LAP3 is a human gene whose product lAP3 (Leucine Aminopeptidase 3) is a cytosolic metalloexopeptidase that hydrolyzes N-terminal amino acids from peptides and proteins. It plays crucial roles in protein turnover, antigen processing, and peptide hormone metabolism. Variants in LAP3 have been implicated in Alzheimer's Disease, Parkinson's Disease, Cancer. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration. [1]
LAP3 (Leucine Aminopeptidase 3) is a cytosolic metalloexopeptidase that hydrolyzes N-terminal amino acids from peptides and proteins. It plays crucial roles in protein turnover, antigen processing, and peptide hormone metabolism.
Protein Turnover: LAP3 participates in the degradation of misfolded and damaged proteins, working alongside the proteasome and lysosomal systems.
Antigen Processing: The enzyme generates antigenic peptides for presentation via MHC class I molecules, crucial for immune surveillance of abnormal cells.
Peptide Hormone Metabolism: LAP3 processes bioactive peptides including enkephalins, bradykinin, and angiotensin, modulating neuropeptide signaling in the brain.
Regulation of Apoptosis: LAP3 interacts with caspase pathways and can promote or inhibit cell death depending on context.
LAP3 is implicated in AD through its role in amyloid precursor protein (APP) processing and Aβ peptide degradation. The enzyme can hydrolyze Aβ42, potentially reducing aggregation. However, altered LAP3 expression in AD brain may contribute to impaired peptide clearance.
In PD, LAP3 participates in α-synuclein degradation pathways. It may help clear aggregated α-synuclein through proteolytic cleavage. Altered LAP3 activity could contribute to the accumulation of toxic protein aggregates.
LAP3 is frequently overexpressed in various cancers including glioblastoma. High LAP3 levels correlate with aggressive tumor growth and poor prognosis. The enzyme supports cancer cell proliferation and survival.
LAP3 functions through several mechanisms:
Key LAP3 substrates include:
LAP3 is widely expressed in:
In the brain, LAP3 is expressed in:
Expression is induced by:
LAP3 is a potential therapeutic target for:
LAP3 expression levels may serve as a biomarker for:
LAP3 belongs to the M17 family of metalloaminopeptidases:
These family members share structural homology but have distinct substrate specificities and cellular localizations.
Liao et al. LAP3 in glioblastoma (2020). 2020. ↩︎