PCMT1 Gene: Protein-L-Isoaspartate (D-Aspartate) O-Methyltransferase 1
A key protein repair enzyme involved in protein damage repair, cellular aging, and neurodegeneration.
Gene Information Card
| Symbol | PCMT1 |
|---|---|
| Full Name | Protein-L-isoaspartate (D-aspartate) O-methyltransferase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q25.1 |
| NCBI Gene ID | 5110 ncbi.nlm.nih.gov/gene/5110 |
| Ensembl ID | ENSG00000120265 |
| UniProt ID | P22061 |
| OMIM ID | 176850 |
| HGNC ID | 8728 |
| Aliases | PIMT, MGC12458, DKFZp686L24168 |
Description
PCMT1 encodes protein-L-isoaspartate (D-aspartate) O-methyltransferase, an enzyme that repairs damaged proteins by catalyzing the methylation of L-isoaspartyl and D-aspartyl residues. This repair mechanism is crucial for maintaining protein integrity under physiological stress and aging. The enzyme is widely expressed and plays a role in cellular homeostasis, neuronal function, and protection against protein aggregation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer's disease | Reduced PCMT1 activity leads to accumulation of isoaspartate-modified proteins, contributing to amyloid plaque formation and neurodegeneration. | ClinVar, PubMed |
| Parkinson's disease | Impaired protein repair may exacerbate alpha-synuclein aggregation and dopaminergic neuron loss. | ClinVar, PubMed |
| Cancer (various types) | Altered PCMT1 expression affects cell proliferation and apoptosis; mutations may influence tumor progression. | COSMIC, PubMed |
| Aging-related disorders | Decline in PCMT1 activity with age correlates with increased protein damage and cellular senescence. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High |
| Heart | Medium | Medium |
| Liver | Medium | Medium |
| Kidney | Medium | Medium |
| Testis | High | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | High | Cervical cancer cell line |
| HEK293 | High | Embryonic kidney cells |
| SH-SY5Y | High | Neuroblastoma cell line |
| HepG2 | Medium | Liver cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.482C>T (p.Ala161Val) | Missense | Rare | Reduced enzyme activity, associated with neurological phenotypes |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of protein expression, potential loss-of-function |
| c.374G>A (p.Arg125His) | Missense | Rare | Altered substrate binding, reduced catalytic efficiency |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish methyltransferase activity, leading to accumulation of damaged proteins.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression may have oncogenic effects in some cancers.
Dominant Negative (DN)
Not well characterized; some missense variants may interfere with dimerization, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • protein-L-isoaspartate (D-aspartate) O-methyltransferase activity | • methyltransferase activity |
| • protein repair | • response to oxidative stress |
| • cellular protein modification process | • cytoplasm |
| • cytosol | • nucleus |
Pathways
• Protein repair pathway
• Aspartate and asparagine metabolism
• Cellular response to stress
Protein Summary
PCMT1 is a 245-amino acid enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine to L-isoaspartyl and D-aspartyl residues in damaged proteins, converting them to normal L-aspartyl residues. This repair process is essential for maintaining protein function and preventing aggregation. The enzyme is ubiquitously expressed, with high levels in brain and testis. Its activity declines with age, contributing to age-related diseases. Mutations in PCMT1 are rare but can lead to neurological deficits and increased cancer risk.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PCMT1 Knockout HEK293 Cell Line | EDJ-KQ5416 | Human | 5110 | Details Get a Quote |
| PCMT1 Knockout A-549 Cell Line | EDJ-KQ28577 | Human | 5110 | Details Get a Quote |
| PCMT1 Knockout HCT 116 Cell Line | EDJ-KQ28578 | Human | 5110 | Details Get a Quote |
| PCMT1 Knockout HeLa Cell Line | EDJ-KQ28579 | Human | 5110 | Details Get a Quote |
