ID   IDH3G_HUMAN             Reviewed;         393 AA.
AC   P51553; E9PDD5; Q9BUU5;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   27-MAR-2024, entry version 223.
DE   RecName: Full=Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial;
DE   AltName: Full=Isocitric dehydrogenase subunit gamma;
DE   AltName: Full=NAD(+)-specific ICDH subunit gamma;
DE   Flags: Precursor;
GN   Name=IDH3G;
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 [GENOMIC DNA / MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=9286695; DOI=10.1006/geno.1997.4822;
RA   Brenner V., Nyakatura G., Rosenthal A., Platzer M.;
RT   "Genomic organization of two novel genes on human Xq28: compact head to
RT   head arrangement of IDH gamma and TRAP delta is conserved in rat and
RT   mouse.";
RL   Genomics 44:8-14(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Heart;
RX   PubMed=10601238; DOI=10.1074/jbc.274.52.36866;
RA   Kim Y.-O., Koh H.-J., Kim S.-H., Jo S.-H., Huh J.-W., Jeong K.-S.,
RA   Lee I.J., Song B.J., Huh T.-L.;
RT   "Identification and functional characterization of a novel, tissue-specific
RT   NAD+-dependent isocitrate dehydrogenase beta subunit isoform.";
RL   J. Biol. Chem. 274:36866-36875(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15772651; DOI=10.1038/nature03440;
RA   Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA   Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA   Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA   Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA   Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA   Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA   Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA   Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA   Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA   Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA   Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA   Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA   Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA   Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA   Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA   Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA   Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA   Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA   Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA   Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA   Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA   Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA   Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA   Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA   Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA   Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA   Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA   Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA   Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA   McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA   Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA   Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA   Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA   Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA   Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA   Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA   Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA   Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA   Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA   d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA   Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA   Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA   Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA   Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA   Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA   Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA   Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA   Rogers J., Bentley D.R.;
RT   "The DNA sequence of the human X chromosome.";
RL   Nature 434:325-337(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Placenta, 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   [5]
RP   SUBCELLULAR LOCATION.
RX   PubMed=11256614; DOI=10.1093/embo-reports/kvd058;
RA   Simpson J.C., Wellenreuther R., Poustka A., Pepperkok R., Wiemann S.;
RT   "Systematic subcellular localization of novel proteins identified by large-
RT   scale cDNA sequencing.";
RL   EMBO Rep. 1:287-292(2000).
RN   [6]
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   [7]
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   [8]
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   [9]
RP   FUNCTION, SUBUNIT, ACTIVITY REGULATION, COFACTOR, AND MUTAGENESIS OF
RP   LYS-190.
RX   PubMed=28139779; DOI=10.1038/srep41882;
RA   Ma T., Peng Y., Huang W., Liu Y., Ding J.;
RT   "The beta and gamma subunits play distinct functional roles in the
RT   alpha2betagamma heterotetramer of human NAD-dependent isocitrate
RT   dehydrogenase.";
RL   Sci. Rep. 7:41882-41882(2017).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 40-393 IN COMPLEX WITH MAGNESIUM
RP   AND CITRATE, X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 40-393 OF MUTANT
RP   ALA-190 IN COMPLEX WITH MAGNESIUM; ADP AND CITRATE, SUBUNIT, COFACTOR,
RP   ACTIVITY REGULATION, ALLOSTERIC ACTIVATION, AND MUTAGENESIS OF ASN-117;
RP   THR-120; SER-130; ASN-133; ARG-136; ARG-167; GLU-173; TYR-174; LYS-190;
RP   ASP-229; TYR-276; ARG-311; ASN-312; THR-313; LYS-315 AND ASN-324.
RX   PubMed=28098230; DOI=10.1038/srep40921;
RA   Ma T., Peng Y., Huang W., Ding J.;
RT   "Molecular mechanism of the allosteric regulation of the alphagamma
RT   heterodimer of human NAD-dependent isocitrate dehydrogenase.";
RL   Sci. Rep. 7:40921-40921(2017).
CC   -!- FUNCTION: Regulatory subunit which plays a role in the allosteric
CC       regulation of the enzyme catalyzing the decarboxylation of isocitrate
CC       (ICT) into alpha-ketoglutarate. The heterodimer composed of the alpha
CC       (IDH3A) and beta (IDH3B) subunits and the heterodimer composed of the
CC       alpha (IDH3A) and gamma (IDH3G) subunits, have considerable basal
CC       activity but the full activity of the heterotetramer (containing two
CC       subunits of IDH3A, one of IDH3B and one of IDH3G) requires the assembly
CC       and cooperative function of both heterodimers.
