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Information on EC 3.4.21.106 - hepsin and Organism(s) Homo sapiens
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3.4.21.106 hepsinSpecify your search results
Word Map
- 3.4.21.106
- prostate
- matriptase
- medicine
- hai-1
- prostasin
-
trypsin-like
-
ttsps
- pro-hgf
- amacr
-
tmprss3
-
uromodulin
- biotechnology
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
hepsin, tmprss1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
hepsin
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cleavage of C-N-linkage
-
-
CAS REGISTRY NUMBER
COMMENTARY
112398-23-9
-
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-KQSRKFVPY(3-NO2) + H2O
Abz-KQSR + KFVPY(3-NO2)
-
peptide sequence from trask
-
-
?
Abz-RKRRGSRGY(3-NO2) + H2O
Abz-RKRR + GSRGY(3-NO2)
-
peptide sequence from filaggrin
-
-
?
Abz-RQRRALEKY(3-NO2) + H2O
Abz-RQRR + ALEKY(3-NO2)
-
peptide sequence from alphaEbeta7 integrin
-
-
?
Abz-SKGRSLIGY(3-NO2) + H2O
Abz-SKGR + SLIGY(3-NO2)
-
peptide sequence from PAR-2
-
-
?
Abz-SKLRVVGGY(3-NO2) + H2O
Abz-SKLR + VVGGY(3-NO2)
-
peptide sequence from proMSP-1
-
-
?
acetyl-KQLR-7-amido-4-methylcoumarin + H2O
?
-
most active tetrapeptide substrate
-
-
?
acetyl-PVDR-7-amido-4-methylcoumarin + H2O
?
-
least active tetrapeptide substrate
-
-
?
Boc-QAR-7-amido-4-methylcoumarin + H2O
Boc-QAR + 7-amino-4-methylcoumarin
-
-
-
?
epidermal growth factor receptor + H2O
?
-
hepsin cleavage of epidermal growth factor receptor is not dependent on receptor tyrosine phosphorylation
-
-
?
L-Asp-L-Ala-L-Ala-L-Arg-4-nitroanilide + H2O
L-Asp-L-Ala-L-Ala-L-Arg + 4-nitroaniline
-
-
-
-
?
L-Asp-L-Lys-(gamma-Cbo)-L-Pro-L-Arg-4-nitroanilide + H2O
L-Asp-L-Lys-(gamma-Cbo)-L-Pro-L-Arg + 4-nitroaniline
-
-
-
-
?
laminin-332 + H2O
?
-
by Western blotting and mass spectrometry, it is shown that hepsin cleaves the beta3 chain of rat Laminin-332. N-terminal sequencing identifies the cleavage site at beta3 Arg245, in a sequence context (SQLR245 cleavage LQGSCFC) conserved among species and in remarkable agreement with reported consensus target sequences for hepsin activity
-
-
?
N-acetyl-KQLR-7-amido-4-methylcoumarin + H2O
N-acetyl-KQLR + 7-amino-4-methylcoumarin
-
-
-
?
N-acetyl-L-Lys-L-Arg-L-Leu-L-Arg-7-amido-4-carbamoylmethylcoumarin + H2O
?
-
-
-
-
?
pro-hepatocyte growth factor + H2O
active hepatocyte growth factor
-
hepsin-mediated pro-HGF activation may be critical in the pathogenesis of human prostate cancer
-
-
?
pro-macrophage-stimulating protein + H2O
?
-
the cleavage site is between Arg(483) and Val(484). At least 50% of the substrate is processed within 1 h at a hepsin concentration of 2.4 nM and at a molar enzyme to substrate ratio of 1:500
-
-
?
pro-urokinase-type plasminogen activator + H2O
active high molecular weight urokinase-type plasminogen activator
-
cleavage at the Lys158-Ile159 (P1-P1') peptide bond
-
-
?
prostasin pro-peptide + H2O
prostasin
-
hepsin activates prostasin, cleavage occurs at Arg44
-
-
?
single-chain hepatocyte growth factor + H2O
two-chain hepatocyte growth factor
efficiently converted by soluble form of hepsin comprising the entire extracellular domain
-
-
?
t-butyloxycarbonyl-Gln-Ala-Arg-7-amido-4-methylcoumaryl-7-amide + H2O
t-butyloxycarbonyl-Gln-Ala-Arg + 7-amino-4-methylcoumarin
-
-
-
?
zymogen factor VII + H2O
factor VIIa
-
cleaves between Arg152 and Ile153
-
?
Abz-RQARVVGGY(3-NO2) + H2O
Abz-RQAR + VVGGY(3-NO2)
-
peptide sequence from matriptase
-
-
?
hepatocyte growth factor precursor + H2O
?
-
potential substrate for hepsin in vivo
-
-
?
hepatocyte growth factor precursor + H2O
?
