ID   IDHC_RAT                Reviewed;         414 AA.
AC   P41562; P80300;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   27-MAR-2024, entry version 164.
DE   RecName: Full=Isocitrate dehydrogenase [NADP] cytoplasmic;
DE            Short=IDH;
DE            Short=IDH1;
DE            EC=1.1.1.42 {ECO:0000269|PubMed:8083215};
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;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION,
RP   CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RX   PubMed=8083215; DOI=10.1016/s0021-9258(17)31629-0;
RA   Jennings G.T., Sechi S., Stevenson P.M., Tuckey R.C., Parmelee D.,
RA   McAlister-Henn L.;
RT   "Cytosolic NADP(+)-dependent isocitrate dehydrogenase. Isolation of rat
RT   cDNA and study of tissue-specific and developmental expression of mRNA.";
RL   J. Biol. Chem. 269:23128-23134(1994).
RN   [2]
RP   PROTEIN SEQUENCE OF 389-400, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA   Lubec G., Afjehi-Sadat L.;
RL   Submitted (NOV-2006) to UniProtKB.
RN   [3]
RP   PARTIAL PROTEIN SEQUENCE, AND CHARACTERIZATION.
RC   TISSUE=Ovary;
RX   PubMed=7787968; DOI=10.1159/000474966;
RA   Sechi S., Parmelee D., Roller P.R., Jennings G.T.;
RT   "Structural characterization of cytosolic NADP(+)-dependent isocitrate
RT   dehydrogenase from rat ovary.";
RL   Enzyme Protein 48:27-36(1994).
RN   [4]
RP   SUBCELLULAR LOCATION.
RX   PubMed=10521434; DOI=10.1074/jbc.274.43.30527;
RA   Geisbrecht B.V., Gould S.J.;
RT   "The human PICD gene encodes a cytoplasmic and peroxisomal NADP(+)-
RT   dependent isocitrate dehydrogenase.";
RL   J. Biol. Chem. 274:30527-30533(1999).
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 (PubMed:10521434). Plays a critical role in the generation
CC       of NADPH, an important cofactor in many biosynthesis pathways (By
CC       similarity). May act as a corneal epithelial crystallin and may be
CC       involved in maintaining corneal epithelial transparency (By
CC       similarity). {ECO:0000250|UniProtKB:O75874,
CC       ECO:0000250|UniProtKB:Q9XSG3, ECO:0000269|PubMed:10521434}.
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:0000305|PubMed:10521434};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19630;
CC         Evidence={ECO:0000305|PubMed:10521434};
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 {ECO:0000269|PubMed:10521434,
CC       ECO:0000269|PubMed:8083215}. Peroxisome {ECO:0000269|PubMed:10521434}.
CC   -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:8083215}.
CC   -!- PTM: The N-terminus is blocked.
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; L35317; AAA59356.1; -; mRNA.
DR   PIR; A54756; A54756.
DR   RefSeq; NP_113698.1; NM_031510.1.
DR   RefSeq; XP_006245111.1; XM_006245049.3.
DR   RefSeq; XP_008765298.1; XM_008767076.2.
DR   AlphaFoldDB; P41562; -.
DR   SMR; P41562; -.
DR   BioGRID; 246640; 2.
DR   STRING; 10116.ENSRNOP00000020322; -.
DR   iPTMnet; P41562; -.
DR   PhosphoSitePlus; P41562; -.
DR   jPOST; P41562; -.
DR   PaxDb; 10116-ENSRNOP00000020322; -.
DR   Ensembl; ENSRNOT00000108404.1; ENSRNOP00000081635.1; ENSRNOG00000015020.8.
DR   Ensembl; ENSRNOT00055038891; ENSRNOP00055031566; ENSRNOG00055022679.
DR   Ensembl; ENSRNOT00060036194; ENSRNOP00060029765; ENSRNOG00060020894.
DR   Ensembl; ENSRNOT00065045000; ENSRNOP00065036885; ENSRNOG00065026102.
