NPEPPS Gene

HGNC Family	Aminopeptidases
Name	aminopeptidase puromycin sensitive
Description	This gene encodes the puromycin-sensitive aminopeptidase, a zinc metallopeptidase which hydrolyzes amino acids from the N-terminus of its substrate. The protein has been localized to both the cytoplasm and to cellular membranes. This enzyme degrades enkaphalins in the brain, and studies in mouse suggest that it is involved in proteolytic events regulating the cell cycle. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNPEPPS (also known as puromycin‐sensitive aminopeptidase or PSA) is a cytosolic zinc metallopeptidase that plays a critical role in protein quality control by degrading aggregation‐prone peptides. For instance, enhanced NPEPPS activity protects against the accumulation of toxic polyglutamine‐rich fragments by promoting macroautophagy, thereby reducing the aggregate burden observed in polyQ diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In tauopathies, NPEPPS directly degrades both total and hyperphosphorylated tau protein, with its overexpression reducing tau levels and its inhibition or knockdown leading to attenuated tau clearance in neuronal models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, mutational analyses have underlined the importance of key catalytic residues for proper substrate binding and transition state stabilization, emphasizing the enzyme’s precise biochemical mechanism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in maintaining proteostasis, NPEPPS contributes to immune functions by processing proteasome‐derived peptides and facilitating their trimming for presentation on MHC Class I molecules. This function is part of a coordinated activity with other aminopeptidases and has been implicated in genetic associations with diverse immune‐mediated disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent studies have further broadened the scope of NPEPPS functions by linking its expression to metabolic and oncogenic processes. In the liver, reduced NPEPPS expression correlates with nonalcoholic fatty liver disease, where its deficiency promotes triglyceride accumulation and impairs fatty acid β‑oxidation through diminished NRF2 stabilization and antioxidant responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Downregulation of NPEPPS in prostate cancer cell models has been associated with suppressed cellular proliferation, migration, and invasion, while analyses in colorectal cancer hint at a broader involvement of cytosolic peptidases in tumor behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, genetic screening studies in ankylosing spondylitis and investigations into microRNA‐mediated regulation in lung cancer models further implicate NPEPPS in modulating pathological and inflammatory responses as well as cancer-related pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Fiona M Menzies, Raphael Hourez, Sara Imarisio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Puromycin-sensitive aminopeptidase protects against aggregation-prone proteins via autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddq385"}], "href": "https://doi.org/10.1093/hmg/ddq385"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20829225"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20829225"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lili C Kudo, Liubov Parfenova, Guijie Ren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Puromycin-sensitive aminopeptidase (PSA/NPEPPS) impedes development of neuropathology in hPSA/TAU(P301L) double-transgenic mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddr065"}], "href": "https://doi.org/10.1093/hmg/ddr065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21320871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21320871"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kentaro Yanagi, Toshihisa Tanaka, Kiyoko Kato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of puromycin-sensitive aminopeptidase in proteolysis of tau protein in cultured cells, and attenuated proteolysis of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) mutant tau."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Psychogeriatrics (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1479-8301.2010.00307.x"}], "href": "https://doi.org/10.1111/j.1479-8301.2010.00307.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20377816"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20377816"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Michael W Thompson, Louis B Hersh "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of conserved residues of the human puromycin-sensitive aminopeptidase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Peptides (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.peptides.2003.07.012"}], "href": "https://doi.org/10.1016/j.peptides.2003.07.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14706550"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14706550"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "N Agrawal, M A Brown "}, {"type": "b", "children": [{"type": "t", "text": "Genetic associations and functional characterization of M1 aminopeptidases and immune-mediated diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Immun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/gene.2014.46"}], "href": "https://doi.org/10.1038/gene.2014.46"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25142031"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25142031"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Bangliang Huang, Xin Xiong, Linlin Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PSA controls hepatic lipid metabolism by regulating the NRF2 signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jmcb/mjab033"}], "href": "https://doi.org/10.1093/jmcb/mjab033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34048566"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34048566"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Suk Hee Lee, Hwan Gyu Kim "}, {"type": "b", "children": [{"type": "t", "text": "Cobalt chloride-induced downregulation of puromycin-sensitive aminopeptidase suppresses the migration and invasion of PC-3 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Microbiol Biotechnol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4014/jmb.0807.438"}], "href": "https://doi.org/10.4014/jmb.0807.438"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19494703"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19494703"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Itxaro Perez, Lorena Blanco, Begoña Sanz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered Activity and Expression of Cytosolic Peptidases in Colorectal Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Med Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijms.11808"}], "href": "https://doi.org/10.7150/ijms.11808"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26078706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26078706"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xuqi Zheng, Qiuxia Li, Xiaomin Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of 47 Non-MHC Ankylosing Spondylitis Susceptibility Loci Regarding Associated Variants across Whites and Han Chinese."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Rheumatol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3899/jrheum.190184"}], "href": "https://doi.org/10.3899/jrheum.190184"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31523044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31523044"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Fang Lv, Qi Xue "}, {"type": "b", "children": [{"type": "t", "text": "[MiR-614 inhibited lung cancer cell invasion and proliferation via targeting PSA]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhongguo Fei Ai Za Zhi (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3779/j.issn.1009-3419.2014.10.02"}], "href": "https://doi.org/10.3779/j.issn.1009-3419.2014.10.02"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25342037"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25342037"}]}]}]}
Synonyms	AAP-S, MP100
Proteins	PSA_HUMAN
NCBI Gene ID	9520
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NPEPPS has 8,885 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 113 datasets.

Click the + buttons to view associations for NPEPPS from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NPEPPS Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by NPEPPS gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NPEPPS gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of NPEPPS gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of NPEPPS gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of NPEPPS gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NPEPPS gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of NPEPPS gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NPEPPS gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NPEPPS gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of NPEPPS gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of NPEPPS gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NPEPPS protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of NPEPPS gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NPEPPS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of NPEPPS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of NPEPPS gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NPEPPS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NPEPPS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with NPEPPS protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with NPEPPS protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NPEPPS gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NPEPPS gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NPEPPS gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by NPEPPS gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with NPEPPS gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with NPEPPS gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with NPEPPS gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with NPEPPS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NPEPPS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for NPEPPS protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at NPEPPS gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of NPEPPS gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NPEPPS gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing NPEPPS from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of NPEPPS gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with NPEPPS gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing NPEPPS from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of NPEPPS gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of NPEPPS gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of NPEPPS gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.