| IED ID | IndEnz0002012742 |
| Enzyme Type ID | protease012742 |
| 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 | Homo sapiens (Human) |
| 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 Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MIPVSLVVVVVGGWTVVYLTDLVLKSSVYFKHSYEDWLENNGLSISPFHIRWQTAVFNRAFYSWGRRKARMLYQWFNFGMVFGVIAMFSSFFLLGKTLMQTLAQMMADSPSSYSSSSSSSSSSSSSSSSSSSSSSSLHNEQVLQVVVPGINLPVNQLTYFFTAVLISGVVHEIGHGIAAIREQVRFNGFGIFLFIIYPGAFVDLFTTHLQLISPVQQLRIFCAGIWHNFVLALLGILALVLLPVILLPFYYTGVGVLITEVAEDSPAIGPRGLFVGDLVTHLQDCPVTNVQDWNECLDTIAYEPQIGYCISASTLQQLSFPVRAYKRLDGSTECCNNHSLTDVCFSYRNNFNKRLHTCLPARKAVEATQVCRTNKDCKKSSSSSFCIIPSLETHTRLIKVKHPPQIDMLYVGHPLHLHYTVSITSFIPRFNFLSIDLPVVVETFVKYLISLSGALAIVNAVPCFALDGQWILNSFLDATLTSVIGDNDVKDLIGFFILLGGSVLLAANVTLGLWMVTAR |
| Enzyme Length | 519 |
| Uniprot Accession Number | O43462 |
| Absorption | |
| Active Site | ACT_SITE 172 |
| 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:0000269|PubMed:10805775, ECO:0000269|PubMed:11163209}; |
| 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 (PubMed:11163209, PubMed:10805775). 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 (PubMed:10805775, PubMed:27380894, PubMed:9659902). Mature N-terminal SREBP fragments shuttle to the nucleus and activate gene transcription (PubMed:10805775, PubMed:27380894, PubMed:9659902). Also mediates the second step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B) (PubMed:11163209). Involved in intramembrane proteolysis during bone formation (PubMed:27380894). {ECO:0000269|PubMed:10805775, ECO:0000269|PubMed:11163209, ECO:0000269|PubMed:27380894, ECO:0000269|PubMed:9659902}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (1); Glycosylation (1); Metal binding (2); Mutagenesis (5); Natural variant (9); Region (1); Topological domain (6); Transmembrane (10) |
| Keywords | Cholesterol metabolism;Cytoplasm;Disease variant;Glycoprotein;Hydrolase;Ichthyosis;Lipid metabolism;Membrane;Metal-binding;Metalloprotease;Osteogenesis imperfecta;Palmoplantar keratoderma;Protease;Reference proteome;Steroid metabolism;Sterol metabolism;Transmembrane;Transmembrane helix;Zinc |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Membrane {ECO:0000305|PubMed:19361614}; Multi-pass membrane protein {ECO:0000305|PubMed:19361614}. Cytoplasm {ECO:0000269|PubMed:19361614}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10564271; 11850408; 12138176; 15299016; 15665855; 15938716; 16236796; 16417584; 16469704; 16940180; 17178827; 17712038; 17875199; 18660489; 18704925; 19689518; 20546900; 20854407; 21315478; 21426410; 21719679; 21767813; 22262056; 22705851; 22816986; 23256041; 23316014; 23571157; 24126059; 25625847; 26810754; 28717930; 29951998; 30294811; 30589367; 33743732; 8156598; 8674110; |
| Motif | |
| Gene Encoded By | |
| Mass | 57,444 |
| Kinetics | |
| Metal Binding | METAL 171; /note=Zinc; catalytic; METAL 175; /note=Zinc; catalytic |
| Rhea ID | |
| Cross Reference Brenda | 3.4.24.85; |