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Information on EC 3.4.21.B61 - transmembrane protease serine 11D
for references in articles please use BRENDA:EC3.4.21.B61preliminary BRENDA-supplied EC number
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EC Tree
3.4.21.B61 transmembrane protease serine 11DSpecify your search results
Word Map
- 3.4.21.B61
- proteases
-
protease-activated
-
ttsps
- medicine
- par-2
-
tmprss4
- ace2
- matriptase
-
ha-activating
-
ap-induced
- hai-1
The expected taxonomic range for this enzyme is: Homo sapiens
Reaction Schemes
The enzyme is involved in the proteolytic processing of angiotensin-converting enzyme 2 (ACE2) and of receptor PAR-2. It cleaves and activates the human coronavirus 229E (HCoV-229E) spike glycoprotein which facilitates virus-cell membrane fusions.
Synonyms
tmprss11d, human airway trypsin-like protease, tmprss11a, transmembrane protease serine 11d, transmembrane protease serine 11a, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
HAT
TMPRSS11D
HAT
-
-
ambiguous
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TMPRSS11D
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
The enzyme is involved in the proteolytic processing of angiotensin-converting enzyme 2 (ACE2) and of receptor PAR-2. It cleaves and activates the human coronavirus 229E (HCoV-229E) spike glycoprotein which facilitates virus-cell membrane fusions.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ABZ-Arg-Gln-Asp-Arg-ANB + H2O
ABZ-Arg-Gln-Asp-Arg + 5-amino-2-nitrobenzoate
-
-
-
?
ABZ-Arg-Gln-Asp-Lys-ANB + H2O
ABZ-Arg-Gln-Asp-Lys + 5-amino-2-nitrobenzoate
-
-
-
?
Boc-Gln-Ala-Arg-7-amido-4-methylcoumarin + H2O
Boc-Gln-Ala-Arg + 7-amino-4-methylcoumarin
47.7% of the activity with Boc-Phe-Ser-Arg-7-amido-4-methylcoumarin
-
-
?
Boc-Gln-Arg-Arg-7-amido-4-methylcoumarin + H2O
Boc-Gln-Arg-Arg + 7-amino-4-methylcoumarin
38.0% of the activity with Boc-Phe-Ser-Arg-7-amido-4-methylcoumarin
-
-
?
Boc-Leu-GLy-Arg-7-amido-4-methylcoumarin + H2O
Boc-Leu-Gly-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Boc-Phe-Ser-Arg-4-MCA + H2O
Boc-Phe-Ser-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Boc-Phe-Ser-Arg-7-amido-4-methylcoumarin + H2O
Boc-Phe-Ser-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Boc-Val-Pro-Arg-7-amido-4-methylcoumarin + H2O
Boc-Val-Pro-Arg + 7-amino-4-methylcoumarin
78.8% of the activity with Boc-Phe-Ser-Arg-7-amido-4-methylcoumarin
-
-
?
D-cyclohexylalanine-Pro-Arg-AMC + H2O
D-cyclohexylalanine-Pro-Arg + 7-amino-4-methylcoumarin
-
-
-
?
hemagglutinin precursor HA0 + H2O
?
TMPRSS11A cleaves and activates the influenza A virus hemagglutinin
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-
?
hemagglutinin precursor HA0 + H2O
hemagglutinin HA1 + hemagglutinin HA2
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-
-
?
additional information
?
-
enzyme preferentially cleaves the COOH-terminal side of arginine residues at the PI position of certain peptides. No substrates: Suc-Ala-Ala-Pro-Phe-7-amido-4-methylcoumarin, Suc-Ala-Pro-Ala-7-amido-4-methylcoumarin and Suc-Ala-Ala-Ala-7-amido-4-methylcoumarin
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-
?
