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

General

glycoprotein metalloprotease transmembrane 10 protein

Properties

SIZE: entity length = 519 aa MW = 57 kD COMPARTMENT: cytoplasm MOTIF: cytoplasmic domain {1-3} transmembrane domain {4-24} exoplasmic loop {25-74} transmembrane domain {75-95} transmembrane domain {96-107} MOTIF: cytoplasmic loop {96-95} exoplasmic loop {108-144} MOTIF: serine-rich region {109-136} MOTIF: serine residue (SEVERAL) transmembrane domain {145-169} cytoplasmic loop {170-173} MOTIF: Zn+2-binding site SITE: 171-171 glutamate residue {E172} transmembrane domain {174-186} MOTIF: Zn+2-binding site SITE: 175-175 transmembrane domain {187-209} MOTIF: exoplasmic loop {187-186} cytoplasmic loop {210-228} transmembrane domain {229-251} exoplasmic loop {252-446} MOTIF: cysteine-rich region {285-386} N-glycosylation site {N337} serine-rich region {380-384} MOTIF: serine residue (SEVERAL) transmembrane domain {447-464} transmembrane domain {465-476} MOTIF: cytoplasmic loop {465-464} exoplasmic loop {477-492} transmembrane domain {493-513} cytoplasmic domain {514-519}

Database Correlations

OMIM correlations UniProt O43462 Pfam PF02163 Entrez Gene 51360 Kegg hsa:51360 ENZYME 3.4.24.85

References

UniProt :accession O43462