Reactome | UniProt:P50213 IDH3A

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UniProt:P50213 IDH3A Show undefined attributes

chain	transit peptide:1-27 chain:28-366
checksum	695F6A34F97430CF
comment	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.CATALYTIC ACTIVITY D-threo-isocitrate + NAD(+) = 2-oxoglutarate + CO2 + NADHCOFACTOR Divalent metal cations; Mn(2+) or Mg(2+). Activity higher in presence of Mn(2+) than of Mg(2+). Binds 1 Mg(2+) or Mn(2+) 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.BIOPHYSICOCHEMICAL PROPERTIES kcat is 26.7 sec(-1) for the heterotetramer with isocitrate as substrate. kcat is 14.6 sec(-1) for the heterodimer composed of IDH3A and IDH3B subunits with isocitrate as substrate. kcat is 9.72 sec(-1) for the heterodimer composed of IDH3A and IDH3G subunits with isocitrate as substrate. kcat is 23.4 sec(-1) for the heterotetramer with isocitrate as substrate in the presence of citrate and ATP. kcat is 11.9 sec(-1) for the heterodimer composed of IDH3A and IDH3G subunits with isocitrate as substrate in the presence of citrate and ATP. kcat is 28.4 sec(-1) for the heterotetramer with isocitrate as substrate in the presence of citrate and ADP. kcat is 15.8 sec(-1) for the heterodimer composed of IDH3A and IDH3B subunits with isocitrate as substrate in the presence of citrate and ADP. kcat is 17.6 sec(-1) for the heterodimer composed of IDH3A and IDH3G subunits with isocitrate as substrate in the presence of citrate and ADP.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.INTERACTION The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the isocitrate and isopropylmalate dehydrogenases family.
crossReference	[DatabaseIdentifier:12452737] RefSeq:NP_005521.1 [DatabaseIdentifier:12284685] Pharos - Targets:P50213 [DatabaseIdentifier:12263399] PRO:P50213 [DatabaseIdentifier:12172372] PDB:8GRH [DatabaseIdentifier:12172367] PDB:5YVT [DatabaseIdentifier:12172362] PDB:5GRI [DatabaseIdentifier:12172368] PDB:8GRD [DatabaseIdentifier:12172371] PDB:5GRF [DatabaseIdentifier:12172358] PDB:8GRU [DatabaseIdentifier:12172366] PDB:6KE3 [DatabaseIdentifier:12172355] PDB:6L57 [DatabaseIdentifier:12172363] PDB:5GRH [DatabaseIdentifier:12172369] PDB:5GRE [DatabaseIdentifier:12172360] PDB:6KDF [DatabaseIdentifier:12172356] PDB:6L59 [DatabaseIdentifier:12172365] PDB:5GRL [DatabaseIdentifier:12172359] PDB:8GS5 [DatabaseIdentifier:12172370] PDB:8GRG [DatabaseIdentifier:12172364] PDB:6KDY [DatabaseIdentifier:12172357] PDB:8GRB [DatabaseIdentifier:12172361] PDB:6KDE [DatabaseIdentifier:12172354] PDB:7CE3 [DatabaseIdentifier:12135650] Orphanet:IDH3A [DatabaseIdentifier:12124373] OpenTargets:ENSG00000166411 [DatabaseIdentifier:11850533] IntEnz:1.1.1.41 [DatabaseIdentifier:11839845] HPA:ENSG00000166411-IDH3A [DatabaseIdentifier:11830373] HMDB Protein:HMDBP00899 [DatabaseIdentifier:11802231] GlyGen:P50213 [DatabaseIdentifier:11786766] GeneCards:IDH3A [DatabaseIdentifier:11750175] ENSEMBL:ENST00000299518 [DatabaseIdentifier:11627476] ENSEMBL:ENSP00000299518 [DatabaseIdentifier:11512036] ENSEMBL:ENSG00000166411
databaseName	UniProt
dbId	57062
description	recommendedName: fullName evidence="9"Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial ecNumber evidence="2 3"1.1.1.41 alternativeName: Isocitric dehydrogenase subunit alpha alternativeName: NAD(+)-specific ICDH subunit alpha
displayName	UniProt:P50213 IDH3A
geneName	IDH3A
identifier	P50213
isSequenceChanged	false
keyword	3D-structure Acetylation Alternative splicing Direct protein sequencing Disease variant Magnesium Manganese Metal-binding Mitochondrion NAD Oxidoreductase Phosphoprotein Proteomics identification Reference proteome Retinitis pigmentosa Transit peptide Tricarboxylic acid cycle
modified	[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType	Protein
name	IDH3A
otherIdentifier	11737792_a_at 11737793_a_at 11745965_a_at 11749830_a_at 11756565_x_at 16803436 202069_PM_s_at 202069_s_at 202070_PM_s_at 202070_s_at 231137_PM_at 231137_at 3419 3603200 3603201 3603206 3603210 3603211 3603212 3603213 3603214 3603215 3603216 3603217 3603218 3603219 3603220 3603221 3603222 3603223 3603224 3603225 3603226 3603228 3603229 3603231 3603232 3603233 3603234 3603235 3603236 3603237 3603238 3603240 36195_at 7985134 81140_at A_14_P102928 A_14_P111891 A_14_P127327 A_14_P133899 A_23_P140668 A_24_P167806 GE593140 GE79752 GO:0000287 GO:0004449 GO:0005515 GO:0005634 GO:0005739 GO:0005759 GO:0005975 GO:0006099 GO:0006102 GO:0016491 GO:0016616 GO:0045242 GO:0046872 GO:0051287 HMNXSV003037515 Hs.116413.0.A1_3p_at Hs.250616.0.S1_3p_a_at ILMN_1698533 PH_hs_0013268 TC15000724.hg TC15002299.hg U07681_at g5031776_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-70962] IDH3A [mitochondrial matrix] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:12710030] UCSC:P50213 IDH3A [ReferenceDNASequence:12109783] OMIM:601149 IDH3A [ReferenceDNASequence:12090555] NCBI Gene:3419 IDH3A [ReferenceDNASequence:12006462] Monarch:3419 IDH3A [ReferenceDNASequence:11914148] KEGG:hsa:3419 IDH3A [ReferenceDNASequence:11818405] HGNC:5384 IDH3A [ReferenceDNASequence:11431724] dbSNP Gene:3419 IDH3A [ReferenceDNASequence:11412067] CTD Gene:3419 IDH3A [ReferenceDNASequence:11395489] COSMIC - genes:IDH3A IDH3A [ReferenceDNASequence:11376673] BioGPS Gene:3419 IDH3A [ReferenceDNASequence:ensembl:ENSG00000166411] ENSEMBL:ENSG00000166411 IDH3A
referenceTranscript	[ReferenceRNASequence:12634248] RefSeq:NM_005530.3 IDH3A
schemaClass	ReferenceGeneProduct
secondaryIdentifier	IDH3A_HUMAN D3DW83 Q9H3X0
sequenceLength	366
species	[Species:48887] Homo sapiens
stId	uniprot:P50213
url	http://purl.uniprot.org/uniprot/P50213

Referrals

(interactor)	[UndirectedInteraction:11149011] UniProt:P13569 <-> UniProt:P50213 (IntAct)
(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-70962] IDH3A [mitochondrial matrix]

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