Target Information

Target General Information

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Target ID

T73471 (Former ID: TTDR00510)

Target Name

Serine protease hepsin (HPN)

Synonyms

Transmembrane protease, serine 1; HPN; HEPSIN

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Gene Name

HPN

Target Type

Patented-recorded target

[1]

Function

Plays an essential role in cell growth and maintenance of cell morphology. May mediate the activating cleavage of HGF and MST1/HGFL. Plays a role in the proteolytic processing of ACE2.

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BioChemical Class

Peptidase

UniProt ID

HEPS_HUMAN

EC Number

EC 3.4.21.106

Sequence

MAQKEGGRTVPCCSRPKVAALTAGTLLLLTAIGAASWAIVAVLLRSDQEPLYPVQVSSAD
ARLMVFDKTEGTWRLLCSSRSNARVAGLSCEEMGFLRALTHSELDVRTAGANGTSGFFCV
DEGRLPHTQRLLEVISVCDCPRGRFLAAICQDCGRRKLPVDRIVGGRDTSLGRWPWQVSL
RYDGAHLCGGSLLSGDWVLTAAHCFPERNRVLSRWRVFAGAVAQASPHGLQLGVQAVVYH
GGYLPFRDPNSEENSNDIALVHLSSPLPLTEYIQPVCLPAAGQALVDGKICTVTGWGNTQ
YYGQQAGVLQEARVPIISNDVCNGADFYGNQIKPKMFCAGYPEGGIDACQGDSGGPFVCE
DSISRTPRWRLCGIVSWGTGCALAQKPGVYTKVSDFREWIFQAIKTHSEASGMVTQL

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3D Structure

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PDB

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

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Ligand Name: CRA-1144

Ligand Info

Structure Description

Extracellular domain of human hepsin

PDB:1P57

Method

X-ray diffraction

Resolution

1.75 Å

Mutation

Yes

[3]

PDB Sequence

IVGGRDTSLG

²⁵

RWPWQVSLRY

³⁵

DGAHLCGGSL

⁴⁶

LSGDWVLTAA

⁵⁶

HCFPERNRVL

^65A

SRWRVFAGAV

⁷¹

AQASPHGLQL

⁸³

GVQAVVYHGG

⁹³

YLPFNSNDIA

¹⁰⁴

LVHLSSPLPL

¹¹⁴

TEYIQPVCLP

¹²⁴

AAGQALVDGK

¹³⁴

ICTVTGWGNT

¹⁴⁴

QYYGQQAGVL

¹⁵⁵

QEARVPIISN

¹⁶⁵

DVCNGADFYG

¹⁷⁵

NQIKPKMFCA

¹⁸³

GYPEGGIDAC

¹⁹¹

QGDSGGPFVC

²⁰¹

EDSISRTPRW

^208C

RLCGIVSWGT

²¹⁷

GCALAQKPGV

²²⁷

YTKVSDFREW

²³⁷

IFQAIKTHSE

²⁴⁷

ASGMVTQ

Residue

Distance (Å)

HIS57

1.719

CYS58

4.868

TYR146

4.450

TYR174

4.939

ASP189

2.240

ALA190

2.316

CYS191

3.004

GLN192

2.559

GLY193

3.456

ASP194

3.461

SER195

0.823

GLY196

4.823

VAL213

2.045

Residue

Distance (Å)

SER214

4.192

TRP215

3.390

GLY216

2.871

THR217

4.521

GLY219

2.103

CYS220

2.339

ALA221

3.373

LYS224

4.659

PRO225

4.195

GLY226

2.427

VAL227

3.675

TYR228

4.655

Ligand Name: 2-[6-(1-Hydroxycyclohexyl)pyridin-2-Yl]-1h-Indole-5-Carboximidamide

Ligand Info

Structure Description

Crystal Structure of Serine protease Hepsin in complex with Inhibitor

PDB:5CE1

Method

X-ray diffraction

Resolution

2.50 Å

Mutation

[4]

PDB Sequence

EPLYPVQVSS

⁵⁸

ADARLMVFDK

⁶⁸

TEGTWRLLCS

⁷⁸

SRSNARVAGL

⁸⁸

SCEEMGFLRA

⁹⁸

LTHSELDVRT

¹⁰⁸

AGANGTSGFF

¹¹⁸

CVDEGRLPHT

¹²⁸

QRLLEVISVC

¹³⁸

DCPRGRFLAA

¹⁴⁸

ICQDCGRRKL

¹⁵⁸

IVGGRDTSLG

¹⁷²

RWPWQVSLRY

¹⁸²

DGAHLCGGSL

¹⁹²

LSGDWVLTAA

²⁰²

HCFPERNRVL

²¹²

SRWRVFAGAV

²²²

AQASGLQLGV

²³⁴

QAVVYHGGYL

²⁴⁴

PFRPNSENSN

²⁵⁶

DIALVHLSSP

²⁶⁶

LPLTEYIQPV

²⁷⁶

CLPAAGQALV

²⁸⁶

DGKICTVTGW

²⁹⁶

GNTQYYGQQA

³⁰⁶

GVLQEARVPI

³¹⁶

ISNDVCNGAD

³²⁶

FYGNQIKPKM

³³⁶

FCAGYPEGGI

³⁴⁶

DACQGDSGGP

³⁵⁶

FVCEDSISRT

³⁶⁶

PRWRLCGIVS

³⁷⁶

WGTGCALAQK

³⁸⁶

PGVYTKVSDF

³⁹⁶

REWIFQAIKT

⁴⁰⁶

HSEASGMVTQ

⁴¹⁶

Residue

Distance (Å)

LEU187

3.494

CYS188

4.070

HIS203

2.840

CYS204

4.782

TYR301

3.907

ASP347

2.553

ALA348

3.184

CYS349

4.065

GLN350

3.693

GLY351

4.455

SER353

3.392

VAL375

3.608

Residue

Distance (Å)

SER376

4.096

TRP377

3.661

GLY378

3.656

THR379

4.851

GLY380

2.886

CYS381

3.709

ALA382

4.449

LYS386

4.838

PRO387

4.637

GLY388

3.289

VAL389

4.389

Click to View More Binding Site Information of This Target with Different Ligands

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Similarity Proteins Human Tissue Distribution

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Similarity Proteins

Human Tissue Distribution

There is no similarity protein (E value < 0.005) for this target


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Viral carcinogenesis

NetPath Pathway

[+] 2 NetPath Pathways

IL2 Signaling Pathway

TGF_beta_Receptor Signaling Pathway

References

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REF 1

The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.

REF 2

Hepsin inhibitors. US9182402.

REF 3

The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain. Structure. 2003 Sep;11(9):1123-31.

REF 4

Crystal Structure of Serine protease Hepsin in complex with Inhibitor

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