IDHC_PONAB
ID IDHC_PONAB Reviewed; 414 AA.
AC Q5R9C5; Q5RET8;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 109.
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;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). Plays a critical role in the generation of
CC 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}.
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; CR857428; CAH89719.1; -; mRNA.
DR EMBL; CR859464; CAH91635.1; -; mRNA.
DR RefSeq; NP_001124781.1; NM_001131309.1.
DR RefSeq; XP_009236322.1; XM_009238047.1.
DR RefSeq; XP_009236323.1; XM_009238048.1.
DR RefSeq; XP_009236324.1; XM_009238049.1.
DR AlphaFoldDB; Q5R9C5; -.
DR SMR; Q5R9C5; -.
DR STRING; 9601.ENSPPYP00000014668; -.
DR PRIDE; Q5R9C5; -.
DR Ensembl; ENSPPYT00000015262; ENSPPYP00000014668; ENSPPYG00000013125.
DR GeneID; 100171634; -.
DR KEGG; pon:100171634; -.
DR CTD; 3417; -.
DR eggNOG; KOG1526; Eukaryota.
DR GeneTree; ENSGT00390000012547; -.
DR HOGENOM; CLU_023296_1_1_1; -.
DR InParanoid; Q5R9C5; -.
DR OMA; HGTVQRH; -.
DR OrthoDB; 769322at2759; -.
DR TreeFam; TF300428; -.
DR Proteomes; UP000001595; Chromosome 2B.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005777; C:peroxisome; IEA:Ensembl.
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:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0006103; P:2-oxoglutarate metabolic process; ISS:UniProtKB.
DR GO; GO:0006749; P:glutathione metabolic process; IEA:Ensembl.
DR GO; GO:0006097; P:glyoxylate cycle; IEA:UniProtKB-KW.
DR GO; GO:0006102; P:isocitrate metabolic process; ISS:UniProtKB.
DR GO; GO:0071071; P:regulation of phospholipid biosynthetic process; IEA:Ensembl.
DR GO; GO:0060696; P:regulation of phospholipid catabolic process; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
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; Reference proteome;
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_0000236187"
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"
FT CONFLICT 25
FT /note="L -> Q (in Ref. 1; CAH89719)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="I -> T (in Ref. 1; CAH91635)"
FT /evidence="ECO:0000305"
FT CONFLICT 331
FT /note="A -> V (in Ref. 1; CAH91635)"
FT /evidence="ECO:0000305"
FT CONFLICT 411
FT /note="Q -> L (in Ref. 1; CAH89719)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 414 AA; 46699 MW; 73CB3A9AC5E411BA CRC64;
MSKKISGGSV VEMQGDEMTR IIWELIKEKL IFPYVELDLH SYDLGIENRD ATNDQVTKDA
AEAIKKYNVG VKCATITPDE KRVEEFKLKQ MWKSPNGTIR NILGGTVFRE AIICKNIPRL
VSGWVKPIII GRHAYGDQYR ATDFVVPGPG KVEITYTPSD GTQKVTYLVH NFEEGGGVAM
GMYNQDKSIE DFAHSSFQMA LSKGWPLYLS TKNTILKKYD GRFKDIFQEI YDKQYKSQFE
ARKIWYEHRL IDDMVAQAMK SEGGFIWACK NYDGDVQSDS VAQGYGSLGM MTSVLVCPDG
KTVEAEAAHG TVTRHYRMYQ KGQETSTNPI ASIFAWTRGL AHRAKLDNNK ELAFFANALE
EVSVETIEAG FMTKDLAACI KGLPNVQRSD YLNTFEFMDK LGENLKIKLA QAKL