-
the catalytic domain of hepsin is a highly efficient activator (50% activation at 3.4 nM) of hepatocyte growth factor, the optimal P4-P1 substrate preference for hepsin sequence is Lys-Gln-Leu-Arg which exactly matches the activation sequence of hepatocyte growth factor precursor
-
-
?
additional information
?
-
-
enzyme does not cleave factor VII R152E mutant
-
?
additional information
?
-
-
hepsin reduces cell growth, cell invation and soft agar colony formation after expression in PC-3, LNCaP and DU145 cells
-
?
additional information
?
-
-
P1-P4 substrate specificity, hepsin exhibits strong preference at the P1 position for arginine over lysine, favours theonine, leucine or asparagine at the P2, glutamine or lysine at the P3, and proline or lysine at the P4 position
-
-
?
additional information
?
-
-
does not cleave pro-tissue-type plasminogen activator
-
-
?
additional information
?
-
-
hepsin exhibits trypsin-like catalytic activity that favores Arg at the P1, Thr/Leu/Asn at the P2, Gln/Lys at the P3, and Pro/Lys at the P4 positions
-
-
?
additional information
?
-
-
to study the substrate specificity of type II transmembrane serine proteases internally quenched fluorogenic peptide substrates are used based on the autoactivation sequence of matriptase (RQARVVGG). Positions P4, P3, P2 and P1 are substituted with nonpolar (Ala, Leu), aromatic (Tyr), acid (Glu) and basic (Arg) amino acids, whereas P1 is fixed to Arg. Hepsin shares similarities with matriptase and DESC1, but is markedly more permissive at P2
-
-
?
NATURAL SUBSTRATE
NATURAL 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
hepatocyte growth factor precursor + H2O
?
-
potential substrate for hepsin in vivo
-
-
?
additional information
?
-
-
hepsin reduces cell growth, cell invation and soft agar colony formation after expression in PC-3, LNCaP and DU145 cells
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(S)-N-(4-bromobenzyl)-4-(3-(3-carbamimidoylphenyl)-2-(naphthalene-2-sulfonamido)propanoyl)piperazine-1-carboxamide
inhibitor shows potency and selectivity for hepsin over matriptase and hepatocyte growth factor activator
1-[6-(6-methyl-3H-indol-2-yl)pyridin-2-yl]cyclohexan-1-ol
compounds exhibits inhibition of invasion and migration of hepsin-overexpressing cell line. The selective inhibition of hepsin is likely due to interactions of the midine group at the S1 site with the cyclohexyl ring from the 2-aryl group projecting towards the S1' site and the tert-hydroxyl group interacting with His57 side-chain
4-(2-aminoethyl)-benzenesulfonylfluoride hydrochloride
-
residual hepsin activity: 0%
9-fluorenylmethyloxycarbonyl-NR-ketobenzothiazole
potent and selective inhibitor for hepsin over matriptase
anthralin
-
at 0.067 mM anthralin the hepsin activity is reduced by more than 70%
hepatocyte growth factor activator inhibitor-1
-
potent inhibitor of hepsin activity
-
hepatocyte growth factor activator inhibitor-1-derived Kunitz domain inhibitor
-
KD1, inhibits cleavage of laminin-332 in a dose-dependent manner
-
hepatocyte growth factor activator inhibitor-1B
potent inhibitor of hepsin
-
N-[1-(1,3-benzothiazol-2-yl)-5-carbamimidamido-1-oxopentan-2-yl]-N2-(20-[3,3-dimethyl-5-sulfo-2-[(1E)-3-[(4E)-4-[(2E)-2-(1,3,3-trimethyl-5-sulfo-1,3-dihydro-2H-indol-2-ylidene)ethylidene]cyclohex-1-en-1-yl]prop-1-en-1-yl]-3H-indolium-1-yl]-16-oxo-4,7,10,13-tetraoxa-15-azaicosan-1-oyl)-L-leucinamide
Leu-Arg dipeptide, attached to dye SulfoCy7. Compound shows 1000fold selectivtiy for hepsin over matriptase and selective uptake and retention in hepsin-overexpressing cells
N2-acetyl-N-[1-(1,3-benzothiazol-2-yl)-5-carbamimidamido-1-oxopentan-2-yl]-L-leucinamide
inhibitor based on tetrapeptide hepsin inhibitor acetyl-KQLR-ketothiazole. Hepsin affinity of the (R)-epimer is similar to that of the corresponding (S)-epimer
N2-acetyl-N-[5-carbamimidamido-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]-L-leucinamide
inhibitor based on tetrapeptide hepsin inhibitor acetyl-KQLR-ketothiazole. Hepsin affinity of the (R)-epimer is similar to that of the corresponding (S)-epimer
serpinB12
forms a covalent complex with hepsin. Hepsin cleaves the reactive-site loop after the Arg residue
-
antithrombin III
-
76% inhibition at 0.003 mM, 1U/ml heparin enhances inhibition
-
hepatocyte growth factor activator inhibitor-2
-
potent inhibitor of hepsin activity
-
hepatocyte growth factor activator inhibitor-2
potent inhibitor of hepsin
-
additional information
-
no inhibition by soybean trypsin inhibitor and tissue factor pathway inhibitor
-
additional information
-
hepatocyte growth factor activator inhibitor 1 and hepatocyte growth factor activator inhibitor 2
-
additional information
