IDHP_HUMAN
ID IDHP_HUMAN Reviewed; 452 AA.
AC P48735; B2R6L6; B4DFL2; Q96GT3;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2002, sequence version 2.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Isocitrate dehydrogenase [NADP], mitochondrial;
DE Short=IDH;
DE EC=1.1.1.42 {ECO:0000269|PubMed:22416140, ECO:0000305|PubMed:19228619};
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RA Huh T.-L., Oh I.-U., Kim Y.O., Huh J.-W., Song B.J.;
RL Submitted (NOV-1992) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain cortex, Heart, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, and Skin;
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 [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-67; LYS-106; LYS-155; LYS-166;
RP LYS-180; LYS-256; LYS-263; LYS-272; LYS-275; LYS-282 AND LYS-442, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, ACETYLATION AT LYS-413, AND MUTAGENESIS OF
RP LYS-413.
RX PubMed=22416140; DOI=10.1074/jbc.m112.355206;
RA Yu W., Dittenhafer-Reed K.E., Denu J.M.;
RT "SIRT3 protein deacetylates isocitrate dehydrogenase 2 (IDH2) and regulates
RT mitochondrial redox status.";
RL J. Biol. Chem. 287:14078-14086(2012).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [11]
RP VARIANTS GLM GLY-172; LYS-172 AND MET-172, FUNCTION, CATALYTIC ACTIVITY,
RP AND CHARACTERIZATION OF VARIANTS GLM GLY-172; LYS-172 AND MET-172.
RX PubMed=19228619; DOI=10.1056/nejmoa0808710;
RA Yan H., Parsons D.W., Jin G., McLendon R., Rasheed B.A., Yuan W., Kos I.,
RA Batinic-Haberle I., Jones S., Riggins G.J., Friedman H., Friedman A.,
RA Reardon D., Herndon J., Kinzler K.W., Velculescu V.E., Vogelstein B.,
RA Bigner D.D.;
RT "IDH1 and IDH2 mutations in gliomas.";
RL N. Engl. J. Med. 360:765-773(2009).
RN [12]
RP VARIANTS D2HGA2 GLN-140 AND GLY-140.
RX PubMed=20847235; DOI=10.1126/science.1192632;
RA Kranendijk M., Struys E.A., van Schaftingen E., Gibson K.M., Kanhai W.A.,
RA van der Knaap M.S., Amiel J., Buist N.R., Das A.M., de Klerk J.B.,
RA Feigenbaum A.S., Grange D.K., Hofstede F.C., Holme E., Kirk E.P.,
RA Korman S.H., Morava E., Morris A., Smeitink J., Sukhai R.N., Vallance H.,
RA Jakobs C., Salomons G.S.;
RT "IDH2 mutations in patients with D-2-hydroxyglutaric aciduria.";
RL Science 330:336-336(2010).
RN [13]
RP VARIANTS GLM LEU-158; SER-162 AND LYS-172.
RX PubMed=25495392; DOI=10.1111/neup.12187;
RA Koh J., Cho H., Kim H., Kim S.I., Yun S., Park C.K., Lee S.H., Choi S.H.,
RA Park S.H.;
RT "IDH2 mutation in gliomas including novel mutation.";
RL Neuropathology 35:236-244(2015).
RN [14]
RP VARIANTS SER-172; THR-172 AND TRP-172, AND INVOLVEMENT IN DISEASE.
RX PubMed=26161668; DOI=10.1371/journal.pone.0131998;
RA Jin Y., Elalaf H., Watanabe M., Tamaki S., Hineno S., Matsunaga K.,
RA Woltjen K., Kobayashi Y., Nagata S., Ikeya M., Kato T. Jr., Okamoto T.,
RA Matsuda S., Toguchida J.;
RT "Mutant IDH1 Dysregulates the Differentiation of Mesenchymal Stem Cells in
RT Association with Gene-Specific Histone Modifications to Cartilage- and
RT Bone-Related Genes.";
RL PLoS ONE 10:E0131998-E0131998(2015).