CC       {ECO:0000269|PubMed:28139779}.
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:28098230, ECO:0000269|PubMed:28139779};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000269|PubMed:28139779};
CC       Note=Divalent metal cations; Mn(2+) or Mg(2+). Activity higher in
CC       presence of Mn(2+) than of Mg(2+). Binds 1 Mg(2+) or Mn(2+) ion per
CC       subunit. {ECO:0000269|PubMed:28139779};
CC   -!- ACTIVITY REGULATION: The heterotetramer and the heterodimer composed of
CC       IDH3A and IDH3G subunits can be allosterically activated by citrate
CC       (CIT) or/and ADP, and the two activators can act independently or
CC       synergistically. The heterodimer composed of IDH3A and IDH3B subunits
CC       cannot be allosterically regulated and the allosteric regulation of the
CC       heterotetramer is through the IDH3G subunit and not the IDH3B subunit.
CC       The IDH3G subunit contains the allosteric site which consists of a CIT-
CC       binding site and an ADP-binding site, and the binding of CIT and ADP
CC       causes conformational changes at the allosteric site which are
CC       transmitted to the active site in the catalytic subunit (IDH3A) through
CC       a cascade of conformational changes at the heterodimer interface,
CC       leading to stabilization of the isocitrate-binding at the active site
CC       and thus activation of the enzyme. ATP can activate the heterotetramer
CC       and the heterodimer composed of IDH3A and IDH3G subunits at low
CC       concentrations but inhibits their activities at high concentrations,
CC       whereas ATP exhibits only inhibitory effect on the heterodimer composed
CC       of IDH3A and IDH3B subunits. {ECO:0000269|PubMed:28098230,
CC       ECO:0000269|PubMed:28139779}.
CC   -!- SUBUNIT: Heterooligomer of subunits alpha (IDH3A), beta (IDH3B), and
CC       gamma (IDH3G) in the apparent ratio of 2:1:1. The heterodimer
CC       containing one IDH3A and one IDH3B subunit and the heterodimer
CC       containing one IDH3A and one IDH3G subunit assemble into a
CC       heterotetramer (which contains two subunits of IDH3A, one of IDH3B and
CC       one of IDH3G) and further into the heterooctamer.
CC       {ECO:0000269|PubMed:28098230, ECO:0000269|PubMed:28139779}.
CC   -!- INTERACTION:
CC       P51553; P50213: IDH3A; NbExp=5; IntAct=EBI-1210876, EBI-355999;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:11256614}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P51553-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P51553-2; Sequence=VSP_046771;
CC   -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC       dehydrogenases family. {ECO:0000305}.
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DR   EMBL; Z68907; CAA93143.1; -; mRNA.
DR   EMBL; Z68129; CAA92214.1; -; Genomic_DNA.
DR   EMBL; U52111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; U40272; AAD09357.1; -; mRNA.
DR   EMBL; BC000933; AAH00933.1; -; mRNA.
DR   EMBL; BC001902; AAH01902.1; -; mRNA.
DR   CCDS; CCDS14730.1; -. [P51553-1]
DR   CCDS; CCDS44019.1; -. [P51553-2]
DR   RefSeq; NP_004126.1; NM_004135.3. [P51553-1]
DR   RefSeq; NP_777358.1; NM_174869.2. [P51553-2]
DR   PDB; 5GRE; X-ray; 2.65 A; B=40-393.
DR   PDB; 5GRF; X-ray; 2.50 A; B=40-393.
DR   PDB; 5GRH; X-ray; 2.80 A; B=40-393.
DR   PDB; 5GRI; X-ray; 2.31 A; B=40-393.
DR   PDB; 5GRL; X-ray; 2.79 A; B=40-393.
DR   PDB; 5YVT; X-ray; 2.40 A; B=40-393.
DR   PDB; 6L57; X-ray; 2.30 A; B=40-393.
DR   PDB; 6L59; X-ray; 2.25 A; B=40-393.
DR   PDB; 7CE3; X-ray; 3.47 A; B=40-393.
