IDH3A
entrez
3419
canonical
uniprot
P50213
canonical
ensembl
ENSG00000166411
resolver
ensp
ENSP00000299518
resolver
ensp
ENSP00000559933
resolver
genesymbol
IDH3A
resolver
hgnc
HGNC:5384
resolver
uniprot
B4DJB4
resolver
uniprot
B7Z9J8
resolver
uniprot
D3DW83
resolver
uniprot
E7EWD2
resolver
uniprot
Q9H3X0
resolver
uniprot_entry
B4DJB4_HUMAN
resolver
uniprot_entry
B7Z9J8_HUMAN
resolver
uniprot_entry
IDH3A_HUMAN
resolver
uniprot_sec
D3DW83
resolver
uniprot_sec
E7EWD2
resolver
uniprot_sec
Q9H3X0
resolver
activity_regulation
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. {ECO:0000269|PubMed:28098230, ECO:0000269|PubMed:28139779}.
uniprot
proteins
amino_acid_sequence
MAGPAWISKVSRLLGAFHNPKQVTRGFTGGVQTVTLIPGDGIGPEISAAVMKIFDAAKAPIQWEERNVTAIQGPGGKWMIPSEAKESMDKNKMGLKGPLKTPIAAGHPSMNLLLRKTFDLYANVRPCVSIEGYKTPYTDVNIVTIRENTEGEYSGIEHVIVDGVVQSIKLITEGASKRIAEFAFEYARNNHRSNVTAVHKANIMRMSDGLFLQKCREVAESCKDIKFNEMYLDTVCLNMVQDPSQFDVLVMPNLYGDILSDLCAGLIGGLGVTPSGNIGANGVAIFESVHGTAPDIAGKDMANPTALLLSAVMMLRHMGLFDHAARIEAACFATIKDGKSLTKDLGGNAKCSDFTEEICRRVKDLD
uniprot
proteins
disease_involvement
DISEASE: Retinitis pigmentosa 90 (RP90) [MIM:619007]: A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP90 is an autosomal recessive form. {ECO:0000269|PubMed:28412069, ECO:0000269|PubMed:30058936, ECO:0000269|PubMed:31012789}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
1.1.1.41
uniprot
proteins
function
FUNCTION: 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. {ECO:0000269|PubMed:28139779}.
uniprot
proteins
mass_dalton
39592
uniprot
proteins
mutagenesis
MUTAGEN 152; /note="E->A: No significant effect on the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate and ADP."; /evidence="ECO:0000269|PubMed:28098230"; MUTAGEN 153; /note="Y->F: Complete loss of activity of the heterotetramer, heterodimer composed of IDH3A and IDH3B subunits and the heterodimer composed of IDH3A and IDH3G subunits with no effect on their oligomeric states."; /evidence="ECO:0000269|PubMed:28139779"; MUTAGEN 169; /note="K->A: Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate and ADP."; /evidence="ECO:0000269|PubMed:28098230"; MUTAGEN 200; /note="K->A: Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate."; /evidence="ECO:0000269|PubMed:28098230"; MUTAGEN 202; /note="N->A: Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate."; /evidence="ECO:0000269|PubMed:28098230"; MUTAGEN 208; /note="D->A: Complete loss of the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate and ADP."; /evidence="ECO:0000269|PubMed:28098230"; MUTAGEN 255; /note="Y->A: Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate and ADP."; /evidence="ECO:0000269|PubMed:28098230
uniprot
proteins
protein_family
Isocitrate and isopropylmalate dehydrogenases family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
28098230
uniprot
proteins
pubmed
28139779
uniprot
proteins
pubmed
28412069
uniprot
proteins
pubmed
30058936
uniprot
proteins
pubmed
31012789
uniprot
proteins
pubmed
7755589
uniprot
proteins
sequence_length
366
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion.
uniprot
proteins