| + |
ACE2 | up-regulates activity 
cleavage
|
AGT |
0.75 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256317 |
His42 |
RVYIHPFhLVIHNES |
in vitro |
|
| pmid |
sentence |
| 11815627 |
The ACE2 hydrolytic activity is dependent on the C terminus sequence of the substrate, which is evident from the data with the angiotensin peptides. After 2 h, ACE2 hydrolyzes Ang I partially and Ang II completely, although there is no hydrolysis of angiotensin 1–9, angiotensin 1–7, and angiotensin 1–5, which possess the same N terminus. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256315 |
Pro40 |
GDRVYIHpFHLVIHN |
in vitro |
|
| pmid |
sentence |
| 11815627 |
The ACE2 hydrolytic activity is dependent on the C terminus sequence of the substrate, which is evident from the data with the angiotensin peptides. After 2 h, ACE2 hydrolyzes Ang I partially and Ang II completely, although there is no hydrolysis of angiotensin 1–9, angiotensin 1–7, and angiotensin 1–5, which possess the same N terminus. |
|
| Publications: |
2 |
Organism: |
In Vitro |
| Pathways: | COVID-19 Causal Network, Fibrosis, SARS-CoV FIBROSIS |
| + |
ACE2 | up-regulates activity
cleavage
|
Angiotensin-1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260221 |
His42 |
RVYIHPFhLVIHNES |
in vitro |
|
| pmid |
sentence |
| 11815627 |
The ACE2 hydrolytic activity is dependent on the C terminus sequence of the substrate, which is evident from the data with the angiotensin peptides. After 2 h, ACE2 hydrolyzes Ang I partially and Ang II completely, although there is no hydrolysis of angiotensin 1–9, angiotensin 1–7, and angiotensin 1–5, which possess the same N terminus. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260222 |
Pro40 |
GDRVYIHpFHLVIHN |
in vitro |
|
| pmid |
sentence |
| 11815627 |
The ACE2 hydrolytic activity is dependent on the C terminus sequence of the substrate, which is evident from the data with the angiotensin peptides. After 2 h, ACE2 hydrolyzes Ang I partially and Ang II completely, although there is no hydrolysis of angiotensin 1–9, angiotensin 1–7, and angiotensin 1–5, which possess the same N terminus. |
|
| Publications: |
2 |
Organism: |
In Vitro |
| Pathways: | COVID-19 Causal Network, Fibrosis, SARS-CoV FIBROSIS |
| + |
captopril | down-regulates activity 
chemical inhibition
|
ACE2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261069 |
|
|
in vitro |
|
| pmid |
sentence |
| 9187274 |
The interaction of captopril at one active site of wild-type ACE impeding substrate interaction with the other active site. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
ACE2 | up-regulates 
|
Receptor_mediated_ endocytosis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260235 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18554741 |
Endocytosis of the Receptor-Binding Domain of SARS-CoV Spike Protein Together With Virus Receptor ACE2. Here, we demonstrate that the RBD spike protein alone can be internalized together with ACE2. We propose that after binding to ACE2, the RBD spike protein activates the ACE2 mediated cellular endocytosis signal pathway, by which SARS-CoV enters the susceptible cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY |
| + |
S | down-regulates activity
binding
|
ACE2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260742 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 32125455 |
SARS-CoV and likely SARS-CoV-2 lead to downregulation of the ACE2 receptor, but not ACE, through binding of the spike protein with ACE2. This leads to viral entry and replication, as well as severe lung injury. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY, SARS-CoV FIBROSIS |
| + |
S | down-regulates activity
binding
|
ACE2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260283 |
|
|
Chlorocebus aethiops |
|
| pmid |
sentence |
| 18554741 |
Cell entry of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by the viral spike (S) protein. Amino acids 319-510 on the S protein have been mapped as the receptor-binding domain (RBD), which mediates binding to the SARS-CoV receptor angiotensin converting enzyme 2 (ACE2) on SARS-CoV susceptible cells. Here, we demonstrate that the RBD spike protein alone can be internalized together with ACE2. We propose that after binding to ACE2, the RBD spike protein activates the ACE2 mediated cellular endocytosis signal pathway, by which SARS-CoV enters the susceptible cells. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260216 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14670965 |
The coronavirus spike (S) protein mediates infection of receptor-expressing host cells and is a critical target for antiviral neutralizing antibodies. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for the coronavirus (severe acute respiratory syndrome (SARS)-CoV) that causes SARS. Here we demonstrate that a 193-amino acid fragment of the S protein (residues 318-510) bound ACE2 more efficiently than did the full S1 domain (residues 12-672). Smaller S protein fragments, expressing residues 327-510 or 318-490, did not detectably bind ACE2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260291 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16988814 |
