PMC:7556165 / 4655-7721 JSON TXT

Annnotations TAB JSON ListView MergeView

LitCovid-sample-MedDRA

LitCovid-sample-CHEBI

LitCovid-sample-PD-NCBITaxon

{"project":"LitCovid-sample-PD-NCBITaxon","denotations":[{"id":"T28","span":{"begin":30,"end":35},"obj":"Species"},{"id":"T29","span":{"begin":1493,"end":1498},"obj":"Species"},{"id":"T30","span":{"begin":1696,"end":1701},"obj":"Species"},{"id":"T31","span":{"begin":1921,"end":1928},"obj":"Species"},{"id":"T33","span":{"begin":1965,"end":1970},"obj":"Species"},{"id":"T34","span":{"begin":2390,"end":2395},"obj":"Species"}],"attributes":[{"id":"A31","pred":"ncbi_taxonomy_id","subj":"T31","obj":"NCBItxid:6960"},{"id":"A32","pred":"ncbi_taxonomy_id","subj":"T31","obj":"NCBItxid:50557"},{"id":"A33","pred":"ncbi_taxonomy_id","subj":"T33","obj":"NCBItxid:9606"},{"id":"A30","pred":"ncbi_taxonomy_id","subj":"T30","obj":"NCBItxid:9606"},{"id":"A29","pred":"ncbi_taxonomy_id","subj":"T29","obj":"NCBItxid:9606"},{"id":"A34","pred":"ncbi_taxonomy_id","subj":"T34","obj":"NCBItxid:9606"},{"id":"A28","pred":"ncbi_taxonomy_id","subj":"T28","obj":"NCBItxid:9606"}],"namespaces":[{"prefix":"NCBItxid","uri":"http://purl.bioontology.org/ontology/NCBITAXON/"}],"text":"ACE System and ACE2 Discovery\nHuman Angiotensin-converting enzyme (ACE) belongs to the M2 gluzincin family of metalloproteinases and (Ehlers and Riordan, 1989; Masuyer et al., 2014) exists in two forms, namely somatic ACE (sACE) and germinal ACE (tACE). Both are derived from the same gene, controlled by alternative promotors. sACE is an integral membrane protein, which can be also cleaved by ACE secretases to produce a circulating form of the enzyme (Natesh et al., 2003).\nsACE, hereafter referred to simply as ACE, has been extensively studied, because of its crucial role in the homeostasis of renin-angiotensin-aldosterone (RAAS) system and in cardiovascular diseases (Takimoto-Ohnishi and Murakami, 2019). The two extracellular domains N and C domains of ACE (Wei et al., 1991; Jaspard et al., 1993; Natesh et al., 2003; Riordan, 2003) can both hydrolase two crucial peptides, namely angiotensin I and bradykinin, with the same efficiency. Indeed, ACE carries out the cleavage of two amino acids (dipeptidase action) from the C-terminal part of angiotensin I to generate angiotensin II, which exerts a potent vasopressor, proliferative, and profibrotic effect. Moreover, ACE mediates the cleavage and inactivation of bradykinin, which is a vasodilator hypotensive peptide. The pivotal role of ACE in the RAAS system allows a refined blood pressure control and salt homeostasis (Sayer and Bhat, 2014).\nFollowing the ACE discovery in mid-1950s, despite intense research in the field, no human homologs of the enzyme have been found for more than 50 years (Isaac et al., 1998; Riordan, 2003). It was only in 2000 that two independent research groups identified, almost simultaneously, a new human ACE-like enzyme, with two different approaches. Tipnis et al. (2000) searched for new metalloproteases in an expressed sequence tag (EST) database, finding an ACE homolog (ACEH) with a single domain, similar to that of insects. Subsequently they cloned it from a human lymphoma cDNA library. Interestingly ACEH showed high homology (40% identity and 60% similarity) with ACE, particularly around the HEXXH sequence and highly conserved glutamate residue, involved in zinc binding. Moreover, they demonstrated the presence of seven glycosylation sites (Tipnis et al., 2000). In the same year, Donoghue et al. (2000b) were searching for new genes involved in heart failure and identified a human cDNA ACE homolog, named ACE2, among 19,000 5’end sequences by RACE (rapid amplification of cDNA ends) in the heart ventricle cDNA library, obtained from a woman with idiopathic dilated cardiomyopathy. ACE2 showed a transmembrane domain, a zinc catalytic domain 42% identical to ACE and a signal peptide. Like ACE, ACE2 seemed to be an ectoenzyme type I protein. The authors identified ACE2 transcripts quite exclusively in the heart and in the kidney, suggesting a role for ACE2 in the local RAAS control (Donoghue et al., 2000b). In the following years, ACE2 was intensively studied, its structure and function were enlightened, and tentative inhibitors were developed."}

