ID IDHP_RAT Reviewed; 452 AA. AC P56574; Q6DGF1; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 12-DEC-2006, sequence version 2. DT 27-MAR-2024, entry version 150. DE RecName: Full=Isocitrate dehydrogenase [NADP], mitochondrial; DE Short=IDH; DE EC=1.1.1.42 {ECO:0000250|UniProtKB:P48735}; DE AltName: Full=ICD-M; DE AltName: Full=IDP; DE AltName: Full=NADP(+)-specific ICDH; DE AltName: Full=Oxalosuccinate decarboxylase; DE Flags: Precursor; GN Name=Idh2; 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 [LARGE SCALE MRNA]. RC TISSUE=Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [2] RP PROTEIN SEQUENCE OF 40-52, AND SUBCELLULAR LOCATION. RC STRAIN=Wistar; TISSUE=Heart; RA Li X.-P., Pleissner K.-P., Scheler C., Regitz-Zagrosek V., Salikov J., RA Jungblut P.R.; RL Submitted (SEP-1998) to UniProtKB. RN [3] RP PROTEIN SEQUENCE OF 61-67; 70-89; 113-122; 141-149; 181-188; 244-251; RP 262-272; 289-299; 341-353 AND 414-426, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus; RA Lubec G., Chen W.-Q.; RL Submitted (APR-2007) to UniProtKB. CC -!- FUNCTION: Plays a role in intermediary metabolism and energy CC production. It may tightly associate or interact with the pyruvate CC dehydrogenase complex. {ECO:0000250|UniProtKB:P48735}. 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:P48735}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P33198}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000250|UniProtKB:P33198}; CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit. CC {ECO:0000250|UniProtKB:P33198}; CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P33198}. CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|Ref.2}. CC -!- PTM: Acetylation at Lys-413 dramatically reduces catalytic activity. CC Deacetylated by SIRT3 (By similarity). {ECO:0000250|UniProtKB:P48735}. CC -!- MISCELLANEOUS: On the 2D-gel the determined pI of this protein (spot CC P8) is: 9.0, its MW is: 42 kDa. CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate CC dehydrogenases family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BC076398; AAH76398.1; -; mRNA. DR RefSeq; NP_001014183.1; NM_001014161.1. DR AlphaFoldDB; P56574; -. DR SMR; P56574; -. DR BioGRID; 262802; 7. DR IntAct; P56574; 4. DR MINT; P56574; -. DR STRING; 10116.ENSRNOP00000019059; -. DR CarbonylDB; P56574; -. DR GlyGen; P56574; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; P56574; -. DR PhosphoSitePlus; P56574; -. DR jPOST; P56574; -. DR PaxDb; 10116-ENSRNOP00000019059; -. DR Ensembl; ENSRNOT00055014131; ENSRNOP00055011350; ENSRNOG00055008350. DR Ensembl; ENSRNOT00060007158; ENSRNOP00060005417; ENSRNOG00060004276. DR Ensembl; ENSRNOT00065052524; ENSRNOP00065043165; ENSRNOG00065030465. DR GeneID; 361596; -. DR KEGG; rno:361596; -. DR UCSC; RGD:1597139; rat. DR AGR; RGD:1597139; -. DR CTD; 3418; -. DR RGD; 1597139; Idh2. DR VEuPathDB; HostDB:ENSRNOG00000013949; -. DR eggNOG; KOG1526; Eukaryota. DR InParanoid; P56574; -. DR OrthoDB; 423at2759; -. DR PhylomeDB; P56574; -. DR TreeFam; TF300428; -. DR BRENDA; 1.1.1.42; 5301. DR Reactome; R-RNO-2151201; Transcriptional activation of mitochondrial biogenesis. DR Reactome; R-RNO-71403; Citric acid cycle (TCA cycle). DR SABIO-RK; P56574; -. DR PRO; PR:P56574; -. DR Proteomes; UP000002494; Chromosome 1. DR Bgee; ENSRNOG00000013949; Expressed in heart and 19 other cell types or tissues. DR ExpressionAtlas; P56574; baseline and differential. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0005777; C:peroxisome; 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: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:0006741; P:NADP biosynthetic process; IMP:RGD. DR GO; GO:0006739; P:NADP metabolic process; IBA:GO_Central. DR GO; GO:1903976; P:negative regulation of glial cell migration; IMP:RGD. DR GO; GO:0060253; P:negative regulation of glial cell proliferation; IMP:RGD. DR GO; GO:1904465; P:negative regulation of matrix metallopeptidase secretion; IMP: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; P56574; RN. PE 1: Evidence at protein level; KW Acetylation; Direct protein sequencing; Glyoxylate bypass; Magnesium; KW Manganese; Metal-binding; Mitochondrion; NADP; Oxidoreductase; KW