IDH3A_MESAU
ID IDH3A_MESAU Reviewed; 134 AA.
AC P86225;
DT 18-MAY-2010, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial {ECO:0000250|UniProtKB:P50213};
DE EC=1.1.1.41;
DE AltName: Full=Isocitric dehydrogenase subunit alpha {ECO:0000250|UniProtKB:P50213};
DE AltName: Full=NAD(+)-specific ICDH subunit alpha {ECO:0000250|UniProtKB:P50213};
DE Flags: Fragments;
GN Name=IDH3A {ECO:0000250|UniProtKB:P50213};
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=20400973; DOI=10.1038/aja.2010.19;
RA Kameshwari D.B., Bhande S., Sundaram C.S., Kota V., Siva A.B., Shivaji S.;
RT "Glucose-regulated protein precursor (GRP78) and tumor rejection antigen
RT (GP96) are unique to hamster caput epididymal spermatozoa.";
RL Asian J. Androl. 12:344-355(2010).
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 Evidence={ECO:0000250|UniProtKB:P50213};
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 {ECO:0000250|UniProtKB:P50213}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000255}.
CC -!- CAUTION: The order of the peptides shown is unknown. {ECO:0000305}.
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DR AlphaFoldDB; P86225; -.
DR SMR; P86225; -.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0004449; F:isocitrate dehydrogenase (NAD+) activity; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
PE 1: Evidence at protein level;
KW Magnesium; Manganese; Metal-binding; Mitochondrion; NAD; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Tricarboxylic acid cycle.
FT CHAIN <1..>134
FT /note="Isocitrate dehydrogenase [NAD] subunit alpha,
FT mitochondrial"
FT /id="PRO_0000394308"
FT BINDING 64
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 74
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT BINDING 95
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P50213"
FT MOD_RES 37
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D6R2"
FT MOD_RES 50
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9D6R2"
FT NON_CONS 12..13
FT /evidence="ECO:0000305"
FT NON_CONS 45..46
FT /evidence="ECO:0000305"
FT NON_CONS 54..55
FT /evidence="ECO:0000305"
FT NON_TER 1
FT NON_TER 134
SQ SEQUENCE 134 AA; 14881 MW; 72773443217D96BB CRC64;
MRPGVAAVAA VRIFDAAKAP IQWEERNVTA IQGPGGKWMI PPEAKGPLKT PIAAGHPSMN
LLLRKTFDLY ANVRPCVSIE GYKTPYTDVN IVTIRRIAEF AFEYARDMAN PTALLLSAVM
MLRCSDFTEE ICRR