LitCovid-sample-sentences

{"project":"LitCovid-sample-sentences","denotations":[{"id":"T33","span":{"begin":0,"end":29},"obj":"Sentence"},{"id":"T34","span":{"begin":30,"end":253},"obj":"Sentence"},{"id":"T35","span":{"begin":254,"end":476},"obj":"Sentence"},{"id":"T36","span":{"begin":477,"end":713},"obj":"Sentence"},{"id":"T37","span":{"begin":714,"end":947},"obj":"Sentence"},{"id":"T38","span":{"begin":948,"end":1168},"obj":"Sentence"},{"id":"T39","span":{"begin":1169,"end":1280},"obj":"Sentence"},{"id":"T40","span":{"begin":1281,"end":1408},"obj":"Sentence"},{"id":"T41","span":{"begin":1409,"end":1597},"obj":"Sentence"},{"id":"T42","span":{"begin":1598,"end":1749},"obj":"Sentence"},{"id":"T43","span":{"begin":1750,"end":1929},"obj":"Sentence"},{"id":"T44","span":{"begin":1930,"end":1993},"obj":"Sentence"},{"id":"T45","span":{"begin":1994,"end":2182},"obj":"Sentence"},{"id":"T46","span":{"begin":2183,"end":2275},"obj":"Sentence"},{"id":"T47","span":{"begin":2276,"end":2596},"obj":"Sentence"},{"id":"T48","span":{"begin":2597,"end":2699},"obj":"Sentence"},{"id":"T49","span":{"begin":2700,"end":2757},"obj":"Sentence"},{"id":"T50","span":{"begin":2758,"end":2926},"obj":"Sentence"},{"id":"T51","span":{"begin":2927,"end":3066},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"ACE System and ACE2 Discovery\nHuman Angiotensin-converting enzyme (ACE) belongs to the M2 gluzincin family of metalloproteinases and (Ehlers and Riordan, 1989; Masuyer et al., 2014) exists in two forms, namely somatic ACE (sACE) and germinal ACE (tACE). Both are derived from the same gene, controlled by alternative promotors. sACE is an integral membrane protein, which can be also cleaved by ACE secretases to produce a circulating form of the enzyme (Natesh et al., 2003).\nsACE, hereafter referred to simply as ACE, has been extensively studied, because of its crucial role in the homeostasis of renin-angiotensin-aldosterone (RAAS) system and in cardiovascular diseases (Takimoto-Ohnishi and Murakami, 2019). The two extracellular domains N and C domains of ACE (Wei et al., 1991; Jaspard et al., 1993; Natesh et al., 2003; Riordan, 2003) can both hydrolase two crucial peptides, namely angiotensin I and bradykinin, with the same efficiency. Indeed, ACE carries out the cleavage of two amino acids (dipeptidase action) from the C-terminal part of angiotensin I to generate angiotensin II, which exerts a potent vasopressor, proliferative, and profibrotic effect. Moreover, ACE mediates the cleavage and inactivation of bradykinin, which is a vasodilator hypotensive peptide. The pivotal role of ACE in the RAAS system allows a refined blood pressure control and salt homeostasis (Sayer and Bhat, 2014).\nFollowing the ACE discovery in mid-1950s, despite intense research in the field, no human homologs of the enzyme have been found for more than 50 years (Isaac et al., 1998; Riordan, 2003). It was only in 2000 that two independent research groups identified, almost simultaneously, a new human ACE-like enzyme, with two different approaches. Tipnis et al. (2000) searched for new metalloproteases in an expressed sequence tag (EST) database, finding an ACE homolog (ACEH) with a single domain, similar to that of insects. Subsequently they cloned it from a human lymphoma cDNA library. Interestingly ACEH showed high homology (40% identity and 60% similarity) with ACE, particularly around the HEXXH sequence and highly conserved glutamate residue, involved in zinc binding. Moreover, they demonstrated the presence of seven glycosylation sites (Tipnis et al., 2000). In the same year, Donoghue et al. (2000b) were searching for new genes involved in heart failure and identified a human cDNA ACE homolog, named ACE2, among 19,000 5’end sequences by RACE (rapid amplification of cDNA ends) in the heart ventricle cDNA library, obtained from a woman with idiopathic dilated cardiomyopathy. ACE2 showed a transmembrane domain, a zinc catalytic domain 42% identical to ACE and a signal peptide. Like ACE, ACE2 seemed to be an ectoenzyme type I protein. The authors identified ACE2 transcripts quite exclusively in the heart and in the kidney, suggesting a role for ACE2 in the local RAAS control (Donoghue et al., 2000b). In the following years, ACE2 was intensively studied, its structure and function were enlightened, and tentative inhibitors were developed."}

LitCovid-sample-PD-UBERON

{"project":"LitCovid-sample-PD-UBERON","denotations":[{"id":"T8","span":{"begin":1341,"end":1346},"obj":"Body_part"},{"id":"T9","span":{"begin":2359,"end":2364},"obj":"Body_part"},{"id":"T10","span":{"begin":2505,"end":2510},"obj":"Body_part"},{"id":"T11","span":{"begin":2823,"end":2828},"obj":"Body_part"},{"id":"T12","span":{"begin":2840,"end":2846},"obj":"Body_part"}],"attributes":[{"id":"A11","pred":"uberon_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A10","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A9","pred":"uberon_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A12","pred":"uberon_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/UBERON_0002113"},{"id":"A8","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"text":"ACE System and ACE2 Discovery\nHuman Angiotensin-converting enzyme (ACE) belongs to the M2 gluzincin family of metalloproteinases and (Ehlers and Riordan, 1989; Masuyer et al., 2014) exists in two forms, namely somatic ACE (sACE) and germinal ACE (tACE). Both are derived from the same gene, controlled by alternative promotors. sACE is an integral membrane protein, which can be also cleaved by ACE secretases to produce a circulating form of the enzyme (Natesh et al., 2003).\nsACE, hereafter referred to simply as ACE, has been extensively studied, because of its crucial role in the homeostasis of renin-angiotensin-aldosterone (RAAS) system and in cardiovascular diseases (Takimoto-Ohnishi and Murakami, 2019). The two extracellular domains N and C domains of ACE (Wei et al., 1991; Jaspard et al., 1993; Natesh et al., 2003; Riordan, 2003) can both hydrolase two crucial peptides, namely angiotensin I and bradykinin, with the same efficiency. Indeed, ACE carries out the cleavage of two amino acids (dipeptidase action) from the C-terminal part of angiotensin I to generate angiotensin II, which exerts a potent vasopressor, proliferative, and profibrotic effect. Moreover, ACE mediates the cleavage and inactivation of bradykinin, which is a vasodilator hypotensive peptide. The pivotal role of ACE in the RAAS system allows a refined blood pressure control and salt homeostasis (Sayer and Bhat, 2014).\nFollowing the ACE discovery in mid-1950s, despite intense research in the field, no human homologs of the enzyme have been found for more than 50 years (Isaac et al., 1998; Riordan, 2003). It was only in 2000 that two independent research groups identified, almost simultaneously, a new human ACE-like enzyme, with two different approaches. Tipnis et al. (2000) searched for new metalloproteases in an expressed sequence tag (EST) database, finding an ACE homolog (ACEH) with a single domain, similar to that of insects. Subsequently they cloned it from a human lymphoma cDNA library. Interestingly ACEH showed high homology (40% identity and 60% similarity) with ACE, particularly around the HEXXH sequence and highly conserved glutamate residue, involved in zinc binding. Moreover, they demonstrated the presence of seven glycosylation sites (Tipnis et al., 2000). In the same year, Donoghue et al. (2000b) were searching for new genes involved in heart failure and identified a human cDNA ACE homolog, named ACE2, among 19,000 5’end sequences by RACE (rapid amplification of cDNA ends) in the heart ventricle cDNA library, obtained from a woman with idiopathic dilated cardiomyopathy. ACE2 showed a transmembrane domain, a zinc catalytic domain 42% identical to ACE and a signal peptide. Like ACE, ACE2 seemed to be an ectoenzyme type I protein. The authors identified ACE2 transcripts quite exclusively in the heart and in the kidney, suggesting a role for ACE2 in the local RAAS control (Donoghue et al., 2000b). In the following years, ACE2 was intensively studied, its structure and function were enlightened, and tentative inhibitors were developed."}

