IDHP_RAT
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 03-AUG-2022, entry version 142.
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}.
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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 iPTMnet; P56574; -.
DR PhosphoSitePlus; P56574; -.
DR jPOST; P56574; -.
DR PaxDb; P56574; -.
DR PRIDE; P56574; -.
DR GeneID; 361596; -.
DR KEGG; rno:361596; -.
DR UCSC; RGD:1597139; rat.
DR CTD; 3418; -.
DR RGD; 1597139; Idh2.
DR VEuPathDB; HostDB:ENSRNOG00000013949; -.
DR eggNOG; KOG1526; Eukaryota.
DR InParanoid; P56574; -.
DR OMA; IQKRWPL; -.
DR OrthoDB; 769322at2759; -.
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 tissues.
DR ExpressionAtlas; P56574; baseline and differential.
DR Genevisible; P56574; RN.
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: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: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 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; 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
