General Information:

Id: 11,846
Diseases: SARS-CoV infection
Homo sapiens
primary airway epithelia isolated from human donor trachea or bronchi; HEK293 cells; HeLa cells
article/cited
Reference: Jia HP et al.(2009) Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia Am. J. Physiol. Lung Cell Mol. Physiol. 297: L84-L96 [PMID: 19411314]

Interaction Information:

Comment Calmodulin inhibitors increase ACE2 shedding in HEK cells, suggesting that a calcium signaling pathway is involved in ACE2 release. (cited information)
Formal Description
Interaction-ID: 116940

drug/chemical compound

Calmodulin inhibitor

increases_activity of

in HEK cells; concerning ACE2, suggesting that a calcium signaling pathway is involved in ACE2 release
Comment It was found that ionomycin rapidly induced ACE2 shedding in human airway epithelial cells suggests a role for intracellular calcium signaling.
Formal Description
Interaction-ID: 116941

increases_activity of

process

ACE2 ectodomain proteolysis

in human airway epithelial cells; suggests a role for intracellular calcium signaling
Comment Constitutive generation of soluble ACE2 was inhibited by DPC 333, implicating a disintegrin and metalloprotease 17 (ADAM17).
Formal Description
Interaction-ID: 116942

drug/chemical compound

DPC 333

decreases_quantity of

gene/protein

ACE2, soluble

implicating ADAM17
Comment Phorbol ester, ionomycin, endotoxin, and IL-1beta and TNFalpha acutely induced ACE2 release, further supporting that ADAM17 and ADAM10 regulate ACE2 cleavage.
Formal Description
Interaction-ID: 116943

increases_quantity of

gene/protein

ACE2, soluble

supporting that ADAM17 and ADAM10 regulate ACE2 cleavage
Comment Soluble ACE2 was enzymatically active and partially inhibited virus entry into target cells via sACE2 competition for S protein binding.
Formal Description
Interaction-ID: 116944

gene/protein

ACE2, soluble

decreases_activity of

Comment A point mutation in the ACE2 ectodomain, L584A, markedly attenuated shedding. The resultant ACE2-L584A mutant trafficked to the cell membrane and facilitated SARS-CoV entry into target cells, suggesting that the ACE2 ectodomain regulates its release and that residue L584 might be part of a putative sheddase “recognition motif”. Thus ACE2 must be cell associated to serve as a CoV receptor and soluble ACE2 might play a role in modifying inflammatory processes at the airway mucosal surface.
Formal Description
Interaction-ID: 116945

gene/protein mutant

ACE2-p.L584A

decreases_activity of

process

ACE2 ectodomain proteolysis

Comment sACE2 (soluble ACE2) retains its terminal carboxypeptidase activity in airway surface liquid, as well as its ability to bind the virus SARS-CoV via S protein binding. The release of sACE2 from epithelia was both constitutive and inducible, regulated by sheddases and inflammatory stimuli.
Formal Description
Interaction-ID: 116947

gene/protein

ACE2, soluble

interacts (colocalizes) with

environment

SARS-CoV S protein

Comment Calmodulin inhibitors increase ACE2 shedding in HEK cells, suggesting that a calcium signaling pathway is involved in ACE2 release. (cited information)
Formal Description
Interaction-ID: 116948

drug/chemical compound

Calmodulin inhibitor

increases_activity of

process

ACE2 ectodomain proteolysis

in HEK cells; suggesting that a calcium signaling pathway is involved in ACE2 release
Comment Phorbol ester, ionomycin, endotoxin, and IL-1beta and TNFalpha acutely induced ACE2 release, further supporting that ADAM17 and ADAM10 regulate ACE2 cleavage.
Formal Description
Interaction-ID: 116949

increases_quantity of

gene/protein

ACE2, soluble

supporting that ADAM17 and ADAM10 regulate ACE2 cleavage
Comment Phorbol ester, ionomycin, endotoxin, and IL-1beta and TNFalpha acutely induced ACE2 release, further supporting that ADAM17 and ADAM10 regulate ACE2 cleavage.
Formal Description
Interaction-ID: 116950

drug/chemical compound

Endotoxin

increases_quantity of

gene/protein

ACE2, soluble

supporting that ADAM17 and ADAM10 regulate ACE2 cleavage
Comment Phorbol ester, ionomycin, endotoxin, and IL-1beta and TNFalpha acutely induced ACE2 release, further supporting that ADAM17 and ADAM10 regulate ACE2 cleavage.
Formal Description
Interaction-ID: 116951

