ME1 (Malic Enzyme 1): A Key Metabolic Regulator in Lipogenesis and Cellular Redox Homeostasis
Comprehensive gene overview of ME1, its genomic context, protein function, expression patterns, and clinical relevance in metabolic and oncogenic pathways.
Gene Information Card
| Symbol | ME1 |
|---|---|
| Full Name | Malic Enzyme 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q12 |
| NCBI Gene ID | 4199 ncbi.nlm.nih.gov/gene/4199 |
| Ensembl ID | ENSG00000065882 |
| UniProt ID | P48163 |
| OMIM ID | 154250 |
| HGNC ID | 6984 |
| Aliases | MALIC-1, MES, NADP-ME, cytosolic malic enzyme 1 |
Description
The ME1 gene encodes the cytosolic malic enzyme 1, a homotetrameric protein that catalyzes the oxidative decarboxylation of L-malate to pyruvate, producing NADPH and CO2. This reaction is a critical source of NADPH for fatty acid biosynthesis and for maintaining cellular redox balance against oxidative stress. ME1 is highly expressed in lipogenic tissues and is frequently upregulated in various cancers, where it supports anabolic metabolism and tumor growth. Its activity links glucose and glutamine metabolism to lipid synthesis, making it a potential therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | ME1 overexpression supports cancer cell proliferation by providing NADPH for de novo lipogenesis and antioxidant defense. It is implicated in tumor growth, metastasis, and poor prognosis in cancers such as colorectal, lung, and breast cancer. | High expression observed in tumor tissues; knockdown studies show reduced cell proliferation and increased oxidative stress. |
| Metabolic Syndrome / Obesity | ME1 is involved in lipid metabolism; its activity is associated with fatty acid synthesis in adipose tissue and liver. Dysregulation may contribute to metabolic disorders. | Animal models with altered ME1 activity show changes in fat accumulation and insulin sensitivity. |
| Neuroblastoma | ME1 expression is linked to MYCN-amplified neuroblastoma, where it contributes to metabolic reprogramming and tumor aggressiveness. | Studies show ME1 is a downstream target of MYCN and is required for tumor cell survival. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose Tissue | High | High expression in subcutaneous and visceral fat, consistent with its role in lipogenesis. |
| Liver | High | Expressed in hepatocytes, supporting fatty acid synthesis. |
| Adrenal Gland | High | Expression in steroidogenic tissues for NADPH supply. |
| Breast | Medium | Moderate expression; elevated in some breast cancer subtypes. |
| Lung | Medium | Moderate expression; upregulated in lung cancer. |
| Brain | Low | Low expression in normal brain tissue. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (Liver) | High | Liver cancer cell line with high lipogenic activity. |
| MCF7 (Breast) | Medium | Breast cancer cell line; expression correlates with estrogen receptor status. |
| A549 (Lung) | Medium | Lung carcinoma cell line. |
| HeLa (Cervical) | Medium | Cervical cancer cell line. |
| K562 (Leukemia) | Low | Chronic myeloid leukemia cell line with low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.757G>A (p.Ala253Thr) | Missense | Rare (MAF < 0.01) | Reported in ClinVar; functional impact not fully characterized, may affect enzyme activity. |
| c.1159C>T (p.Arg387Cys) | Missense | Rare | Potential loss-of-function variant; found in population databases. |
| c.888+1G>A | Splice donor | Rare | Predicted to disrupt splicing; likely leads to loss of function. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ME1 are rare and not well characterized. They are predicted to reduce NADPH production, potentially impairing lipogenesis and cellular antioxidant capacity. No specific disease phenotype has been firmly established for germline loss-of-function mutations.
Gain of Function (GOF)
Gain-of-function is primarily observed through gene amplification or transcriptional upregulation in cancers, rather than through specific activating mutations. Increased ME1 expression enhances NADPH supply and promotes tumor growth.
Dominant Negative (DN)
No dominant-negative mutations have been reported for ME1. The enzyme functions as a homotetramer, and it is unclear if mutant subunits could interfere with wild-type function.
View complete mutation data：
Gene Ontology (GO)
| • Malic enzyme activity | • Oxidoreductase activity |
| • NADP binding | • Metal ion binding |
| • Malate dehydrogenase (decarboxylating) (NADP+) activity | • Cytoplasm |
| • Cytosol | • Lipid biosynthetic process |
| • NADPH regeneration | • Pyruvate metabolic process |
| • Carbohydrate metabolic process |
Pathways
• Pyruvate metabolism
• Fatty acid biosynthesis
• Metabolic reprogramming in cancer
• Glutathione-mediated detoxification (via NADPH)
• Tricarboxylic acid (TCA) cycle (anaplerotic/cataplerotic)
Protein Summary
The ME1 protein (UniProt P48163) is a 572-amino-acid cytosolic enzyme that forms a homotetramer. It requires a divalent metal ion (Mn2+ or Mg2+) for catalytic activity. The enzyme catalyzes the reversible oxidative decarboxylation of malate to pyruvate, concomitantly reducing NADP+ to NADPH. This reaction is a major source of NADPH in the cytosol, essential for reductive biosynthesis (fatty acids, cholesterol) and for the regeneration of reduced glutathione, protecting cells from oxidative damage. ME1 is a key node connecting glycolysis, glutaminolysis, and lipid metabolism. Its expression is regulated by sterol regulatory element-binding proteins (SREBPs) and is often elevated in proliferating cells and tumors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| YME1L1 Knockout HEK293 Cell Line | EDJ-KQ971 | Human | 10730 | Details Get a Quote |
| PSME1 Knockout HEK293 Cell Line | EDJ-KQ2869 | Human | 5720 | Details Get a Quote |
| ME1 Knockout HEK293 Cell Line | EDJ-KQ5192 | Human | 4199 | Details Get a Quote |
| EME1 Knockout HEK293 Cell Line | EDJ-KQ9815 | Human | 146956 | Details Get a Quote |
| MGME1 Knockout HEK293 Cell Line | EDJ-KQ11015 | Human | 92667 | Details Get a Quote |
| PPME1 Knockout HEK293 Cell Line | EDJ-KQ11088 | Human | 51400 | Details Get a Quote |
| BRME1 Knockout HEK293 Cell Line | EDJ-KQ12569 | Human | 79173 | Details Get a Quote |
| YME1L1 Knockout HCT 116 Cell Line | EDJ-KQ19981 | Human | 10730 | Details Get a Quote |
| YME1L1 Knockout HeLa Cell Line | EDJ-KQ19982 | Human | 10730 | Details Get a Quote |
| ME1 Knockout A-549 Cell Line | EDJ-KQ28182 | Human | 4199 | Details Get a Quote |
| ME1 Knockout HCT 116 Cell Line | EDJ-KQ28183 | Human | 4199 | Details Get a Quote |
| ME1 Knockout HeLa Cell Line | EDJ-KQ28184 | Human | 4199 | Details Get a Quote |
| EME1 Knockout A-549 Cell Line | EDJ-KQ37956 | Human | 146956 | Details Get a Quote |
| EME1 Knockout HCT 116 Cell Line | EDJ-KQ37957 | Human | 146956 | Details Get a Quote |
| EME1 Knockout HeLa Cell Line | EDJ-KQ37958 | Human | 146956 | Details Get a Quote |
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