MDH1

Protein identityUniProt · HPA

UniProt accession

P40925

Gene

MDH1

Ensembl

ENSG00000014641

Chromosome

2

Canonical length

334 aa

Protein class

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

Subcellular location

Centrosome,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes an enzyme that catalyzes the NAD/NADH-dependent, reversible oxidation of malate to oxaloacetate in many metabolic pathways, including the citric acid cycle. Two main isozymes are known to exist in eukaryotic cells: one is found in the mitochondrial matrix and the other in the cytoplasm. This gene encodes the cytosolic isozyme, which plays a key role in the malate-aspartate shuttle that allows malate to pass through the mitochondrial membrane to be transformed into oxaloacetate for further cellular processes. Alternatively spliced transcript variants have been found for this gene. A recent study showed that a C-terminally extended isoform is produced by use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism, and that this isoform is localized in the peroxisomes. Pseudogenes have been identified on chromosomes X and 6. [provided by RefSeq, Feb 2016]

Canonical amino-acid sequenceUniProt

334 residues, UniProt reviewed canonical sequence.

>P40925|MDH1
     1  MSEPIRVLVT GAAGQIAYSL LYSIGNGSVF GKDQPIILVL LDITPMMGVL DGVLMELQDC
    61  ALPLLKDVIA TDKEDVAFKD LDVAILVGSM PRREGMERKD LLKANVKIFK SQGAALDKYA
   121  KKSVKVIVVG NPANTNCLTA SKSAPSIPKE NFSCLTRLDH NRAKAQIALK LGVTANDVKN
   181  VIIWGNHSST QYPDVNHAKV KLQGKEVGVY EALKDDSWLK GEFVTTVQQR GAAVIKARKL
   241  SSAMSAAKAI CDHVRDIWFG TPEGEFVSMG VISDGNSYGV PDDLLYSFPV VIKNKTWKFV
   301  EGLPINDFSR EKMDLTAKEL TEEKESAFEF LSSA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MDH1 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)

0.24

Highest tissue expression

1,722 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MDH1.

Disease | AllUniProt

Conditions MDH1 is implicated in, by any mechanism.

• Developmental and epileptic encephalopathy 88 (DEE88) MIM:618959

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 58 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Developmental and epileptic encephalopathy, 88

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)

0.37

gnomAD pLI

0.93

gnomAD missense Z

1.18

DepMap mean gene effect

-0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• malate metabolic process
• malate-aspartate shuttle
• NAD+ metabolic process
• NADP+ metabolic process
• oxaloacetate metabolic process
• tricarboxylic acid cycle

Molecular functions

• L-malate dehydrogenase (NAD+) activity
• malic enzyme activity
• (2R)-hydroxyphenylpyruvate reductase [NAD(P)H] activity
• diiodophenylpyruvate reductase (NAD+) activity

Cellular components

• centrosome
• cytoplasm
• cytosol
• extracellular exosome
• extracellular space

Protein domainsUniProt · Pfam · InterPro

• Lactate/malate dehydrogenase, N-terminal
• Malate dehydrogenase, active site
• L-lactate/malate dehydrogenase
• Malate dehydrogenase, type 2
• 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, NAD-dependent, cytosolic

KeywordsUniProt

• Acetylation
• Cytoplasm
• Epilepsy
• Methylation
• NAD
• Oxidoreductase
• Phosphoprotein
• Tricarboxylic acid cycle
• Ubl conjugation