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5-oxo-N-(phenylmethanesulfonyl)-5-(piperazin-1-yl)-D-norvalyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
-
5-oxo-N-(phenylmethanesulfonyl)-5-[4-(pyrimidin-2-yl)piperazin-1-yl]-D-norvalyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
-
5-[4-[(benzyloxy)carbonyl]piperazin-1-yl]-5-oxo-N-(phenylmethanesulfonyl)-D-norvalyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
-
BABIM
ratio of inhibitor to protease concentration achieving 50% inhibition is 71
benzyl 4-[(3R)-4-[(2S)-2-[[(4-carbamimidoylphenyl)methyl]carbamoyl]pyrrolidin-1-yl]-4-oxo-3-[(phenylmethanesulfonyl)amino]butanoyl]piperazine-1-carboxylate
-
camostat
ratio of inhibitor to protease concentration achieving 50% inhibition is 20
hepatocyte growth factor activator inhibitor type 1
a soluble form of hepatocyte growth factor activator inhibitor HAI-1 inhibits the protease activity of HAT in vitro
-
hepatocyte growth factor activator inhibitor type-1
coexpression of hepatocyte growth factor activator inhibitor type HAI-1 interferes with hemagglutinin cleavage by HAT. HAI-1 expression inhibits influenza A virus spread in cells transfected with HAT
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N-(phenylmethanesulfonyl)-4-carbamimidoyl-D-phenylalanyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
-
N-(phenylmethanesulfonyl)-4-cyano-D-phenylalanyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
-
N-(phenylmethanesulfonyl)-D-alpha-aspartyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
-
N-(phenylmethanesulfonyl)-D-cyclohexylalanyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
-
N-(phenylmethanesulfonyl)-D-leucyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
-
N-(phenylmethanesulfonyl)-D-phenylalanyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
-
N-(phenylmethanesulfonyl)-D-valyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
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N-[(4-carbamimidoylphenyl)methyl]-1-[(2R)-4-(morpholin-4-yl)-4-oxo-2-[(phenylmethanesulfonyl)amino]butanoyl]-L-prolinamide
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N-[(4-carbamimidoylphenyl)methyl]-1-[(2R)-4-oxo-2-[(phenylmethanesulfonyl)amino]-4-[4-(propan-2-yl)piperazin-1-yl]butanoyl]-L-prolinamide
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N-[(4-carbamimidoylphenyl)methyl]-1-[(2R)-4-oxo-2-[(phenylmethanesulfonyl)amino]-4-[4-(pyrimidin-2-yl)piperazin-1-yl]butanoyl]-L-prolinamide
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N-[(4-carbamimidoylphenyl)methyl]-1-[(2R)-4-[4-(3,5-dimethylphenyl)piperazin-1-yl]-4-oxo-2-[(phenylmethanesulfonyl)amino]butanoyl]-L-prolinamide
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N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-2-aminobutanoylamide
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N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-alaninamide
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N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-argininamide
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N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-isoleucinamide
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N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-leucinamide
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N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-norvalinamide
inhibitor suppresses replication of H1 and H3 influenza viruses in a HAT-expressing MDCK cell model
N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-phenylalaninamide
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N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
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N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-serinamide
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N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-valinamide
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N2-(phenylmethanesulfonyl)-D-arginyl-N1-[(4-carbamimidoylphenyl)methyl]-L-aspartamide
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N2-(phenylmethanesulfonyl)-D-arginyl-N6-[(benzyloxy)carbonyl]-N-[(4-carbamimidoylphenyl)methyl]-L-lysinamide
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N2-(phenylmethanesulfonyl)-D-homoarginyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
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N2-(phenylmethanesulfonyl)-D-homophenylalanyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
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N2-(phenylmethanesulfonyl)-D-lysyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
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N2-(phenylmethanesulfonyl)-N-tert-butoxy-D-asparaginyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
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N2-(phenylmethanesulfonyl)-N6-(benzyloxycarbonyl)-D-lysyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
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N2-(phenylmethanesulfonyl)-O-(tert-butyl)-D-glutamyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
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Nafamostat
ratio of inhibitor to protease concentration achieving 50% inhibition is 191
ovomucoid trypsin inhibitor
spread of viral infection in MDCK cells expressing HAT is markedly suppressed
-
Pefabloc SC
spread of viral infection in MDCK cells expressing HAT is markedly suppressed
tert-butyl N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-alpha-asparaginate
-
Aprotinin
ratio of inhibitor to protease concentration achieving 50% inhibition is 147
Aprotinin
spread of viral infection in MDCK cells expressing HAT is completely inhibited
benzamidine
ratio of inhibitor to protease concentration achieving 50% inhibition is 1400000
Soybean trypsin inhibitor
spread of viral infection in MDCK cells expressing HAT is completely inhibited
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Carcinogenesis
Cell Surface Human Airway Trypsin-Like Protease Is Lost During Squamous Cell Carcinogenesis.
