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Literature summary for 3.4.21.122 extracted from

  • Boettcher-Friebertshaeuser, E.; Freuer, C.; Sielaff, F.; Schmidt, S.; Eickmann, M.; Uhlendorff, J.; Steinmetzer, T.; Klenk, H.D.; Garten, W.
    Cleavage of influenza virus hemagglutinin by airway proteases TMPRSS2 and HAT differs in subcellular localization and susceptibility to protease inhibitors (2010), J. Virol., 84, 5605-5614 .
    View publication on PubMedView publication on EuropePMC
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Cloned(Commentary)

Cloned (Comment) Organism
expression in MDCK cell Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
3-cyclohexyl-N-(phenylmethanesulfonyl)-D-alanyl-N-[(4-carbamimidoylphenyl)methyl]-N6-decanoyl-L-lysinamide peptide mimetic inhibitor. Cleavage of HA0 and the spread of A/Hamburg/09 in TMPRSS2-expressing cells are strongly inhibited by the decanoylated inhibitor. Only low amounts of progeny virions are detected in supernatants of inhibitor-treated cells at 24 h p.i. due to the suppression of proteolytic activation of HA and thus the suppression of virus propagation Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cell surface
-
 Homo sapiens 9986
-
membrane
-
 Homo sapiens 16020
-

Organism

Organism UniProt Comment Textmining
Homo sapiens O15393
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
Boc-Leu-GLy-Arg-7-amido-4-methylcoumarin + H2O
-
 Homo sapiens Boc-Leu-Gly-Arg + 7-amino-4-methylcoumarin
-
 ?
hemagglutinin precursor HA0 + H2O
-
 Homo sapiens hemagglutinin HA1 + hemagglutinin HA2
-
 ?

Subunits

Subunits Comment Organism
? x * 70000, full-length protein, x * 30000, processed form, SDS-PAGE Homo sapiens

General Information

General Information Comment Organism
physiological function hemagglutinin is cleaved by membrane-bound TMPRSS2 and protease HAT and not by soluble forms released into the supernatant. TMPRSS2 cleaves newly synthesized hemagglutinin within the cell and is not able to support the proteolytic activation of hemagglutinin of incoming virions. Cleavage activation of hemagglutinin and virus spread in TMPRSS2-expressing cells can be suppressed by peptide mimetic protease inhibitors Homo sapiens