IDHC_MICME
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 03-AUG-2022, entry version 93.
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 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 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