Carcinogenesis
High TMPRSS11D protein expression predicts poor overall survival in non-small cell lung cancer.
Carcinoma
A novel tumor suppressor gene ECRG4 interacts directly with TMPRSS11A (ECRG1) to inhibit cancer cell growth in esophageal carcinoma.
Carcinoma, Non-Small-Cell Lung
High TMPRSS11D protein expression predicts poor overall survival in non-small cell lung cancer.
Coronavirus Infections
Intracellular autoactivation of TMPRSS11A, an airway epithelial transmembrane serine protease.
Coronavirus Infections
TMPRSS11A activates the influenza A virus hemagglutinin and the MERS coronavirus spike protein and is insensitive against blockade by HAI-1.
Infections
Azithromycin Downregulates Gene Expression of IL-1? and Pathways Involving TMPRSS2 and TMPRSS11D Required by SARS-CoV-2.
Infections
Host serine proteases TMPRSS2 and TMPRSS11D mediate proteolytic activation and trypsin-independent infection in group A rotaviruses.
Infections
Single-cell RNA sequencing of SARS-CoV-2 cell entry factors in the preconceptional human endometrium.
Infections
TMPRSS11A activates the influenza A virus hemagglutinin and the MERS coronavirus spike protein and is insensitive against blockade by HAI-1.
Influenza, Human
Influenza virus activating host proteases: Identification, localization and inhibitors as potential therapeutics.
Influenza, Human
Matriptase proteolytically activates influenza virus and promotes multicycle replication in the human airway epithelium.
Influenza, Human
Novel insights into proteolytic cleavage of influenza virus hemagglutinin.
Influenza, Human
The proteolytic activation of A (H3N2) Influenza virus hemagglutinin is facilitated by different type II transmembrane serine proteases.
Influenza, Human
TMPRSS11A activates the influenza A virus hemagglutinin and the MERS coronavirus spike protein and is insensitive against blockade by HAI-1.
Leukemia, Myeloid, Acute
Ectopic expression of human airway trypsin-like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth.
Lung Neoplasms
High TMPRSS11D protein expression predicts poor overall survival in non-small cell lung cancer.
Neoplasm Metastasis
High TMPRSS11D protein expression predicts poor overall survival in non-small cell lung cancer.
Neoplasms
A novel tumor suppressor gene ECRG4 interacts directly with TMPRSS11A (ECRG1) to inhibit cancer cell growth in esophageal carcinoma.
Neoplasms
Cell Surface Human Airway Trypsin-Like Protease Is Lost During Squamous Cell Carcinogenesis.
Neoplasms
Ectopic expression of human airway trypsin-like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth.
Neoplasms
[Study on Genetype in Lung Squamous Carcinoma by High-throughput of ?Transcriptome Sequence].
Psoriasis
Human airway trypsin-like protease induces PAR-2-mediated IL-8 release in psoriasis vulgaris.
Pulmonary Fibrosis
Human airway trypsin-like protease exerts potent, antifibrotic action in pulmonary fibrosis.
Severe Acute Respiratory Syndrome
Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease.
Severe Acute Respiratory Syndrome
Intracellular autoactivation of TMPRSS11A, an airway epithelial transmembrane serine protease.
