P70404 · IDHG1_MOUSE
- ProteinIsocitrate dehydrogenase [NAD] subunit gamma 1, mitochondrial
- GeneIdh3g
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids393 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score4/5
Function
function
Regulatory subunit which plays a role in the allosteric regulation of the enzyme catalyzing 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.
Cofactor
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Note: Divalent metal cations; Mn2+ or Mg2+. Activity higher in presence of Mn2+ than of Mg2+. Binds 1 Mg2+ or Mn2+ ion per subunit.
Activity regulation
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.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 120 | citrate (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: T | ||||||
Binding site | 133 | citrate (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: N | ||||||
Binding site | 136 | substrate | ||||
Sequence: R | ||||||
Binding site | 167 | substrate | ||||
Sequence: R | ||||||
Binding site | 254 | Mn2+ (UniProtKB | ChEBI); ligand shared with catalytic subunit | ||||
Sequence: D | ||||||
Binding site | 254 | substrate | ||||
Sequence: D | ||||||
Binding site | 312 | ADP (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: N | ||||||
Binding site | 313 | ADP (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: T | ||||||
Binding site | 324 | ADP (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: N |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | isocitrate dehydrogenase complex (NAD+) | |
Cellular Component | mitochondrion | |
Molecular Function | ATP binding | |
Molecular Function | isocitrate dehydrogenase (NAD+) activity | |
Molecular Function | magnesium ion binding | |
Molecular Function | NAD binding | |
Biological Process | 2-oxoglutarate metabolic process | |
Biological Process | isocitrate metabolic process | |
Biological Process | NADH metabolic process | |
Biological Process | tricarboxylic acid cycle |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameIsocitrate dehydrogenase [NAD] subunit gamma 1, mitochondrial
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP70404
Proteomes
Organism-specific databases
Subcellular Location
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-39 | Mitochondrion | ||||
Sequence: MALKVAIAAGGAAKAMLKPTLLCRPWEVLAAHVAPRRSI | ||||||
Chain | PRO_0000014451 | 40-393 | Isocitrate dehydrogenase [NAD] subunit gamma 1, mitochondrial | |||
Sequence: SSQQTIPPSAKYGGRHTVTMIPGDGIGPELMLHVKSVFRHACVPVDFEEVHVSSNADEEDIRNAIMAIRRNRVALKGNIETNHNLPPSHKSRNNILRTSLDLYANVIHCKSLPGVVTRHKDIDILIVRENTEGEYSSLEHESVAGVVESLKIITKAKSLRIAEYAFKLAQESGRKKVTAVHKANIMKLGDGLFLQCCREVAAHYPQITFDSMIVDNTTMQLVSRPQQFDVMVMPNLYGNIVNNVCAGLVGGPGLVAGANYGHVYAVFETATRNTGKSIANKNIANPTATLLASCMMLDHLKLHSYATSIRKAVLASMDNENMHTPDIGGQGTTSQAIQDIIRHIRIINGRAVEA | ||||||
Modified residue | 130 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 206 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 226 | N6-succinyllysine | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
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.
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length393
- Mass (Da)42,785
- Last updated1997-02-01 v1
- Checksum4023560C44C1F4D3
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U68564 EMBL· GenBank· DDBJ | AAC53340.1 EMBL· GenBank· DDBJ | mRNA | ||
AF133093 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |