Puromycin-sensitive aminopeptidase

Function

Aminopeptidase with broad substrate specificity for several peptides. Involved in proteolytic events essential for cell growth and viability. May act as regulator of neuropeptide activity. Plays a role in the antigen-processing pathway for MHC class I molecules. Involved in the N-terminal trimming of cytotoxic T-cell epitope precursors. Digests the poly-Q peptides found in many cellular proteins. Digests tau from normal brain more efficiently than tau from Alzheimer disease brain.

Classification

Family (Pfam)

PF11838 ERAP1_C, PF01433 Peptidase_M1, PF17900 Peptidase_M1_N

InterPro

Aminopeptidase_N-like_N, Aminopeptidase_N-like_N_sf, ERAP1-like_C_dom, M1_APN-typ, Peptidase_M1, Peptidase_M1_aminopeptidases, Peptidase_M1_dom, Peptidase_M4/M1_CTD_sf

Functional cluster

Oxidoreductases & Polyketide Synthases

Experimental structures · PDB · 3

• 8SW0 X-ray 2.30A
• 8SW1 X-ray 3.65A
• 9O5K EM 3.19A

A predicted model is available from AlphaFold.

Gene Ontology · 13

• GO:0005829 cytosol
• GO:0070062 extracellular exosome
• GO:0005576 extracellular region
• GO:0005634 nucleus
• GO:0016285 alanyl aminopeptidase activity
• GO:0004177 aminopeptidase activity
• GO:0070006 metalloaminopeptidase activity
• GO:0008270 zinc ion binding
• GO:0071456 cellular response to hypoxia
• GO:0043171 peptide catabolic process
• GO:1903955 positive regulation of protein targeting to mitochondrion
• GO:0000209 protein polyubiquitination
• GO:0006508 proteolysis

Drugs targeting this protein · 1

• TOSEDOSTAT inhibitor

Related proteins · sequence + function similarity

• Puromycin-sensitive aminopeptidase 1.00
• Aminopeptidase M1-A 0.90
• Aminopeptidase M1-B 0.89
• Aminopeptidase M1-C 0.88
• Aminopeptidase M1 0.87
• Aminopeptidase M1-D 0.84
• Aminopeptidase 1 0.82
• Endoplasmic reticulum aminopeptidase 1 0.81
• Puromycin-sensitive aminopeptidase-like protein 0.81
• Puromycin-sensitive aminopeptidase 0.81
• Aminopeptidase 2, mitochondrial 0.79
• Endoplasmic reticulum aminopeptidase 1 0.79

Literature · 14 cited papers

• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Cytosolic aminopeptidases influence MHC class I-mediated antigen presentation in an allele-dependent manner. J. Immunol. · 2009
• Puromycin-sensitive aminopeptidase is the major peptidase responsible for digesting polyglutamine sequences released by proteasomes during protein degradation. EMBO J. · 2007
• Degradation of tau protein by puromycin-sensitive aminopeptidase in vitro. Biochemistry · 2006
• DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Mutation of active site residues of the puromycin-sensitive aminopeptidase: conversion of the enzyme into a catalytically inactive binding protein. Arch. Biochem. Biophys. · 2003
• Human puromycin-sensitive aminopeptidase: cloning of 3' UTR, evidence for a polymorphism at a.a. 140 and refined chromosomal localization to 17q21. Cytogenet. Cell Genet. · 2001
• Two new proteases in the MHC class I processing pathway. Nat. Immunol. · 2000
• Puromycin-sensitive alanyl aminopeptidase from human liver cytosol: purification and characterization. Forensic Sci. Int. · 2000
• … and 2 more in the literature graph