Squamous Cell Carcinoma of Head and Neck
Screening and clinical significance of tumor markers in head and neck squamous cell carcinoma through bioinformatics analysis.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000068
5-oxo-N-(phenylmethanesulfonyl)-5-(piperazin-1-yl)-D-norvalyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000017
5-oxo-N-(phenylmethanesulfonyl)-5-[4-(pyrimidin-2-yl)piperazin-1-yl]-D-norvalyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000038
5-[4-[(benzyloxy)carbonyl]piperazin-1-yl]-5-oxo-N-(phenylmethanesulfonyl)-D-norvalyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000135
benzyl 4-[(3R)-4-[(2S)-2-[[(4-carbamimidoylphenyl)methyl]carbamoyl]pyrrolidin-1-yl]-4-oxo-3-[(phenylmethanesulfonyl)amino]butanoyl]piperazine-1-carboxylate
pH 9.5, temperature not specified in the publication
0.000168
N-(phenylmethanesulfonyl)-4-carbamimidoyl-D-phenylalanyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000311
N-(phenylmethanesulfonyl)-4-cyano-D-phenylalanyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.001425
N-(phenylmethanesulfonyl)-D-alpha-aspartyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000108
N-(phenylmethanesulfonyl)-D-cyclohexylalanyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.00012
N-(phenylmethanesulfonyl)-D-leucyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000098
N-(phenylmethanesulfonyl)-D-phenylalanyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000076
N-(phenylmethanesulfonyl)-D-valyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000183
N-[(4-carbamimidoylphenyl)methyl]-1-[(2R)-4-(morpholin-4-yl)-4-oxo-2-[(phenylmethanesulfonyl)amino]butanoyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.00021
N-[(4-carbamimidoylphenyl)methyl]-1-[(2R)-4-oxo-2-[(phenylmethanesulfonyl)amino]-4-[4-(propan-2-yl)piperazin-1-yl]butanoyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000043
N-[(4-carbamimidoylphenyl)methyl]-1-[(2R)-4-oxo-2-[(phenylmethanesulfonyl)amino]-4-[4-(pyrimidin-2-yl)piperazin-1-yl]butanoyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000073
N-[(4-carbamimidoylphenyl)methyl]-1-[(2R)-4-[4-(3,5-dimethylphenyl)piperazin-1-yl]-4-oxo-2-[(phenylmethanesulfonyl)amino]butanoyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000014
N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-2-aminobutanoylamide
pH 9.5, temperature not specified in the publication
0.00003
N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-alaninamide
pH 9.5, temperature not specified in the publication
0.000457
N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-argininamide
pH 9.5, temperature not specified in the publication
0.000023
N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-isoleucinamide
pH 9.5, temperature not specified in the publication
0.000047
N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-leucinamide
pH 9.5, temperature not specified in the publication
0.000015
N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-norvalinamide
pH 9.5, temperature not specified in the publication
0.000057
N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-phenylalaninamide
pH 9.5, temperature not specified in the publication
0.000019
N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000034
N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-serinamide
pH 9.5, temperature not specified in the publication
0.000022
N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-valinamide
pH 9.5, temperature not specified in the publication
0.000422
N2-(phenylmethanesulfonyl)-D-arginyl-N1-[(4-carbamimidoylphenyl)methyl]-L-aspartamide
pH 9.5, temperature not specified in the publication
0.000034
N2-(phenylmethanesulfonyl)-D-arginyl-N6-[(benzyloxy)carbonyl]-N-[(4-carbamimidoylphenyl)methyl]-L-lysinamide
pH 9.5, temperature not specified in the publication
0.000013
N2-(phenylmethanesulfonyl)-D-homoarginyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000063
N2-(phenylmethanesulfonyl)-D-homophenylalanyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.00004
N2-(phenylmethanesulfonyl)-D-lysyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000038
N2-(phenylmethanesulfonyl)-N-tert-butoxy-D-asparaginyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000053
N2-(phenylmethanesulfonyl)-N6-(benzyloxycarbonyl)-D-lysyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000036
N2-(phenylmethanesulfonyl)-O-(tert-butyl)-D-glutamyl-N-[(4-carbamimidoylphenyl)methyl]-L-prolinamide
pH 9.5, temperature not specified in the publication
0.000512
tert-butyl N2-(phenylmethanesulfonyl)-D-arginyl-N-[(4-carbamimidoylphenyl)methyl]-L-alpha-asparaginate
pH 9.5, temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
both HAT and substrate urokinase-type plasminogen activator receptor uPAR are expressed in the human bronchial epithelium
brenda
ciliated cells of bronchial epithelium and/or at the basal part of cilia
brenda
additional information
bronchial and intestinal smooth muscle cells are negative for HAT staining
brenda
additional information
no expression in submucosal glands or mast cells
brenda
additional information
-
no expression in submucosal glands or mast cells
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
cytoplasm of ciliated cells of bronchial epithelium and/or at the basal part of cilia
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
ACE2 processing by HAT or TMPRSS2 is required for augmentation of SARS-S-driven entry. In contrast, ACE2 cleavage is dispensable for activation of the viral S protein
physiological function
both HAT and protease-activated receptor PAR2 agonist peptide enhance the exocytosis of mucin5AC protein. HAT enhances the expression of mucin5AC mRNA. Transfection with an siRNA against the PAR2 receptor or Gaq/11 protein effectively attenuates the HAT-induced cellular responses
physiological function