antibody hH35 potently inhibits hepsin enzymatic activity at nanomolar concentrations, showing non-linear, slow, tight-binding inhibition
-
additional information
-
antibody hH35 potently inhibits hepsin enzymatic activity at nanomolar concentrations, showing non-linear, slow, tight-binding inhibition
-
additional information
synthesis of a heterobivalent inhibitor, targeting both hepsin and prostate-specific membrane antigen, EC 3.4.17.21. The compound is based on an amidine-containing indole analog linked with Lys-urea-Glu for binding to prostate-specific membrane antigen, and the optical dye SulfoCy7. Compound shows selective binding and retention in both prostate-specific membrane antigen and hepsin high-expressing cells
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
resveratrol
-
hepsin activity increases in dose-dependent manner in the presence of resveratrol
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.05
L-Asp-L-Ala-L-Ala-L-Arg-4-nitroanilide
-
in 0.3M Tris-HCl, 0.3 M imidazole, and 0.5 M NaCl, pH 8.4, at 37°C
0.05
L-Asp-L-Lys-(gamma-Cbo)-L-Pro-L-Arg-4-nitroanilide
-
in 0.3M Tris-HCl, 0.3 M imidazole, and 0.5 M NaCl, pH 8.4, at 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0001
1-[6-(6-methyl-3H-indol-2-yl)pyridin-2-yl]cyclohexan-1-ol
pH not specified in the publication, temperature not specified in the publication
0.0000017
9-fluorenylmethyloxycarbonyl-NR-ketobenzothiazole
pH not specified in the publication, temperature not specified in the publication
0.001
hepatocyte growth factor activator inhibitor-1B, hepatocyte growth factor activator inhibitor-2
completely inhibits
-
0.000022
N-[1-(1,3-benzothiazol-2-yl)-5-carbamimidamido-1-oxopentan-2-yl]-N2-(20-[3,3-dimethyl-5-sulfo-2-[(1E)-3-[(4E)-4-[(2E)-2-(1,3,3-trimethyl-5-sulfo-1,3-dihydro-2H-indol-2-ylidene)ethylidene]cyclohex-1-en-1-yl]prop-1-en-1-yl]-3H-indolium-1-yl]-16-oxo-4,7,10,13-tetraoxa-15-azaicosan-1-oyl)-L-leucinamide
pH not specified in the publication, temperature not specified in the publication
0.000003
N2-acetyl-N-[1-(1,3-benzothiazol-2-yl)-5-carbamimidamido-1-oxopentan-2-yl]-L-leucinamide
pH not specified in the publication, temperature not specified in the publication
0.000022
N2-acetyl-N-[5-carbamimidamido-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]-L-leucinamide
pH not specified in the publication, temperature not specified in the publication
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
chinese patient with hepatocellular carcinoma combined hepatitis B virus infection, strain WhuTJ-37
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
non-transmembrane isoform highly expressed, whereas transmembrane hepsin is expressed at a relatively lower level
-
upregulation of hepsin mRNA in estrogen receptor alpha-positive breast tumors compared with estrogen receptor alpha-negative breast tumors
-
non-transmembrane isoform expressed at highest level among investigated cell lines, transmembrane isoform hardly detectable
-
hepsin expression is significantly higher in endometrial cancer compared to normal endometrium and endometrial hyperplasia. High levels of hepsin expression are associated with advanced stage, high grade, depth of myometrial invasion, cervical involvement, lymph node metastasis, lymph vascular space involvement, ovarian metastasis, and peritoneal cytology of endometrial cancer
additional information
-
transient transfection of hepsin increases the progress of apoptosis/supresses proliferation. Inhibition of cell growth in monolayer culture. Increased accumulation of p53-dependent apoptosis and caspases-3, -6, and -7 in stabley transfected BG-1 cells
in ovarian cancer hepsin expression is mainly confined to the epithelial cells and not the adjacent stroma
-
elevated hepsin mRNA expression levels in ca. 58% of low grade tumors and ca. 84% of more advanced ovarian carcinomas. Hepsin mRNA expression is significantly higher in primary ovarian serous papillary carcinomas compared to that in omental metastasis
-
hepsin mRNA levels in early stage cancer are similar to that in normal controls but mRNA levels decrease in more advanced cancers. Patients with lower hepsin mRNA levels have poorer survival rate. In contrast, another study reports lower hepsin mRNA expression in early stage cancers, in some cases of advanced cancer overexpression of hepsin mRNA and patients with high hepsin mRNA levels with poorer survival rates
additional information
-
enzyme is present in most tissues, highest level in liver
additional information
-
hepsin presence increases significantly during embryo development in intensity and in the number of tissues
additional information
-
no activity in SV40 immortalized neonatal epithelial 267B1 cells, DU-145 cells, PC3 cells and SV40 immortalized normal prostate cells
