METAP2: Methionine Aminopeptidase 2 – A Key Regulator of Protein Processing and Angiogenesis
Comprehensive genomic, transcriptomic, and proteomic overview of METAP2, including its role in cancer, genetic variants, and expression profiles.
Gene Information Card
| Symbol | METAP2 |
|---|---|
| Full Name | methionyl aminopeptidase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q22 |
| NCBI Gene ID | 10988 ncbi.nlm.nih.gov/gene/10988 |
| Ensembl ID | ENSG00000111144 |
| UniProt ID | P50579 |
| OMIM ID | 601870 |
| HGNC ID | 6987 |
| Aliases | MAP2, MNPEP, p67eIF2, MetAP2 |
Description
METAP2 (methionyl aminopeptidase 2) encodes a member of the methionine aminopeptidase family that catalyzes the removal of N-terminal methionine from nascent proteins, a critical step for protein stability and function. The protein also possesses eIF2α phosphorylation-independent anti-apoptotic activity and is a target of the angiogenesis inhibitor fumagillin. METAP2 is involved in cell cycle regulation, angiogenesis, and tumor growth.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Overexpression promotes angiogenesis and cell proliferation; inhibition reduces tumor growth | COSMIC, ClinVar, PubMed |
| Obesity | Genetic variants associated with body mass index in GWAS | ClinVar, PubMed |
| Neurodevelopmental disorders | Rare missense variants reported in patients with intellectual disability | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Heart | 12.8 | Medium |
| Liver | 18.5 | High |
| Kidney | 14.1 | Medium |
| Lung | 11.3 | Medium |
| Testis | 20.7 | High |
| Pancreas | 9.6 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 22.4 | Cervical cancer cell line |
| A549 | 18.9 | Lung cancer cell line |
| MCF7 | 16.3 | Breast cancer cell line |
| HEK293 | 14.7 | Embryonic kidney cell line |
| K562 | 12.1 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123G>A (p.Gly375Arg) | Missense | 0.02% (gnomAD) | Unknown functional impact; reported in ClinVar |
| c.1465C>T (p.Arg489Trp) | Missense | 0.01% (gnomAD) | Associated with neurodevelopmental disorder in ClinVar |
| c.1A>G (p.Met1?) | Start loss | Rare | Likely loss of function; reported in COSMIC |
Mutation functional classification
Loss of Function (LOF)
Start loss and nonsense mutations are predicted to cause loss of function, reducing methionine aminopeptidase activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in curated databases.
Dominant Negative (DN)
No dominant-negative mutations described in literature or databases.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Angiogenesis (KEGG hsa04370)
• Protein processing in endoplasmic reticulum (KEGG hsa04141)
• Methionine metabolism
Protein Summary
METAP2 is a 478-amino-acid protein that functions as a homodimeric metalloprotease. It removes N-terminal methionine from nascent polypeptides, a prerequisite for subsequent N-terminal modifications. The protein also binds to eIF2α and inhibits its phosphorylation, thereby protecting cells from apoptosis. METAP2 is the target of the anti-angiogenic drug fumagillin and its analogs, which covalently modify the active-site histidine. The protein is widely expressed, with highest levels in testis and liver.
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