Reference proteome; Transit peptide; Tricarboxylic acid cycle. FT TRANSIT 1..39 FT /note="Mitochondrion" FT /evidence="ECO:0000269|Ref.2" FT CHAIN 40..452 FT /note="Isocitrate dehydrogenase [NADP], mitochondrial" FT /id="PRO_0000083581" FT BINDING 115..117 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:O75874" FT BINDING 117 FT /ligand="D-threo-isocitrate" FT /ligand_id="ChEBI:CHEBI:15562" FT /evidence="ECO:0000250|UniProtKB:P33198" FT BINDING 122 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:O75874" FT BINDING 134..140 FT /ligand="D-threo-isocitrate" FT /ligand_id="ChEBI:CHEBI:15562" FT /evidence="ECO:0000250|UniProtKB:P33198" FT BINDING 149 FT /ligand="D-threo-isocitrate" FT /ligand_id="ChEBI:CHEBI:15562" FT /evidence="ECO:0000250|UniProtKB:P33198" FT BINDING 172 FT /ligand="D-threo-isocitrate" FT /ligand_id="ChEBI:CHEBI:15562" FT /evidence="ECO:0000250|UniProtKB:P33198" FT BINDING 291 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000250|UniProtKB:P33198" FT BINDING 299 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:O75874" FT BINDING 314 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000250|UniProtKB:P33198" FT BINDING 349..354 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:O75874" FT BINDING 367 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:O75874" FT SITE 179 FT /note="Critical for catalysis" FT /evidence="ECO:0000250|UniProtKB:P33198" FT SITE 251 FT /note="Critical for catalysis" FT /evidence="ECO:0000250|UniProtKB:P33198" FT MOD_RES 45 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 48 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 67 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P48735" FT MOD_RES 69 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 80 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 80 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 106 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P48735" FT MOD_RES 106 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 155 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P48735" FT MOD_RES 166 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P48735" FT MOD_RES 166 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 180 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P48735" FT MOD_RES 180 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 193 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 193 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 199 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 256 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P48735" FT MOD_RES 256 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 263 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P48735" FT MOD_RES 272 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P48735" FT MOD_RES 275 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P48735" FT MOD_RES 280 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 282 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P48735" FT MOD_RES 282 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 384 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 384 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 400 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P54071" FT MOD_RES 413 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P48735" FT MOD_RES 442 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P48735" FT CONFLICT 49 FT /note="P -> K (in Ref. 2; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 52 FT /note="E -> V (in Ref. 2; AA sequence)" FT /evidence="ECO:0000305" SQ SEQUENCE 452 AA; 50967 MW; 2466E1CC2C2CE9D1 CRC64; MAGYLRAVSS LCRASGSTRT WAPAALNVPS WPEQPRRHYA EKRIKVEKPV VEMDGDEMTR IIWQFIKEKL ILPHVDVQLK YFDLGLPNRD QTNDQVTIDS ALATQKYSVA VKCATITPDE ARVEEFKLKK MWKSPNGTIR NILGGTVFRE PIICKNIPRL VPGWTKPITI GRHAHGDQYK ATDFVVDRAG MFKLVFTPKD GSGAKEWEVY NFPAGGVGMG MYNTDESISG FAHSCFQYSI QKKWPLYLST KNTIMKAYDG RFKDIFQEIF DKHYKTDFDK NKIWYEHRLI DDMVAQVLKS SGGFVWACKN YDGDVQSDIL AQGFGSLGLM TSVLVCPDGK TIEAEAAHGT VTRHYREHQK GRPTSTNPIA SIFAWTRGLE HRGKLDGNQD LIRFAQTLEK VCVQTVESGA MTKDLAGCIH GLSNVKLNEH FLNTTDFLDT IKSNLDRALG KQ //