DR   PDB; 8GRG; X-ray; 2.70 A; B=40-393.
DR   PDB; 8GRH; X-ray; 2.51 A; B=40-393.
DR   PDB; 8GS5; X-ray; 4.49 A; D/H/L/P=40-393.
DR   PDBsum; 5GRE; -.
DR   PDBsum; 5GRF; -.
DR   PDBsum; 5GRH; -.
DR   PDBsum; 5GRI; -.
DR   PDBsum; 5GRL; -.
DR   PDBsum; 5YVT; -.
DR   PDBsum; 6L57; -.
DR   PDBsum; 6L59; -.
DR   PDBsum; 7CE3; -.
DR   PDBsum; 8GRG; -.
DR   PDBsum; 8GRH; -.
DR   PDBsum; 8GS5; -.
DR   AlphaFoldDB; P51553; -.
DR   SMR; P51553; -.
DR   BioGRID; 109647; 66.
DR   ComplexPortal; CPX-553; Mitochondrial isocitrate dehydrogenase complex (NAD+).
DR   CORUM; P51553; -.
DR   IntAct; P51553; 11.
DR   MINT; P51553; -.
DR   STRING; 9606.ENSP00000217901; -.
DR   DrugBank; DB06757; Manganese.
DR   DrugBank; DB00157; NADH.
DR   GlyGen; P51553; 3 sites, 1 O-linked glycan (3 sites).
DR   iPTMnet; P51553; -.
DR   PhosphoSitePlus; P51553; -.
DR   SwissPalm; P51553; -.
DR   BioMuta; IDH3G; -.
DR   DMDM; 1708404; -.
DR   EPD; P51553; -.
DR   jPOST; P51553; -.
DR   MassIVE; P51553; -.
DR   MaxQB; P51553; -.
DR   PaxDb; 9606-ENSP00000217901; -.
DR   PeptideAtlas; P51553; -.
DR   ProteomicsDB; 19639; -.
DR   ProteomicsDB; 56332; -. [P51553-1]
DR   Pumba; P51553; -.
DR   Antibodypedia; 408; 283 antibodies from 32 providers.
DR   DNASU; 3421; -.
DR   Ensembl; ENST00000217901.10; ENSP00000217901.5; ENSG00000067829.20. [P51553-1]
DR   Ensembl; ENST00000370092.7; ENSP00000359110.3; ENSG00000067829.20. [P51553-2]
DR   GeneID; 3421; -.
DR   KEGG; hsa:3421; -.
DR   MANE-Select; ENST00000217901.10; ENSP00000217901.5; NM_004135.4; NP_004126.1.
DR   UCSC; uc004fip.4; human. [P51553-1]
DR   AGR; HGNC:5386; -.
DR   CTD; 3421; -.
DR   GeneCards; IDH3G; -.
DR   HGNC; HGNC:5386; IDH3G.
DR   HPA; ENSG00000067829; Low tissue specificity.
DR   MIM; 300089; gene.
DR   neXtProt; NX_P51553; -.
DR   OpenTargets; ENSG00000067829; -.
DR   PharmGKB; PA29634; -.
DR   VEuPathDB; HostDB:ENSG00000067829; -.
DR   eggNOG; KOG0784; Eukaryota.
DR   GeneTree; ENSGT00950000182989; -.
DR   InParanoid; P51553; -.
DR   OMA; PWSCDYY; -.
DR   OrthoDB; 143577at2759; -.
DR   PhylomeDB; P51553; -.
DR   TreeFam; TF315033; -.
DR   BioCyc; MetaCyc:ENSG00000067829-MONOMER; -.
DR   BRENDA; 1.1.1.41; 2681.
DR   PathwayCommons; P51553; -.
DR   Reactome; R-HSA-1268020; Mitochondrial protein import.
DR   Reactome; R-HSA-71403; Citric acid cycle (TCA cycle).
DR   SABIO-RK; P51553; -.
DR   SignaLink; P51553; -.
DR   SIGNOR; P51553; -.
DR   BioGRID-ORCS; 3421; 8 hits in 788 CRISPR screens.
DR   ChiTaRS; IDH3G; human.
DR   GeneWiki; IDH3G; -.
DR   GenomeRNAi; 3421; -.