LitCovid-sample-Pubtator

LitCovid-sample-UniProt

LitCovid-sample-PD-IDO

{"project":"LitCovid-sample-PD-IDO","denotations":[{"id":"T18","span":{"begin":666,"end":674},"obj":"http://purl.obolibrary.org/obo/OGMS_0000031"},{"id":"T19","span":{"begin":1341,"end":1346},"obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"T20","span":{"begin":2247,"end":2252},"obj":"http://purl.obolibrary.org/obo/BFO_0000029"},{"id":"T21","span":{"begin":2999,"end":3007},"obj":"http://purl.obolibrary.org/obo/BFO_0000034"}],"text":"ACE System and ACE2 Discovery\nHuman Angiotensin-converting enzyme (ACE) belongs to the M2 gluzincin family of metalloproteinases and (Ehlers and Riordan, 1989; Masuyer et al., 2014) exists in two forms, namely somatic ACE (sACE) and germinal ACE (tACE). Both are derived from the same gene, controlled by alternative promotors. sACE is an integral membrane protein, which can be also cleaved by ACE secretases to produce a circulating form of the enzyme (Natesh et al., 2003).\nsACE, hereafter referred to simply as ACE, has been extensively studied, because of its crucial role in the homeostasis of renin-angiotensin-aldosterone (RAAS) system and in cardiovascular diseases (Takimoto-Ohnishi and Murakami, 2019). The two extracellular domains N and C domains of ACE (Wei et al., 1991; Jaspard et al., 1993; Natesh et al., 2003; Riordan, 2003) can both hydrolase two crucial peptides, namely angiotensin I and bradykinin, with the same efficiency. Indeed, ACE carries out the cleavage of two amino acids (dipeptidase action) from the C-terminal part of angiotensin I to generate angiotensin II, which exerts a potent vasopressor, proliferative, and profibrotic effect. Moreover, ACE mediates the cleavage and inactivation of bradykinin, which is a vasodilator hypotensive peptide. The pivotal role of ACE in the RAAS system allows a refined blood pressure control and salt homeostasis (Sayer and Bhat, 2014).\nFollowing the ACE discovery in mid-1950s, despite intense research in the field, no human homologs of the enzyme have been found for more than 50 years (Isaac et al., 1998; Riordan, 2003). It was only in 2000 that two independent research groups identified, almost simultaneously, a new human ACE-like enzyme, with two different approaches. Tipnis et al. (2000) searched for new metalloproteases in an expressed sequence tag (EST) database, finding an ACE homolog (ACEH) with a single domain, similar to that of insects. Subsequently they cloned it from a human lymphoma cDNA library. Interestingly ACEH showed high homology (40% identity and 60% similarity) with ACE, particularly around the HEXXH sequence and highly conserved glutamate residue, involved in zinc binding. Moreover, they demonstrated the presence of seven glycosylation sites (Tipnis et al., 2000). In the same year, Donoghue et al. (2000b) were searching for new genes involved in heart failure and identified a human cDNA ACE homolog, named ACE2, among 19,000 5’end sequences by RACE (rapid amplification of cDNA ends) in the heart ventricle cDNA library, obtained from a woman with idiopathic dilated cardiomyopathy. ACE2 showed a transmembrane domain, a zinc catalytic domain 42% identical to ACE and a signal peptide. Like ACE, ACE2 seemed to be an ectoenzyme type I protein. The authors identified ACE2 transcripts quite exclusively in the heart and in the kidney, suggesting a role for ACE2 in the local RAAS control (Donoghue et al., 2000b). In the following years, ACE2 was intensively studied, its structure and function were enlightened, and tentative inhibitors were developed."}

