IDHC_RAT
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 03-AUG-2022, entry version 156.
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; P41562; -.
DR PRIDE; P41562; -.
DR Ensembl; ENSRNOT00000108404; ENSRNOP00000081635; ENSRNOG00000015020.
DR GeneID; 24479; -.
DR KEGG; rno:24479; -.
DR UCSC; RGD:2862; rat.
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; 769322at2759; -.
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 tissues.
DR Genevisible; P41562; RN.
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:0004448; F:isocitrate dehydrogenase activity; ISO: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 InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR004790; Isocitrate_DH_NADP.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR PANTHER; PTHR11822; PTHR11822; 1.
DR Pfam; PF00180; Iso_dh; 1.
DR PIRSF; PIRSF000108; IDH_NADP; 1.
DR SMART; SM01329; Iso_dh; 1.
DR TIGRFAMs; TIGR00127; nadp_idh_euk; 1.
DR PROSITE; PS00470; IDH_IMDH; 1.
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
