PMC:7443692 / 6427-8029 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7443692","sourcedb":"PMC","sourceid":"7443692","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7443692","text":"ACE2 is an integral membrane metalloproteinase that regulates the renin-angiotensin system (Tikellis et al., 2011). Both SARS-CoV-1 and SARS-CoV-2 have co-opted ACE2 to function as the receptor by which these viruses attach and fuse with host cells (Hoffmann et al., 2020; Li et al., 2003). ACE2 is cleavable by ADAM proteases at the cell surface (Lambert et al., 2005), resulting in the shedding of a soluble ectodomain that can be detected in apical secretions of various epithelial layers (gastric, airway, etc.) and in serum (Epelman et al., 2009). The N-terminal extracellular domain of ACE2 contains six canonical sequons for N-linked glycosylation and several potential O-linked sites. Several nonsynonymous single-nucleotide polymorphisms (SNPs) in the ACE2 gene have been identified in the human population and could potentially alter ACE2 glycosylation and/or affinity of the receptor for the viral Spike protein (Li et al., 2005). Given that glycosylation can affect the half-life of circulating glycoproteins in addition to modulating the affinity of their interactions with receptors and immune/inflammatory signaling pathways (Marth and Grewal, 2008; Varki, 2017), understanding the impact of glycosylation of ACE2 with respect to its binding of SARS-CoV-2 Spike glycoprotein is of high importance. The proposed use of soluble extracellular domains of ACE2 as decoy, competitive inhibitors for SARS-CoV-2 infection emphasizes the critical need for understanding the glycosylation profile of ACE2 so that optimally active biologics can be produced (Lei et al., 2020; Monteil et al., 2020).","tracks":[{"project":"LitCovid-sample-MedDRA","denotations":[{"id":"T8","span":{"begin":66,"end":71},"obj":"http://purl.bioontology.org/ontology/MEDDRA/10022891"}],"attributes":[{"id":"A8","pred":"meddra_id","subj":"T8","obj":"http://purl.bioontology.org/ontology/MEDDRA/10038555"},{"subj":"T8","pred":"source","obj":"LitCovid-sample-MedDRA"}]},{"project":"LitCovid-sample-CHEBI","denotations":[{"id":"T27","span":{"begin":72,"end":83},"obj":"Chemical"},{"id":"T28","span":{"begin":722,"end":732},"obj":"Chemical"},{"id":"T29","span":{"begin":915,"end":922},"obj":"Chemical"},{"id":"T30","span":{"begin":1007,"end":1020},"obj":"Chemical"},{"id":"T31","span":{"begin":1277,"end":1289},"obj":"Chemical"}],"attributes":[{"id":"A27","pred":"chebi_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/CHEBI_48433"},{"id":"A28","pred":"chebi_id","subj":"T28","obj":"http://purl.obolibrary.org/obo/CHEBI_36976"},{"id":"A29","pred":"chebi_id","subj":"T29","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A30","pred":"chebi_id","subj":"T30","obj":"http://purl.obolibrary.org/obo/CHEBI_17089"},{"id":"A31","pred":"chebi_id","subj":"T31","obj":"http://purl.obolibrary.org/obo/CHEBI_17089"},{"subj":"T27","pred":"source","obj":"LitCovid-sample-CHEBI"},{"subj":"T28","pred":"source","obj":"LitCovid-sample-CHEBI"},{"subj":"T29","pred":"source","obj":"LitCovid-sample-CHEBI"},{"subj":"T30","pred":"source","obj":"LitCovid-sample-CHEBI"},{"subj":"T31","pred":"source","obj":"LitCovid-sample-CHEBI"}]},{"project":"LitCovid-sample-PD-NCBITaxon","denotations":[{"id":"T30","span":{"begin":121,"end":129},"obj":"Species"},{"id":"T31","span":{"begin":136,"end":146},"obj":"Species"},{"id":"T32","span":{"begin":209,"end":216},"obj":"Species"},{"id":"T33","span":{"begin":799,"end":804},"obj":"Species"},{"id":"T34","span":{"begin":1260,"end":1270},"obj":"Species"},{"id":"T35","span":{"begin":1408,"end":1418},"obj":"Species"}],"attributes":[{"id":"A30","pred":"ncbi_taxonomy_id","subj":"T30","obj":"NCBItxid:694009"},{"id":"A31","pred":"ncbi_taxonomy_id","subj":"T31","obj":"NCBItxid:2697049"},{"id":"A32","pred":"ncbi_taxonomy_id","subj":"T32","obj":"NCBItxid:10239"},{"id":"A33","pred":"ncbi_taxonomy_id","subj":"T33","obj":"NCBItxid:9606"},{"id":"A34","pred":"ncbi_taxonomy_id","subj":"T34","obj":"NCBItxid:2697049"},{"id":"A35","pred":"ncbi_taxonomy_id","subj":"T35","obj":"NCBItxid:2697049"},{"subj":"T30","pred":"source","obj":"LitCovid-sample-PD-NCBITaxon"},{"subj":"T31","pred":"source","obj":"LitCovid-sample-PD-NCBITaxon"},{"subj":"T32","pred":"source","obj":"LitCovid-sample-PD-NCBITaxon"},{"subj":"T33","pred":"source","obj":"LitCovid-sample-PD-NCBITaxon"},{"subj":"T34","pred":"source","obj":"LitCovid-sample-PD-NCBITaxon"},{"subj":"T35","pred":"source","obj":"LitCovid-sample-PD-NCBITaxon"}],"namespaces":[{"prefix":"NCBItxid","uri":"http://purl.bioontology.org/ontology/NCBITAXON/"}]},{"project":"LitCovid-sample-sentences","denotations":[{"id":"T34","span":{"begin":0,"end":115},"obj":"Sentence"},{"id":"T35","span":{"begin":116,"end":290},"obj":"Sentence"},{"id":"T36","span":{"begin":291,"end":552},"obj":"Sentence"},{"id":"T37","span":{"begin":553,"end":692},"obj":"Sentence"},{"id":"T38","span":{"begin":693,"end":941},"obj":"Sentence"},{"id":"T39","span":{"begin":942,"end":1312},"obj":"Sentence"},{"id":"T40","span":{"begin":1313,"end":1602},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T34","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T35","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T36","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T37","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T38","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T39","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T40","pred":"source","obj":"LitCovid-sample-sentences"}]},{"project":"LitCovid-sample-PD-UBERON","denotations":[{"id":"T1","span":{"begin":66,"end":90},"obj":"Body_part"},{"id":"T2","span":{"begin":523,"end":528},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0018229"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0001977"},{"subj":"T1","pred":"source","obj":"LitCovid-sample-PD-UBERON"},{"subj":"T2","pred":"source","obj":"LitCovid-sample-PD-UBERON"}]},{"project":"LitCovid-sample-PD-MONDO","denotations":[{"id":"T23","span":{"begin":121,"end":129},"obj":"Disease"},{"id":"T24","span":{"begin":136,"end":146},"obj":"Disease"},{"id":"T25","span":{"begin":1260,"end":1270},"obj":"Disease"},{"id":"T26","span":{"begin":1408,"end":1418},"obj":"Disease"},{"id":"T27","span":{"begin":1419,"end":1428},"obj":"Disease"}],"attributes":[{"id":"A23","pred":"mondo_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A24","pred":"mondo_id","subj":"T24","obj":"http://purl.obolibrary.or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