MBTPS1
Description
The MBTPS1 (membrane bound transcription factor peptidase, site 1) is a protein-coding gene located on chromosome 16.
MBTPS1, also known as Site-1 Protease (S1P) or Subtilisin/kexin-isozyme 1 (SKI-1), is an enzyme encoded by the MBTPS1 gene in humans. It belongs to the subtilisin-like proprotein convertase family, which processes protein and peptide precursors in the secretory pathway. S1P cleaves the endoplasmic reticulum loop of sterol regulatory element-binding protein (SREBP) transcription factors. It undergoes autocatalytic processing in the endoplasmic reticulum (ER) to form a heterodimer, which then exits the ER and sorts to the cis/medial-Golgi where it acquires catalytic activity. MBTPS1 is a type 1 membrane-bound protease expressed ubiquitously and regulates cholesterol and lipid homeostasis by cleaving substrates at non-basic residues. Mutations in the MBTPS1 gene can be associated with lysosomal dysfunction.
MBTPS1, also known as Site-1 Protease (S1P), is a serine protease that cleaves after hydrophobic or small residues, requiring an Arg or Lys at the P4 position. It acts on various substrates, including SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6, ATF6B, and FAM20C. Specifically, it cleaves after Arg-Ser-Val-Leu (SREBP2), Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF), and its own propeptide after Arg-Arg-Leu-Leu. Its role encompasses the initial step in activating sterol regulatory element-binding proteins (SREBPs) like SREBF1/SREBP1 and SREBF2/SREBP2, as well as the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B). MBTPS1 also mediates the cleavage of GNPTAB into subunits alpha and beta, crucial for lysosome biogenesis. It cleaves the FAM20C propeptide, enabling its secretion from the Golgi apparatus membrane and boosting its kinase activity, thereby promoting osteoblast differentiation and biomineralization. MBTPS1 is involved in regulating M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes and activates CREB3L2/BBF2H7, a transcriptional activator of MIA3/TANGO and other genes controlling mega vesicle formation. This function contributes to the regulation of mega vesicle-mediated collagen trafficking. In astrocytes and osteoblasts, it mediates the initial step in activating the transcription factor CREB3L1 upon DNA damage and ER stress, leading to cell cycle inhibition.
MBTPS1 is also known as PCSK8, S1P, SEDKF, SKI-1.
