IDH3A_BOVIN
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 03-AUG-2022, entry version 123.
DE RecName: Full=Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial;
DE EC=1.1.1.41;
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;
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].
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 CHARACTERIZATION.
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: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}.
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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 IntAct; P41563; 1.
DR STRING; 9913.ENSBTAP00000008177; -.
DR PaxDb; P41563; -.
DR PeptideAtlas; P41563; -.
DR PRIDE; P41563; -.
DR GeneID; 282446; -.
DR KEGG; bta:282446; -.
DR CTD; 3419; -.
DR eggNOG; KOG0785; Eukaryota.
DR InParanoid; P41563; -.
DR OrthoDB; 868374at2759; -.
DR SABIO-RK; P41563; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005962; C:mitochondrial isocitrate dehydrogenase complex (NAD+); IEA:UniProt.
DR GO; GO:0005739; C:mitochondrion; ISS:AgBase.
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:0006102; P:isocitrate metabolic process; IBA:GO_Central.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
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; 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 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