LitCovid-sample-PD-FMA

{"project":"LitCovid-sample-PD-FMA","denotations":[{"id":"T19","span":{"begin":285,"end":289},"obj":"Body_part"},{"id":"T20","span":{"begin":357,"end":364},"obj":"Body_part"},{"id":"T21","span":{"begin":992,"end":1003},"obj":"Body_part"},{"id":"T22","span":{"begin":1341,"end":1346},"obj":"Body_part"},{"id":"T23","span":{"begin":2359,"end":2364},"obj":"Body_part"},{"id":"T24","span":{"begin":2505,"end":2510},"obj":"Body_part"},{"id":"T25","span":{"begin":2749,"end":2756},"obj":"Body_part"},{"id":"T26","span":{"begin":2823,"end":2828},"obj":"Body_part"},{"id":"T27","span":{"begin":2840,"end":2846},"obj":"Body_part"}],"attributes":[{"id":"A26","pred":"fma_id","subj":"T26","obj":"http://purl.org/sig/ont/fma/fma7088"},{"id":"A22","pred":"fma_id","subj":"T22","obj":"http://purl.org/sig/ont/fma/fma9670"},{"id":"A23","pred":"fma_id","subj":"T23","obj":"http://purl.org/sig/ont/fma/fma7088"},{"id":"A19","pred":"fma_id","subj":"T19","obj":"http://purl.org/sig/ont/fma/fma74402"},{"id":"A21","pred":"fma_id","subj":"T21","obj":"http://purl.org/sig/ont/fma/fma82739"},{"id":"A24","pred":"fma_id","subj":"T24","obj":"http://purl.org/sig/ont/fma/fma7088"},{"id":"A20","pred":"fma_id","subj":"T20","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A27","pred":"fma_id","subj":"T27","obj":"http://purl.org/sig/ont/fma/fma7203"},{"id":"A25","pred":"fma_id","subj":"T25","obj":"http://purl.org/sig/ont/fma/fma67257"}],"text":"ACE System and ACE2 Discovery\nHuman Angiotensin-converting enzyme (ACE) belongs to the M2 gluzincin family of metalloproteinases and (Ehlers and Riordan, 1989; Masuyer et al., 2014) exists in two forms, namely somatic ACE (sACE) and germinal ACE (tACE). Both are derived from the same gene, controlled by alternative promotors. sACE is an integral membrane protein, which can be also cleaved by ACE secretases to produce a circulating form of the enzyme (Natesh et al., 2003).\nsACE, hereafter referred to simply as ACE, has been extensively studied, because of its crucial role in the homeostasis of renin-angiotensin-aldosterone (RAAS) system and in cardiovascular diseases (Takimoto-Ohnishi and Murakami, 2019). The two extracellular domains N and C domains of ACE (Wei et al., 1991; Jaspard et al., 1993; Natesh et al., 2003; Riordan, 2003) can both hydrolase two crucial peptides, namely angiotensin I and bradykinin, with the same efficiency. Indeed, ACE carries out the cleavage of two amino acids (dipeptidase action) from the C-terminal part of angiotensin I to generate angiotensin II, which exerts a potent vasopressor, proliferative, and profibrotic effect. Moreover, ACE mediates the cleavage and inactivation of bradykinin, which is a vasodilator hypotensive peptide. The pivotal role of ACE in the RAAS system allows a refined blood pressure control and salt homeostasis (Sayer and Bhat, 2014).\nFollowing the ACE discovery in mid-1950s, despite intense research in the field, no human homologs of the enzyme have been found for more than 50 years (Isaac et al., 1998; Riordan, 2003). It was only in 2000 that two independent research groups identified, almost simultaneously, a new human ACE-like enzyme, with two different approaches. Tipnis et al. (2000) searched for new metalloproteases in an expressed sequence tag (EST) database, finding an ACE homolog (ACEH) with a single domain, similar to that of insects. Subsequently they cloned it from a human lymphoma cDNA library. Interestingly ACEH showed high homology (40% identity and 60% similarity) with ACE, particularly around the HEXXH sequence and highly conserved glutamate residue, involved in zinc binding. Moreover, they demonstrated the presence of seven glycosylation sites (Tipnis et al., 2000). In the same year, Donoghue et al. (2000b) were searching for new genes involved in heart failure and identified a human cDNA ACE homolog, named ACE2, among 19,000 5’end sequences by RACE (rapid amplification of cDNA ends) in the heart ventricle cDNA library, obtained from a woman with idiopathic dilated cardiomyopathy. ACE2 showed a transmembrane domain, a zinc catalytic domain 42% identical to ACE and a signal peptide. Like ACE, ACE2 seemed to be an ectoenzyme type I protein. The authors identified ACE2 transcripts quite exclusively in the heart and in the kidney, suggesting a role for ACE2 in the local RAAS control (Donoghue et al., 2000b). In the following years, ACE2 was intensively studied, its structure and function were enlightened, and tentative inhibitors were developed."}

LitCovid-sample-PD-MONDO

{"project":"LitCovid-sample-PD-MONDO","denotations":[{"id":"T37","span":{"begin":651,"end":674},"obj":"Disease"},{"id":"T38","span":{"begin":1835,"end":1838},"obj":"Disease"},{"id":"T39","span":{"begin":1971,"end":1979},"obj":"Disease"},{"id":"T40","span":{"begin":2359,"end":2372},"obj":"Disease"},{"id":"T41","span":{"begin":2562,"end":2595},"obj":"Disease"}],"attributes":[{"id":"A40","pred":"mondo_id","subj":"T40","obj":"http://purl.obolibrary.org/obo/MONDO_0005252"},{"id":"A39","pred":"mondo_id","subj":"T39","obj":"http://purl.obolibrary.org/obo/MONDO_0005062"},{"id":"A41","pred":"mondo_id","subj":"T41","obj":"http://purl.obolibrary.org/obo/MONDO_0016333"},{"id":"A37","pred":"mondo_id","subj":"T37","obj":"http://purl.obolibrary.org/obo/MONDO_0004995"},{"id":"A38","pred":"mondo_id","subj":"T38","obj":"http://purl.obolibrary.org/obo/MONDO_0023726"}],"text":"ACE System and ACE2 Discovery\nHuman Angiotensin-converting enzyme (ACE) belongs to the M2 gluzincin family of metalloproteinases and (Ehlers and Riordan, 1989; Masuyer et al., 2014) exists in two forms, namely somatic ACE (sACE) and germinal ACE (tACE). Both are derived from the same gene, controlled by alternative promotors. sACE is an integral membrane protein, which can be also cleaved by ACE secretases to produce a circulating form of the enzyme (Natesh et al., 2003).\nsACE, hereafter referred to simply as ACE, has been extensively studied, because of its crucial role in the homeostasis of renin-angiotensin-aldosterone (RAAS) system and in cardiovascular diseases (Takimoto-Ohnishi and Murakami, 2019). The two extracellular domains N and C domains of ACE (Wei et al., 1991; Jaspard et al., 1993; Natesh et al., 2003; Riordan, 2003) can both hydrolase two crucial peptides, namely angiotensin I and bradykinin, with the same efficiency. Indeed, ACE carries out the cleavage of two amino acids (dipeptidase action) from the C-terminal part of angiotensin I to generate angiotensin II, which exerts a potent vasopressor, proliferative, and profibrotic effect. Moreover, ACE mediates the cleavage and inactivation of bradykinin, which is a vasodilator hypotensive peptide. The pivotal role of ACE in the RAAS system allows a refined blood pressure control and salt homeostasis (Sayer and Bhat, 2014).\nFollowing the ACE discovery in mid-1950s, despite intense research in the field, no human homologs of the enzyme have been found for more than 50 years (Isaac et al., 1998; Riordan, 2003). It was only in 2000 that two independent research groups identified, almost simultaneously, a new human ACE-like enzyme, with two different approaches. Tipnis et al. (2000) searched for new metalloproteases in an expressed sequence tag (EST) database, finding an ACE homolog (ACEH) with a single domain, similar to that of insects. Subsequently they cloned it from a human lymphoma cDNA library. Interestingly ACEH showed high homology (40% identity and 60% similarity) with ACE, particularly around the HEXXH sequence and highly conserved glutamate residue, involved in zinc binding. Moreover, they demonstrated the presence of seven glycosylation sites (Tipnis et al., 2000). In the same year, Donoghue et al. (2000b) were searching for new genes involved in heart failure and identified a human cDNA ACE homolog, named ACE2, among 19,000 5’end sequences by RACE (rapid amplification of cDNA ends) in the heart ventricle cDNA library, obtained from a woman with idiopathic dilated cardiomyopathy. ACE2 showed a transmembrane domain, a zinc catalytic domain 42% identical to ACE and a signal peptide. Like ACE, ACE2 seemed to be an ectoenzyme type I protein. The authors identified ACE2 transcripts quite exclusively in the heart and in the kidney, suggesting a role for ACE2 in the local RAAS control (Donoghue et al., 2000b). In the following years, ACE2 was intensively studied, its structure and function were enlightened, and tentative inhibitors were developed."}