additional information
-
both isoforms hardly detectable in SW-1417 cells, Colo-201 cells, Colo-205 cells, SW-1222 cells, LS-180 cells, HT-29 cell and LoVo cells
additional information
-
present in LNCaP-17 and LNCaP-34 cells, absent in HPAC cells
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
hepsin is detected in the cytoplasm and membrane of hepatocytes. In ovarian tumor cells, cytoplasmic localization of hepsin is prevalent in mucinous, endometrioid and transitional cell carcinomas, while the majority of serous and clear cell carcinomas display membranous localization
hepsin is detected in the cytoplasm and membrane of hepatocytes. In ovarian tumor cells, cytoplasmic localization of hepsin is prevalent in mucinous, endometrioid and transitional cell carcinomas, while the majority of serous and clear cell carcinomas display membranous localization. Membrane-associated hepsin protein is present at desmosomal junctions, where it colocalizes with its putative proteolytic substrate hepatocyte growth factor
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
the macrophage-stimulating protein/RON signaling pathway is regulated by hepsin in tissue homeostasis and in disease pathologies, such as in cancer and immune disorders
physiological function
hepsin inhibits the internal ribosome entry site activity and expression of CDK11p58,which is associated with cell cycle progression and pro-apoptotic signaling in prostate cancer. Hepsin suppresses CDK11p58 internal ribosome entry site activity in prostate cancer by modulating transacting factor unr expression and eIF-2alpha phosphorylation. Hepsin inhibits the expression of unr by directly binding to unr internal ribosome entry site element and suppressing its activity, and also represses eIF-2alpha phosphorylation through down-regulating the expression and phosphorylation of general control nonderepressible-2
physiological function
addition of hepsin to osteoarthritis cartilage in explant culture induces significant collagen and aggrecan release and activates metalloproteinases proMMP-1 and proMMP-3. Hepsin directly cleaves the aggrecan core protein at a cleavage site within the interglobular domain. Hepsin expression correlates with synovitis as well as tumour necrosis factor alpha expression, and is induced in cartilage by a pro-inflammatory stimulus. Hepsin demonstrates markedly reduced capacity to activate proteinase-activated receptor-2, compared with matriptase
physiological function
hepsin alone and not matriptase or HGFA plays a key role in diminishing epithelial cell membrane integrity through degradation of desmogelin-2 in breast cancer cells
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). HEPS_HUMAN
417
1
45011
Swiss-Prot
Secretory Pathway (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30000
-
SDS-PAGE, autocatalytically processed form consisting of amino acids 163-417
35000
-
amino sequence analysis in both non-reduction and reduction conditions of non-transmembrane isoform
45000
51000
75000
-
Western blot analysis, SDS-PAGE, non-transmembrane isoform expressed in HEK-293T cells
45000
-
Western blot analysis, SDS-PAGE, transmembrane isoform expressed in HEK-293T cells, amino sequence analysis of transmembrane isoform
45000
-
SDS-PAGE, molecular weight of used fragment containing amino acids 45-417
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
larger size of enzyme in cell extracts as compared to cell-free translation assay may be due to glycosylation, possible site for N-linked carbohydrate chain attachment is at amino acid 112
proteolytic modification
-
gene contains a cleavage site for protease activation
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
extracellular portion of hepsin, starting at residue 46 and continuing to the end of the coding region, hanging drop vapor diffusion method
-
has scavenger receptor-like cysteine-rich domain and a large loop between residues 241 and 256, which may represent a major determinant for its substrate recognition
-
hepsin in complex with antibody hH35, hanging drop vapor diffusion method, using 18% (w/v) PEG 3350, 0.15 M Mg2SO4 and 0.01 M BaCl2
molecular docking of inhibitor. The P1 and P2 binding sites are occupied by the conserved Arg and then the variable second side chain, respectively. The 9-fluorenylmethyloxycarbonyl group forms pi-pi interactions with the conserved Trp in the P4 pocket
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H203A/D257A/S353A
overexpression of catalytically inactive mutant hepsin abrogates its ability to induce tumor growth in a mouse model
additional information
additional information
-
