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EC 3.4.24.85 Details
show Brenda entryEC number
3.4.24.85
Accepted name
S2P endopeptidase
Reaction
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 DRSRILL483┼CVLTFLCLSFNPLTSLLQWGGA, in which the membrane-spanning segment is underlined. The residues NP (bold), 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.
CAS registry number
752251-31-3
Comment
Type example of peptidase family M50. 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.
History
created 2003
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1 Oxidoreductases
3 Hydrolases
3.4.24.2 created 1972, deleted 1992 3.4.24.4 created 1972 [EC 3.4.99.13 and EC 3.4.99.22 both created 1972, incorporated 1978], deleted 1992 3.4.24.5 created 1978, deleted 1989 3.4.24.8 created 1978, deleted 1992 3.4.24.9 created 1978, deleted 1992
