 1.
DR   PANTHER; PTHR43504; ISOCITRATE DEHYDROGENASE [NADP]; 1.
DR   PANTHER; PTHR43504:SF1; ISOCITRATE DEHYDROGENASE [NADP]; 1.
DR   Pfam; PF00180; Iso_dh; 1.
DR   SMART; SM01329; Iso_dh; 1.
DR   SUPFAM; SSF53659; Isocitrate/Isopropylmalate dehydrogenase-like; 1.
DR   PROSITE; PS00470; IDH_IMDH; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Direct protein sequencing; Glyoxylate bypass; Magnesium;
KW   Manganese; Metal-binding; NADP; Oxidoreductase; Reference proteome;
KW   Tricarboxylic acid cycle.
FT   CHAIN           1..475
FT                   /note="Isocitrate dehydrogenase [NADP]"
FT                   /id="PRO_0000083570"
FT   BINDING         104
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P08200"
FT   BINDING         113
FT                   /ligand="D-threo-isocitrate"
FT                   /ligand_id="ChEBI:CHEBI:15562"
FT                   /evidence="ECO:0000250|UniProtKB:P08200"
FT   BINDING         115
FT                   /ligand="D-threo-isocitrate"
FT                   /ligand_id="ChEBI:CHEBI:15562"
FT                   /evidence="ECO:0000250|UniProtKB:P08200"
FT   BINDING         119
FT                   /ligand="D-threo-isocitrate"
FT                   /ligand_id="ChEBI:CHEBI:15562"
FT                   /evidence="ECO:0000250|UniProtKB:P08200"
FT   BINDING         129
FT                   /ligand="D-threo-isocitrate"
FT                   /ligand_id="ChEBI:CHEBI:15562"
FT                   /evidence="ECO:0000250|UniProtKB:P08200"
FT   BINDING         153
FT                   /ligand="D-threo-isocitrate"
FT                   /ligand_id="ChEBI:CHEBI:15562"
FT                   /evidence="ECO:0000250|UniProtKB:P08200"
FT   BINDING         362
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P08200"
FT   BINDING         394..400
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P08200"
FT   BINDING         407
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P08200"
FT   BINDING         446
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P08200"
FT   BINDING         450
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P08200"
FT   SITE            160
FT                   /note="Critical for catalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P08200"
FT   SITE            237
FT                   /note="Critical for catalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P08200"
FT   CONFLICT        60..62
FT                   /note="REE -> ERK (in Ref. 2; BAA16835)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        83..84
FT                   /note="IF -> YL (in Ref. 2; BAA16835)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        223
FT                   /note="K -> L (in Ref. 2; BAA16835)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        247
FT                   /note="P -> A (in Ref. 2; BAA16835)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        273
FT                   /note="C -> L (in Ref. 2; BAA16835)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   475 AA;  52275 MW;  6F3254A8BBA75F92 CRC64;
     MYEKLQPPSV GSKITFVAGK PVVPNDPIIP YIRGDGTGVD IWPATELVIN AAIAKAYGGR
     EEINWFKVYA GDEACELYGT YQIFPEDTLT AIKEYGVAIK GPLTTPVGGG IRSLNVALRQ
     IFDLYTCVRP CRYYPGTPSP HKTPEKLDII VYRENTEDIY LGIEWAEGTE GAKKLIAYLN
     DELIPTTPAL GKKQIRLDSG IGIKPISKTG SQRLVRRAIL HAKRLPKAKQ MVTLVHKGNI
     MKFTEGPFRD WGYELATTEF RAECVTERES WICGNKESNP DLTIEANAHM IDPGYDTLTE
     EKQAVIKQEV EQVLNSIWES HGNGQWKEKV MVNDRIADSI FQQIQTRPDE YSILATMNLN
     GDYLSDAAAA VVGGLGMGPG ANIGDSAAIF EATHGTAPKH AGLDRINPGS VILSGVMMLE
     FMGWQEAADL IKKGIGAAIA NREVTYDLAR LMEPKVDKPL KCSEFAQAIV SHFDD
//