biological functions and effects of hepsin are analysed in vitro and in vivo, using endometrial cancer cell lines Ishikawa, HEC-1A, stably transfected with human hepsin. A significant inhibitory effect on cell growth in a monolayer culture system and in anchorage-independent cell growth in soft agar in vitro is observed. In a xenograft model, growth inhibitory effects are shown observed when compared with the effects of mock-transfected cells used as a control. Hepsin shows potential inhibitory effects mediated by the induction of 14-3-3sigma expression which leads to both cell cycle arrest at the G2/M phase through cyclin B and cyclin A and the p53-dependent pathway activated by increasing the level of Bak and reducing the level of Bcl-2 and Bcl-xL
additional information
-
hepsin-overexpressing LNCaP prostate cancer cells also exhibit increased migration on Laminin-332
additional information
overexpression of hepsin promotes ovarian tumor growth in a mouse model
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by nickel-nitrilotriacetic acid affinity chromatography, ion-exchange chromatography or affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cDNA of full lenth hepsin inserted into vector pRK5E, His-tagged hepsin cDNA inserted into vector pCMV.PD5, expression in a chinese hamster ovary expression system
expressed in Escherichia coli strains BL21(DE3), BL21(DE3) Codon Plus RIL, and Rosetta pLysS
-
fragment containing amino acids 45-417 is expressed as a C-terminal His-tagged fusion protein in Drosophila S2 cells
-
full-length hepsin cDNA construct transiently transfected in BG-1 cell lines. Hepsin stable transfectant BG-1 cells injected in nude mice
-
inserted in a baculovirus expression vector under the control of a polyhedrin promoter and expressed in T.in.Pro cells. cDNA of full-length hepsin inserted into a mammalian expression vector overexpressed in LNCaP cells
-
prostate cancer cell lines stably transfected with a hepsin expressing plasmid. Stable transfection of hepsin cDNA in ovarian cancer cell lines. Overexpression in transgenic mice
-
transmembrane isoform and non-transmembrane isoform cloned into vector pcDNA3/Myc-His-(-C), both isoforms expressed in BHK-21 cells, non-transmembrane isoform expressed in bacteria strain DE3, overexpression of myc-tagged non-transmembrane hepsin in HEK-293 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
hepsin expression correlates with synovitis as well as tumour necrosis factor alpha expression, and is induced in cartilage by a pro-inflammatory stimulus
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
biotechnology
-
the aim of this study is to establish a cell line that directly secrets rFVIIa into cell culture medium: Factor VII and hepsin cDNAs are isolated from HepG2 cell line and cloned into pcDNA3-1 vector. The constructs are co-trasfected to CHO cell line. A cell line that permanently expresses recombinant factor VII (rFVII) and hepsin is established. FVIIa protein is secreted to medium of CHO cells co-transfected with pcNDA3-1-FVII and pcNDA3-1-hepsin. A three- to fourfold decrease in clotting time is observed when human FVII-depleted plasma is used in combination with human thromboplastin in the presence of rFVII, confirming the biological activity of rFVII. A cell line is established expressing FVIIa using genetic engineering methods
medicine
medicine
-
expression of the non-transmembrane isoform in vivo does not exert any apparent inhibitory effect on cell growth
medicine
-
hepsin expression in tumours is dysregulated and may influence tumorigenesis through inappropiate activation and/or regulation of hepatocyte growth factor receptor functions
medicine
hepsin is a potent activator of pro-hepatocyte growth factor, thus contributing to tumor progression
medicine
hepsin is significantly decreased in pT2 or greater tumor samples, while expression does not differ between the normal and cancerous tissue of pT1 tumors, survival in patients bearing tumors with hepsin expression below the 10th percentile expression of hepsin in noncancerous tissue is poorer than that in patients with tumors with expression above that cutoff, the level of hepsin is found to be a significant predictor of death from renal cell carcinoma
medicine
-
hepsin significantly inhibits cell growth in the monolayer, anchorage-independent cell growth in soft agar in vitro, and tumorigenicity in vivo in ovarian cancer cell lines, through up-regulation of p53-dependent apoptosis and caspase-3, -6, and -7 activations
medicine
human hepsin interacts directly with X protein of human hepatitis B virus both in vitro and in vivo, their interaction appears to play a role in both promoting cell proliferation and blocking apoptosis in human liver tumor cell and normal liver cell lines, promotes expression of viral protein HBeAg in Hep-G2.2.1.5 cells, thus stimulating viral replication