CC -!- FUNCTION: Plays a role in intermediary metabolism and energy production
CC (PubMed:22416140, PubMed:19228619). It may tightly associate or
CC interact with the pyruvate dehydrogenase complex (PubMed:22416140,
CC PubMed:19228619). {ECO:0000269|PubMed:19228619,
CC ECO:0000269|PubMed:22416140}.
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:0000269|PubMed:22416140, ECO:0000305|PubMed:19228619};
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:0000250|UniProtKB:P33198}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P48735-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P48735-2; Sequence=VSP_056278;
CC -!- PTM: Acetylation at Lys-413 dramatically reduces catalytic activity.
CC Deacetylated by SIRT3. {ECO:0000269|PubMed:22416140}.
CC -!- DISEASE: D-2-hydroxyglutaric aciduria 2 (D2HGA2) [MIM:613657]: A
CC neurometabolic disorder causing developmental delay, epilepsy,
CC hypotonia, and dysmorphic features. Both a mild and a severe phenotype
CC exist. The severe phenotype is homogeneous and is characterized by
CC early infantile-onset epileptic encephalopathy and cardiomyopathy. The
CC mild phenotype has a more variable clinical presentation. Diagnosis is
CC based on the presence of an excess of D-2-hydroxyglutaric acid in the
CC urine. {ECO:0000269|PubMed:20847235}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Glioma (GLM) [MIM:137800]: Gliomas are benign or malignant
CC central nervous system neoplasms derived from glial cells. They
CC comprise astrocytomas and glioblastoma multiforme that are derived from
CC astrocytes, oligodendrogliomas derived from oligodendrocytes and
CC ependymomas derived from ependymocytes. {ECO:0000269|PubMed:19228619,
CC ECO:0000269|PubMed:25495392}. Note=The gene represented in this entry
CC is involved in disease pathogenesis.
CC -!- DISEASE: Note=enetic variations are associated with cartilaginous
CC tumors such as enchondroma or chondrosarcoma.
CC {ECO:0000269|PubMed:26161668}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
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DR EMBL; X69433; CAA49208.1; -; mRNA.
DR EMBL; AK294148; BAG57473.1; -; mRNA.
DR EMBL; AK312627; BAG35513.1; -; mRNA.
DR EMBL; AK316388; BAH14759.1; -; mRNA.
DR EMBL; AC087284; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092769; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471101; EAX02082.1; -; Genomic_DNA.
DR EMBL; BC009244; AAH09244.1; -; mRNA.
DR EMBL; BC071828; AAH71828.1; -; mRNA.
DR CCDS; CCDS10359.1; -. [P48735-1]
DR CCDS; CCDS76792.1; -. [P48735-2]
DR PIR; S57499; S57499.
DR RefSeq; NP_001276839.1; NM_001289910.1. [P48735-2]
DR RefSeq; NP_001277043.1; NM_001290114.1.
DR RefSeq; NP_002159.2; NM_002168.3. [P48735-1]
DR PDB; 4JA8; X-ray; 1.55 A; A/B=41-452.
DR PDB; 5GIS; X-ray; 1.93 A; C=165-180.
DR PDB; 5I95; X-ray; 1.54 A; A=40-452.
DR PDB; 5I96; X-ray; 1.55 A; A/B=1-452.
DR PDB; 5SVN; X-ray; 2.10 A; A/B=40-452.
DR PDB; 5SVO; X-ray; 1.87 A; A/B=40-452.
DR PDB; 6ADI; X-ray; 1.97 A; A/B=41-452.
DR PDB; 6UJ7; X-ray; 1.90 A; C/F=134-143.
DR PDB; 6UJ8; X-ray; 2.25 A; C/F=134-143.
DR PDB; 6UJ9; X-ray; 2.90 A; C=134-143.
DR PDB; 6VFZ; X-ray; 1.99 A; A/B=1-452.
DR PDBsum; 4JA8; -.
DR PDBsum; 5GIS; -.
DR PDBsum; 5I95; -.
DR PDBsum; 5I96; -.
DR PDBsum; 5SVN; -.
DR PDBsum; 5SVO; -.
