membrane-bound transcription factor site-2 protease; endopeptidase S2P; sterol regulatory element-binding proteins intramembrane protease; SREBPs intramembrane protease (MBTPS2, S2P)

Function

• intramembrane proteolysis of sterol-regulatory element-binding proteins (SREBPs) within the first transmembrane segment thus releasing the N-terminal segment with a portion of the transmembrane domain attached
• site-2 cleavage comes after site-1 cleavage which takes place in the lumenal loop
• cleaves several type-2 transmembrane proteins that function as transcription factors within membrane-spanning domains
• known substrates include:
  • sterol regulatory element-binding proteins SREBP1 & SREBP2
  • forms of the transcriptional activator ATF6
• SREBP2 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 MBTPS2
• replacement of either of these residues does not prevent cleavage, but there is no cleavage if both of these residues are replaced

Cofactor: binds 1 Zn+2 per subunit

Structure

belongs to the peptidase M50A family

Compartment

• membrane (probable), cytoplasm

Expression

• expressed in heart, brain, placenta, lung, liver, muscle, kidney & pancreas

Pathology

• defects in MBTPS2 are the cause of: ichthyosis follicularis-atrichia-photophobia syndrome
• defects in MBTPS2 are a cause of keratosis follicularis spinulosa decalvans, X-linked

More general terms

• metalloprotease
• transmembrane 10 protein
• glycoprotein

Additional terms

• prostate cancer

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=51360
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:51360
• OMIM: https://mirror.omim.org/entry/300294
• OMIM: https://mirror.omim.org/entry/308205
• OMIM: https://mirror.omim.org/entry/308800
• UniProt: http://www.uniprot.org/uniprot/O43462.html