membrane-bound transcription factor site-1 protease (S1P endopeptidase, site-1 protease, subtilisin/kexin-isozyme 1, SKI-1, MBTPS1, KIAA0091, S1P, SKI1)

Function

• catalyzes 1st step in the proteolytic activation of sterol regulatory element-binding proteins (SREBP)
• other substrates include BDNF & ATF6
• cleaves after hydrophobic or small residues, provided Arg or Lys in position P4
• cleaves known substrates after Arg-Ser-Val-Leu (SERBP-2), Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) & its own propeptide after Arg-Arg-Leu-Leu
• processes precursors containing basic residues at P4 & hydrophobic/aliphatic residues at P2
• 148 kD zymogen is processed progressively into 2 membrane- bound 120 & 106 kD forms in the endoplasmic reticulum, & late into a secreted 98 kD form
  • propeptide is autocatalytically removed through an i intramolecular cleavage after Leu-186
• inhibited by Cu+2, Zn+2, but not Ni+2 or Co+2
• inhibited by its prosegment, but not by smaller fragments

Cofactor: Ca+2

Compartment

• endoplasmic reticulum membrane, Golgi membrane
• may sort to other organelles, including lysosomal &/or endosomal compartment

Expression

• widely expressed
• down-regulated by sterols

More general terms

• protease; proteinase; endopeptidase
• glycoprotein
• membrane protein

Database

• OMIM: https://mirror.omim.org/entry/603355
• UniProt: http://www.uniprot.org/uniprot/Q14703.html