DR PDBsum; 6ADI; -.
DR PDBsum; 6UJ7; -.
DR PDBsum; 6UJ8; -.
DR PDBsum; 6UJ9; -.
DR PDBsum; 6VFZ; -.
DR AlphaFoldDB; P48735; -.
DR SMR; P48735; -.
DR BioGRID; 109644; 233.
DR CORUM; P48735; -.
DR DIP; DIP-61416N; -.
DR IntAct; P48735; 25.
DR MINT; P48735; -.
DR STRING; 9606.ENSP00000331897; -.
DR BindingDB; P48735; -.
DR ChEMBL; CHEMBL3991501; -.
DR DrugBank; DB13874; Enasidenib.
DR DrugBank; DB01727; Isocitric Acid.
DR DrugCentral; P48735; -.
DR CarbonylDB; P48735; -.
DR GlyGen; P48735; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P48735; -.
DR MetOSite; P48735; -.
DR PhosphoSitePlus; P48735; -.
DR SwissPalm; P48735; -.
DR BioMuta; IDH2; -.
DR DMDM; 20141568; -.
DR OGP; P48735; -.
DR UCD-2DPAGE; P48735; -.
DR CPTAC; CPTAC-221; -.
DR CPTAC; CPTAC-222; -.
DR EPD; P48735; -.
DR jPOST; P48735; -.
DR MassIVE; P48735; -.
DR MaxQB; P48735; -.
DR PaxDb; P48735; -.
DR PeptideAtlas; P48735; -.
DR PRIDE; P48735; -.
DR ProteomicsDB; 4054; -.
DR ProteomicsDB; 55932; -. [P48735-1]
DR ABCD; P48735; 1 sequenced antibody.
DR Antibodypedia; 15858; 476 antibodies from 44 providers.
DR DNASU; 3418; -.
DR Ensembl; ENST00000330062.8; ENSP00000331897.4; ENSG00000182054.10. [P48735-1]
DR Ensembl; ENST00000540499.2; ENSP00000446147.2; ENSG00000182054.10. [P48735-2]
DR GeneID; 3418; -.
DR KEGG; hsa:3418; -.
DR MANE-Select; ENST00000330062.8; ENSP00000331897.4; NM_002168.4; NP_002159.2.
DR UCSC; uc002box.4; human. [P48735-1]
DR CTD; 3418; -.
DR DisGeNET; 3418; -.
DR GeneCards; IDH2; -.
DR HGNC; HGNC:5383; IDH2.
DR HPA; ENSG00000182054; Group enriched (skeletal muscle, tongue).
DR MalaCards; IDH2; -.
DR MIM; 137800; phenotype.
DR MIM; 147650; gene.
DR MIM; 613657; phenotype.
DR neXtProt; NX_P48735; -.
DR OpenTargets; ENSG00000182054; -.
DR Orphanet; 251589; Anaplastic astrocytoma.
DR Orphanet; 251663; Anaplastic oligoastrocytoma.
DR Orphanet; 251630; Anaplastic oligodendroglioma.
DR Orphanet; 79315; D-2-hydroxyglutaric aciduria.
DR Orphanet; 251601; Fibrillary astrocytoma.
DR Orphanet; 251604; Gemistocytic astrocytoma.
DR Orphanet; 163634; Maffucci syndrome.
DR Orphanet; 251656; Oligoastrocytoma.
DR Orphanet; 251627; Oligodendroglioma.
DR Orphanet; 296; Ollier disease.
DR Orphanet; 251598; Protoplasmic astrocytoma.
DR PharmGKB; PA29631; -.
DR VEuPathDB; HostDB:ENSG00000182054; -.
DR eggNOG; KOG1526; Eukaryota.
DR GeneTree; ENSGT00390000012547; -.
DR HOGENOM; CLU_023296_1_1_1; -.
DR InParanoid; P48735; -.
DR OMA; IQKRWPL; -.
DR OrthoDB; 1029485at2759; -.
DR PhylomeDB; P48735; -.
DR TreeFam; TF300428; -.
DR BioCyc; MetaCyc:HS00021-MON; -.