DR   Pharos; P51553; Tbio.
DR   PRO; PR:P51553; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; P51553; Protein.
DR   Bgee; ENSG00000067829; Expressed in right hemisphere of cerebellum and 210 other cell types or tissues.
DR   ExpressionAtlas; P51553; baseline and differential.
DR   GO; GO:0005962; C:mitochondrial isocitrate dehydrogenase complex (NAD+); IPI:ComplexPortal.
DR   GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; IDA:LIFEdb.
DR   GO; GO:0005730; C:nucleolus; IDA:HPA.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004449; F:isocitrate dehydrogenase (NAD+) activity; ISS:UniProtKB.
DR   GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR   GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR   GO; GO:0005975; P:carbohydrate metabolic process; NAS:ProtInc.
DR   GO; GO:0006102; P:isocitrate metabolic process; ISS:UniProtKB.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IDA:ComplexPortal.
DR   Gene3D; 3.40.718.10; Isopropylmalate Dehydrogenase; 1.
DR   InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR   InterPro; IPR004434; Isocitrate_DH_NAD.
DR   InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR   NCBIfam; TIGR00175; mito_nad_idh; 1.
DR   PANTHER; PTHR11835; DECARBOXYLATING DEHYDROGENASES-ISOCITRATE, ISOPROPYLMALATE, TARTRATE; 1.
DR   PANTHER; PTHR11835:SF42; ISOCITRATE DEHYDROGENASE [NAD] SUBUNIT GAMMA, MITOCHONDRIAL; 1.
DR   Pfam; PF00180; Iso_dh; 1.
DR   SMART; SM01329; Iso_dh; 1.
DR   SUPFAM; SSF53659; Isocitrate/Isopropylmalate dehydrogenase-like; 1.
DR   PROSITE; PS00470; IDH_IMDH; 1.
DR   Genevisible; P51553; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ATP-binding; Magnesium; Manganese;
KW   Metal-binding; Mitochondrion; Nucleotide-binding; Reference proteome;
KW   Transit peptide; Tricarboxylic acid cycle.
FT   TRANSIT         1..39
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250"
FT   CHAIN           40..393
FT                   /note="Isocitrate dehydrogenase [NAD] subunit gamma,
FT                   mitochondrial"
FT                   /id="PRO_0000014449"
FT   BINDING         120
FT                   /ligand="citrate"
FT                   /ligand_id="ChEBI:CHEBI:16947"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   BINDING         133
FT                   /ligand="citrate"
FT                   /ligand_id="ChEBI:CHEBI:16947"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   BINDING         136
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   BINDING         167
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   BINDING         254
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_note="ligand shared with catalytic subunit"
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   BINDING         254
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   BINDING         312
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   BINDING         313
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   BINDING         324
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   VAR_SEQ         361..393
FT                   /note="MHTPDIGGQGTTSEAIQDVIRHIRVINGRAVEA -> VRFPSHPTLLPRPVS
FT                   PCSLL (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_046771"
FT   MUTAGEN         117
FT                   /note="N->A: No effect on the activation of the heterodimer
FT                   composed of IDH3A and IDH3G subunits by citrate."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   MUTAGEN         120
FT                   /note="T->A: Significantly impairs the activation of the
FT                   heterodimer composed of IDH3A and IDH3G subunits by
FT                   citrate."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   MUTAGEN         130
FT                   /note="S->A: No significant effect on the activation of the
FT                   heterodimer composed of IDH3A and IDH3G subunits by
FT                   citrate."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   MUTAGEN         133
FT                   /note="N->A: Significantly impairs the activation of the
FT                   heterodimer composed of IDH3A and IDH3G subunits by
FT                   citrate."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   MUTAGEN         136
FT                   /note="R->A: Significantly impairs the activation of the
FT                   heterodimer composed of IDH3A and IDH3G subunits by
FT                   citrate."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   MUTAGEN         167
FT                   /note="R->A: Significantly impairs the activation of the
FT                   heterodimer composed of IDH3A and IDH3G subunits by
FT                   citrate."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   MUTAGEN         173
FT                   /note="E->A: No effect on the activation of the heterodimer
FT                   composed of IDH3A and IDH3G subunits by citrate and ADP."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   MUTAGEN         174
FT                   /note="Y->F: Significantly impairs the activation of the
FT                   heterodimer composed of IDH3A and IDH3G subunits by
FT                   citrate."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   MUTAGEN         190
FT                   /note="K->A: Complete loss of the activation of the
FT                   heterotetramer and the heterodimer composed of IDH3A and
FT                   IDH3G subunits by citrate and ADP."
