Target Information
| Target General Information | Top | |||||
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| Target ID |
T67339
(Former ID: TTDI03481)
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| Target Name |
Channel-activating protease 1 (CAP1)
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| Synonyms |
Serine protease 8; Prostasin; CAP1
Click to Show/Hide
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| Gene Name |
PRSS8
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Possesses a trypsin-like cleavage specificity with a preference for poly-basic substrates. Stimulates epithelial sodium channel (ENaC) activity through activating cleavage of the gamma subunits (SCNN1G).
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| UniProt ID | ||||||
| EC Number |
EC 3.4.21.-
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| Sequence |
MAQKGVLGPGQLGAVAILLYLGLLRSGTGAEGAEAPCGVAPQARITGGSSAVAGQWPWQV
SITYEGVHVCGGSLVSEQWVLSAAHCFPSEHHKEAYEVKLGAHQLDSYSEDAKVSTLKDI IPHPSYLQEGSQGDIALLQLSRPITFSRYIRPICLPAANASFPNGLHCTVTGWGHVAPSV SLLTPKPLQQLEVPLISRETCNCLYNIDAKPEEPHFVQEDMVCAGYVEGGKDACQGDSGG PLSCPVEGLWYLTGIVSWGDACGARNRPGVYTLASSYASWIQSKVTELQPRVVPQTQESQ PDSNLCGSHLAFSSAPAQGLLRPILFLPLGLALGLLSPWLSEH Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T96EYH | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: 1-[4-(Hydroxymethyl)phenyl]guanidine | Ligand Info | |||||
| Structure Description | The Crystal Structure of Prostasin Complexed with Camostat at 1.6 Angstroms Resolution | PDB:3FVF | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | Yes | [2] |
| PDB Sequence |
ITGGSSAVAG
25 QWPWQVSITY35 EGVHVCGGSL46 VSEQWVLSAA56 HCFPSEHHKE58H AYEVKLGAHQ 72 LDSYSEDAKV82 STLKDIIPHP92 SYLQEGSQGD102 IALLQLSRPI112 TFSRYIRPIS 122 LPAAQASFPN132 GLHCTVTGWG142 HVAPSVSLLT144H PKPLQQLEVP161 LISRETCNSL 171 YNIDAKPEEP172I HFVQEDMVCA183 GYVEGGKDAC191 QGDSGGPLSC201 PVEGLWYLTG 211 IVSWGDACGA221 RNRPGVYTLA231 SSYASWIQSK241 VTELQPRV
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HIS57
4.440
TYR172
4.033
ASP189
2.829
ALA190
2.770
CYS191
3.372
GLN192
3.316
GLY193
3.503
ASP194
4.022
SER195
1.342
VAL213
3.571
SER214
3.871
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| Ligand Name: Benzyl [(1s)-5-Amino-1-{[(1s)-1-({(1s)-5-Amino-1-[(S)-1,3-Benzoxazol-2-Yl(Hydroxy)methyl]pentyl}carbamoyl)-3-Phenylpropyl]carbamoyl}pentyl]carbamate | Ligand Info | |||||
| Structure Description | X-ray structure of human prostasin in complex with Benzoxazole warhead peptidomimic, lysine in P3 | PDB:3E16 | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | Yes | [1] |
| PDB Sequence |
ITGGSSAVAG
25 QWPWQVSITY35 EGVHVCGGSL46 VSEQWVLSAA56 HCFPSEHHKE58H AYEVKLGAHQ 72 LDSYSEDAKV82 STLKDIIPHP92 SYLQEGSQGD102 IALLQLSRPI112 TFSRYIRPIS 122 LPAAQASFPN132 GLHCTVTGWG142 HVAPSVSLLT144H PKPLQQLEVP161 LISRETCNSL 171 YNIDAKPEEP172I HFVQEDMVCA183 GYVEGGKDAC191 QGDSGGPLSC201 PVEGLWYLTG 211 IVSWGDACGA221 RNRPGVYTLA231 SSYASWIQSK241 VTELQPR
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VAL41
4.824
CYS42
4.651
HIS57
2.822
TYR94
4.151
GLU97
3.562
GLY98
3.176
ASP102
3.775
PRO172I
3.269
HIS172J
3.345
PHE172K
3.544
ASP189
4.252
ALA190
2.898
CYS191
3.436
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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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
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There is no similarity protein (E value < 0.005) for this target
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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.
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| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | Discovery of inhibitors of the channel-activating protease prostasin (CAP1/PRSS8) utilizing structure-based design. Bioorg Med Chem Lett. 2008 Nov 15;18(22):5895-9. | |||||
| REF 2 | Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations. Protein Sci. 2009 May;18(5):1081-94. | |||||
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