DR BRENDA; 1.1.1.42; 2681.
DR PathwayCommons; P48735; -.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-HSA-71403; Citric acid cycle (TCA cycle).
DR SABIO-RK; P48735; -.
DR SignaLink; P48735; -.
DR SIGNOR; P48735; -.
DR BioGRID-ORCS; 3418; 12 hits in 1080 CRISPR screens.
DR ChiTaRS; IDH2; human.
DR GeneWiki; IDH2; -.
DR GenomeRNAi; 3418; -.
DR Pharos; P48735; Tclin.
DR PRO; PR:P48735; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P48735; protein.
DR Bgee; ENSG00000182054; Expressed in apex of heart and 208 other tissues.
DR ExpressionAtlas; P48735; baseline and differential.
DR Genevisible; P48735; HS.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005777; C:peroxisome; IEA:Ensembl.
DR GO; GO:0004450; F:isocitrate dehydrogenase (NADP+) activity; IDA:CACAO.
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:0005975; P:carbohydrate metabolic process; NAS:ProtInc.
DR GO; GO:0006097; P:glyoxylate cycle; IEA:UniProtKB-KW.
DR GO; GO:0006102; P:isocitrate metabolic process; ISS:UniProtKB.
DR GO; GO:0006739; P:NADP metabolic process; IBA:GO_Central.
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 3D-structure; Acetylation; Alternative splicing; Disease variant;
KW Glyoxylate bypass; Magnesium; Manganese; Metal-binding; Mitochondrion;
KW NADP; Oxidoreductase; Reference proteome; Transit peptide;
KW Tricarboxylic acid cycle.
FT TRANSIT 1..39
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P56574"
FT CHAIN 40..452
FT /note="Isocitrate dehydrogenase [NADP], mitochondrial"
FT /id="PRO_0000014420"
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:0007744|PubMed:19608861"
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:0007744|PubMed:19608861"
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:0007744|PubMed:19608861"
FT MOD_RES 166
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
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:0007744|PubMed:19608861"
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:0007744|PubMed:19608861"
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:0007744|PubMed:19608861"
FT MOD_RES 272
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 275
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
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:0007744|PubMed:19608861"
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:0000269|PubMed:22416140"
FT MOD_RES 442
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..52
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056278"
FT VARIANT 140
FT /note="R -> G (in D2HGA2; dbSNP:rs267606870)"
FT /evidence="ECO:0000269|PubMed:20847235"
FT /id="VAR_065174"
FT VARIANT 140
FT /note="R -> Q (in D2HGA2; dbSNP:rs121913502)"
FT /evidence="ECO:0000269|PubMed:20847235"
FT /id="VAR_065175"
FT VARIANT 158
FT /note="P -> L (in GLM; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:25495392"
FT /id="VAR_073181"
FT VARIANT 162
FT /note="P -> S (in GLM; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:25495392"
FT /id="VAR_073182"
FT VARIANT 172
FT /note="R -> G (in GLM; somatic mutation; reduces enzymatic
FT activity; dbSNP:rs1057519906)"
FT /evidence="ECO:0000269|PubMed:19228619"
FT /id="VAR_073183"
FT VARIANT 172
FT /note="R -> K (in GLM; somatic mutation; reduces enzymatic
FT activity; dbSNP:rs121913503)"
FT /evidence="ECO:0000269|PubMed:19228619,
FT ECO:0000269|PubMed:25495392"
FT /id="VAR_073184"
FT VARIANT 172
FT /note="R -> M (in GLM; somatic mutation; reduces enzymatic
FT activity; dbSNP:rs121913503)"
FT /evidence="ECO:0000269|PubMed:19228619"
FT /id="VAR_073185"
FT VARIANT 172
FT /note="R -> S (found in patients with cartilagenous tumors;
FT dbSNP:rs1057519736)"
FT /evidence="ECO:0000269|PubMed:26161668"
FT /id="VAR_076512"
FT VARIANT 172
FT /note="R -> T (found in patients with cartilagenous
FT tumors)"
FT /evidence="ECO:0000269|PubMed:26161668"
FT /id="VAR_076513"
FT VARIANT 172
FT /note="R -> W (found in patients with cartilagenous tumors;
FT dbSNP:rs1057519906)"
FT /evidence="ECO:0000269|PubMed:26161668"
FT /id="VAR_076514"
FT MUTAGEN 413
FT /note="K->A: 44-fold loss in activity."
