ID   IDH3A_BOVIN             Reviewed;         366 AA.
AC   P41563;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   04-NOV-2026, entry version 134.
DE   RecName: Full=Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial {ECO:0000305|PubMed:7654189};
DE            EC=1.1.1.41 {ECO:0000269|PubMed:7654189};
DE   AltName: Full=Isocitrate dehydrogenase subunits 3/4;
DE   AltName: Full=Isocitric dehydrogenase subunit alpha;
DE   AltName: Full=NAD(+)-specific ICDH subunit alpha;
DE   Flags: Precursor;
GN   Name=IDH3A {ECO:0000250|UniProtKB:P50213};
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC   TISSUE=Heart;
RX   PubMed=7654189; DOI=10.1042/bj3100507;
RA   Zeng Y., Weiss C., Yao T.T., Huang J., Siconolfi-Baez L., Hsu P.,
RA   Rushbrook J.I.;
RT   "Isocitrate dehydrogenase from bovine heart: primary structure of subunit
RT   3/4.";
RL   Biochem. J. 310:507-516(1995).
RN   [2]
RP   IDENTIFICATION.
RC   TISSUE=Heart;
RX   PubMed=215197; DOI=10.1021/bi00618a003;
RA   Rushbrook J.I., Harvey R.A.;
RT   "Nicotinamide adenine dinucleotide dependent isocitrate dehydrogenase from
RT   beef heart: subunit heterogeneity and enzyme dissociation.";
RL   Biochemistry 17:5339-5346(1978).
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:0000269|PubMed:7654189}.
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:0000269|PubMed:7654189};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23633;
CC         Evidence={ECO:0000269|PubMed:7654189};
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}.
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DR   EMBL; U07980; AAC18425.1; -; mRNA.
DR   PIR; S58435; S58435.
DR   RefSeq; NP_777069.1; NM_174644.2.
DR   AlphaFoldDB; P41563; -.
DR   SMR; P41563; -.
DR   FunCoup; P41563; 2199.
DR   IntAct; P41563; 1.
DR   STRING; 9913.ENSBTAP00000008177; -.
DR   GlyGen; P41563; 1 site.
DR   PaxDb; 9913-ENSBTAP00000008177; -.
DR   PeptideAtlas; P41563; -.
DR   GeneID; 282446; -.
DR   KEGG; bta:282446; -.
DR   CTD; 3419; -.
DR   eggNOG; KOG0785; Eukaryota.
DR   InParanoid; P41563; -.
DR   OMA; AAIIKFV; -.
DR   OrthoDB; 10261637at2759; -.
DR   SABIO-RK; P41563; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0005739; C:mitochondrion; ISS:AgBase.
DR   GO; GO:0004449; F:isocitrate dehydrogenase (NAD+) activity; EXP:UniProtKB.
DR   GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR   GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR   GO; GO:0006102; P:isocitrate metabolic process; IBA:GO_Central.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR   FunFam; 3.40.718.10:FF:000003; Isocitrate dehydrogenase [NAD] subunit, mitochondrial; 1.
DR   Gene3D; 3.40.718.10; Isopropylmalate Dehydrogenase; 1.
DR   InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
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:SF34; ISOCITRATE DEHYDROGENASE [NAD] SUBUNIT ALPHA, MITOCHONDRIAL; 1.
DR   Pfam; PF00180; Iso_dh; 1.
DR   SMART; SM01329; Iso_dh; 1.
DR   SUPFAM; SSF53659; Isocitrate/Isopropylmalate dehydrogenase-like; 1.
DR   PROSITE; PS00470; IDH_IMDH; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Magnesium; Manganese; Metal-binding; Mitochondrion; NAD;
KW   Oxidoreductase; Phosphoprotein; Reference proteome; Transit peptide;
KW   Tricarboxylic acid cycle.
FT   TRANSIT         1..27
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250|UniProtKB:P50213"
FT   CHAIN           28..366
FT                   /note="Isocitrate dehydrogenase [NAD] subunit alpha,
FT                   mitochondrial"
FT                   /id="PRO_0000014435"
FT   BINDING         115
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P50213"
FT   BINDING         125
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P50213"
FT   BINDING         146
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P50213"
FT   BINDING         233
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P50213"
FT   BINDING         257
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P50213"
FT   BINDING         261
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P50213"
FT   SITE            153
FT                   /note="Critical for catalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P50213"
FT   SITE            200
FT                   /note="Critical for catalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P50213"
FT   MOD_RES         77
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9D6R2"
FT   MOD_RES         101
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9D6R2"
FT   MOD_RES         223
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9D6R2"
FT   MOD_RES         343
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P50213"
FT   MOD_RES         343
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9D6R2"
FT   MOD_RES         350
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9D6R2"
SQ   SEQUENCE   366 AA;  39668 MW;  B169D59B30E51C9F CRC64;
     MAGPAWISKV SRLLGAFHNQ KQVTRGFAGG VKTVTLIPGD GIGPEISAAV MKIFDAAKAP
     IQWEERNVAA IQGPGGKWMI PPEAKESMDK NKMGLKGPLK TPIAAGHPSM NLLLRKTFDL
     YANVRPCVSI EGYKTPYHDV NIVTIRENTE GEYSGIEHVI VDGVVQSIKL ITEAASKRIA
     EFAFEYARNN HRSNVTAVHK ANIMRMSDGL FLQKCREVAE NCKDIKFNEM YLDTVCLNMV
     QDPSQFDVLV MPNLYGDILS DLCAGLIGGL GVTPSGNIGA NGVAIFESVH GTAPDIAGKD
     MANPTALLLS AVMMLRHMGL FDHAAKIETA CFATIKDGKS LTKDLGGNSK CSDFTEEICR
     RVKDLD
//