PGPEP1 (pyroglutamyl-peptidase I)
PGPEP1 (Pyroglutamyl-peptidase I) encodes a member of the pyroglutamyl-peptidase family, a group of evolutionarily conserved enzymes that play a critical role in maintaining cellular proteostasis by regulating the post-translational modification and degradation of proteins. The primary function of the PGPEP1 protein is to catalyze the hydrolysis of N-terminal pyroglutamate, a cyclic form of glutamic acid, from peptides and proteins, thereby serving as a key step in the maturation of neuropeptides and hormonal precursors. This enzymatic activity is predominantly localized to the cytoplasm, although specific isoforms may also be found in lysosomes, where they contribute to the breakdown of modified peptide substrates. By removing the N-terminal pyroglutamate, PGPEP1 ensures the proper activation or inactivation of signaling molecules, such as thyrotropin-releasing hormone (TRH), and prevents the accumulation of inactive or potentially toxic modified peptides. Disruption of this process, whether through loss-of-function mutations that lead to the buildup of pyroglutamylated peptides or overexpression that causes aberrant degradation of peptide substrates, can significantly interfere with intracellular signaling pathways and metabolic homeostasis. While the specific mechanisms linking PGPEP1 to human pathology are still under investigation, emerging evidence suggests its involvement in neurological disorders and metabolic dysregulations, highlighting the importance of precise control over N-terminal peptide processing in maintaining neuronal and systemic health.
Gene Ontology
Subcellular localization of PGPEP1 (and its protein):
- plasma membrane
- cytoplasm
- extracellular
- golgi
- vesicle
- cytoskeleton
- endoplasmic reticulum
- nucleus
- endosome
- lysosome
- mitochondrion
Gene Ontology (GO) terms for PGPEP1:
| Interacting Gene | Interaction | Source/Score |
| Disease | Score | NofPmids | NofSnps | Source |
| Schizophrenia | 0.002638474 | 1 | 1 | BeFree_GAD |
| Coronary Artery Disease | 0.002638474 | 1 | 1 | BeFree_GAD |
| Tobacco Use Disorder | 0.002367032 | 1 | 0 | GAD |
| Mental disorders | 0.002367032 | 1 | 1 | GAD |
| Pneumocystis jiroveci pneumonia | 0.001900093 | 7 | 0 | BeFree |
| Spina Bifida | 0.000814326 | 3 | 0 | BeFree |
| Malignant neoplasm of breast | 0.000542884 | 2 | 0 | BeFree |
| Exencephaly | 0.000542884 | 2 | 0 | BeFree |
| Coronary heart disease | 0.000542884 | 2 | 0 | BeFree |
| Pneumonia | 0.000542884 | 2 | 0 | BeFree |
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