FT                   /evidence="ECO:0000269|PubMed:28098230,
FT                   ECO:0000269|PubMed:28139779"
FT   MUTAGEN         229
FT                   /note="D->A: Significantly impairs the activation of the
FT                   heterodimer composed of IDH3A and IDH3G subunits by citrate
FT                   and ADP."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   MUTAGEN         276
FT                   /note="Y->F: Significantly impairs the activation of the
FT                   heterodimer composed of IDH3A and IDH3G subunits by citrate
FT                   and ADP."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   MUTAGEN         311
FT                   /note="R->A: Significantly impairs the activation of the
FT                   heterodimer composed of IDH3A and IDH3G subunits by
FT                   citrate."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   MUTAGEN         312
FT                   /note="N->A: Significantly impairs the activation of the
FT                   heterodimer composed of IDH3A and IDH3G subunits by ADP."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   MUTAGEN         313
FT                   /note="T->A: Significantly impairs the activation of the
FT                   heterodimer composed of IDH3A and IDH3G subunits by ADP."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   MUTAGEN         315
FT                   /note="K->A: No significant effect on the activation of the
FT                   heterodimer composed of IDH3A and IDH3G subunits by ADP."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   MUTAGEN         324
FT                   /note="N->A: Complete loss of the activation of the
FT                   heterodimer composed of IDH3A and IDH3G subunits by ADP."
FT                   /evidence="ECO:0000269|PubMed:28098230"
FT   CONFLICT        267
FT                   /note="F -> L (in Ref. 4; AAH01902)"
FT                   /evidence="ECO:0000305"
FT   STRAND          55..60
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   HELIX           66..79
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   STRAND          83..88
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   STRAND          95..97
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   HELIX           98..110
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   STRAND          111..115
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   HELIX           131..138
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   STRAND          143..149
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   STRAND          152..154
FT                   /evidence="ECO:0007829|PDB:5GRH"
FT   STRAND          162..168
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   STRAND          170..172
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   STRAND          178..182
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   STRAND          185..193
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   HELIX           194..210
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   STRAND          215..220
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   TURN            222..224
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   HELIX           228..240
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   STRAND          246..252
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   HELIX           253..260
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   HELIX           264..266
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   STRAND          268..272
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   HELIX           274..288
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   TURN            291..293
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   STRAND          295..299
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   STRAND          304..308
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   HELIX           315..317
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   TURN            318..321
FT                   /evidence="ECO:0007829|PDB:6L57"
FT   HELIX           326..338
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   HELIX           342..356
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   HELIX           359..361
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   HELIX           364..366
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   HELIX           372..382
FT                   /evidence="ECO:0007829|PDB:6L59"
FT   TURN            384..386
FT                   /evidence="ECO:0007829|PDB:8GRH"
FT   STRAND          389..391
FT                   /evidence="ECO:0007829|PDB:8GRG"
SQ   SEQUENCE   393 AA;  42794 MW;  A0870F2B7D228A37 CRC64;
     MALKVATVAG SAAKAVLGPA LLCRPWEVLG AHEVPSRNIF SEQTIPPSAK YGGRHTVTMI
     PGDGIGPELM LHVKSVFRHA CVPVDFEEVH VSSNADEEDI RNAIMAIRRN RVALKGNIET
     NHNLPPSHKS RNNILRTSLD LYANVIHCKS LPGVVTRHKD IDILIVRENT EGEYSSLEHE
     SVAGVVESLK IITKAKSLRI AEYAFKLAQE SGRKKVTAVH KANIMKLGDG LFLQCCREVA
     ARYPQITFEN MIVDNTTMQL VSRPQQFDVM VMPNLYGNIV NNVCAGLVGG PGLVAGANYG
     HVYAVFETAT RNTGKSIANK NIANPTATLL ASCMMLDHLK LHSYATSIRK AVLASMDNEN
     MHTPDIGGQG TTSEAIQDVI RHIRVINGRA VEA
//