both HAT expression and activity are upregulated in human idiopathic pulmonary fibrosis specimens. Adenoviral overexpression of HAT before bleomycin challenge attenuates lung injury as well as extracellular matrix deposition in the bleomycin-induced pulmonary fibrosis model. In vitro, HATprevents specific fibrosis-associated responses in primary human pulmonary fibroblasts and induces the expression of mediators associated with the prostaglandin E2 pathway
physiological function
both proteases HAT and TMPRSS2 are coexpressed with 2,6-linked sialic acids, the major receptor determinant of human influenza viruses, throughout the human respiratory tract
physiological function
cotransfection of mammalian cells with plasmids encoding hemagglutinin of influenza viruses and protease TMPRSS2 or HAT results in hemagglutinin cleavage in situ. Transient expression of either protease in MDCK cells enables multicycle replication of influenza viruses in these cells in the absence of exogenous trypsin
physiological function
HAT activates SARS-spike protein S in the context of surrogate systems and authentic SARS-CoV infection and is coexpressed with the viral receptor angiotensin-converting enzyme ACE2 in bronchial epithelial cells and pneumocytes. HAT cleaves SARS-S at R667 and activates SARS-S for cell-cell fusion in cis and trans. Cleavage activation of SARS-S by HAT does not bypass the need for cathepsin activity
physiological function
HAT enhances IL-8 mRNA expression in bronchial epithelial cells at concentrations of 10-100 mU/ml, and PAR2 activating peptide PAR2-AP also enhances IL-8 release and IL-8 mRNA expression. Both HAT- and PAR2 AP-induced IL-8 mRNA elevation is significantly depressed in PAR2 siRNA-transfected bronchial epithelial cells
physiological function
hemagglutinin is cleaved by membrane-bound TMPRSS2 and protease HAT and not by soluble forms released into the supernatant. HAT cleaves newly synthesized hemagglutinin before or during the release of progeny virions and hemagglutinin of incoming viruses prior to endocytosis at the cell surface. Cleavage activation of hemagglutinin and virus spread in HAT-expressing cells can be suppressed by peptide mimetic protease inhibitors
physiological function
MDCK cells with inducible expression of either TMPRSS2 or protease HAT cells support growth of human and avian influenza viruses of different subtypes in the absence of exogenous trypsin. Multicycle viral replication in both cell lines is markedly suppressed in the presence of serine protease inhibitors
physiological function
presence of enzyme enhances SARS S-mediated pseudovirus entry into cells
physiological function
proteases TMPRSS2 and HAT cleave the HCoV-229E spike protein (229E-S) and augment 229E-S-driven cell-cell fusion. Engineered expression of TMPRSS2 and HAT renders 229E-S-driven virus-cell fusion insensitive to an inhibitor of cathepsin L
physiological function
proteolytic regulation of uPAR by HAT is likely to modulate cell adherence and motility. Membrane coexpression of the two partners produces a constitutive and extensive shedding of the uPAR D1 domain, occurring for membrane-associated HAT concentrations in the nanomolar range. The truncated receptor is unable to bind two of the major uPAR ligands, the adhesive matrix protein vitronectin and the serine protease urokinase
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
x * 52000, full-length transmembrane form, x * 27000, processed soluble active form, x * 25000, residual transmembrane form, SDS-PAGE. Proteolytic cleavage within the SEA domain close to the transmembrane domain generates a 15000 Da fragment
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
HAT is proteolytically activated in cultured mammalian cells transfected with its expression vector, and a soluble form of active HAT is released into the conditioned medium. The proteolytic activation of HAT requires its own serine protease activity
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
both TMPRSS11D mRNA and protein expression levels are significantly higher in non-small cell lung cancer tumorous tissues than in adjacent normal tissues. High TMPRSS11D protein expression is associated with high TNM stages, and high TMPRSS11D protein expression is an independent prognostic marker in non-small cell lung cancer
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
both HAT expression and activity are upregulated in human idiopathic pulmonary fibrosis specimens
medicine
both TMPRSS11D mRNA and protein expression levels are significantly higher in non-small cell lung cancer tumorous tissues than in adjacent normal tissues. High TMPRSS11D protein expression is associated with high TNM stages, and high TMPRSS11D protein expression is an independent prognostic marker in non-small cell lung cancer
medicine
cotransfection of mammalian cells with plasmids encoding hemagglutinin of influenza viruses and protease TMPRSS2 or human airway trypsin-like protease HAT results in hemagglutinin cleavage in situ. Transient expression of either protease in MDCK cells enables multicycle replication of influenza viruses in these cells in the absence of exogenous trypsin
medicine
HAT can stimulate mucin5AC hypersecretion through a PAR2-mediated signaling pathway in 16HBE bronchial epithelial cells
medicine
MDCK cells with inducible expression of either TMPRSS2 or protease HAT cells support growth of human and avian influenza viruses of different subtypes in the absence of exogenous trypsin. Multicycle viral replication in both cell lines is markedly suppressed in the presence of serine protease inhibitors
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Beaufort, N.; Leduc, D.; Eguchi, H.; Mengele, K.; Hellmann, D.; Masegi, T.; Kamimura, T.; Yasuoka, S.; Fend, F.; Chignard, M.; Pidard, D.
