ID   IDHC_MICME              Reviewed;         414 AA.
AC   Q9Z2K9;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   27-MAR-2024, entry version 97.
DE   RecName: Full=Isocitrate dehydrogenase [NADP] cytoplasmic;
DE            Short=IDH;
DE            Short=IDH1;
DE            EC=1.1.1.42 {ECO:0000250|UniProtKB:O88844};
DE   AltName: Full=Cytosolic NADP-isocitrate dehydrogenase;
DE   AltName: Full=IDPc;
DE   AltName: Full=NADP(+)-specific ICDH;
DE   AltName: Full=Oxalosuccinate decarboxylase;
GN   Name=IDH1; Synonyms=IDP2;
OS   Microtus mexicanus (Mexican vole).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC   Cricetidae; Arvicolinae; Microtus.
OX   NCBI_TaxID=79689;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Liver;
RX   PubMed=9866202; DOI=10.1093/oxfordjournals.molbev.a025894;
RA   Nekrutenko A., Hillis D.M., Patton J.C., Bradley R.D., Baker R.J.;
RT   "Cytosolic isocitrate dehydrogenase in humans, mice, and voles and
RT   phylogenetic analysis of the enzyme family.";
RL   Mol. Biol. Evol. 15:1674-1684(1998).
CC   -!- FUNCTION: Catalyzes the NADP(+)-dependent oxidative decarboxylation of
CC       isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate),
CC       which is required by other enzymes such as the phytanoyl-CoA
CC       dioxygenase. Plays a critical role in the generation of NADPH, an
CC       important cofactor in many biosynthesis pathways (By similarity). May
CC       act as a corneal epithelial crystallin and may be involved in
CC       maintaining corneal epithelial transparency (By similarity).
CC       {ECO:0000250|UniProtKB:O75874, ECO:0000250|UniProtKB:Q9XSG3}.
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:0000250|UniProtKB:O88844};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19630;
CC         Evidence={ECO:0000250|UniProtKB:O88844};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:O88844};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:O88844};
CC       Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit.
CC       {ECO:0000250|UniProtKB:O88844};
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:O88844}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:P41562}.
CC   -!- PTM: Acetylation at Lys-374 dramatically reduces catalytic activity.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC       dehydrogenases family. {ECO:0000305}.
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DR   EMBL; AF048831; AAD02924.1; -; mRNA.
DR   AlphaFoldDB; Q9Z2K9; -.
DR   SMR; Q9Z2K9; -.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0004450; F:isocitrate dehydrogenase (NADP+) activity; ISS:UniProtKB.
DR   GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR   GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR   GO; GO:0006103; P:2-oxoglutarate metabolic process; ISS:UniProtKB.
DR   GO; GO:0006097; P:glyoxylate cycle; IEA:UniProtKB-KW.
DR   GO; GO:0006102; P:isocitrate metabolic process; ISS:UniProtKB.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.718.10; Isopropylmalate Dehydrogenase; 1.
DR   InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR   InterPro; IPR004790; Isocitrate_DH_NADP.
DR   InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR   NCBIfam; TIGR00127; nadp_idh_euk; 1.
DR   PANTHER; PTHR11822:SF21; ISOCITRATE DEHYDROGENASE [NADP], MITOCHONDRIAL; 1.
DR   PANTHER; PTHR11822; NADP-SPECIFIC ISOCITRATE DEHYDROGENASE; 1.
DR   Pfam; PF00180; Iso_dh; 1.
DR   PIRSF; PIRSF000108; IDH_NADP; 1.
DR   SMART; SM01329; Iso_dh; 1.
DR   SUPFAM; SSF53659; Isocitrate/Isopropylmalate dehydrogenase-like; 1.
DR   PROSITE; PS00470; IDH_IMDH; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Cytoplasm; Glyoxylate bypass; Magnesium; Manganese;
KW   Metal-binding; NADP; Oxidoreductase; Phosphoprotein;
KW   Tricarboxylic acid cycle.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   CHAIN           2..414
FT                   /note="Isocitrate dehydrogenase [NADP] cytoplasmic"
FT                   /id="PRO_0000083576"
FT   BINDING         75..77
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         77
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         82
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         94..100
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         109
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         132
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         212
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   BINDING         252
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         260
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         275
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         279
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         310..315
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         328
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   SITE            139
FT                   /note="Critical for catalysis"
FT                   /evidence="ECO:0000250"
FT   SITE            212
FT                   /note="Critical for catalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   MOD_RES         42
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   MOD_RES         81
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   MOD_RES         126
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   MOD_RES         224
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   MOD_RES         233
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   MOD_RES         243
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   MOD_RES         321
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   MOD_RES         389
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   MOD_RES         400
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
SQ   SEQUENCE   414 AA;  46678 MW;  D8ECB20509B87902 CRC64;
     MSKKIHGGSV VEMQGDEMTR IIWELIKEKL ILPYVELDLH SYDLGIENRD ATNDQVTKDA
     AEAIKKYNVG VKCATITPDE KRVEEFKLKQ MWKSPNGTIR NILGGTVFRE AIICKNIPRL
     VTGWVKPIII GRHAYGDQYR ATDFVVPGPG KVEITFTPKD GSQKVTYLVH SFEEGGGVAM
     GMYNQDKSIE DFAHSSFQMA LSKGWPLYLS TKNTILKKYD GRFKDIFQEI YDKQYKSQFE
     AQKIWYEHRL IDDMVAQAMK SEGGFIWACK NYDGDVQSDS VAQGYGSLGM MTSVLICPDG
     KTVEAEAAHG TVTRHYRMHQ KGQETSTNPI ASIFAWSRGL AHRARLDNNT ELSFFAKALE
     EVCIETIEAG FMTKDLAACI KGLPNVQRSD YLNTFEFMDK LGENLKAKLA QAKL
//