General Information:

Id: 11,748
Diseases: COVID-19
Homo sapiens
review
Reference: Sriram K and Insel PA(2020) A hypothesis for pathobiology and treatment of COVID-19: The centrality of ACE1/ACE2 imbalance Br J Pharmacol 177: 4825-4844 [PMID: 32333398]

Interaction Information:

Comment Compared to SARS-COV-1, SARS-CoV-2 has about 4-fold higher affinity for ACE2.
Formal Description
Interaction-ID: 116293

environment

SARS-CoV-2

interacts (colocalizes) with

gene/protein

ACE2

Drugbank entries Show/Hide entries for ACE2
Comment Renin is secreted from the kidney and angiotensinogen is produced and secreted by the liver.
Formal Description
Interaction-ID: 116294

tissue/cell line

kidney

increases_quantity of

gene/protein

REN

Drugbank entries Show/Hide entries for REN
Comment Renin is secreted from the kidney and angiotensinogen is produced and secreted by the liver.
Formal Description
Interaction-ID: 116300

tissue/cell line

liver

increases_quantity of

gene/protein

AGT

Comment Renin cleaves AGT to form Angiotensin 1 (ANG 1), which in turn generates ANG II or ANG 1-9, primarily from the actions of ACE1 and ACE2, respectively.
Formal Description
Interaction-ID: 116302

gene/protein

Renin

decreases_quantity of

gene/protein

AGT

Comment Renin cleaves AGT to form Angiotensin 1 (ANG 1), which in turn generates ANG II or ANG 1-9, primarily from the actions of ACE1 and ACE2, respectively.
Formal Description
Interaction-ID: 116304

gene/protein

Renin

increases_quantity of

gene/protein

Angiotensin I

Comment Renin cleaves AGT to form Angiotensin 1 (ANG 1), which in turn generates ANG II or ANG 1-9, primarily from the actions of ACE1 and ACE2, respectively.
Formal Description
Interaction-ID: 116310

gene/protein

AGT

increases_quantity of

gene/protein

Angiotensin I

via cleavage by renin
Comment Renin cleaves AGT to form Angiotensin 1 (ANG 1), which in turn generates ANG II or ANG 1-9, primarily from the actions of ACE1 and ACE2, respectively.
Formal Description
Interaction-ID: 116361

gene/protein

Angiotensin I

increases_quantity of

gene/protein

Angiotensin II

via cleavage by ACE
Comment Renin cleaves AGT to form Angiotensin 1 (ANG 1), which in turn generates ANG II or ANG 1-9, primarily from the actions of ACE1 and ACE2, respectively.
Formal Description
Interaction-ID: 116362

gene/protein

ACE

increases_quantity of

gene/protein

Angiotensin II

Drugbank entries Show/Hide entries for ACE
Comment Renin cleaves AGT to form Angiotensin 1 (ANG 1), which in turn generates ANG II or ANG 1-9, primarily from the actions of ACE1 and ACE2, respectively.
Formal Description
Interaction-ID: 116363

gene/protein

ACE

decreases_quantity of

gene/protein

Angiotensin I

Drugbank entries Show/Hide entries for ACE
Comment Renin cleaves AGT to form Angiotensin 1 (ANG 1), which in turn generates ANG II or ANG 1-9, primarily from the actions of ACE1 and ACE2, respectively.
Formal Description
Interaction-ID: 116364

gene/protein

Angiotensin I

increases_quantity of

gene/protein

Angiotensin (1-9)

via the catalytic activity of ACE2
Comment Renin cleaves AGT to form Angiotensin 1 (ANG 1), which in turn generates ANG II or ANG 1-9, primarily from the actions of ACE1 and ACE2, respectively.
Formal Description
Interaction-ID: 116365

gene/protein

ACE2

increases_quantity of

gene/protein

Angiotensin (1-9)

Drugbank entries Show/Hide entries for ACE2
Comment Renin cleaves AGT to form Angiotensin 1 (ANG 1), which in turn generates ANG II or ANG 1-9, primarily from the actions of ACE1 and ACE2, respectively.
Formal Description
Interaction-ID: 116366

gene/protein

ACE2

decreases_quantity of

gene/protein

Angiotensin I

Drugbank entries Show/Hide entries for ACE2
Comment ANG II is cleaved by multiple enzymes, most importantly ACE2, to form ANG (1-7). ANG II also forms ANG IV via the action of aminopeptidases.
Formal Description
Interaction-ID: 116367

gene/protein

Angiotensin II

increases_quantity of

gene/protein

Angiotensin (1-7)

via cleavage by ACE2 and other enzymes
Comment ANG II is cleaved by multiple enzymes, most importantly ACE2, to form ANG (1-7). ANG II also forms ANG IV via the action of aminopeptidases.
Formal Description
Interaction-ID: 116368

gene/protein

Angiotensin II

increases_quantity of

gene/protein

Angiotensin IV

via cleavage by aminopeptidases
Comment ANG II is cleaved by multiple enzymes, e.g. prolyl endopeptidase (PREP), but most importantly ACE2, to form ANG (1-7). ANG II also forms ANG IV via the action of aminopeptidases.
Formal Description
Interaction-ID: 116369

gene/protein

ACE2

increases_quantity of

gene/protein

Angiotensin (1-7)