medicine
-
association of five of eleven single nucleotide polymorphisms on the hepsin gene HPN with susceptibility to prostate cancer among men of European descent. Association of one of the single nucleotide polymorphisms with Gleason score, which suggests a role of HPN in tumor aggressiveness
medicine
-
hepsin has a potential therapeutic effect that inhibits through upregulation of p53-dependent apoptosis and caspase-3, -6, and -7 activations. Hepsin may be useful in ovarian cancer treatment
medicine
-
hepsin is one of the most upregulated genes in prostate cancer. Upregulation appears to correlate with disease progression. Role of hepsin is more important in cancer cell migration/invasion than cell proliferation. Hepsin mRNA expression appears to be lower in hormone-refractory prostate cancer compared to clinically localized prostate cancer. Single nucleotide polymorphisms are associated with prostate cancer susceptibility. In contrast, prostate cancer cell lines stably transfected with a hepsin expressing plasmid grow slower and are less invasive in culture. Similarly, stable transfection of hepsin cDNA in ovarian cancer cell lines promotes apoptosis and inhibits tumor cell growth
medicine
-
hepsin may initiate plasmin-mediated proteolytic pathways at the tumor/stroma interface that lead to basement membrane disruption and tumor progression
medicine
-
hepsin protein expression may be an important indication for high risk of endometrial cancer
medicine
-
direct cleavage of Laminin-332 may be one mechanism by which hepsin promotes prostate tumor progression and metastasis, possibly by up-regulating prostate cancer cell motility
medicine
-
germline genetic variation of HPN does not seem to contribute to risk of prostate cancer or prognosis
medicine
alpha-methylacyl-CoA racemase and hepsin are unable to diagnose prostate cancer with better true positive and false negative rates than prostate-specific antigen. There are no correlations between alpha-methylacyl-CoA racemase levels, hepsin levels, tumor stage of benign prostate hyperplasia and prostate cancer, and Gleason score
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Leytus, S.P.; Loeb, K.R.; Hagen, F.S.; Kurachi, K.; Davie, E.W.
A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells
Biochemistry
27
1067-1074
1988
Homo sapiens
Tsuji, A.; Torres-Rosado, A.; Arai, T.; Chou, S.H.; Kurachi, K.
Characterization of hepsin, a membrane bound protease
Biomed. Biochim. Acta
50
791-793
1991
Homo sapiens, Papio ursinus
Srikantan, V.; Valladares, M.; Rhim, J.S.; Moul, J.W.; Srivastava, S.
Hepsin inhibits cell growth/invasion in prostate cancer cells
Cancer Res.
62
6812-6816
2002
Homo sapiens
Tsuji, A.; Torres-Rosado, A.; Arai, T.; Le Beau, M.M.; Lemons, R.S.; Chou, S.H.; Kurachi, K.
Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization
J. Biol. Chem.
266
16948-16953
1991
Homo sapiens, Papio ursinus
Kazama, Y.; Hamamoto, T.; Foster, D.C.; Kisiel, W.
Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation
J. Biol. Chem.
270
66-72
1995
Homo sapiens
Kurachi, K.; Torres-Rosado, A.; Tsuji, A.
Hepsin
Methods Enzymol.
244
100-114
1994
Cricetulus griseus, Homo sapiens, Papio ursinus
Torres-Rosado, A.; O'Shea, K.S.; Tsuji, A.; Chou, S.H.; Kurachi, K.
Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth
Proc. Natl. Acad. Sci. USA
90
7181-7185
1993
Homo sapiens
Somoza, J.R.; Ho, J.D.; Luong, C.; Ghate, M.; Sprengeler, P.A.; Mortara, K.; Shrader, W.D.; Sperandio, D.; Chan, H.; McGrath, M.E.; Katz, B.A.
The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain
Structure
11
1123-1131
2003
Homo sapiens
Zhang, J.L.; Zhao, W.G.; Wu, K.L.; Wang, K.; Zhang, X.; Gu, C.F.; Li, Y.; Zhu, Y.; Wu, J.G.
Human hepatitis B virus X protein promotes cell proliferation and inhibits cell apoptosis through interacting with a serine protease hepsin
Arch. Virol.
150
721-741
2005
Homo sapiens (P05981), Homo sapiens
Herter, S.; Piper, D.E.; Aaron, W.; Gabriele, T.; Cutler, G.; Cao, P.; Bhatt, A.S.; Choe, Y.; Craik, C.S.; Walker, N.; Meininger, D.; Hoey, T.; Austin, R.J.
Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers
Biochem. J.
390
125-136
2005
Homo sapiens
Li, Y.; Yu, Z.; Zhao, X.; Shen, S.
Identification and characterization of hepsin/-TM, a non-transmembrane hepsin isoform
Biochim. Biophys. Acta
1681
157-165
2005
Homo sapiens
Kirchhofer, D.; Peek, M.; Lipari, M.T.; Billeci, K.; Fan, B.; Moran, P.
Hepsin activates pro-hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor-1B (HAI-1B) and HAI-2
FEBS Lett.
579
1945-1950
2005
Homo sapiens (P05981)
Nakamura, K.; Nasu, Y.; Hongo, A.; Matsuo, T.; Kodama, J.; Ebara, S.; Nagai, A.; Abrzua, F.; Kumon, H.; Hiramatsu, Y.
