UniProtKB - P86225 (IDH3A_MESAU)
Protein
Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial
Gene
IDH3A
Organism
Mesocricetus auratus (Golden hamster)
Status
Functioni
Catalytic subunit of the enzyme which catalyzes the decarboxylation of isocitrate (ICT) into alpha-ketoglutarate. The heterodimer composed of the alpha (IDH3A) and beta (IDH3B) subunits and the heterodimer composed of the alpha (IDH3A) and gamma (IDH3G) subunits, have considerable basal activity but the full activity of the heterotetramer (containing two subunits of IDH3A, one of IDH3B and one of IDH3G) requires the assembly and cooperative function of both heterodimers.By similarity
Caution
The order of the peptides shown is unknown.Curated
Catalytic activityi
- EC:1.1.1.41By similarity
Cofactori
Mg2+By similarity, Mn2+By similarityNote: Divalent metal cations; Mn2+ or Mg2+. Activity higher in presence of Mn2+ than of Mg2+. Binds 1 Mg2+ or Mn2+ ion per subunit.By similarity
Activity regulationi
The heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits can be allosterically activated by citrate (CIT) or/and ADP, and the two activators can act independently or synergistically. The heterodimer composed of IDH3A and IDH3B subunits cannot be allosterically regulated and the allosteric regulation of the heterotetramer is through the IDH3G subunit and not the IDH3B subunit. The IDH3G subunit contains the allosteric site which consists of a CIT-binding site and an ADP-binding site, and the binding of CIT and ADP causes conformational changes at the allosteric site which are transmitted to the active site in the catalytic subunit (IDH3A) through a cascade of conformational changes at the heterodimer interface, leading to stabilization of the isocitrate-binding at the active site and thus activation of the enzyme. ATP can activate the heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits at low concentrations but inhibits their activities at high concentrations, whereas ATP exhibits only inhibitory effect on the heterodimer composed of IDH3A and IDH3B subunits.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 64 | SubstrateBy similarity | 1 | |
Binding sitei | 74 | SubstrateBy similarity | 1 | |
Binding sitei | 95 | SubstrateBy similarity | 1 |
GO - Molecular functioni
- isocitrate dehydrogenase (NAD+) activity Source: UniProtKB
- magnesium ion binding Source: UniProtKB
GO - Biological processi
- tricarboxylic acid cycle Source: UniProtKB-KW
Keywordsi
Molecular function | Oxidoreductase |
Biological process | Tricarboxylic acid cycle |
Ligand | Magnesium, Manganese, Metal-binding, NAD |
Names & Taxonomyi
Protein namesi | Recommended name: Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrialBy similarity (EC:1.1.1.41)Alternative name(s): Isocitric dehydrogenase subunit alphaBy similarity NAD(+)-specific ICDH subunit alphaBy similarity |
Gene namesi | Name:IDH3ABy similarity |
Organismi | Mesocricetus auratus (Golden hamster) |
Taxonomic identifieri | 10036 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Cricetidae › Cricetinae › Mesocricetus |
Proteomesi |
|
Subcellular locationi
Mitochondrion
- Mitochondrion By similarity
Mitochondrion
- mitochondrion Source: UniProtKB-SubCell
Keywords - Cellular componenti
MitochondrionPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000394308 | ‹1 – ›134 | Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrialAdd BLAST | ›134 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 37 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 50 | PhosphothreonineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinInteractioni
Subunit structurei
Heterooligomer of subunits alpha (IDH3A), beta (IDH3B), and gamma (IDH3G) in the apparent ratio of 2:1:1. The heterodimer containing one IDH3A and one IDH3B subunit and the heterodimer containing one IDH3A and one IDH3G subunit assemble into a heterotetramer (which contains two subunits of IDH3A, one of IDH3B and one of IDH3G) and further into the heterooctamer.
By similarityFamily & Domainsi
Sequence similaritiesi
Belongs to the isocitrate and isopropylmalate dehydrogenases family.Sequence analysis
Family and domain databases
InterProi | View protein in InterPro IPR024084, IsoPropMal-DH-like_dom |
Pfami | View protein in Pfam PF00180, Iso_dh, 1 hit |
SMARTi | View protein in SMART SM01329, Iso_dh, 1 hit |
i Sequence
Sequence statusi: Fragments.
P86225-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MRPGVAAVAA VRIFDAAKAP IQWEERNVTA IQGPGGKWMI PPEAKGPLKT
60 70 80 90 100
PIAAGHPSMN LLLRKTFDLY ANVRPCVSIE GYKTPYTDVN IVTIRRIAEF
110 120 130
AFEYARDMAN PTALLLSAVM MLRCSDFTEE ICRR
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Non-terminal residuei | 1 | 1 | ||
Non-adjacent residuesi | 12 – 13 | Curated | 2 | |
Non-adjacent residuesi | 45 – 46 | Curated | 2 | |
Non-adjacent residuesi | 54 – 55 | Curated | 2 | |
Non-terminal residuei | 134 | 1 |
Cross-referencesi
3D structure databases
SMRi | P86225 |
ModBasei | Search... |
Family and domain databases
InterProi | View protein in InterPro IPR024084, IsoPropMal-DH-like_dom |
Pfami | View protein in Pfam PF00180, Iso_dh, 1 hit |
SMARTi | View protein in SMART SM01329, Iso_dh, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | IDH3A_MESAU | |
Accessioni | P86225Primary (citable) accession number: P86225 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 18, 2010 |
Last sequence update: | May 18, 2010 | |
Last modified: | December 2, 2020 | |
This is version 38 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families