LitCovid-sample-PD-MAT

{"project":"LitCovid-sample-PD-MAT","denotations":[{"id":"T8","span":{"begin":1341,"end":1346},"obj":"http://purl.obolibrary.org/obo/MAT_0000083"},{"id":"T9","span":{"begin":1341,"end":1346},"obj":"http://purl.obolibrary.org/obo/MAT_0000315"},{"id":"T10","span":{"begin":2359,"end":2364},"obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"T11","span":{"begin":2505,"end":2520},"obj":"http://purl.obolibrary.org/obo/MAT_0000497"},{"id":"T12","span":{"begin":2505,"end":2510},"obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"T13","span":{"begin":2823,"end":2828},"obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"T14","span":{"begin":2840,"end":2846},"obj":"http://purl.obolibrary.org/obo/MAT_0000119"}],"text":"ACE System and ACE2 Discovery\nHuman Angiotensin-converting enzyme (ACE) belongs to the M2 gluzincin family of metalloproteinases and (Ehlers and Riordan, 1989; Masuyer et al., 2014) exists in two forms, namely somatic ACE (sACE) and germinal ACE (tACE). Both are derived from the same gene, controlled by alternative promotors. sACE is an integral membrane protein, which can be also cleaved by ACE secretases to produce a circulating form of the enzyme (Natesh et al., 2003).\nsACE, hereafter referred to simply as ACE, has been extensively studied, because of its crucial role in the homeostasis of renin-angiotensin-aldosterone (RAAS) system and in cardiovascular diseases (Takimoto-Ohnishi and Murakami, 2019). The two extracellular domains N and C domains of ACE (Wei et al., 1991; Jaspard et al., 1993; Natesh et al., 2003; Riordan, 2003) can both hydrolase two crucial peptides, namely angiotensin I and bradykinin, with the same efficiency. Indeed, ACE carries out the cleavage of two amino acids (dipeptidase action) from the C-terminal part of angiotensin I to generate angiotensin II, which exerts a potent vasopressor, proliferative, and profibrotic effect. Moreover, ACE mediates the cleavage and inactivation of bradykinin, which is a vasodilator hypotensive peptide. The pivotal role of ACE in the RAAS system allows a refined blood pressure control and salt homeostasis (Sayer and Bhat, 2014).\nFollowing the ACE discovery in mid-1950s, despite intense research in the field, no human homologs of the enzyme have been found for more than 50 years (Isaac et al., 1998; Riordan, 2003). It was only in 2000 that two independent research groups identified, almost simultaneously, a new human ACE-like enzyme, with two different approaches. Tipnis et al. (2000) searched for new metalloproteases in an expressed sequence tag (EST) database, finding an ACE homolog (ACEH) with a single domain, similar to that of insects. Subsequently they cloned it from a human lymphoma cDNA library. Interestingly ACEH showed high homology (40% identity and 60% similarity) with ACE, particularly around the HEXXH sequence and highly conserved glutamate residue, involved in zinc binding. Moreover, they demonstrated the presence of seven glycosylation sites (Tipnis et al., 2000). In the same year, Donoghue et al. (2000b) were searching for new genes involved in heart failure and identified a human cDNA ACE homolog, named ACE2, among 19,000 5’end sequences by RACE (rapid amplification of cDNA ends) in the heart ventricle cDNA library, obtained from a woman with idiopathic dilated cardiomyopathy. ACE2 showed a transmembrane domain, a zinc catalytic domain 42% identical to ACE and a signal peptide. Like ACE, ACE2 seemed to be an ectoenzyme type I protein. The authors identified ACE2 transcripts quite exclusively in the heart and in the kidney, suggesting a role for ACE2 in the local RAAS control (Donoghue et al., 2000b). In the following years, ACE2 was intensively studied, its structure and function were enlightened, and tentative inhibitors were developed."}

