MDH2

Protein identityUniProt · HPA

UniProt accession

P40926

Gene

MDH2

Ensembl

ENSG00000146701

Chromosome

7

Canonical length

338 aa

Protein class

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

Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. The protein encoded by this gene is localized to the mitochondria and may play pivotal roles in the malate-aspartate shuttle that operates in the metabolic coordination between cytosol and mitochondria. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

Canonical amino-acid sequenceUniProt

338 residues, UniProt reviewed canonical sequence.

>P40926|MDH2
     1  MLSALARPAS AALRRSFSTS AQNNAKVAVL GASGGIGQPL SLLLKNSPLV SRLTLYDIAH
    61  TPGVAADLSH IETKAAVKGY LGPEQLPDCL KGCDVVVIPA GVPRKPGMTR DDLFNTNATI
   121  VATLTAACAQ HCPEAMICVI ANPVNSTIPI TAEVFKKHGV YNPNKIFGVT TLDIVRANTF
   181  VAELKGLDPA RVNVPVIGGH AGKTIIPLIS QCTPKVDFPQ DQLTALTGRI QEAGTEVVKA
   241  KAGAGSATLS MAYAGARFVF SLVDAMNGKE GVVECSFVKS QETECTYFST PLLLGKKGIE
   301  KNLGIGKVSS FEEKMISDAI PELKASIKKG EDFVKTLK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MDH2 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)

0.27

Highest tissue expression

653 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MDH2.

Disease | AllUniProt

Conditions MDH2 is implicated in, by any mechanism.

• Developmental and epileptic encephalopathy 51 (DEE51) MIM:617339

Disease | GeneticClinVar

21 pathogenic / likely-pathogenic of 736 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Developmental and epileptic encephalopathy, 51
• Infantile encephalopathy
• Inborn genetic diseases

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)

0.81

gnomAD pLI

0.01

gnomAD missense Z

0.03

DepMap mean gene effect

-0.23

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 9% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• aerobic respiration
• gluconeogenesis
• malate metabolic process
• malate-aspartate shuttle
• tricarboxylic acid cycle

Molecular functions

• identical protein binding
• L-malate dehydrogenase (NAD+) activity
• RNA binding
• L-malate dehydrogenase (NADP+) activity

Cellular components

• cytoplasm
• extracellular exosome
• membrane
• mitochondrial matrix
• mitochondrion
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Lactate/malate dehydrogenase, N-terminal
• Malate dehydrogenase, active site
• L-lactate/malate dehydrogenase
• Lactate dehydrogenase/glycoside hydrolase, family 4, C-terminal
• Lactate/malate dehydrogenase, C-terminal
• NAD(P)-binding domain superfamily
• lactate/malate dehydrogenase, NAD binding domain
• lactate/malate dehydrogenase, alpha/beta C-terminal domain
• Malate dehydrogenase, type 1

KeywordsUniProt

• Acetylation
• Epilepsy
• Glycoprotein
• Mitochondrion
• NAD
• Oxidoreductase
• Phosphoprotein
• Transit peptide
• Tricarboxylic acid cycle

InteractionsUniProt · HPA

Protein binding partners of MDH2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CLIP1