ME2

Protein identityUniProt · HPA

UniProt accession

P23368

Gene

ME2

Ensembl

ENSG00000082212

Chromosome

18

Canonical length

584 aa

Protein class

Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Mitochondria

Quaternary structure

Homotetramer

OverviewNCBI Gene

This gene encodes a mitochondrial NAD-dependent malic enzyme, a homotetrameric protein, that catalyzes the oxidative decarboxylation of malate to pyruvate. It had previously been weakly linked to a syndrome known as Friedreich ataxia that has since been shown to be the result of mutation in a completely different gene. Certain single-nucleotide polymorphism haplotypes of this gene have been shown to increase the risk for idiopathic generalized epilepsy. Alternatively spliced transcript variants encoding different isoforms found for this gene. [provided by RefSeq, Dec 2009]

Canonical amino-acid sequenceUniProt

584 residues, UniProt reviewed canonical sequence.

>P23368|ME2
     1  MLSRLRVVST TCTLACRHLH IKEKGKPLML NPRTNKGMAF TLQERQMLGL QGLLPPKIET
    61  QDIQALRFHR NLKKMTSPLE KYIYIMGIQE RNEKLFYRIL QDDIESLMPI VYTPTVGLAC
   121  SQYGHIFRRP KGLFISISDR GHVRSIVDNW PENHVKAVVV TDGERILGLG DLGVYGMGIP
   181  VGKLCLYTAC AGIRPDRCLP VCIDVGTDNI ALLKDPFYMG LYQKRDRTQQ YDDLIDEFMK
   241  AITDRYGRNT LIQFEDFGNH NAFRFLRKYR EKYCTFNDDI QGTAAVALAG LLAAQKVISK
   301  PISEHKILFL GAGEAALGIA NLIVMSMVEN GLSEQEAQKK IWMFDKYGLL VKGRKAKIDS
   361  YQEPFTHSAP ESIPDTFEDA VNILKPSTII GVAGAGRLFT PDVIRAMASI NERPVIFALS
   421  NPTAQAECTA EEAYTLTEGR CLFASGSPFG PVKLTDGRVF TPGQGNNVYI FPGVALAVIL
   481  CNTRHISDSV FLEAAKALTS QLTDEELAQG RLYPPLANIQ EVSINIAIKV TEYLYANKMA
   541  FRYPEPEDKA KYVKERTWRS EYDSLLPDVY EWPESASSPP VITE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ME2 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)

0.23

Highest tissue expression

86 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ME2.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 105 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• See cases

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)

1.06

gnomAD pLI

0

gnomAD missense Z

0.97

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• malate metabolic process
• regulation of NADP metabolic process

Molecular functions

• electron transfer activity
• malate dehydrogenase (decarboxylating) (NADP+) activity
• malic enzyme activity
• metal ion binding
• NAD binding
• oxaloacetate decarboxylase activity
• malate dehydrogenase (decarboxylating) (NAD+) activity

Cellular components

• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Malic oxidoreductase
• Malic enzyme, N-terminal domain
• Malic enzyme, NAD-binding
• Malic enzyme, conserved site
• NAD(P)-binding domain superfamily
• Malic enzyme, N-terminal domain superfamily
• Aminoacid dehydrogenase-like, N-terminal domain superfamily
• Malic enzyme, N-terminal domain
• Malic enzyme, NAD binding domain

KeywordsUniProt

• Acetylation
• Allosteric enzyme
• Metal-binding
• Mitochondrion
• NAD
• Oxidoreductase
• Transit peptide