LitCovid-sample-PD-GO-BP-0

{"project":"LitCovid-sample-PD-GO-BP-0","denotations":[{"id":"T9","span":{"begin":585,"end":596},"obj":"http://purl.obolibrary.org/obo/GO_0042592"},{"id":"T10","span":{"begin":1373,"end":1384},"obj":"http://purl.obolibrary.org/obo/GO_0042592"},{"id":"T11","span":{"begin":2233,"end":2246},"obj":"http://purl.obolibrary.org/obo/GO_0070085"}],"text":"ACE System and ACE2 Discovery\nHuman Angiotensin-converting enzyme (ACE) belongs to the M2 gluzincin family of metalloproteinases and (Ehlers and Riordan, 1989; Masuyer et al., 2014) exists in two forms, namely somatic ACE (sACE) and germinal ACE (tACE). Both are derived from the same gene, controlled by alternative promotors. sACE is an integral membrane protein, which can be also cleaved by ACE secretases to produce a circulating form of the enzyme (Natesh et al., 2003).\nsACE, hereafter referred to simply as ACE, has been extensively studied, because of its crucial role in the homeostasis of renin-angiotensin-aldosterone (RAAS) system and in cardiovascular diseases (Takimoto-Ohnishi and Murakami, 2019). The two extracellular domains N and C domains of ACE (Wei et al., 1991; Jaspard et al., 1993; Natesh et al., 2003; Riordan, 2003) can both hydrolase two crucial peptides, namely angiotensin I and bradykinin, with the same efficiency. Indeed, ACE carries out the cleavage of two amino acids (dipeptidase action) from the C-terminal part of angiotensin I to generate angiotensin II, which exerts a potent vasopressor, proliferative, and profibrotic effect. Moreover, ACE mediates the cleavage and inactivation of bradykinin, which is a vasodilator hypotensive peptide. The pivotal role of ACE in the RAAS system allows a refined blood pressure control and salt homeostasis (Sayer and Bhat, 2014).\nFollowing the ACE discovery in mid-1950s, despite intense research in the field, no human homologs of the enzyme have been found for more than 50 years (Isaac et al., 1998; Riordan, 2003). It was only in 2000 that two independent research groups identified, almost simultaneously, a new human ACE-like enzyme, with two different approaches. Tipnis et al. (2000) searched for new metalloproteases in an expressed sequence tag (EST) database, finding an ACE homolog (ACEH) with a single domain, similar to that of insects. Subsequently they cloned it from a human lymphoma cDNA library. Interestingly ACEH showed high homology (40% identity and 60% similarity) with ACE, particularly around the HEXXH sequence and highly conserved glutamate residue, involved in zinc binding. Moreover, they demonstrated the presence of seven glycosylation sites (Tipnis et al., 2000). In the same year, Donoghue et al. (2000b) were searching for new genes involved in heart failure and identified a human cDNA ACE homolog, named ACE2, among 19,000 5’end sequences by RACE (rapid amplification of cDNA ends) in the heart ventricle cDNA library, obtained from a woman with idiopathic dilated cardiomyopathy. ACE2 showed a transmembrane domain, a zinc catalytic domain 42% identical to ACE and a signal peptide. Like ACE, ACE2 seemed to be an ectoenzyme type I protein. The authors identified ACE2 transcripts quite exclusively in the heart and in the kidney, suggesting a role for ACE2 in the local RAAS control (Donoghue et al., 2000b). In the following years, ACE2 was intensively studied, its structure and function were enlightened, and tentative inhibitors were developed."}

LitCovid-sample-PD-HP

{"project":"LitCovid-sample-PD-HP","denotations":[{"id":"T8","span":{"begin":651,"end":674},"obj":"Phenotype"},{"id":"T9","span":{"begin":1971,"end":1979},"obj":"Phenotype"},{"id":"T10","span":{"begin":2359,"end":2372},"obj":"Phenotype"},{"id":"T11","span":{"begin":2573,"end":2595},"obj":"Phenotype"}],"attributes":[{"id":"A8","pred":"hp_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/HP_0001626"},{"id":"A9","pred":"hp_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/HP_0002665"},{"id":"A11","pred":"hp_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/HP_0001644"},{"id":"A10","pred":"hp_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/HP_0001635"}],"text":"ACE System and ACE2 Discovery\nHuman Angiotensin-converting enzyme (ACE) belongs to the M2 gluzincin family of metalloproteinases and (Ehlers and Riordan, 1989; Masuyer et al., 2014) exists in two forms, namely somatic ACE (sACE) and germinal ACE (tACE). Both are derived from the same gene, controlled by alternative promotors. sACE is an integral membrane protein, which can be also cleaved by ACE secretases to produce a circulating form of the enzyme (Natesh et al., 2003).\nsACE, hereafter referred to simply as ACE, has been extensively studied, because of its crucial role in the homeostasis of renin-angiotensin-aldosterone (RAAS) system and in cardiovascular diseases (Takimoto-Ohnishi and Murakami, 2019). The two extracellular domains N and C domains of ACE (Wei et al., 1991; Jaspard et al., 1993; Natesh et al., 2003; Riordan, 2003) can both hydrolase two crucial peptides, namely angiotensin I and bradykinin, with the same efficiency. Indeed, ACE carries out the cleavage of two amino acids (dipeptidase action) from the C-terminal part of angiotensin I to generate angiotensin II, which exerts a potent vasopressor, proliferative, and profibrotic effect. Moreover, ACE mediates the cleavage and inactivation of bradykinin, which is a vasodilator hypotensive peptide. The pivotal role of ACE in the RAAS system allows a refined blood pressure control and salt homeostasis (Sayer and Bhat, 2014).\nFollowing the ACE discovery in mid-1950s, despite intense research in the field, no human homologs of the enzyme have been found for more than 50 years (Isaac et al., 1998; Riordan, 2003). It was only in 2000 that two independent research groups identified, almost simultaneously, a new human ACE-like enzyme, with two different approaches. Tipnis et al. (2000) searched for new metalloproteases in an expressed sequence tag (EST) database, finding an ACE homolog (ACEH) with a single domain, similar to that of insects. Subsequently they cloned it from a human lymphoma cDNA library. Interestingly ACEH showed high homology (40% identity and 60% similarity) with ACE, particularly around the HEXXH sequence and highly conserved glutamate residue, involved in zinc binding. Moreover, they demonstrated the presence of seven glycosylation sites (Tipnis et al., 2000). In the same year, Donoghue et al. (2000b) were searching for new genes involved in heart failure and identified a human cDNA ACE homolog, named ACE2, among 19,000 5’end sequences by RACE (rapid amplification of cDNA ends) in the heart ventricle cDNA library, obtained from a woman with idiopathic dilated cardiomyopathy. ACE2 showed a transmembrane domain, a zinc catalytic domain 42% identical to ACE and a signal peptide. Like ACE, ACE2 seemed to be an ectoenzyme type I protein. The authors identified ACE2 transcripts quite exclusively in the heart and in the kidney, suggesting a role for ACE2 in the local RAAS control (Donoghue et al., 2000b). In the following years, ACE2 was intensively studied, its structure and function were enlightened, and tentative inhibitors were developed."}