FT /evidence="ECO:0000269|PubMed:22416140"
FT MUTAGEN 413
FT /note="K->Q: 20-fold decrease in Vmax."
FT /evidence="ECO:0000269|PubMed:22416140"
FT MUTAGEN 413
FT /note="K->R: No appreciable difference in Km for isocitrate
FT and NADP."
FT /evidence="ECO:0000269|PubMed:22416140"
FT CONFLICT 34
FT /note="Q -> H (in Ref. 1; CAA49208)"
FT /evidence="ECO:0000305"
FT CONFLICT 435
FT /note="T -> M (in Ref. 1; CAA49208)"
FT /evidence="ECO:0000305"
FT STRAND 50..54
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 57..69
FT /evidence="ECO:0007829|PDB:5I95"
FT TURN 70..74
FT /evidence="ECO:0007829|PDB:5I95"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 86..91
FT /evidence="ECO:0007829|PDB:5I95"
FT TURN 92..94
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 95..107
FT /evidence="ECO:0007829|PDB:5I95"
FT STRAND 108..112
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 120..126
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 135..143
FT /evidence="ECO:0007829|PDB:5I95"
FT STRAND 146..151
FT /evidence="ECO:0007829|PDB:5I95"
FT STRAND 169..173
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 177..180
FT /evidence="ECO:0007829|PDB:5I95"
FT STRAND 182..186
FT /evidence="ECO:0007829|PDB:5I95"
FT STRAND 190..196
FT /evidence="ECO:0007829|PDB:5I95"
FT STRAND 205..214
FT /evidence="ECO:0007829|PDB:5I95"
FT STRAND 216..220
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 225..242
FT /evidence="ECO:0007829|PDB:5I95"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:5I95"
FT TURN 252..254
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 258..273
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 275..280
FT /evidence="ECO:0007829|PDB:5I95"
FT STRAND 285..289
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 290..299
FT /evidence="ECO:0007829|PDB:5I95"
FT STRAND 304..308
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 310..324
FT /evidence="ECO:0007829|PDB:5I95"
FT STRAND 329..335
FT /evidence="ECO:0007829|PDB:5I95"
FT STRAND 342..345
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 352..359
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 369..386
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 389..407
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 413..420
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 422..424
FT /evidence="ECO:0007829|PDB:5I95"
FT TURN 427..429
FT /evidence="ECO:0007829|PDB:5I95"
FT HELIX 434..449
FT /evidence="ECO:0007829|PDB:5I95"
SQ SEQUENCE 452 AA; 50909 MW; 4DDC830AFC06AB52 CRC64;
MAGYLRVVRS LCRASGSRPA WAPAALTAPT SQEQPRRHYA DKRIKVAKPV VEMDGDEMTR
IIWQFIKEKL ILPHVDIQLK YFDLGLPNRD QTDDQVTIDS ALATQKYSVA VKCATITPDE
ARVEEFKLKK MWKSPNGTIR NILGGTVFRE PIICKNIPRL VPGWTKPITI GRHAHGDQYK
ATDFVADRAG TFKMVFTPKD GSGVKEWEVY NFPAGGVGMG MYNTDESISG FAHSCFQYAI
QKKWPLYMST KNTILKAYDG RFKDIFQEIF DKHYKTDFDK NKIWYEHRLI DDMVAQVLKS
SGGFVWACKN YDGDVQSDIL AQGFGSLGLM TSVLVCPDGK TIEAEAAHGT VTRHYREHQK
GRPTSTNPIA SIFAWTRGLE HRGKLDGNQD LIRFAQMLEK VCVETVESGA MTKDLAGCIH
GLSNVKLNEH FLNTTDFLDT IKSNLDRALG RQ
