Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT3FDB1)

• DTT Name: HUMAN transmembrane protease serine 2 (TMPRSS2)
• Synonyms: TMPRSS2 protease; TMPRSS2
• Gene Name: TMPRSS2
• BioChemical Class: Peptidase
• UniProt ID: TMPS2_HUMAN
• TTD ID: T99908
• EC Number: EC 3.4.21.-
• Sequence:
  MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
  SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
  DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
  GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
  CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
  PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
  VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
  TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
  TDWIYRQMRADG
• 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.
• KEGG Pathway:
  Influenza A (hsa05164)
  Coronavirus disease - COVID-19 (hsa05171)
  Transcriptional misregulation in cancer (hsa05202)
  Prostate cancer (hsa05215)
• Reactome Pathway:
  Attachment and Entry (R-HSA-9694614)
  Attachment and Entry (R-HSA-9678110)

Molecular Interaction Atlas (MIA) of This DTT

1 Drugs in Phase 2 Trial Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Camostat mesylate	DMVLXMG	Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2/3 Trial	[2]

References

• [1] Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
• [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.