LitCovid-sample-GO-BP

{"project":"LitCovid-sample-GO-BP","denotations":[{"id":"T9","span":{"begin":585,"end":596},"obj":"http://purl.obolibrary.org/obo/GO_0042592"},{"id":"T10","span":{"begin":1373,"end":1384},"obj":"http://purl.obolibrary.org/obo/GO_0042592"},{"id":"T11","span":{"begin":2233,"end":2246},"obj":"http://purl.obolibrary.org/obo/GO_0070085"}],"text":"ACE System and ACE2 Discovery\nHuman Angiotensin-converting enzyme (ACE) belongs to the M2 gluzincin family of metalloproteinases and (Ehlers and Riordan, 1989; Masuyer et al., 2014) exists in two forms, namely somatic ACE (sACE) and germinal ACE (tACE). Both are derived from the same gene, controlled by alternative promotors. sACE is an integral membrane protein, which can be also cleaved by ACE secretases to produce a circulating form of the enzyme (Natesh et al., 2003).\nsACE, hereafter referred to simply as ACE, has been extensively studied, because of its crucial role in the homeostasis of renin-angiotensin-aldosterone (RAAS) system and in cardiovascular diseases (Takimoto-Ohnishi and Murakami, 2019). The two extracellular domains N and C domains of ACE (Wei et al., 1991; Jaspard et al., 1993; Natesh et al., 2003; Riordan, 2003) can both hydrolase two crucial peptides, namely angiotensin I and bradykinin, with the same efficiency. Indeed, ACE carries out the cleavage of two amino acids (dipeptidase action) from the C-terminal part of angiotensin I to generate angiotensin II, which exerts a potent vasopressor, proliferative, and profibrotic effect. Moreover, ACE mediates the cleavage and inactivation of bradykinin, which is a vasodilator hypotensive peptide. The pivotal role of ACE in the RAAS system allows a refined blood pressure control and salt homeostasis (Sayer and Bhat, 2014).\nFollowing the ACE discovery in mid-1950s, despite intense research in the field, no human homologs of the enzyme have been found for more than 50 years (Isaac et al., 1998; Riordan, 2003). It was only in 2000 that two independent research groups identified, almost simultaneously, a new human ACE-like enzyme, with two different approaches. Tipnis et al. (2000) searched for new metalloproteases in an expressed sequence tag (EST) database, finding an ACE homolog (ACEH) with a single domain, similar to that of insects. Subsequently they cloned it from a human lymphoma cDNA library. Interestingly ACEH showed high homology (40% identity and 60% similarity) with ACE, particularly around the HEXXH sequence and highly conserved glutamate residue, involved in zinc binding. Moreover, they demonstrated the presence of seven glycosylation sites (Tipnis et al., 2000). In the same year, Donoghue et al. (2000b) were searching for new genes involved in heart failure and identified a human cDNA ACE homolog, named ACE2, among 19,000 5’end sequences by RACE (rapid amplification of cDNA ends) in the heart ventricle cDNA library, obtained from a woman with idiopathic dilated cardiomyopathy. ACE2 showed a transmembrane domain, a zinc catalytic domain 42% identical to ACE and a signal peptide. Like ACE, ACE2 seemed to be an ectoenzyme type I protein. The authors identified ACE2 transcripts quite exclusively in the heart and in the kidney, suggesting a role for ACE2 in the local RAAS control (Donoghue et al., 2000b). In the following years, ACE2 was intensively studied, its structure and function were enlightened, and tentative inhibitors were developed."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T8","span":{"begin":651,"end":674},"obj":"Phenotype"},{"id":"T9","span":{"begin":1971,"end":1979},"obj":"Phenotype"},{"id":"T10","span":{"begin":2359,"end":2372},"obj":"Phenotype"},{"id":"T11","span":{"begin":2573,"end":2595},"obj":"Phenotype"}],"attributes":[{"id":"A8","pred":"hp_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/HP_0001626"},{"id":"A9","pred":"hp_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/HP_0002665"},{"id":"A10","pred":"hp_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/HP_0001635"},{"id":"A11","pred":"hp_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/HP_0001644"}],"text":"ACE System and ACE2 Discovery\nHuman Angiotensin-converting enzyme (ACE) belongs to the M2 gluzincin family of metalloproteinases and (Ehlers and Riordan, 1989; Masuyer et al., 2014) exists in two forms, namely somatic ACE (sACE) and germinal ACE (tACE). Both are derived from the same gene, controlled by alternative promotors. sACE is an integral membrane protein, which can be also cleaved by ACE secretases to produce a circulating form of the enzyme (Natesh et al., 2003).\nsACE, hereafter referred to simply as ACE, has been extensively studied, because of its crucial role in the homeostasis of renin-angiotensin-aldosterone (RAAS) system and in cardiovascular diseases (Takimoto-Ohnishi and Murakami, 2019). The two extracellular domains N and C domains of ACE (Wei et al., 1991; Jaspard et al., 1993; Natesh et al., 2003; Riordan, 2003) can both hydrolase two crucial peptides, namely angiotensin I and bradykinin, with the same efficiency. Indeed, ACE carries out the cleavage of two amino acids (dipeptidase action) from the C-terminal part of angiotensin I to generate angiotensin II, which exerts a potent vasopressor, proliferative, and profibrotic effect. Moreover, ACE mediates the cleavage and inactivation of bradykinin, which is a vasodilator hypotensive peptide. The pivotal role of ACE in the RAAS system allows a refined blood pressure control and salt homeostasis (Sayer and Bhat, 2014).\nFollowing the ACE discovery in mid-1950s, despite intense research in the field, no human homologs of the enzyme have been found for more than 50 years (Isaac et al., 1998; Riordan, 2003). It was only in 2000 that two independent research groups identified, almost simultaneously, a new human ACE-like enzyme, with two different approaches. Tipnis et al. (2000) searched for new metalloproteases in an expressed sequence tag (EST) database, finding an ACE homolog (ACEH) with a single domain, similar to that of insects. Subsequently they cloned it from a human lymphoma cDNA library. Interestingly ACEH showed high homology (40% identity and 60% similarity) with ACE, particularly around the HEXXH sequence and highly conserved glutamate residue, involved in zinc binding. Moreover, they demonstrated the presence of seven glycosylation sites (Tipnis et al., 2000). In the same year, Donoghue et al. (2000b) were searching for new genes involved in heart failure and identified a human cDNA ACE homolog, named ACE2, among 19,000 5’end sequences by RACE (rapid amplification of cDNA ends) in the heart ventricle cDNA library, obtained from a woman with idiopathic dilated cardiomyopathy. ACE2 showed a transmembrane domain, a zinc catalytic domain 42% identical to ACE and a signal peptide. Like ACE, ACE2 seemed to be an ectoenzyme type I protein. The authors identified ACE2 transcripts quite exclusively in the heart and in the kidney, suggesting a role for ACE2 in the local RAAS control (Donoghue et al., 2000b). In the following years, ACE2 was intensively studied, its structure and function were enlightened, and tentative inhibitors were developed."}