Hepsin shows inhibitory effects through apoptotic pathway on ovarian cancer cell lines
Int. J. Oncol.
28
393-398
2006
Homo sapiens
Roemer, A.; Schwettmann, L.; Jung, M.; Stephan, C.; Roigas, J.; Kristiansen, G.; Loening, S.A.; Lichtinghagen, R.; Jung, K.
The membrane proteases adams and hepsin are differentially expressed in renal cell carcinoma. Are they potential tumor markers?
J. Urol.
172
2162-2166
2004
Homo sapiens (P05981), Homo sapiens
Matsuo, T.; Nakamura, K.; Takamoto, N.; Kodama, J.; Hongo, A.; Abrzua, F.; Nasu, Y.; Kumon, H.; Hiramatsu, Y.
Expression of the serine protease hepsin and clinical outcome of human endometrial cancer
Anticancer Res.
28
159-164
2008
Homo sapiens
Wu, Q.; Parry, G.
Hepsin and prostate cancer
Front. Biosci.
12
5052-5059
2007
Homo sapiens, Mus musculus, Rattus norvegicus
Pal, P.; Xi, H.; Kaushal, R.; Sun, G.; Jin, C.H.; Jin, L.; Suarez, B.K.; Catalona, W.J.; Deka, R.
Variants in the HEPSIN gene are associated with prostate cancer in men of European origin
Hum. Genet.
120
187-192
2006
Homo sapiens
Moran, P.; Li, W.; Fan, B.; Vij, R.; Eigenbrot, C.; Kirchhofer, D.
Pro-urokinase-type plasminogen activator is a substrate for hepsin
J. Biol. Chem.
281
30439-30446
2006
Homo sapiens
Beliveau, F.; Desilets, A.; Leduc, R.
Probing the substrate specificities of matriptase, matriptase-2, hepsin and DESC1 with internally quenched fluorescent peptides
FEBS J.
276
2213-2226
2009
Homo sapiens
Miao, J.; Mu, D.; Ergel, B.; Singavarapu, R.; Duan, Z.; Powers, S.; Oliva, E.; Orsulic, S.
Hepsin colocalizes with desmosomes and induces progression of ovarian cancer in a mouse model
Int. J. Cancer
123
2041-2047
2008
Homo sapiens (P05981)
Nakamura, K.; Takamoto, N.; Abarzua, F.; Hongo, A.; Kodama, J.; Nasu, Y.; Kumon, H.; Hiramatsu, Y.
Hepsin inhibits the cell growth of endometrial cancer
Int. J. Mol. Med.
22
389-397
2008
Homo sapiens
Tripathi, M.; Nandana, S.; Yamashita, H.; Ganesan, R.; Kirchhofer, D.; Quaranta, V.
Laminin-332 is a substrate for hepsin, a protease associated with prostate cancer progression
J. Biol. Chem.
283
30576-30584
2008
Homo sapiens
Halabian, R.; Roudkenar, M.H.; Esmaeili, N.S.; Masroori, N.; Roushandeh, A.M.; Najafabadi, A.J.
Establishment of a cell line expressing recombinant factor VII and its subsequent conversion to active form FVIIa through hepsin by genetic engineering method
Vox Sang.
96
309-315
2009
Homo sapiens
Owen, K.A.; Qiu, D.; Alves, J.; Schumacher, A.M.; Kilpatrick, L.M.; Li, J.; Harris, J.L.; Ellis, V.
Pericellular activation of hepatocyte growth factor by the transmembrane serine proteases matriptase and hepsin, but not by the membrane-associated protease uPA
Biochem. J.
426
219-228
2010
Homo sapiens
Chen, M.; Chen, L.M.; Lin, C.Y.; Chai, K.X.
Hepsin activates prostasin and cleaves the extracellular domain of the epidermal growth factor receptor
Mol. Cell. Biochem.
337
259-266
2010
Homo sapiens
Holt, S.K.; Kwon, E.M.; Lin, D.W.; Ostrander, E.A.; Stanford, J.L.
Association of hepsin gene variants with prostate cancer risk and prognosis
Prostate
70
1012-1019
2010
Homo sapiens
Koschubs, T.; Dengl, S.; Duerr, H.; Kaluza, K.; Georges, G.; Hartl, C.; Jennewein, S.; Lanzendoerfer, M.; Auer, J.; Stern, A.; Huang, K.S.; Packman, K.; Gubler, U.; Kostrewa, D.; Ries, S.; Hansen, S.; Kohnert, U.; Cramer, P.; Mundigl, O.
Allosteric antibody inhibition of human Hepsin protease
Biochem. J.
442
483-494
2012
Homo sapiens (P05981), Homo sapiens
Raevskaya, A.A.; Kuznetsova, E.M.; Savvateeva, M.V.; Severin, S.E.
