IDHG1_RAT
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 03-AUG-2022, entry version 140.
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}.
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 IntAct; P41565; 1.
DR MINT; P41565; -.
DR STRING; 10116.ENSRNOP00000053220; -.
DR iPTMnet; P41565; -.
DR PhosphoSitePlus; P41565; -.
DR jPOST; P41565; -.
DR PaxDb; P41565; -.
DR PRIDE; P41565; -.
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:0005962; C:mitochondrial isocitrate dehydrogenase complex (NAD+); ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004449; F:isocitrate dehydrogenase (NAD+) activity; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0006102; P:isocitrate metabolic process; IDA:RGD.
DR GO; GO:0006734; P:NADH metabolic process; IDA:RGD.
DR GO; GO:0045926; P:negative regulation of growth; IMP:RGD.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IDA:RGD.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR004434; Isocitrate_DH_NAD.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
DR TIGRFAMs; TIGR00175; mito_nad_idh; 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