The human airway trypsin-like protease modulates the urokinase receptor (uPAR, CD87) structure and functions
Am. J. Physiol. Lung Cell. Mol. Physiol.
292
L1263-L1272
2007
Homo sapiens (O60235), Homo sapiens
brenda
Yasuoka, S.; Ohnishi, T.; Kawano, S.; Tsuchihashi, S.; Ogawara, M.; Masuda, K.; Yamaoka, K.; Takahashi, M.; Sano, T.
Purification, characterization, and localization of a novel trypsin-like protease found in the human airway
Am. J. Respir. Cell Mol. Biol.
16
300-308
1997
Homo sapiens (O60235)
brenda
Liu, C.; Li, Q.; Zhou, X.; Kolosov, V.; Perelman, J.
Human airway trypsin-like protease induces mucin5AC hypersecretion via a protease-activated receptor 2-mediated pathway in human airway epithelial cells
Arch. Biochem. Biophys.
535
234-240
2013
Homo sapiens (O60235), Homo sapiens
brenda
Miki, M.; Yasuoka, S.; Tsutsumi, R.; Nakamura, Y.; Hajime, M.; Takeuchi, Y.; Miki, K.; Kitada, S.; Maekura, R.
Human airway trypsin-like protease enhances interleukin-8 synthesis in bronchial epithelial cells by activating protease-activated receptor 2
Arch. Biochem. Biophys.
664
167-173
2019
Homo sapiens (O60235), Homo sapiens
brenda
Wysocka, M.; Spichalska, B.; Lesner, A.; Jaros, M.; Brzozowski, K.; Legowska, A.; Rolka, K.
Substrate specificity and inhibitory study of human airway trypsin-like protease
Bioorg. Med. Chem.
18
5504-5509
2010
Homo sapiens (O60235), Homo sapiens
brenda
Sielaff, F.; Boettcher-Friebertshaeuser, E.; Meyer, D.; Saupe, S.; Volk, I.; Garten, W.; Steinmetzer, T.
Development of substrate analogue inhibitors for the human airway trypsin-like protease HAT
Bioorg. Med. Chem. Lett.
21
4860-4864
2011
Homo sapiens (O60235), Homo sapiens
brenda
Menou, A.; Flajolet, P.; Duitman, J.; Justet, A.; Moog, S.; Jaillet, M.; Tabeze, L.; Solhonne, B.; Garnier, M.; Mal, H.; Mordant, P.; Castier, Y.; Cazes, A.; Sallenave, J.M.; Mailleux, A.A.; Crestani, B.
Human airway trypsin-like protease exerts potent, antifibrotic action in pulmonary fibrosis
FASEB J.
32
1250-1264
2018
Homo sapiens (O60235), Homo sapiens
brenda
Takahashi, M.; Sano, T.; Yamaoka, K.; Kamimura, T.; Umemoto, N.; Nishitani, H.; Yasuoka, S.
Localization of human airway trypsin-like protease in the airway An immunohistochemical study
Histochem. Cell Biol.
115
181-187
2001
Homo sapiens (O60235), Homo sapiens
brenda
Kato, M.; Hashimoto, T.; Shimomura, T.; Kataoka, H.; Ohi, H.; Kitamura, N.