gene/protein

IL1B

increases_quantity of

gene/protein

ACE2, soluble

supporting that ADAM17 and ADAM10 regulate ACE2 cleavage
Drugbank entries Show/Hide entries for IL1B
Comment Phorbol ester, ionomycin, endotoxin, and IL-1beta and TNFalpha acutely induced ACE2 release, further supporting that ADAM17 and ADAM10 regulate ACE2 cleavage.
Formal Description
Interaction-ID: 116952

gene/protein

TNF

increases_quantity of

gene/protein

ACE2, soluble

supporting that ADAM17 and ADAM10 regulate ACE2 cleavage
Drugbank entries Show/Hide entries for TNF
Comment A point mutation in the ACE2 ectodomain, L584A, markedly attenuated shedding. The resultant ACE2-L584A mutant trafficked to the cell membrane and facilitated SARS-CoV entry into target cells, suggesting that the ACE2 ectodomain regulates its release and that residue L584 might be part of a putative sheddase “recognition motif”. Thus ACE2 must be cell associated to serve as a CoV receptor and soluble ACE2 might play a role in modifying inflammatory processes at the airway mucosal surface.
Formal Description
Interaction-ID: 116953

gene/protein mutant

ACE2-p.L584A

increases_activity of

ACE2-L584A mutant trafficked to the cell membrane and facilitated SARS-CoV entry into target cells
Comment ACE2 must be cell attached to function as a SARS-CoV receptor. Soluble ACE2 might play a role in modifying inflammatory processes at the airway mucosal surface.
Formal Description
Interaction-ID: 116954

gene/protein

ACE2, membrane-bound

increases_activity of

functioning as a SARS-CoV receptor
Comment The proinflammatory cytokines IL-1beta and TNFalpha induced sACE2 (soluble ACE2) release. They enhanced ACE2 shedding from airway epithelia.
Formal Description
Interaction-ID: 116956

process

ACE2 ectodomain proteolysis

increases_quantity of

gene/protein

ACE2, soluble

Comment The proinflammatory cytokines IL-1beta and TNFalpha induced sACE2 (soluble ACE2) release. They enhanced ACE2 shedding from airway epithelia.
Formal Description
Interaction-ID: 116957

gene/protein

IL1B

increases_activity of

process

ACE2 ectodomain proteolysis

from airway epithelia
Drugbank entries Show/Hide entries for IL1B
Comment The proinflammatory cytokines IL-1beta and TNFalpha induced sACE2 (soluble ACE2) release. They enhanced ACE2 shedding from airway epithelia.
Formal Description
Interaction-ID: 116958

gene/protein

TNF

increases_activity of

process

ACE2 ectodomain proteolysis

from airway epithelia
Drugbank entries Show/Hide entries for TNF
Comment ACE2-RBD interacts with the SARS-CoV S protein. The SARS CoV spike receptor-binding domain is bound to ACE2.
Formal Description
Interaction-ID: 121044

gene/protein

ACE2

interacts (colocalizes) with

environment

SARS-CoV S protein

Drugbank entries Show/Hide entries for ACE2
Comment ADAM17 is responsible for constitutive ACE2 shedding in primary human airway epithelial cells.
Formal Description
Interaction-ID: 121046

gene/protein

ADAM17

increases_quantity of

gene/protein

ACE2, soluble

in primary human airway epithelial cells
Drugbank entries Show/Hide entries for ADAM17
Comment ACE2 is shed from human airway epithelia, a site of SARS-CoV infection.
Formal Description
Interaction-ID: 121117

gene/protein

ACE2

increases_activity of

disease

SARS-CoV infection

Drugbank entries Show/Hide entries for ACE2
Comment Additional data indicate that SARS-CoV S protein or SARS virus infection directly downregulates pulmonary ACE2 expression. (cited information)
Formal Description
Interaction-ID: 121118

disease

SARS-CoV infection

decreases_expression of

gene/protein

ACE2

Drugbank entries Show/Hide entries for ACE2
Comment Additional data indicate that SARS-CoV S protein or SARS virus infection directly downregulates pulmonary ACE2 expression. (cited information)
Formal Description
Interaction-ID: 121119

environment

SARS-CoV S protein

decreases_expression of

gene/protein

ACE2

Drugbank entries Show/Hide entries for ACE2