ID IDH3G_MACFA Reviewed; 355 AA. AC P41564; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 02-SEP-2026, entry version 114. 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; Fragment; GN Name=IDH3G; OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; OC Cercopithecidae; Cercopithecinae; Macaca. OX NCBI_TaxID=9541; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Testis; RX PubMed=8240232; DOI=10.1042/bj2950347; RA Nichols B.J., Hall L., Perry A.C.F., Denton R.M.; RT "Molecular cloning and deduced amino acid sequences of the gamma-subunits RT of rat and monkey NAD(+)-isocitrate dehydrogenases."; RL Biochem. J. 295:347-350(1993). 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:0000250|UniProtKB:P51553}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P51553}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000250|UniProtKB:P51553}; 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:0000250|UniProtKB:P51553}; 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:0000250|UniProtKB:P51553}. 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:0000250|UniProtKB:P51553}. CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P51553}. CC Photoreceptor inner segment {ECO:0000250|UniProtKB:P51553}. CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate CC dehydrogenases family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X74124; CAA52224.1; -; mRNA. DR PIR; S39065; S39065. DR AlphaFoldDB; P41564; -. DR SMR; P41564; -. DR STRING; 9541.ENSMFAP00000039635; -. DR eggNOG; KOG0784; Eukaryota. DR Proteomes; UP000233100; Unplaced. DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB. DR GO; GO:0001917; C:photoreceptor inner segment; ISS:UniProtKB. DR GO; GO:0004449; F:isocitrate dehydrogenase (NAD+) 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:0006102; P:isocitrate metabolic process; ISS:UniProtKB. DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:InterPro. DR FunFam; 3.40.718.10:FF:000011; Isocitrate dehydrogenase [NAD] subunit, mitochondrial; 1. 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:SF78; 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. PE 2: Evidence at transcript level; KW ATP-binding; Magnesium; Manganese; Metal-binding; Mitochondrion; KW Nucleotide-binding; Reference proteome; Transit peptide; KW Tricarboxylic acid cycle. FT TRANSIT <1..1 FT /note="Mitochondrion" FT /evidence="ECO:0000250" FT CHAIN 2..355 FT /note="Isocitrate dehydrogenase [NAD] subunit gamma, FT mitochondrial" FT /id="PRO_0000014450" FT BINDING 82 FT /ligand="citrate" FT /ligand_id="ChEBI:CHEBI:16947" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 95 FT /ligand="citrate" FT /ligand_id="ChEBI:CHEBI:16947" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 98 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 129 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 216 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_note="ligand shared with catalytic subunit" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 216 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 274 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 275 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000250|UniProtKB:P51553" FT BINDING 286 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000250|UniProtKB:P51553" FT NON_TER 1 SQ SEQUENCE 355 AA; 38881 MW; CC1EEFF0582B6813 CRC64; ISSQQTIPPS AKYGGRHTVT MIPGDGIGPE LMLHVKSVFR HACVPVDFEE VHVSSNADEE DIRNAIMAIR RNRVALKGNI ETNHNLPPSH KSRNNILRTS LDLYANVIHC KSLPGVVTRH KDIDILIVRE NTEGEYSSLE HESVAGVVES LKIITKAKSL RIAEYAFKLA QESGRKKVTA VHKANIMKLG DGLFLQCCRE VAARYPQITF ENMIVDNTTM QLVSRPQQFD VMVMPNLYGN IVNNVCAGLV GGPGLVAGAN YGHVYAVFET ATRNTGKSIA NKNIANPTAT LLASCMMLDH LKLHSYATSI RKAVLASMDN ENMHTPDIGG QGTTSEAIQD IIRHIRVING RAVEA //