Drugbank entries Show/Hide entries for ACE2
Comment ANG II is cleaved by multiple enzymes, e.g. prolyl endopeptidase (PREP), but most importantly ACE2, to form ANG (1-7). ANG II also forms ANG IV via the action of aminopeptidases.
Formal Description
Interaction-ID: 116370

gene/protein

ACE2

decreases_quantity of

gene/protein

Angiotensin II

Drugbank entries Show/Hide entries for ACE2
Comment Both, ANG II and ANG IV act primarily via the angiotensin II receptor type 1 (AGTR1).
Formal Description
Interaction-ID: 116371

gene/protein

Angiotensin II

increases_activity of

gene/protein

AGTR1

Drugbank entries Show/Hide entries for AGTR1
Comment Both, ANG II and ANG IV act primarily via the angiotensin II receptor type 1 (AGTR1).
Formal Description
Interaction-ID: 116372

gene/protein

Angiotensin IV

increases_activity of

gene/protein

AGTR1

Drugbank entries Show/Hide entries for AGTR1
Comment ANG (1-7) acts primarily via the G protein-coupled receptor MAS1, and forms ANG (1-5), which signals via MRGPRD. ANG (1-7) can also act via the AGTR2 receptor but with much lower affinity than ANG II.
Formal Description
Interaction-ID: 116373

gene/protein

Angiotensin (1-7)

increases_activity of

gene/protein

MAS1

Comment ANG (1-7) acts primarily via the G protein-coupled receptor MAS1, and forms ANG (1-5), which signals via MRGPRD. ANG (1-7) can also act via the AGTR2 receptor but with much lower affinity than ANG II.
Formal Description
Interaction-ID: 116375

gene/protein

Angiotensin (1-7)

increases_quantity of

gene/protein

Angiotensin (1-5)

Comment ANG (1-7) acts primarily via the G protein-coupled receptor MAS1, and forms ANG (1-5), which signals via MRGPRD. ANG (1-7) can also act via the AGTR2 receptor but with much lower affinity than ANG II.
Formal Description
Interaction-ID: 116376

gene/protein

Angiotensin (1-5)

increases_activity of

gene/protein

MRGPRD

Comment ANG (1-7) acts primarily via the G protein-coupled receptor MAS1, and forms ANG (1-5), which signals via MRGPRD. ANG (1-7) can also act via the AGTR2 receptor but with much lower affinity than ANG II.
Formal Description
Interaction-ID: 116378

gene/protein

Angiotensin (1-7)

increases_activity of

gene/protein

AGTR2

but with lower affinity than ANG II
Drugbank entries Show/Hide entries for AGTR2
Comment ANG (1-7) acts primarily via the G protein-coupled receptor MAS1, and forms ANG (1-5), which signals via MRGPRD. ANG (1-7) can also act via the AGTR2 receptor but with much lower affinity than ANG II.
Formal Description
Interaction-ID: 116379

gene/protein

Angiotensin II

increases_activity of

gene/protein

AGTR2

with higher affinity than Angiotensin (1-7)
Drugbank entries Show/Hide entries for AGTR2
Comment ACE2, in particular its catalytic ectodomain, can be shed from cells into the circulation as soluble ACE2, an action mediated by the metalloprotease ADAM17, an activator of Notch pathway.
Formal Description
Interaction-ID: 116388

gene/protein

ADAM17

affects_activity of

gene/protein

ACE2

via proteolysis
Drugbank entries Show/Hide entries for ADAM17 or ACE2
Comment ACE2, in particular its catalytic ectodomain, can be shed from cells into the circulation as soluble ACE2, an action mediated by the metalloprotease ADAM17, an activator of Notch pathway.
Formal Description
Interaction-ID: 116392

gene/protein

ADAM17

increases_quantity of

gene/protein

ACE2, soluble

via proteolysis
Drugbank entries Show/Hide entries for ADAM17
Comment ANG II increases ADAM17 activity leading to higher levels of soluble ACE2.
Formal Description
Interaction-ID: 116393

gene/protein

Angiotensin II

increases_activity of

gene/protein

ADAM17

Drugbank entries Show/Hide entries for ADAM17
Comment ANG II is cleaved by multiple enzymes, e.g. prolyl endopeptidase (PREP), but most importantly ACE2, to form ANG (1-7). ANG II also forms ANG IV via the action of aminopeptidases.
Formal Description
Interaction-ID: 116398

gene/protein

PREP

increases_quantity of

gene/protein

Angiotensin (1-7)

Drugbank entries Show/Hide entries for PREP
Comment Infection of cells by SARS viruses that bind ACE2 results in two effects: inhibition of ACE2 activity and decrease of ACE2 expression in infected cells. A decrease in ACE activity creates an imbalance in signaling by ACE1 and ACE2 products.
Formal Description
Interaction-ID: 116406

environment

SARS virus

decreases_activity of

gene/protein

ACE2

by binding to ACE2
Drugbank entries Show/Hide entries for ACE2
Comment Infection of cells by SARS viruses that bind ACE2 results in two effects: inhibition of ACE2 activity and decrease of ACE2 expression in infected cells. A decrease in ACE activity creates an imbalance in signaling by ACE1 and ACE2 products.
Formal Description
Interaction-ID: 116440

environment

SARS virus

decreases_expression of

gene/protein

ACE2

Drugbank entries Show/Hide entries for ACE2
Comment ACE2, in particular its catalytic ectodomain, can be shed from cells into the circulation as soluble ACE2, an action mediated by the metalloprotease ADAM17, an activator of Notch pathway.
Formal Description
Interaction-ID: 116481

gene/protein

ADAM17

increases_activity of

Drugbank entries Show/Hide entries for ADAM17