ID   IDH3A_PIG               Reviewed;          90 AA.
AC   P56471;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1998, sequence version 1.
DT   25-MAY-2022, entry version 84.
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: Fragments;
GN   Name=IDH3A;
OS   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823;
RN   [1]
RP   PROTEIN SEQUENCE.
RC   TISSUE=Heart;
RX   PubMed=2252888; DOI=10.1021/bi00488a010;
RA   Huang Y.C., Colman R.F.;
RT   "Subunit location and sequences of the cysteinyl peptides of pig heart NAD-
RT   dependent isocitrate dehydrogenase.";
RL   Biochemistry 29:8266-8273(1990).
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   -!- 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}.
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DR   AlphaFoldDB; P56471; -.
DR   SMR; P56471; -.
DR   PeptideAtlas; P56471; -.
DR   PRIDE; P56471; -.
DR   SABIO-RK; P56471; -.
DR   Proteomes; UP000008227; Unplaced.
DR   Proteomes; UP000314985; Unplaced.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0004449; F:isocitrate dehydrogenase (NAD+) activity; IDA:UniProtKB.
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; IDA:UniProtKB.
DR   InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR   Pfam; PF00180; Iso_dh; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Mitochondrion; NAD; Oxidoreductase;
KW   Reference proteome; Tricarboxylic acid cycle.
FT   CHAIN           1..>90
FT                   /note="Isocitrate dehydrogenase [NAD] subunit alpha,
FT                   mitochondrial"
FT                   /id="PRO_0000083590"
FT   NON_CONS        35..36
FT                   /evidence="ECO:0000305"
FT   NON_CONS        48..49
FT                   /evidence="ECO:0000305"
FT   NON_CONS        60..61
FT                   /evidence="ECO:0000305"
FT   NON_CONS        70..71
FT                   /evidence="ECO:0000305"
FT   NON_TER         90
SQ   SEQUENCE   90 AA;  9691 MW;  C843422E73477480 CRC64;
     AGGVKTVTLI PGDGIGPEIS AAVMKIFDAA KAPIQANVRP CVSIEGYKFN EMYLDTVCLN
     IETACFATIK CSDFTEEICR EVAENCKDIK