IDH2

Protein identityUniProt · HPA

UniProt accession

P48735

Gene

IDH2

Ensembl

ENSG00000182054

Chromosome

15

Canonical length

452 aa

Protein class

Cancer-related genes, Citric acid cycle related proteins, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Mitochondria

Quaternary structure

Homodimer

OverviewNCBI Gene

Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. Each NADP(+)-dependent isozyme is a homodimer. The protein encoded by this gene is the NADP(+)-dependent isocitrate dehydrogenase found in the mitochondria. It plays a role in intermediary metabolism and energy production. This protein may tightly associate or interact with the pyruvate dehydrogenase complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

Canonical amino-acid sequenceUniProt

452 residues, UniProt reviewed canonical sequence.

>P48735|IDH2
     1  MAGYLRVVRS LCRASGSRPA WAPAALTAPT SQEQPRRHYA DKRIKVAKPV VEMDGDEMTR
    61  IIWQFIKEKL ILPHVDIQLK YFDLGLPNRD QTDDQVTIDS ALATQKYSVA VKCATITPDE
   121  ARVEEFKLKK MWKSPNGTIR NILGGTVFRE PIICKNIPRL VPGWTKPITI GRHAHGDQYK
   181  ATDFVADRAG TFKMVFTPKD GSGVKEWEVY NFPAGGVGMG MYNTDESISG FAHSCFQYAI
   241  QKKWPLYMST KNTILKAYDG RFKDIFQEIF DKHYKTDFDK NKIWYEHRLI DDMVAQVLKS
   301  SGGFVWACKN YDGDVQSDIL AQGFGSLGLM TSVLVCPDGK TIEAEAAHGT VTRHYREHQK
   361  GRPTSTNPIA SIFAWTRGLE HRGKLDGNQD LIRFAQMLEK VCVETVESGA MTKDLAGCIH
   421  GLSNVKLNEH FLNTTDFLDT IKSNLDRALG RQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IDH2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

1,504 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IDH2.

Disease | AllUniProt

Conditions IDH2 is implicated in, by any mechanism.

• D-2-hydroxyglutaric aciduria 2 (D2HGA2) MIM:613657
• Glioma (GLM) MIM:137800

Disease | GeneticClinVar

6 pathogenic / likely-pathogenic of 292 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• D-2-hydroxyglutaric aciduria 2
• Neoplasm
• Inborn genetic diseases
• IDH2-related mitochondrial disease
• Maffucci syndrome

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.38

gnomAD pLI

0.88

gnomAD missense Z

1.34

DepMap mean gene effect

-0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• 2-oxoglutarate metabolic process
• carbohydrate metabolic process
• glyoxylate cycle
• isocitrate metabolic process
• NADP+ biosynthetic process
• NADP+ metabolic process
• negative regulation of glial cell migration
• negative regulation of glial cell proliferation
• negative regulation of matrix metallopeptidase secretion
• tricarboxylic acid cycle

Molecular functions

• isocitrate dehydrogenase (NADP+) activity
• magnesium ion binding
• NAD binding

Cellular components

• cytosol
• extracellular exosome
• mitochondrial matrix
• mitochondrion
• peroxisome

Protein domainsUniProt · Pfam · InterPro

• Isocitrate dehydrogenase NADP-dependent
• Isocitrate/isopropylmalate dehydrogenase, conserved site
• Isopropylmalate dehydrogenase-like domain
• Isocitrate/isopropylmalate dehydrogenase

KeywordsUniProt

• Acetylation
• Glyoxylate bypass
• Magnesium
• Manganese
• Metal-binding
• Mitochondrion
• NADP
• Oxidoreductase
• Transit peptide
• Tricarboxylic acid cycle

InteractionsUniProt · HPA

Protein binding partners of IDH2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SIRT3