| IED ID | IndEnz0002015636 |
| Enzyme Type ID | protease015636 |
| Protein Name |
Membrane-bound transcription factor site-1 protease EC 3.4.21.112 Endopeptidase S1P Subtilisin/kexin isozyme 1 SKI-1 |
| Gene Name | Mbtps1 S1p Ski1 |
| Organism | Rattus norvegicus (Rat) |
| 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 Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MKLVNIWLLLLVVLLCGKKHLGDRLGKKAFEKAPCPSCSHLTLKVEFSSTVVEYEYIVAFNGYFTAKARNSFISSALKSSEVDNWRIIPRNNPSSDYPSDFEVIQIKEKQKAGLLTLEDHPNIKRVTPQRKVFRSLKFAESDPIVPCNETRWSQKWQSSRPLKRASLSLGSGFWHATGRHSSRRLLRAIPRQVAQTLQADVLWQMGYTGANVRVAVFDTGLSEKHPHFKNVKERTNWTNERTLDDGLGHGTFVAGVIASMRECQGFAPDAELHIFRVFTNNQVSYTSWFLDAFNYAILKKIDVLNLSIGGPDFMDHPFVDKVWELTANNVIMVSAIGNDGPLYGTLNNPADQMDVIGVGGIDFEDNIARFSSRGMTTWELPGGYGRVKPDIVTYGAGVRGSGVKGGCRALSGTSVASPVVAGAVTLLVSTVQKRELVNPASVKQALIASARRLPGVNMFEQGHGKLDLLRAYQILSSYKPQASLSPSYIDLTECPYMWPYCSQPIYYGGMPTIVNVTILNGMGVTGRIVDKPEWRPYLPQNGDNIEVAFSYSSVLWPWSGYLAISISVTKKAASWEGIAQGHIMITVASPAETELKNGAEHTSTVKLPIKVKIIPTPPRSKRVLWDQYHNLRYPPGYFPRDNLRMKNDPLDWNGDHVHTNFRDMYQHLRSMGYFVEVLGAPFTCFDATQYGTLLMVDSEEEYFPEEIAKLRRDVDNGLSLVVFSDWYNTSVMRKVKFYDENTRQWWMPDTGGANVPALNELLSVWNMGFSDGLYEGEFALANHDMYYASGCSIARFPEDGVVITQTFKDQGLEVLKQETAVVDNVPILGLYQIPAEGGGRIVLYGDSNCLDDSHRQKDCFWLLDALLQYTSYGVTPPSLSHSGNRQRPPSGAGLAPPERMEGNHLHRYSKVLEAHLGDPKPRPLPACPHLSWAKPQPLNETAPSNLWKHQKLLSIDLDKVVLPNFRSNRPQVRPLSPGESGAWDIPGGIMPGRYNQEVGQTIPVFAFLGAMVALAFFVVQISKAKSRPKRRRPRAKRPQLAQQAHPARTPSV |
| Enzyme Length | 1052 |
| Uniprot Accession Number | Q9WTZ3 |
| Absorption | |
| Active Site | ACT_SITE 218; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU01240; ACT_SITE 249; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU01240; ACT_SITE 414; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU01240 |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by divalent copper and zinc ions, but not by nickel or cobalt. Inhibited by its prosegment, but not smaller fragments thereof. Inhibited by 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor. {ECO:0000250|UniProtKB:Q14703}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Processes precursors containing basic and hydrophobic/aliphatic residues at P4 and P2, respectively, with a relatively relaxed acceptance of amino acids at P1 and P3.; EC=3.4.21.112; Evidence={ECO:0000269|PubMed:9990022}; |
| DNA Binding | |
| EC Number | 3.4.21.112 |
| Enzyme Function | FUNCTION: Serine protease that cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4: known substrates are SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6 and ATF6B. Cleaves substrates after Arg-Ser-Val-Leu (SREBP2), Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide after Arg-Arg-Leu-Leu. Catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2. Also mediates the first step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B). Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes. Involved in the regulation of M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes. It is required for the activation of CREB3L2/BBF2H7, a transcriptional activator of MIA3/TANGO and other genes controlling mega vesicle formation. Therefore, it plays a key role in the regulation of mega vesicle-mediated collagen trafficking. {ECO:0000250|UniProtKB:Q14703}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Chain (1); Domain (1); Glycosylation (6); Modified residue (1); Propeptide (1); Region (2); Sequence conflict (1); Signal peptide (1); Site (1); Topological domain (2); Transmembrane (1) |
| Keywords | Autocatalytic cleavage;Calcium;Cholesterol metabolism;Endoplasmic reticulum;Glycoprotein;Golgi apparatus;Hydrolase;Lipid metabolism;Membrane;Phosphoprotein;Protease;Reference proteome;Serine protease;Signal;Steroid metabolism;Sterol metabolism;Transmembrane;Transmembrane helix;Zymogen |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q14703}; Single-pass type I membrane protein {ECO:0000255}. Golgi apparatus membrane {ECO:0000269|PubMed:9990022}; Single-pass type I membrane protein {ECO:0000255}. Note=May sort to other organelles, including lysosomal and/or endosomal compartments. {ECO:0000250|UniProtKB:Q14703}. |
| Modified Residue | MOD_RES 168; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q14703 |
| Post Translational Modification | PTM: The 148 kDa zymogen is processed progressively into two membrane-bound 120 and 106 kDa forms in the endoplasmic reticulum, and late into a secreted 98 kDa form. The propeptide is autocatalytically removed through an intramolecular cleavage after Leu-186. Further cleavage generates 14, 10, and 8 kDa intermediates. {ECO:0000250|UniProtKB:Q14703}. |
| Signal Peptide | SIGNAL 1..17; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 18323777; |
| Motif | |
| Gene Encoded By | |
| Mass | 117,462 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.21.112; |