ID   IDHG1_RAT               Reviewed;         393 AA.
AC   P41565; P70577;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-1998, sequence version 2.
DT   02-SEP-2026, entry version 154.
DE   RecName: Full=Isocitrate dehydrogenase [NAD] subunit gamma 1, mitochondrial;
DE   AltName: Full=Isocitric dehydrogenase subunit gamma;
DE   AltName: Full=NAD(+)-specific ICDH subunit gamma;
DE   Flags: Precursor;
GN   Name=Idh3g;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24.
RC   STRAIN=HAN/WIST;
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 [GENOMIC DNA] OF 6-393.
RC   STRAIN=Wistar; TISSUE=Epididymis;
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).
RN   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
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}.
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DR   EMBL; U63009; AAC53341.1; -; Genomic_DNA.
DR   EMBL; X74125; CAA52225.1; -; mRNA.
DR   PIR; S39064; S39064.
DR   AlphaFoldDB; P41565; -.
DR   SMR; P41565; -.
DR   ComplexPortal; CPX-557; Mitochondrial isocitrate dehydrogenase complex (NAD+).
DR   FunCoup; P41565; 1758.
DR   IntAct; P41565; 1.
DR   MINT; P41565; -.
DR   STRING; 10116.ENSRNOP00000073128; -.
DR   iPTMnet; P41565; -.
DR   PhosphoSitePlus; P41565; -.
DR   jPOST; P41565; -.
DR   PaxDb; 10116-ENSRNOP00000073128; -.
DR   AGR; RGD:2863; -.
DR   RGD; 2863; Idh3g.
DR   eggNOG; KOG0784; Eukaryota.
DR   InParanoid; P41565; -.
DR   PhylomeDB; P41565; -.
DR   Reactome; R-RNO-71403; Citric acid cycle (TCA cycle).
DR   SABIO-RK; P41565; -.
DR   PRO; PR:P41565; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0045242; C:isocitrate dehydrogenase complex (NAD+); ISO:RGD.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0001917; C:photoreceptor inner segment; ISS:UniProtKB.
DR   GO; GO:0008047; F:enzyme activator activity; ISO:RGD.
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; ISO:RGD.
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   1: Evidence at protein level;
KW   Acetylation; ATP-binding; Magnesium; Manganese; Metal-binding;
KW   Mitochondrion; Nucleotide-binding; Phosphoprotein; 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 1,
FT                   mitochondrial"
FT                   /id="PRO_0000014452"
FT   BINDING         120
FT                   /ligand="citrate"
FT                   /ligand_id="ChEBI:CHEBI:16947"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P51553"
FT   BINDING         133
FT                   /ligand="citrate"
FT                   /ligand_id="ChEBI:CHEBI:16947"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P51553"
FT   BINDING         136
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P51553"
FT   BINDING         167
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P51553"
FT   BINDING         254
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         254
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P51553"
FT   BINDING         312
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P51553"
FT   BINDING         313
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P51553"
FT   BINDING         324
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P51553"
FT   MOD_RES         130
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         206
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P70404"
FT   MOD_RES         226
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P70404"
FT   CONFLICT        7
FT                   /note="I -> V (in Ref. 2; CAA52225)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   393 AA;  42851 MW;  890B1A4BE3543AE4 CRC64;
     MALKVAIAAG SAAKAIFKPA LLCRPWEVLA AHEAPRRSIS SQQTIPPSAK YGGRHTVTMI
     PGDGIGPELM LHVKSVFRHA CVPVDFEEVH VSSNADEEDI RNAIMAIRRN RVALKGNIET
     NHDLPPSHKS RNNILRTSLD LYANVIHCKS LPGVVTRHKD IDILIVRENT EGEYSSLEHE
     SVAGVVESLK IITKAKSLRI AEYAFKLAQE SGRKKVTAVH KANIMKLGDG LFLQCCREVA
     ARYPQITFDS MIVDNTTMQL VSRPQQFDVM VMPNLYGNIV NNVCAGLVGG PGLVAGANYG
     HVYAVFETAT RNTGKSIANK NIANPTATLL ASCMMLDHLK LHSYATSIRK AVLASMDNEN
     MHTPDIGGQG TTSQAIQDII RHIRIINGRA VEA
//