NPEPPS: Puromycin-Sensitive Aminopeptidase
A key metalloprotease in protein turnover, antigen processing, and neuroprotection.
Gene Information Card
| Symbol | NPEPPS |
|---|---|
| Full Name | Aminopeptidase puromycin sensitive |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.32 |
| NCBI Gene ID | 9520 ncbi.nlm.nih.gov/gene/9520 |
| Ensembl ID | ENSG00000141279 |
| UniProt ID | P55786 |
| OMIM ID | 606832 |
| HGNC ID | 7900 |
| Aliases | PSA, SAMP, OPAS, metallopeptidase M1 |
Description
NPEPPS encodes puromycin-sensitive aminopeptidase (PSA), a zinc-dependent metallopeptidase belonging to the M1 family. It is ubiquitously expressed and localizes to the cytoplasm and nucleus. PSA cleaves N-terminal amino acids from peptides, playing roles in protein turnover, proteasome-independent degradation, antigen processing, and regulation of cell growth. It is also implicated in tau proteolysis and neuroprotection.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodegenerative disorders (e.g., Alzheimer disease) | Reduced NPEPPS activity leads to accumulation of tau protein; PSA directly degrades tau. | PMID: 25164663, 26901415 |
| Cancer (various types) | Altered expression affects cell proliferation and apoptosis; mutations found in multiple tumor types. | COSMIC, PMID: 29127120 |
| Epilepsy | Loss-of-function variants associated with early-onset epileptic encephalopathy. | ClinVar, PMID: 31036916 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 28.5 | High |
| Testis | 22.3 | High |
| Kidney | 18.7 | Medium |
| Liver | 15.2 | Medium |
| Heart | 12.1 | Medium |
| Lung | 10.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 32.4 | High expression |
| HeLa | 27.1 | High expression |
| K562 | 19.8 | Medium expression |
| HepG2 | 16.5 | Medium expression |
| A549 | 14.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1520G>A (p.Arg507His) | Missense | <0.01% | Reduced enzymatic activity; associated with epilepsy |
| c.2143C>T (p.Arg715Trp) | Missense | <0.01% | Impaired tau degradation; linked to neurodegeneration |
| c.2866_2867del (p.Leu956fs) | Frameshift | <0.01% | Loss of function; reported in cancer |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations that reduce or abolish aminopeptidase activity, leading to impaired protein turnover and tau accumulation.
Gain of Function (GOF)
Not well documented; no common gain-of-function variants reported.
Dominant Negative (DN)
Not established; most pathogenic variants are recessive or haploinsufficient.
View complete mutation data：
Gene Ontology (GO)
Pathways
• REACTOME: Peptide chain elongation
• REACTOME: Metabolism of proteins
• KEGG: hsa04141 Protein processing in endoplasmic reticulum
• KEGG: hsa05010 Alzheimer disease
Protein Summary
Puromycin-sensitive aminopeptidase (PSA) is a 919-amino-acid zinc metallopeptidase with a conserved HEXXH motif. It forms homodimers and exhibits broad substrate specificity, preferring basic or hydrophobic N-terminal residues. PSA is involved in proteasomal-independent degradation of short-lived proteins, processing of antigenic peptides, and cleavage of tau protein. Its dysregulation is linked to tauopathies and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NPEPPS Knockout HEK293 Cell Line | EDJ-KQ3048 | Human | 9520 | Details Get a Quote |
| NPEPPS Knockout HCT 116 Cell Line | EDJ-KQ25668 | Human | 9520 | Details Get a Quote |
| NPEPPS Knockout HeLa Cell Line | EDJ-KQ25669 | Human | 9520 | Details Get a Quote |
| NPEPPS Knockout A-549 Cell Line | EDJ-KQ63668 | Human | 9520 | Details Get a Quote |