Isolation, purification, and study of properties of recombinant hepsin from Escherichia coli
Biochemistry
75
866-872
2010
Homo sapiens
Ganesan, R.; Kolumam, G.A.; Lin, S.J.; Xie, M.H.; Santell, L.; Wu, T.D.; Lazarus, R.A.; Chaudhuri, A.; Kirchhofer, D.
Proteolytic activation of pro-macrophage-stimulating protein by hepsin
Mol. Cancer Res.
9
1175-1186
2011
Homo sapiens
Zhang, C.; Zhang, M.; Wu, Q.; Peng, J.; Ruan, Y.; Gu, J.
Hepsin inhibits CDK11p58 IRES activity by suppressing unr expression and eIF-2alpha phosphorylation in prostate cancer
Cell. Signal.
27
789-797
2015
Homo sapiens (P05981)
Niehaus, J.Z.; Miedel, M.T.; Good, M.; Wyatt, A.N.; Pak, S.C.; Silverman, G.A.; Luke, C.J.
SERPINB12 is a slow-binding inhibitor of granzyme A and hepsin
Biochemistry
54
6756-6759
2015
Homo sapiens (P05981)
Kim, K.; Kwon, H.; Choi, D.; Lim, T.; Minn, I.; Son, S.H.; Byun, Y.
Design and synthesis of dye-conjugated hepsin inhibitors
Bioorg. Chem.
89
102990
2019
Homo sapiens (P05981)
Franco, F.M.; Jones, D.E.; Harris, P.K.; Han, Z.; Wildman, S.A.; Jarvis, C.M.; Janetka, J.W.
Structure-based discovery of small molecule hepsin and HGFA protease inhibitors Evaluation of potency and selectivity derived from distinct binding pockets
Bioorg. Med. Chem.
23
2328-2343
2015
Homo sapiens (P05981)
Goswami, R.; Wohlfahrt, G.; Toermaekangas, O.; Moilanen, A.; Lakshminarasimhan, A.; Nagaraj, J.; Arumugam, K.N.; Mukherjee, S.; Chacko, A.R.; Krishnamurthy, N.R.; Jaleel, M.; Palakurthy, R.K.; Samiulla, D.S.; Ramachandra, M.
Structure-guided discovery of 2-aryl/pyridin-2-yl-1H-indole derivatives as potent and selective hepsin inhibitors
Bioorg. Med. Chem. Lett.
25
5309-5314
2015
Homo sapiens (P05981)
Kwon, H.; Kim, Y.; Park, K.; Choi, S.A.; Son, S.H.; Byun, Y.
Structure-based design, synthesis, and biological evaluation of Leu-Arg dipeptide analogs as novel hepsin inhibitors
Bioorg. Med. Chem. Lett.
26
310-314
2016
Homo sapiens (P05981)
Subedi, M.; Minn, I.; Chen, J.; Kim, Y.; Ok, K.; Jung, Y.W.; Pomper, M.G.; Byun, Y.
Design, synthesis and biological evaluation of PSMA/hepsin-targeted heterobivalent ligands
Eur. J. Med. Chem.
118
208-218
2016
Homo sapiens (P05981)
Sroka, W.D.; Adamowski, M.; Slupski, P.; Siodmiak, J.; Jarzemski, P.; Odrowaz-Sypniewska, G.; Marszall, M.P.
Alpha-methylacyl-CoA racemase and hepsin as urinary prostate cancer markers
Int. J. Biol. Markers
30
e401-e406
2015
Homo sapiens (P05981)
Damalanka, V.C.; Han, Z.; Karmakar, P.; ODonoghue, A.J.; La Greca, F.; Kim, T.; Pant, S.M.; Helander, J.; Klefstroem, J.; Craik, C.S.; Janetka, J.W.
Discovery of selective matriptase and hepsin serine protease inhibitors useful chemical tools for cancer cell biology
J. Med. Chem.
62
480-490
2019
Homo sapiens (P05981)
Wilkinson, D.J.; Desilets, A.; Lin, H.; Charlton, S.; Del Carmen Arques, M.; Falconer, A.; Bullock, C.; Hsu, Y.C.; Birchall, K.; Hawkins, A.; Thompson, P.; Ferrell, W.R.; Lockhart, J.; Plevin, R.; Zhang, Y.; Blain, E.; Lin, S.W.; Leduc, R.; Milner, J.M.; Rowan, A.D.
The serine proteinase hepsin is an activator of pro-matrix metalloproteinases molecular mechanisms and implications for extracellular matrix turnover
Sci. Rep.
7
16693
2017
Homo sapiens (P05981)
EXTERNAL LINKS (specific for EC-Number 3.4.21.106)
Transporter Classification Database (TCDB): 8.A.131.1.12
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