In acute lung injury, such as acid aspiration, pneumonia, or sepsis, the generation of ANG II from ANG I is enhanced by ACE, and ANG II induces acute lung failure through stimulation of the AT1 receptor, while ACE2 and ANG II type 2 receptor negatively regulate this pathway and protect from acute lung failure. On the other hand, SARS-CoV infection is mediated through binding of the SARS-Spike protein to ACE2 or L-SIGN and down-regulates the protective molecule ACE2, and thus leads to severe lung injury and acute lung failure |
|
| Publications: |
3 |
Organism: |
Chlorocebus Aethiops, Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY, SARS-CoV FIBROSIS |
| + |
ACE2 | form complex 
binding
|
Spike protein-ACE2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260288 |
|
|
Chlorocebus aethiops |
Vero Cell |
| pmid |
sentence |
| 18554741 |
Cell entry of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by the viral spike (S) protein. Amino acids 319-510 on the S protein have been mapped as the receptor-binding domain (RBD), which mediates binding to the SARS-CoV receptor angiotensin converting enzyme 2 (ACE2) on SARS-CoV susceptible cells. Here, we demonstrate that the RBD spike protein alone can be internalized together with ACE2. We propose that after binding to ACE2, the RBD spike protein activates the ACE2 mediated cellular endocytosis signal pathway, by which SARS-CoV enters the susceptible cells. |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| Pathways: | SARS-CoV ATTACHMENT AND ENTRY |
| + |
ACE2 | form complex
binding
|
CoV2 Spike protein-ACE2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260740 |
|
|
Chlorocebus aethiops |
Vero Cell |
| pmid |
sentence |
| 32155444 |
We report here that ACE2 could mediate SARS-CoV-2 S-mediated entry into cells, establishing it as a functional receptor for this newly emerged coronavirus. The SARS-CoV-2 SB engages human ACE2 (hACE2) with comparable affinity to SARS-CoV SB from viral isolates associated with the 2002–2003 epidemic (i.e., binding with high affinity to hACE2). Tight binding to hACE2 could partially explain the efficient transmission of SARS-CoV-2 in humans, as was the case for SARS-CoV. |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| Pathways: | COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY |
| + |
ACE2 | up-regulates activity
cleavage
|
APLN |
0.435 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256316 |
|
|
in vitro |
|
| pmid |
sentence |
| 11815627 |
ACE2 hydrolyzes the hormone apelin-13 with high catalytic efficiency and cleaves apelin-36, whose C-terminal 13 amino acids are identical to those of apelin-13. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
chloroquine | down-regulates activity
chemical inhibition
|
ACE2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260223 |
|
|
Chlorocebus aethiops |
|
| pmid |
sentence |
| 32020029 |
Chloroquine is known to block virus infection by increasing endosomal pH required for virus/cell fusion, as well as interfering with the glycosylation of cellular receptors of SARS-CoV. Our time-of-addition assay demonstrated that chloroquine functioned at both entry, and at post-entry stages of the 2019-nCoV infection in Vero E6 cells |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| Pathways: | COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY, SARS-CoV FIBROSIS |
| + |
ACE2 | up-regulates quantity
cleavage
|
Angiotensin 1-7 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260227 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 32201502 |
At first, ACE2 has been demonstrated to induce conversion of Ang I into Ang (1–7) by means of intermediate production of Ang (1–9), a fragment with unknown function. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Fibrosis, SARS-CoV ATTACHMENT AND ENTRY, SARS-CoV FIBROSIS |
| + |
Angiotensin-1 | up-regulates activity
binding
|
ACE2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260226 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 32201502 |
At first, ACE2 has been demonstrated to induce conversion of Ang I into Ang (1–7) by means of intermediate production of Ang (1–9), a fragment with unknown function. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Fibrosis, SARS-CoV FIBROSIS |
| + |
ACE2 | up-regulates
|
Membrane_fusion |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260286 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 32231345 |
Unlike SARS-CoV, live SARS-CoV-2-infected cells were found to form typical syncytium, suggesting that SARS-CoV-2 may mainly utilize the plasma membrane fusion pathway to enter and replicate inside host cells. Consistently, in the cell–cell fusion system, SARS-CoV-2 S protein could effectively mediate the formation of syncytium between the effector cell and the target cell in the absence of an exogenous proteolytic enzyme, e.g., trypsin, while SARS-CoV S protein could not. Actually, the plasma membrane fusion pathway is more efficient than the endosomal membrane fusion pathway for most viruses because the latter is more prone to activating the host cell antiviral immunity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY |
3.0
ACE2
- 
- 