PMC:7352545 / 60290-62117 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7352545","sourcedb":"PMC","sourceid":"7352545","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7352545","text":"6.3.5. Aminopeptidase N (APN) is a Receptor of α-CoV HCoV-229E\nAmong the six HCoVs, the α-CoV HCoV-229E S protein recognizes hAPN known as CD13 or membrane alanyl aminopeptidase (EC 3.4.11.2). Porcine epidemic diarrhea coronavirus virus (PEDV) binds to protein receptor APN of human- and pig NeuAc species as its co-receptor. Apart from hAPN, TGEV and PEDV bind to SA species [117], although SA recognition by TGEV is not essential in the first step of entry cycle. HCoV-229E recognizes hAPN known as CD13 for its entry receptor. hAPN (PDB: 4FYQ) or CD13 (EC 3.4.11.2), which is a Zn-dependent metalloprotease, has a MW 150 kDa with 967 amino acids. CD13 is a type II TM protein with a short cytoplasmic domain in the N-terminal region and long extracellular region in the CTD. The CTD has a pentapeptide sequence specific for the Zinc–MMPs. The APN binding domain is located on the CTD of PEDV S1 (amino acid 477–629 residues), while the SA-binding domain is found in the N-terminal region of PEDV S1 (amino acid 1–320 residues) [118]. CD13 is also a receptor for HCoV-229E, human cytomegalovirus, porcine CoV TGEV, feline infectious peritonitis virus (FIPV), feline enteric virus (FeCV) and canine-infectious CoVs [119,120,121,122]. Homodimeric CD13 digests luminal peptides. The hAPN-encoding ANPEP gene is a dominant component in proximal tubular epithelial cells, small intestinal cells, macrophages, granulocytes and synaptic membranes. If this gene is defective, leukemia or lymphoma are transformed [123]. Porcine and human APN exhibit about 80% protein identity. FIPV and FeCV are in the same group as HCoV-229E and TGEV. Thus, porcine APN is also an attachment site for pig TGEV with an additional second receptor. HCoV-229E first binds to CD13 and consequently clusters CD13 in caveolae-associated lipid rafts 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