LitCovid-PubTator

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T33","span":{"begin":0,"end":29},"obj":"Sentence"},{"id":"T34","span":{"begin":30,"end":253},"obj":"Sentence"},{"id":"T35","span":{"begin":254,"end":476},"obj":"Sentence"},{"id":"T36","span":{"begin":477,"end":713},"obj":"Sentence"},{"id":"T37","span":{"begin":714,"end":947},"obj":"Sentence"},{"id":"T38","span":{"begin":948,"end":1168},"obj":"Sentence"},{"id":"T39","span":{"begin":1169,"end":1280},"obj":"Sentence"},{"id":"T40","span":{"begin":1281,"end":1408},"obj":"Sentence"},{"id":"T41","span":{"begin":1409,"end":1597},"obj":"Sentence"},{"id":"T42","span":{"begin":1598,"end":1749},"obj":"Sentence"},{"id":"T43","span":{"begin":1750,"end":1929},"obj":"Sentence"},{"id":"T44","span":{"begin":1930,"end":1993},"obj":"Sentence"},{"id":"T45","span":{"begin":1994,"end":2182},"obj":"Sentence"},{"id":"T46","span":{"begin":2183,"end":2275},"obj":"Sentence"},{"id":"T47","span":{"begin":2276,"end":2596},"obj":"Sentence"},{"id":"T48","span":{"begin":2597,"end":2699},"obj":"Sentence"},{"id":"T49","span":{"begin":2700,"end":2757},"obj":"Sentence"},{"id":"T50","span":{"begin":2758,"end":2926},"obj":"Sentence"},{"id":"T51","span":{"begin":2927,"end":3066},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"ACE System and ACE2 Discovery\nHuman Angiotensin-converting enzyme (ACE) belongs to the M2 gluzincin family of metalloproteinases and (Ehlers and Riordan, 1989; Masuyer et al., 2014) exists in two forms, namely somatic ACE (sACE) and germinal ACE (tACE). Both are derived from the same gene, controlled by alternative promotors. sACE is an integral membrane protein, which can be also cleaved by ACE secretases to produce a circulating form of the enzyme (Natesh et al., 2003).\nsACE, hereafter referred to simply as ACE, has been extensively studied, because of its crucial role in the homeostasis of renin-angiotensin-aldosterone (RAAS) system and in cardiovascular diseases (Takimoto-Ohnishi and Murakami, 2019). The two extracellular domains N and C domains of ACE (Wei et al., 1991; Jaspard et al., 1993; Natesh et al., 2003; Riordan, 2003) can both hydrolase two crucial peptides, namely angiotensin I and bradykinin, with the same efficiency. Indeed, ACE carries out the cleavage of two amino acids (dipeptidase action) from the C-terminal part of angiotensin I to generate angiotensin II, which exerts a potent vasopressor, proliferative, and profibrotic effect. Moreover, ACE mediates the cleavage and inactivation of bradykinin, which is a vasodilator hypotensive peptide. The pivotal role of ACE in the RAAS system allows a refined blood pressure control and salt homeostasis (Sayer and Bhat, 2014).\nFollowing the ACE discovery in mid-1950s, despite intense research in the field, no human homologs of the enzyme have been found for more than 50 years (Isaac et al., 1998; Riordan, 2003). It was only in 2000 that two independent research groups identified, almost simultaneously, a new human ACE-like enzyme, with two different approaches. Tipnis et al. (2000) searched for new metalloproteases in an expressed sequence tag (EST) database, finding an ACE homolog (ACEH) with a single domain, similar to that of insects. Subsequently they cloned it from a human lymphoma cDNA library. Interestingly ACEH showed high homology (40% identity and 60% similarity) with ACE, particularly around the HEXXH sequence and highly conserved glutamate residue, involved in zinc binding. Moreover, they demonstrated the presence of seven glycosylation sites (Tipnis et al., 2000). In the same year, Donoghue et al. (2000b) were searching for new genes involved in heart failure and identified a human cDNA ACE homolog, named ACE2, among 19,000 5’end sequences by RACE (rapid amplification of cDNA ends) in the heart ventricle cDNA library, obtained from a woman with idiopathic dilated cardiomyopathy. ACE2 showed a transmembrane domain, a zinc catalytic domain 42% identical to ACE and a signal peptide. Like ACE, ACE2 seemed to be an ectoenzyme type I protein. The authors identified ACE2 transcripts quite exclusively in the heart and in the kidney, suggesting a role for ACE2 in the local RAAS control (Donoghue et al., 2000b). In the following years, ACE2 was intensively studied, its structure and function were enlightened, and tentative inhibitors were developed."}

PMC:7556165 / 4655-7721 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7556165 / 4655-7721 JSON TXT