| IED ID | IndEnz0002018615 |
| Enzyme Type ID | protease018615 |
| Protein Name |
Alkaline extracellular protease AEP EC 3.4.21.62 |
| Gene Name | XPR2 YALI0F31889g |
| Organism | Yarrowia lipolytica (strain CLIB 122 / E 150) (Yeast) (Candida lipolytica) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Saccharomycotina (true yeasts) Saccharomycetes Saccharomycetales Dipodascaceae Yarrowia Yarrowia lipolytica (Candida lipolytica) Yarrowia lipolytica (strain CLIB 122 / E 150) (Yeast) (Candida lipolytica) |
| Enzyme Sequence | MKLATAFTILTAVLAAPLAAPAPAPDAAPAAVPEGPAAAAYSSILSVVAKQSKKFKHHKRDLDEKDQFIVVFDSSATVDQIASEIQKLDSLVDEDSSNGITSALDLPVYTDGSGFLGFVGKFNSTIVDKLKESSVLTVEPDTIVSLPEIPASSNAKRAIQTTPVTQWGLSRISHKKAQTGNYAYVRETVGKHPTVSYVVDSGIRTTHSEFGGRAVWGANFADTQNADLLGHGTHVAGTVGGKTYGVDANTKLVAVKVFAGRSAALSVINQGFTWALNDYISKRDTLPRGVLNFSGGGPKSASQDALWSRATQEGLLVAIAAGNDAVDACNDSPGNIGGSTSGIITVGSIDSSDKISVWSGGQGSNYGTCVDVFAPGSDIISASYQSDSGTLVYSGTSMACPHVAGLASYYLSINDEVLTPAQVEALITESNTGVLPTTNLKGSPNAVAYNGVGI |
| Enzyme Length | 454 |
| Uniprot Accession Number | P09230 |
| Absorption | |
| Active Site | ACT_SITE 200; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU01240; ACT_SITE 231; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU01240; ACT_SITE 397; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU01240 |
| Activity Regulation | ACTIVITY REGULATION: The protease activity is completely inhibited by the serine inhibitor PMSF but is not affected by thiol group inhibitors and in the presence of dithiothreitol (PubMed:6750031). In the presence of high concentrations of o-phenanthroline the protease activity is only partially inhibited (PubMed:6750031). The pro-region plays an inhibitory role and may provide a mechanism for preventing premature activation in the secretory pathway (PubMed:2649495). {ECO:0000269|PubMed:2649495, ECO:0000269|PubMed:6750031}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Hydrolysis of proteins with broad specificity for peptide bonds, and a preference for a large uncharged residue in P1. Hydrolyzes peptide amides.; EC=3.4.21.62; Evidence={ECO:0000269|PubMed:17432872, ECO:0000269|PubMed:2649495, ECO:0000269|PubMed:6750031, ECO:0000269|PubMed:7007321, ECO:0000269|PubMed:870075, ECO:0000269|PubMed:9353927}; |
| DNA Binding | |
| EC Number | 3.4.21.62 |
| Enzyme Function | FUNCTION: Major secreted protein that belongs to the subtilisin family serine proteases. {ECO:0000269|PubMed:17432872, ECO:0000269|PubMed:2649495, ECO:0000269|PubMed:6750031, ECO:0000269|PubMed:7007321, ECO:0000269|PubMed:870075, ECO:0000269|PubMed:9353927}. |
| Temperature Dependency | BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 40 degrees Celsius. {ECO:0000269|PubMed:6750031}; |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 9.0-10.0. {ECO:0000269|PubMed:17432872, ECO:0000269|PubMed:6750031}; |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Chain (1); Domain (2); Glycosylation (1); Mutagenesis (1); Propeptide (1); Signal peptide (1) |
| Keywords | Cleavage on pair of basic residues;Direct protein sequencing;Glycoprotein;Hydrolase;Protease;Reference proteome;Secreted;Serine protease;Signal;Zymogen |
| Interact With | |
| Induction | INDUCTION: Expression is subject to at least 3 different regulatory controls, carbon, sulfur and nitrogen repression (PubMed:870075). Intracellular cysteine and ammonia appear to be the metabolic signals for sulfur and nitrogen repression (PubMed:870075). Moreover, pH regulates expression independently from other metabolic signals, with highest levels of AEP mRNA at pH 6.5 (PubMed:8842151, PubMed:9308186). The transcriptional activator RIM101 and the Rim pathway are required for the alkaline induction of gene expression (PubMed:9199331, PubMed:11861549). Two major upstream activation sequences (UASs) are essential for promoter activity under conditions of repression or full induction. The distal UAS (UAS1) is located at position -790 to -778, whereas the proximal UAS (UAS2) localizes at positions -148 to -124 (PubMed:8264600, PubMed:10206713). {ECO:0000269|PubMed:10206713, ECO:0000269|PubMed:11861549, ECO:0000269|PubMed:8264600, ECO:0000269|PubMed:870075, ECO:0000269|PubMed:8842151, ECO:0000269|PubMed:9199331, ECO:0000269|PubMed:9308186}. |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1634541, ECO:0000269|PubMed:1995632, ECO:0000269|PubMed:22909173, ECO:0000269|PubMed:3211132, ECO:0000269|PubMed:6750031, ECO:0000269|PubMed:7954894, ECO:0000269|PubMed:8798620, ECO:0000269|PubMed:9353927}. Note=Proper secretion requires TSR1. {ECO:0000269|PubMed:8798620}. |
| Modified Residue | |
| Post Translational Modification | PTM: The pro-region is removed through cleavage by XPR6 after Lys156-Arg157, which yields mature active XPR2. {ECO:0000269|PubMed:1634541, ECO:0000269|PubMed:22909173, ECO:0000269|PubMed:3211132, ECO:0000269|PubMed:7954894, ECO:0000269|PubMed:8203153, ECO:0000269|PubMed:9353927}.; PTM: The 10 consecutive -X-Ala- or -X-Pro- dipeptides located over 100 amino acids upstream of the N-terminal of mature XPR2 are subject to dipeptidyl aminopeptidase (DPAPase)-processing (PubMed:9353927). DPAPase activity is not necessary for XPR6 cleavage and for secretion of mature active XPR2 (PubMed:9353927). {ECO:0000269|PubMed:1995632, ECO:0000269|PubMed:2649495, ECO:0000269|PubMed:8203153, ECO:0000269|PubMed:9353927}.; PTM: N-glycosylated. Glycosylation within the pro-region has no effect on secretion and maturation at 18 degrees Celsius, but is required for secretion at 28 degrees Celsius (PubMed:1995632). {ECO:0000269|PubMed:1995632, ECO:0000269|PubMed:3211132, ECO:0000269|PubMed:6750031}. |
| Signal Peptide | SIGNAL 1..15; /evidence=ECO:0000269|PubMed:9353927 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 46,906 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |