IDH3A_MACFA
ID IDH3A_MACFA Reviewed; 347 AA.
AC Q28480;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial;
DE EC=1.1.1.41;
DE AltName: Full=Isocitric dehydrogenase subunit alpha;
DE AltName: Full=NAD(+)-specific ICDH subunit alpha;
DE Flags: Precursor; Fragment;
GN Name=IDH3A;
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=7575427; DOI=10.1042/bj3100917;
RA Nichols B.J., Perry A.C.F., Hall L., Denton R.M.;
RT "Molecular cloning and deduced amino acid sequences of the alpha- and beta-
RT subunits of mammalian NAD(+)-isocitrate dehydrogenase.";
RL Biochem. J. 310:917-922(1995).
CC -!- FUNCTION: Catalytic subunit of the enzyme which catalyzes the
CC decarboxylation of isocitrate (ICT) into alpha-ketoglutarate. The
CC heterodimer composed of the alpha (IDH3A) and beta (IDH3B) subunits and
CC the heterodimer composed of the alpha (IDH3A) and gamma (IDH3G)
CC subunits, have considerable basal activity but the full activity of the
CC heterotetramer (containing two subunits of IDH3A, one of IDH3B and one
CC of IDH3G) requires the assembly and cooperative function of both
CC heterodimers. {ECO:0000250|UniProtKB:P50213}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-threo-isocitrate + NAD(+) = 2-oxoglutarate + CO2 + NADH;
CC Xref=Rhea:RHEA:23632, ChEBI:CHEBI:15562, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.41;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P50213};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P50213};
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:P50213};
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:P50213}.
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:P50213}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA60637.1; Type=Erroneous initiation; Evidence={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; X87172; CAA60637.1; ALT_INIT; mRNA.
DR PIR; S58664; S58664.
DR AlphaFoldDB; Q28480; -.
DR SMR; Q28480; -.
DR IntAct; Q28480; 1.
DR MINT; Q28480; -.
DR STRING; 9541.XP_005560256.1; -.
DR eggNOG; KOG0785; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005962; C:mitochondrial isocitrate dehydrogenase complex (NAD+); IEA:UniProt.
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:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Acetylation; Magnesium; Manganese; Metal-binding; Mitochondrion; NAD;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Transit peptide;
KW Tricarboxylic acid cycle.
FT TRANSIT <1..8
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 9..347
FT /note="Isocitrate dehydrogenase [NAD] subunit alpha,
FT mitochondrial"
FT /id="PRO_0000014437"
FT BINDING 14..42
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255"
FT BINDING 96
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 106
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 127
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 214
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 238
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 242
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT SITE 134
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT SITE 181
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT MOD_RES 58
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D6R2"
FT MOD_RES 82
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9D6R2"
FT MOD_RES 204
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D6R2"
FT MOD_RES 324
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT MOD_RES 324
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9D6R2"
FT MOD_RES 331
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D6R2"
FT NON_TER 1
SQ SEQUENCE 347 AA; 37598 MW; 9100B663642131B9 CRC64;
QKQVTRGFTG GVQTVTLIPG DGIGPEISAA VMKIFDAAKA PIQWEERNVT AIQGPGGKWM
IPSEAKESMD KNKMGLKGPL KTPIAAGHPS MNLLLRKTFD LYANVRPCVS IEGYKTPYTD
VNIVTIRENT EGEYSGIEHV IVDGVVQSIK LITEGGSKRI AEFAFEYARN NHRSNVTAVH
KANIMRMSDG LFLQKCREVA ENCKDIKFNE MYLDTVCLNM VQDPSQFDVL VMPNLYGDIL
SDLCAGLIGG LGVTPSGNIG ANGVAIFESV HGTAPDIAGK DMANPTALLL SAVMMLRHMG
LFDHAARIEA ACFATIKDGK SLTKDLGGNA KCSDFTEEIC RRVKDLD
