General Information:

Id: 11,676 (click here to show other Interactions for entry)
Diseases: Immunological
SARS-CoV infection
Homo sapiens
HEK293T cells
article
Reference: Heurich A et al.(2014) TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein J. Virol. 88: 1293-1307 [PMID: 24227843]

Interaction Information:

Comment Type II transmembrane serine proteases TMPRSS2 and HAT cleave and activate the spike protein (S) of SARS-CoV so that it can bind to the host receptor angiotensin converting enzyme 2 (ACE2) for membrane fusion. (cited information)
Formal Description
Interaction-ID: 116034

gene/protein

ACE2

increases_activity of

by functioning as receptor for the virus surface protein spike SARS-S
Drugbank entries Show/Hide entries for ACE2
Comment TMPRSS2, HAT, and hepsin not only cleave and activate the spike protein (S) of SARS-CoV, in addition, they cleave the SARS-CoV receptor ACE2. ACE2 processing is required for augmentation of SARS-S-driven entry. Arginine and lysine residues within ACE2 amino acids 697 to 716 are essential for ACE2 cleavage by TMPRSS2 and HAT. This indicates that TMPRSS2 facilitates SARS-CoV infection via two independent mechanisms, cleavage of ACE2, which might promote viral uptake, and cleavage of SARS-S, which activates the S protein for membrane fusion.
Formal Description
Interaction-ID: 116055

gene/protein

TMPRSS2

affects_activity of

gene/protein

ACE2

via proteolytic processing to improve SARS-S-driven transduction
Drugbank entries Show/Hide entries for ACE2
Comment TMPRSS2, HAT, and hepsin cleave ACE2. Arginine and lysine residues within ACE2 amino acids 697 to 716 are essential for ACE2 cleavage by TMPRSS2 and HAT.
Formal Description
Interaction-ID: 116056

gene/protein

TMPRSS11D

affects_activity of

gene/protein

ACE2

via proteolytic processing to improve SARS-S-driven transduction
Drugbank entries Show/Hide entries for ACE2
Comment TMPRSS2, HAT, and hepsin cleave ACE2.
Formal Description
Interaction-ID: 116057

gene/protein

HPN

affects_activity of

gene/protein

ACE2

via proteolytic processing
Drugbank entries Show/Hide entries for HPN or ACE2
Comment SARS-S binding to ACE2 triggers processing of ACE2 by ADAM17. This process, which facilitates shedding of ACE2 into the extracellular space, promotes uptake of SARS-CoV into cells. (cited information)
Formal Description
Interaction-ID: 117128

environment

SARS-CoV S protein

interacts (colocalizes) with

gene/protein

ACE2

Drugbank entries Show/Hide entries for ACE2
Comment ADAM17, the ACE2 sheddase, requires arginine and lysine residues within ACE2 amino acids 652 to 659 for receptor cleavage and competes with TMPRSS2 for ACE2 processing.
Formal Description
Interaction-ID: 117211

gene/protein

ADAM17

decreases_quantity of

gene/protein

ACE2

via proteolytic processing
Drugbank entries Show/Hide entries for ADAM17 or ACE2
Comment ADAM17, the ACE2 sheddase, requires arginine and lysine residues within ACE2 amino acids 652 to 659 for receptor cleavage and competes with TMPRSS2 for ACE2 processing.
Formal Description
Interaction-ID: 119246

gene/protein

ACE2

increases_quantity of

gene/protein

ACE2, soluble

via proteolytic activity of ADAM17
Drugbank entries Show/Hide entries for ACE2