Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T99908
|
|||||
| Target Name |
HUMAN transmembrane protease serine 2 (TMPRSS2)
|
|||||
| Synonyms |
TMPRSS2 protease; TMPRSS2
Click to Show/Hide
|
|||||
| Gene Name |
TMPRSS2
|
|||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | COVID-19 [ICD-11: 1D6Y] | |||||
| Function |
Serine protease that proteolytically cleaves and activates the viral spike glycoproteins which facilitate virus- cell membrane fusions; spike proteins are synthesized and maintained in precursor intermediate folding states and proteolysis permits the refolding and energy release required to create stable virus-cell linkages and membrane coalescence. Facilitates human SARS coronavirus (SARS-CoV) infection via two independent mechanisms, proteolytic cleavage of ACE2, which might promote viral uptake, and cleavage of coronavirus spike glycoprotein which activates the glycoprotein for cathepsin L- independent host cell entry. Proteolytically cleaves and activates the spike glycoproteins of human coronavirus 229E (HCoV-229E) and human coronavirus EMC (HCoV-EMC) and the fusion glycoproteins F0 of Sendai virus (SeV), human metapneumovirus (HMPV), human parainfluenza 1, 2, 3, 4a and 4b viruses (HPIV). Essential for spread and pathogenesis of influenza A virus (strains H1N1, H3N2 and H7N9); involved in proteolytic cleavage and activation of hemagglutinin (HA) protein which is essential for viral infectivity.
Click to Show/Hide
|
|||||
| BioChemical Class |
Peptidase
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 3.4.21.-
|
|||||
| Sequence |
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF TDWIYRQMRADG Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Drugs in Phase 2 Trial | [+] 1 | + | ||||
| 1 | Camostat mesylate | Drug Info | Phase 2 | Coronavirus Disease 2019 (COVID-19) | [2], [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | Camostat mesylate | Drug Info | [1], [2] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: 4-Guanidinobenzoic acid | Ligand Info | |||||
| Structure Description | Crystal structure of human TMPRSS2 in complex with Nafamostat | PDB:7MEQ | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [4] |
| PDB Sequence |
CVRLYGPNFI
157 LQVYSSSWHP170 VCQDDWNENY180 GRAACRDMGY190 KNNFYSSQGI200 VDSFMKLNTS 215 AIYKKLYHSD229 ACSSKAVVSL239 RCIACGVNLN249 IVGGESALPG265 AWPWQVSLHV 275 QNVHVCGGSI285 ITPEWIVTAA295 HCVEKPLNNP305 WHWTAFAGIL315 RQSFMFYGAG 325 YQVEKVISHP335 NYDSKTKNND345 IALMKLQKPL355 TFNDLVKPVC365 LPNPGMMLQP 375 EQLCWISGWG385 ATEEKGKTSE395 VLNAAKVLLI405 ETQRCNSRYV415 YDNLITPAMI 425 CAGFLQGNVD435 SCQGDSGGPL445 VTSKNNIWWL455 IGDTSWGSGC465 AKAYRPGVYG 475 NVMVFTDWIY485 RQMRAD
|
|||||
|
|
HIS296
4.423
TYR416
4.471
ASP435
2.762
SER436
2.790
CYS437
3.391
GLN438
3.499
GLY439
3.372
ASP440
3.855
SER441
1.468
THR459
3.689
SER460
4.034
|
|||||
| 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).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
|
|
|
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.
|
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
|---|---|---|---|---|---|
| Closeness centrality | 2.13E-01 | Radiality | 1.37E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 6.10E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47. | |||||
| REF 2 | SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. | |||||
| REF 3 | ClinicalTrials.gov (NCT04353284) Camostat Mesylate in COVID-19 Outpatients | |||||
| REF 4 | Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation. Nat Chem Biol. 2022 Sep;18(9):963-971. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.