Hepatocyte growth factor activator inhibitor type 1 inhibits protease activity and proteolytic activation of human airway trypsin-like protease
J. Biochem.
151
179-187
2012
Homo sapiens (O60235), Homo sapiens
brenda
Zmora, P.; Hoffmann, M.; Kollmus, H.; Moldenhauer, A.S.; Danov, O.; Braun, A.; Winkler, M.; Schughart, K.; Poehlmann, S.
TMPRSS11A activates the influenza A virus hemagglutinin and the MERS coronavirus spike protein and is insensitive against blockade by HAI-1
J. Biol. Chem.
293
13863-13873
2018
Homo sapiens (O60235), Homo sapiens (Q6ZMR5), Homo sapiens
brenda
Boettcher, E.; Matrosovich, T.; Beyerle, M.; Klenk, H.D.; Garten, W.; Matrosovich, M.
Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium
J. Virol.
80
9896-9898
2006
Homo sapiens (O60235)
brenda
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
J. Virol.
84
5605-5614
2010
Homo sapiens (O60235)
brenda
Bertram, S.; Glowacka, I.; Mueller, M.A.; Lavender, H.; Gnirss, K.; Nehlmeier, I.; Niemeyer, D.; He, Y.; Simmons, G.; Drosten, C.; Soilleux, E.J.; Jahn, O.; Steffen, I.; Poehlmann, S.
Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease
J. Virol.
85
13363-13372
2011
Homo sapiens (O60235), Homo sapiens
brenda
Shulla, A.; Heald-Sargent, T.; Subramanya, G.; Zhao, J.; Perlman, S.; Gallagher, T.
A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry
J. Virol.
85
873-882
2011
Homo sapiens (O60235)
brenda
Baron, J.; Tarnow, C.; Mayoli-Nuessle, D.; Schilling, E.; Meyer, D.; Hammami, M.; Schwalm, F.; Steinmetzer, T.; Guan, Y.; Garten, W.; Klenk, H.D.; Boettcher-Friebertshaeuser, E.
Matriptase, HAT, and TMPRSS2 activate the hemagglutinin of H9N2 influenza A viruses
J. Virol.
87
1811-1820
2013
Homo sapiens (O60235)
brenda
Bertram, S.; Dijkman, R.; Habjan, M.; Heurich, A.; Gierer, S.; Glowacka, I.; Welsch, K.; Winkler, M.; Schneider, H.; Hofmann-Winkler, H.; Thiel, V.; Poehlmann, S.
TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell entry and is expressed in viral target cells in the respiratory epithelium
J. Virol.
87
6150-6160
2013
Homo sapiens (O60235)
brenda
Heurich, A.; Hofmann-Winkler, H.; Gierer, S.; Liepold, T.; Jahn, O.; Poehlmann, S.
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
2014
Homo sapiens (O60235)
brenda
Cao, X.; Tang, Z.; Huang, F.; Jin, Q.; Zhou, X.; Shi, J.
High TMPRSS11D protein expression predicts poor overall survival in non-small cell lung cancer
Oncotarget
8
12812-12819
2017
Homo sapiens (O60235), Homo sapiens
brenda
Nimishakavi, S.; Raymond, W.W.; Gruenert, D.C.; Caughey, G.H.
Divergent inhibitor susceptibility among airway lumen-accessible tryptic proteases
PLoS One
10
e0141169
2015
Homo sapiens (O60235)
brenda
Bertram, S.; Heurich, A.; Lavender, H.; Gierer, S.; Danisch, S.; Perin, P.; Lucas, J.M.; Nelson, P.S.; Poehlmann, S.; Soilleux, E.J.
Influenza and SARS-coronavirus activating proteases TMPRSS2 and HAT are expressed at multiple sites in human respiratory and gastrointestinal tracts
PLoS ONE
7
e35876
2012
Homo sapiens (O60235)
brenda
Boettcher, E.; Freuer, C.; Steinmetzer, T.; Klenk, H.D.; Garten, W.
MDCK cells that express proteases TMPRSS2 and HAT provide a cell system to propagate influenza viruses in the absence of trypsin and to study cleavage of HA and its inhibition
Vaccine
27
6324-6329
2009
Homo sapiens (O60235)
brenda
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