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ENZYME entry: EC

Accepted Name
S2P endopeptidase
Alternative Name(s)
membrane-bound transcription factor site 2 protease
site-2 protease
sterol-regulatory element-binding proteins intramembrane protease
Reaction catalysed
Cleaves several transcription factors that are type-2 transmembrane proteins within membrane-spanning domains. Known substrates include sterol regulatory element-binding protein (SREBP) -1, SREBP-2 and forms of the transcriptional activator ATF6. SREBP-2 is cleaved at the site 477-DRSRILL-|-CVLTFLCLSFNPLTSLLQWGGA-505. The residues Asn-Pro, 11 residues distal to the site of cleavage in the membrane-spanning domain, are important for cleavage by S2P endopeptidase. Replacement of either of these residues does not prevent cleavage, but there is no cleavage if both of these residues are replaced
  • The transcription factors SREBP-1 and -2 are synthesized as precursor proteins that are attached to the membranes of the endoplasmic reticulum and two cleavages are needed to release the active factor so that it can move to the nucleus.
  • This enzyme cleaves the second of these, and is thus the 'site 2 protease', S2P.
  • Belongs to peptidase family M50.
PRIAM enzyme-specific profiles3.4.24.85
KEGG Ligand Database for Enzyme Nomenclature3.4.24.85
IUBMB Enzyme Nomenclature3.4.24.85
MEDLINEFind literature relating to
Rhea expert-curated reactions3.4.24.85

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