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Protein

Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial

Gene

IDH3G

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

Cofactori

Mg2+2 Publications, Mn2+1 PublicationNote: Divalent metal cations; Mn2+ or Mg2+. Activity higher in presence of Mn2+ than of Mg2+. Binds 1 Mg2+ or Mn2+ ion per subunit.1 Publication

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.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei120Allosteric activator citrate1 Publication1
Binding sitei133Allosteric activator citrate1 Publication1
Binding sitei136Substrate1 Publication1
Binding sitei167Substrate1 Publication1
Metal bindingi254Magnesium or manganese; shared with catalytic subunit1 Publication1
Binding sitei254Substrate1 Publication1
Binding sitei312Allosteric activator ADP1 Publication1
Binding sitei313Allosteric activator ADP1 Publication1
Binding sitei324Allosteric activator ADP1 Publication1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • isocitrate dehydrogenase (NAD+) activity Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • NAD binding Source: InterPro

GO - Biological processi

  • carbohydrate metabolic process Source: ProtInc
  • isocitrate metabolic process Source: UniProtKB
  • tricarboxylic acid cycle Source: UniProtKB-KW

Keywordsi

Biological processTricarboxylic acid cycle
LigandATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000067829-MONOMER
ReactomeiR-HSA-1268020 Mitochondrial protein import
R-HSA-71403 Citric acid cycle (TCA cycle)
SABIO-RKiP51553

Names & Taxonomyi

Protein namesi
Recommended name:
Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial
Alternative name(s):
Isocitric dehydrogenase subunit gamma
NAD(+)-specific ICDH subunit gamma
Gene namesi
Name:IDH3G
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000067829.18
HGNCiHGNC:5386 IDH3G
MIMi300089 gene
neXtProtiNX_P51553

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi117N → A: No effect on the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate. 1 Publication1
Mutagenesisi120T → A: Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate. 1 Publication1
Mutagenesisi130S → A: No significant effect on the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate. 1 Publication1
Mutagenesisi133N → A: Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate. 1 Publication1
Mutagenesisi136R → A: Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate. 1 Publication1
Mutagenesisi167R → A: Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate. 1 Publication1
Mutagenesisi173E → A: No effect on the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate and ADP. 1 Publication1
Mutagenesisi174Y → F: Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate. 1 Publication1
Mutagenesisi190K → A: Complete loss of the activation of the heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits by citrate and ADP. 2 Publications1
Mutagenesisi229D → A: Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate and ADP. 1 Publication1
Mutagenesisi276Y → F: Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate and ADP. 1 Publication1
Mutagenesisi311R → A: Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate. 1 Publication1
Mutagenesisi312N → A: Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by ADP. 1 Publication1
Mutagenesisi313T → A: Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by ADP. 1 Publication1
Mutagenesisi315K → A: No significant effect on the activation of the heterodimer composed of IDH3A and IDH3G subunits by ADP. 1 Publication1
Mutagenesisi324N → A: Complete loss of the activation of the heterodimer composed of IDH3A and IDH3G subunits by ADP. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000067829
PharmGKBiPA29634

Chemistry databases

DrugBankiDB00157 NADH

Polymorphism and mutation databases

BioMutaiIDH3G
DMDMi1708404

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 39MitochondrionBy similarityAdd BLAST39
ChainiPRO_000001444940 – 393Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrialAdd BLAST354

Proteomic databases

EPDiP51553
MaxQBiP51553
PaxDbiP51553
PeptideAtlasiP51553
PRIDEiP51553
ProteomicsDBi56332

PTM databases

iPTMnetiP51553
PhosphoSitePlusiP51553

Expressioni

Gene expression databases

BgeeiENSG00000067829 Expressed in 230 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_IDH3G
ExpressionAtlasiP51553 baseline and differential
GenevisibleiP51553 HS

Organism-specific databases

HPAiHPA000425
HPA002017

Interactioni

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.2 Publications

Protein-protein interaction databases

BioGridi109647, 28 interactors
ComplexPortaliCPX-553 Mitochondrial isocitrate dehydrogenase complex (NAD+)
IntActiP51553, 4 interactors
STRINGi9606.ENSP00000217901

Structurei

Secondary structure

1393
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP51553
SMRiP51553
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0784 Eukaryota
COG0473 LUCA
GeneTreeiENSGT00590000083091
HOGENOMiHOG000021113
HOVERGENiHBG052080
InParanoidiP51553
KOiK00030
OMAiGTSMFEP
OrthoDBiEOG091G094X
PhylomeDBiP51553
TreeFamiTF315033

Family and domain databases

InterProiView protein in InterPro
IPR019818 IsoCit/isopropylmalate_DH_CS
IPR004434 Isocitrate_DH_NAD
IPR024084 IsoPropMal-DH-like_dom
PfamiView protein in Pfam
PF00180 Iso_dh, 1 hit
SMARTiView protein in SMART
SM01329 Iso_dh, 1 hit
TIGRFAMsiTIGR00175 mito_nad_idh, 1 hit
PROSITEiView protein in PROSITE
PS00470 IDH_IMDH, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: P51553-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MALKVATVAG SAAKAVLGPA LLCRPWEVLG AHEVPSRNIF SEQTIPPSAK
60 70 80 90 100
YGGRHTVTMI PGDGIGPELM LHVKSVFRHA CVPVDFEEVH VSSNADEEDI
110 120 130 140 150
RNAIMAIRRN RVALKGNIET NHNLPPSHKS RNNILRTSLD LYANVIHCKS
160 170 180 190 200
LPGVVTRHKD IDILIVRENT EGEYSSLEHE SVAGVVESLK IITKAKSLRI
210 220 230 240 250
AEYAFKLAQE SGRKKVTAVH KANIMKLGDG LFLQCCREVA ARYPQITFEN
260 270 280 290 300
MIVDNTTMQL VSRPQQFDVM VMPNLYGNIV NNVCAGLVGG PGLVAGANYG
310 320 330 340 350
HVYAVFETAT RNTGKSIANK NIANPTATLL ASCMMLDHLK LHSYATSIRK
360 370 380 390
AVLASMDNEN MHTPDIGGQG TTSEAIQDVI RHIRVINGRA VEA
Length:393
Mass (Da):42,794
Last modified:October 1, 1996 - v1
Checksum:iA0870F2B7D228A37
GO
Isoform 2 (identifier: P51553-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     361-393: MHTPDIGGQGTTSEAIQDVIRHIRVINGRAVEA → VRFPSHPTLLPRPVSPCSLL

