Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT1GM2Z)

• DTT Name: Transmembrane protease serine 2 (TMPRSS2)
• Synonyms: TMPRSS2 protease; TMPRSS2
• Gene Name: TMPRSS2
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Peptidase
• UniProt ID: TMPS2_HUMAN
• TTD ID: T01282
• 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 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID21741839C5	DM8PA2V	Discovery agent	N.A.	Investigative	[1]

References

• [1] Development of substrate analogue inhibitors for the human airway trypsin-like protease HAT. Bioorg Med Chem Lett. 2011 Aug 15;21(16):4860-4.