ID IDHG2_RAT Reviewed; 395 AA.
AC Q4QQT5;
DT 30-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 27-MAR-2024, entry version 102.
DE RecName: Full=Probable isocitrate dehydrogenase [NAD] gamma 2, mitochondrial;
DE AltName: Full=Isocitric dehydrogenase subunit gamma 2;
DE AltName: Full=NAD(+)-specific ICDH subunit gamma 2;
DE Flags: Precursor;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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).
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}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
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DR EMBL; CH473979; EDM07215.1; -; Genomic_DNA.
DR EMBL; BC098006; AAH98006.1; -; mRNA.
DR RefSeq; NP_001096833.1; NM_001103363.1.
DR RefSeq; XP_008757687.1; XM_008759465.2.
DR AlphaFoldDB; Q4QQT5; -.
DR SMR; Q4QQT5; -.
DR STRING; 10116.ENSRNOP00000066907; -.
DR jPOST; Q4QQT5; -.
DR PaxDb; 10116-ENSRNOP00000066907; -.
DR GeneID; 100125384; -.
DR KEGG; rno:100125384; -.
DR UCSC; RGD:1642415; rat.
DR AGR; RGD:1642415; -.
DR CTD; 100125384; -.
DR RGD; 1642415; LOC100125384.
DR eggNOG; KOG0784; Eukaryota.
DR HOGENOM; CLU_031953_0_0_1; -.
DR InParanoid; Q4QQT5; -.
DR OrthoDB; 143577at2759; -.
DR PhylomeDB; Q4QQT5; -.
DR PRO; PR:Q4QQT5; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Proteomes; UP000234681; Chromosome 1.
DR Bgee; ENSRNOG00000045720; Expressed in testis.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0006102; P:isocitrate metabolic process; IBA:GO_Central.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR Gene3D; 3.40.718.10; Isopropylmalate Dehydrogenase; 1.
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:SF54; ISOCITRATE DEHYDROGENASE [NAD] GAMMA 2, MITOCHONDRIAL-RELATED; 1.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
DR SUPFAM; SSF53659; Isocitrate/Isopropylmalate dehydrogenase-like; 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..25
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 26..395
FT /note="Probable isocitrate dehydrogenase [NAD] gamma 2,
FT mitochondrial"
FT /id="PRO_0000401934"
FT BINDING 117
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="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51553"
FT BINDING 164
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51553"
FT BINDING 251
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 251
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51553"
FT BINDING 321
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P51553"
SQ SEQUENCE 395 AA; 43568 MW; C9CCD35DC729465B CRC64;
MLAAGSCSVR TILQPALLLG HSREVVCELV TSFRNFCSKY SVPPSPKYGG KHTVTMIPGD
GIGPELMVHV KRIFRSNCVP VEFEEVWATS TSSEEEINNA LMAIRRNRIT LKGNIATNHH
LPAKYKSHNT KFRTALDLYA SVVHFKTFPG VETRHKDIDI LVVRENTEGE YTNLEHESVR
GVVESLKIVT KTKSVRIADY AFRLAQKMGR KKVTVVHKAN IMKLGDGLFL QCCKDVAAHY
PQITLESMII DNTAMQLVSK PQQFDVMLMP NLYGNIINSV CTGLVGGSGI VPGANYGDSY
AIFETGSKEI GQDLAHRNIA NPVAMLLTSC IMLDYLDLQL YAAHIRSAVM ASLQNKSICT
PDIGGQGTTA GVVEYILDHM KDQNSGCQPR FFLST
//
