Detail Information for IndEnz0002004293
IED ID IndEnz0002004293
Enzyme Type ID protease004293
Protein Name Membrane-bound transcription factor site-2 protease
EC 3.4.24.85
Endopeptidase S2P
Sterol regulatory element-binding proteins intramembrane protease
SREBPs intramembrane protease
Gene Name MBTPS2 S2P
Organism Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Cricetidae Cricetinae (hamsters) Cricetulus Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Enzyme Sequence MIPVSLVVVVVGGWTAVYLADLVLKSSVYFKHSYEDWLEKNGLSISPFHIRWQTSVFNRAFYSWGRRKARMLYQWFNFGMVFGVIAMFSSFFLLGKTLMQTLAQMMADSPSSSSSSSSSSSSSSSSSIHNEQVLQVVVPGINLPVNQLTYFFAAVLISGVVHEIGHGIAAIREQVRFNGFGIFLFIIYPGAFVDLFTTHLQLISPVQQLRIFCAGIWHNFVLALLGILALVLLPVILLPFYYTGVGVLITEVAEDSPAIGPRGLFVGDLVTHLQDCPVTNVQDWNECLDTIAYEPQIGYCISASTLQQLSFPVRAYKRLDGSTECCNNHSLTDVCFSYRNNFNKRLHTCLPARKAVEATQVCRTNKDCKTSSSSSFCIVPSLETHTRLIKVKHPPQIDMLYVGHPLHLHYTVSITSFIPRFNFLSIDLPVIVETFVKYLISLSGALAIVNAVPCFALDGQWILNSFLDATLTSVIGDNDVKDLIGFFILLGGSVLLAANVTLGLWMVTAR
Enzyme Length 510
Uniprot Accession Number O54862
Absorption
Active Site ACT_SITE 163; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity CATALYTIC ACTIVITY: 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 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.; EC=3.4.24.85; Evidence={ECO:0000250|UniProtKB:O43462};
DNA Binding
EC Number 3.4.24.85
Enzyme Function FUNCTION: Zinc metalloprotease that mediates intramembrane proteolysis of proteins such as ATF6, ATF6B, SREBF1/SREBP1 and SREBF2/SREBP2. Catalyzes the second step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2: cleaves SREBPs within the first transmembrane segment, thereby releasing the N-terminal segment with a portion of the transmembrane segment attached. Mature N-terminal SREBP fragments shuttle to the nucleus and activate gene transcription. Also mediates the second step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B). Involved in intramembrane proteolysis during bone formation. {ECO:0000250|UniProtKB:O43462}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Active site (1); Chain (1); Glycosylation (1); Metal binding (2); Topological domain (6); Transmembrane (10)
Keywords Cholesterol metabolism;Cytoplasm;Glycoprotein;Hydrolase;Lipid metabolism;Membrane;Metal-binding;Metalloprotease;Protease;Steroid metabolism;Sterol metabolism;Transmembrane;Transmembrane helix;Zinc
Interact With
Induction
Subcellular Location SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:O43462}; Multi-pass membrane protein {ECO:0000250|UniProtKB:O43462}. Cytoplasm {ECO:0000250|UniProtKB:O43462}.
Modified Residue
Post Translational Modification
Signal Peptide
Structure 3D
Cross Reference PDB -
Mapped Pubmed ID -
Motif
Gene Encoded By
Mass 56,499
Kinetics
Metal Binding METAL 162; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095; METAL 166; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095
Rhea ID
Cross Reference Brenda 3.4.24.85;