Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNSM2I)

• DTT Name: Endopeptidase S1P (MBTPS1)
• Synonyms: Subtilisin/kexin-isozyme-1; Subtilisin/kexin-isozyme 1; Site-1 protease; SKI1; SKI-1; S1P; Membrane-bound transcription factor site-1 protease; KIAA0091
• Gene Name: MBTPS1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Peptidase
• UniProt ID: MBTP1_HUMAN
• TTD ID: T67231
• EC Number: EC 3.4.21.112
• Sequence:
  MKLVNIWLLLLVVLLCGKKHLGDRLEKKSFEKAPCPGCSHLTLKVEFSSTVVEYEYIVAF
  NGYFTAKARNSFISSALKSSEVDNWRIIPRNNPSSDYPSDFEVIQIKEKQKAGLLTLEDH
  PNIKRVTPQRKVFRSLKYAESDPTVPCNETRWSQKWQSSRPLRRASLSLGSGFWHATGRH
  SSRRLLRAIPRQVAQTLQADVLWQMGYTGANVRVAVFDTGLSEKHPHFKNVKERTNWTNE
  RTLDDGLGHGTFVAGVIASMRECQGFAPDAELHIFRVFTNNQVSYTSWFLDAFNYAILKK
  IDVLNLSIGGPDFMDHPFVDKVWELTANNVIMVSAIGNDGPLYGTLNNPADQMDVIGVGG
  IDFEDNIARFSSRGMTTWELPGGYGRMKPDIVTYGAGVRGSGVKGGCRALSGTSVASPVV
  AGAVTLLVSTVQKRELVNPASMKQALIASARRLPGVNMFEQGHGKLDLLRAYQILNSYKP
  QASLSPSYIDLTECPYMWPYCSQPIYYGGMPTVVNVTILNGMGVTGRIVDKPDWQPYLPQ
  NGDNIEVAFSYSSVLWPWSGYLAISISVTKKAASWEGIAQGHVMITVASPAETESKNGAE
  QTSTVKLPIKVKIIPTPPRSKRVLWDQYHNLRYPPGYFPRDNLRMKNDPLDWNGDHIHTN
  FRDMYQHLRSMGYFVEVLGAPFTCFDASQYGTLLMVDSEEEYFPEEIAKLRRDVDNGLSL
  VIFSDWYNTSVMRKVKFYDENTRQWWMPDTGGANIPALNELLSVWNMGFSDGLYEGEFTL
  ANHDMYYASGCSIAKFPEDGVVITQTFKDQGLEVLKQETAVVENVPILGLYQIPAEGGGR
  IVLYGDSNCLDDSHRQKDCFWLLDALLQYTSYGVTPPSLSHSGNRQRPPSGAGSVTPERM
  EGNHLHRYSKVLEAHLGDPKPRPLPACPRLSWAKPQPLNETAPSNLWKHQKLLSIDLDKV
  VLPNFRSNRPQVRPLSPGESGAWDIPGGIMPGRYNQEVGQTIPVFAFLGAMVVLAFFVVQ
  INKAKSRPKRRKPRVKRPQLMQQVHPPKTPSV
• Function: Other known substrates are BDNF, GNPTAB and ATF6. Cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4. Cleaves known substrates after Arg-Ser-Val-Leu (SERBP-2), Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide after Arg-Arg-Leu-Leu. Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes. Serine protease that catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs).
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway:
  ATF6 (ATF6-alpha) activates chaperones (R-HSA-381033)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  CREB3 factors activate genes (R-HSA-8874211)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Assembly of active LPL and LIPC lipase complexes (R-HSA-8963889)
  Regulation of cholesterol biosynthesis by SREBP (SREBF) (R-HSA-1655829)

Molecular Interaction Atlas (MIA) of This DTT

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-429242	DMB0OZ3	Discovery agent	N.A.	Investigative	[1]

References

• [1] Aminopyrrolidineamide inhibitors of site-1 protease. Bioorg Med Chem Lett. 2007 Aug 15;17(16):4411-4.