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membrane-bound transcription factor site-1 protease (S1P endopeptidase, site-1 protease, subtilisin/kexin-isozyme 1, SKI-1, MBTPS1, KIAA0091, S1P, SKI1)
Function:
1) catalyzes 1st step in the proteolytic activation of sterol regulatory element-binding proteins (SREBP)
2) other substrates include BDNF & ATF6
3) cleaves after hydrophobic or small residues, provided Arg or Lys in position P4
4) 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
5) processes precursors containing basic residues at P4 & hydrophobic/aliphatic residues at P2
6) 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
7) inhibited by Cu+2, Zn+2, but not Ni+2 or Co+2
8) 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
General
glycoprotein
membrane protein
protease; proteinase; endopeptidase
Properties
SIZE: MW = 118 kD
entity length = 1052 aa
COMPARTMENT: lysosome
golgi
endoplasmic reticulum
endosome
MOTIF: signal sequence {1-17}
proteolytic site {186-187}
Serine protease {218-414}
MOTIF: aspartate residue {D218}
N-glycosylation site {N236}
histidine residue {H249}
N-glycosylation site {N305}
serine residue {S414}
N-glycosylation site {N515}
N-glycosylation site {N728}
N-glycosylation site {N939}
transmembrane domain {999-1021}
proline-rich region
SITE: 1023-1050
MOTIF: proline residue (SEVERAL)
Database Correlations
OMIM 603355
UniProt Q14703
Pfam PF00082
ENZYME 3.4.21.112
References
UniProt :accession Q14703