DR   GeneID; 24479; -.
DR   KEGG; rno:24479; -.
DR   UCSC; RGD:2862; rat.
DR   AGR; RGD:2862; -.
DR   CTD; 3417; -.
DR   RGD; 2862; Idh1.
DR   eggNOG; KOG1526; Eukaryota.
DR   GeneTree; ENSGT00390000012547; -.
DR   HOGENOM; CLU_023296_1_1_1; -.
DR   InParanoid; P41562; -.
DR   OMA; HGTVQRH; -.
DR   OrthoDB; 423at2759; -.
DR   PhylomeDB; P41562; -.
DR   BRENDA; 1.1.1.42; 5301.
DR   Reactome; R-RNO-389542; NADPH regeneration.
DR   Reactome; R-RNO-6798695; Neutrophil degranulation.
DR   Reactome; R-RNO-9033241; Peroxisomal protein import.
DR   SABIO-RK; P41562; -.
DR   PRO; PR:P41562; -.
DR   Proteomes; UP000002494; Chromosome 9.
DR   Bgee; ENSRNOG00000015020; Expressed in ovary and 19 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; ISO:RGD.
DR   GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR   GO; GO:0005777; C:peroxisome; IDA:HGNC-UCL.
DR   GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR   GO; GO:0004450; F:isocitrate dehydrogenase (NADP+) activity; IDA:RGD.
DR   GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR   GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR   GO; GO:0050661; F:NADP binding; IDA:RGD.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR   GO; GO:0006103; P:2-oxoglutarate metabolic process; ISS:UniProtKB.
DR   GO; GO:0008585; P:female gonad development; IEP:RGD.
DR   GO; GO:0006749; P:glutathione metabolic process; ISO:RGD.
DR   GO; GO:0006097; P:glyoxylate cycle; IEA:UniProtKB-KW.
DR   GO; GO:0006102; P:isocitrate metabolic process; IDA:RGD.
DR   GO; GO:0006739; P:NADP metabolic process; IBA:GO_Central.
DR   GO; GO:0071071; P:regulation of phospholipid biosynthetic process; ISO:RGD.
DR   GO; GO:0060696; P:regulation of phospholipid catabolic process; ISO:RGD.
DR   GO; GO:0014070; P:response to organic cyclic compound; IDA:RGD.
DR   GO; GO:0006979; P:response to oxidative stress; ISO:RGD.
DR   GO; GO:0048545; P:response to steroid hormone; IDA:RGD.
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.
DR   Genevisible; P41562; RN.
PE   1: Evidence at protein level;
KW   Acetylation; Cytoplasm; Direct protein sequencing; Glyoxylate bypass;
KW   Magnesium; Manganese; Metal-binding; NADP; Oxidoreductase; Peroxisome;
KW   Phosphoprotein; Reference proteome; 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_0000083580"
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;  46734 MW;  CF69EE8746DC1AF6 CRC64;
     MSRKIHGGSV VEMQGDEMTR IIWELIKEKL ILPYVELDLH SYDLGIENRD ATNDQVTKDA
     AEAIKKYNVG VKCATITPDE KRVEEFKLKQ MWKSPNGTIR NILGGTVFRE AIICKNIPRL
     VTGWVKPIII GRHAYGDQYR ATDFVVPGPG KVEITYTPKD GSQKVTYLVH DFEEGGGVAM
     GMYNQDKSIE DFAHSSFQMA LSKGWPLYLS TKNTILKKYD GRFKDIFQEI YDKQYKSKFE
     AQKIWYEHRL IDDMVAQAMK SEGGFIWACK NYDGDVQSDS VAQGYGSLGM MTSVLICPDG
     KTVEAEAAHG TVTRHYRMYQ KGQETSTNPI ASIFAWSRGL AHRAKLDNNT ELSFFANALE
     EVCIETIEAG FMTKDLAACI KGLPNVQRSD YLNTFEFMDK LGENLKAKLA QAKL
//