Note: Gene prediction based on EST data.
Show »
Length:380
Mass (Da):41,468
Checksum:i2D5987CC70725245
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti267F → L in AAH01902 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_046771361 – 393MHTPD…RAVEA → VRFPSHPTLLPRPVSPCSLL in isoform 2. CuratedAdd BLAST33

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z68907 mRNA Translation: CAA93143.1
Z68129 Genomic DNA Translation: CAA92214.1
U52111 Genomic DNA No translation available.
U40272 mRNA Translation: AAD09357.1
BC000933 mRNA Translation: AAH00933.1
BC001902 mRNA Translation: AAH01902.1
CCDSiCCDS14730.1 [P51553-1]
CCDS44019.1 [P51553-2]
RefSeqiNP_004126.1, NM_004135.3 [P51553-1]
NP_777358.1, NM_174869.2 [P51553-2]
UniGeneiHs.410197

Genome annotation databases

EnsembliENST00000217901; ENSP00000217901; ENSG00000067829 [P51553-1]
ENST00000370092; ENSP00000359110; ENSG00000067829 [P51553-2]
GeneIDi3421
KEGGihsa:3421
UCSCiuc004fip.4 human [P51553-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z68907 mRNA Translation: CAA93143.1
Z68129 Genomic DNA Translation: CAA92214.1
U52111 Genomic DNA No translation available.
U40272 mRNA Translation: AAD09357.1
BC000933 mRNA Translation: AAH00933.1
BC001902 mRNA Translation: AAH01902.1
CCDSiCCDS14730.1 [P51553-1]
CCDS44019.1 [P51553-2]
RefSeqiNP_004126.1, NM_004135.3 [P51553-1]
NP_777358.1, NM_174869.2 [P51553-2]
UniGeneiHs.410197

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5GREX-ray2.65B40-393[»]
5GRFX-ray2.50B40-393[»]
5GRHX-ray2.80B40-393[»]
5GRIX-ray2.31B40-393[»]
5GRLX-ray2.79B40-393[»]
5YVTX-ray2.40B40-393[»]
ProteinModelPortaliP51553
SMRiP51553
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109647, 28 interactors
ComplexPortaliCPX-553 Mitochondrial isocitrate dehydrogenase complex (NAD+)
IntActiP51553, 4 interactors
STRINGi9606.ENSP00000217901

Chemistry databases

DrugBankiDB00157 NADH

PTM databases

iPTMnetiP51553
PhosphoSitePlusiP51553

Polymorphism and mutation databases

BioMutaiIDH3G
DMDMi1708404

Proteomic databases

EPDiP51553
MaxQBiP51553
PaxDbiP51553
PeptideAtlasiP51553
PRIDEiP51553
ProteomicsDBi56332

Protocols and materials databases

DNASUi3421
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000217901; ENSP00000217901; ENSG00000067829 [P51553-1]
ENST00000370092; ENSP00000359110; ENSG00000067829 [P51553-2]
GeneIDi3421
KEGGihsa:3421
UCSCiuc004fip.4 human [P51553-1]

Organism-specific databases

CTDi3421
EuPathDBiHostDB:ENSG00000067829.18
GeneCardsiIDH3G
HGNCiHGNC:5386 IDH3G
HPAiHPA000425
HPA002017
MIMi300089 gene
neXtProtiNX_P51553
OpenTargetsiENSG00000067829
PharmGKBiPA29634
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0784 Eukaryota
COG0473 LUCA
GeneTreeiENSGT00590000083091
HOGENOMiHOG000021113
HOVERGENiHBG052080
InParanoidiP51553
KOiK00030
OMAiGTSMFEP
OrthoDBiEOG091G094X
PhylomeDBiP51553
TreeFamiTF315033

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000067829-MONOMER
ReactomeiR-HSA-1268020 Mitochondrial protein import
R-HSA-71403 Citric acid cycle (TCA cycle)
SABIO-RKiP51553

Miscellaneous databases

ChiTaRSiIDH3G human
GeneWikiiIDH3G
GenomeRNAii3421
PROiPR:P51553
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000067829 Expressed in 230 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_IDH3G
ExpressionAtlasiP51553 baseline and differential
GenevisibleiP51553 HS

Family and domain databases

InterProiView protein in InterPro
IPR019818 IsoCit/isopropylmalate_DH_CS
IPR004434 Isocitrate_DH_NAD
IPR024084 IsoPropMal-DH-like_dom
PfamiView protein in Pfam
PF00180 Iso_dh, 1 hit
SMARTiView protein in SMART
SM01329 Iso_dh, 1 hit
TIGRFAMsiTIGR00175 mito_nad_idh, 1 hit
PROSITEiView protein in PROSITE
PS00470 IDH_IMDH, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiIDH3G_HUMAN
AccessioniPrimary (citable) accession number: P51553
Secondary accession number(s): E9PDD5, Q9BUU5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: September 12, 2018
This is version 189 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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