| IED ID | IndEnz0002009514 |
| Enzyme Type ID | protease009514 |
| Protein Name |
Subtilisin-like protease 1 EC 3.4.21.62 PfSUB-1 |
| Gene Name | SUB1 |
| Organism | Plasmodium falciparum |
| Taxonomic Lineage | cellular organisms Eukaryota Sar Alveolata Apicomplexa Aconoidasida Haemosporida (haemosporidians) Plasmodiidae Plasmodium Plasmodium (Laverania) Plasmodium falciparum |
| Enzyme Sequence | MMLNKKVVALCTLTLHLFCIFLCLGKEVRSEENGKIQDDAKKIVSELRFLEKVEDVIEKSNIGGNEVDADENSFNPDTEVPIEEIEEIKMRELKDVKEEKNKNDNHNNNNNNNNISSSSSSSSNTFGEEKEEVSKKKKKLRLIVSENHATTPSFFQESLLEPDVLSFLESKGNLSNLKNINSMIIELKEDTTDDELISYIKILEEKGALIESDKLVSADNIDISGIKDAIRRGEENIDVNDYKSMLEVENDAEDYDKMFGMFNESHAATSKRKRHSTNERGYDTFSSPSYKTYSKSDYLYDDDNNNNNYYYSHSSNGHNSSSRNSSSSRSRPGKYHFNDEFRNLQWGLDLSRLDETQELINEHQVMSTRICVIDSGIDYNHPDLKDNIELNLKELHGRKGFDDDNNGIVDDIYGANFVNNSGNPMDDNYHGTHVSGIISAIGNNNIGVVGVDVNSKLIICKALDEHKLGRLGDMFKCLDYCISRNAHMINGSFSFDEYSGIFNSSVEYLQRKGILFFVSASNCSHPKSSTPDIRKCDLSINAKYPPILSTVYDNVISVANLKKNDNNNHYSLSINSFYSNKYCQLAAPGTNIYSTAPHNSYRKLNGTSMAAPHVAAIASLIFSINPDLSYKKVIQILKDSIVYLPSLKNMVAWAGYADINKAVNLAIKSKKTYINSNISNKWKKKSRYLH |
| Enzyme Length | 690 |
| Uniprot Accession Number | O61142 |
| Absorption | |
| Active Site | ACT_SITE 374; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU01240; ACT_SITE 430; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU01240; ACT_SITE 608; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU01240 |
| Activity Regulation | ACTIVITY REGULATION: p54 and probably p47 forms are inhibited by the non-covalent interaction with the cleaved propeptide (PubMed:12764150). Inhibited by subtilisin propeptide-like protein SUB1-ProM (By similarity). {ECO:0000250|UniProtKB:Q8I0V0, ECO:0000269|PubMed:12764150}. |
| 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:10617661, ECO:0000269|PubMed:12764150, ECO:0000269|PubMed:24785947}; |
| DNA Binding | |
| EC Number | 3.4.21.62 |
| Enzyme Function | FUNCTION: Serine protease which plays an essential role in merozoite invasion of and egress from host erythrocytes by processing and activating various merozoite surface and parasitophorous vacuole proteins. Mediates the proteolytic maturation of serine proteases SERA4, SERA5 and SERA6 just prior to merozoite egress. Prior to merozoite egress, cleaves merozoite surface proteins MSP1, MSP6 and MSP7, which form the MSP1/6/7 complex, and thereby may prime the parasite cell surface for invasion of fresh erythrocytes. Prior to merozoite egress, cleaves MSRP2 converting it to MSRP2 p25 form, and RAP1 converting it to RAP1 p67 form. {ECO:0000250|UniProtKB:Q8I0V0}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Beta strand (25); Chain (1); Compositional bias (2); Disulfide bond (3); Domain (1); Glycosylation (11); Helix (18); Metal binding (17); Mutagenesis (4); Propeptide (1); Region (3); Sequence conflict (2); Signal peptide (1); Site (3); Turn (7) |
| Keywords | 3D-structure;Calcium;Disulfide bond;Glycoprotein;Hydrolase;Metal-binding;Protease;Secreted;Serine protease;Signal;Zymogen |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9722575}. Parasitophorous vacuole lumen {ECO:0000250|UniProtKB:Q8I0V0}. Note=At the schizont stage, in merozoites, localizes to dense secretory granules called exonemes (PubMed:9722575). Just prior to egress secreted into the parasitophorous vacuole (By similarity). {ECO:0000250|UniProtKB:Q8I0V0, ECO:0000269|PubMed:9722575}. |
| Modified Residue | |
| Post Translational Modification | PTM: The propeptide (p31) is cleaved, probably by autocatalysis, during the transport to or in the Golgi apparatus, and remains non-covalently associated with the p54 form as an inhibitor (PubMed:9722575, PubMed:10617661, PubMed:12764150). p54 is further cleaved into the p45 form (PubMed:9722575, PubMed:10617661). This cleavage is likely occurring in the exoneme prior to egress and is mediated by PMX/plasmepsin X (By similarity). {ECO:0000250|UniProtKB:W7K9M0, ECO:0000269|PubMed:10617661, ECO:0000269|PubMed:12764150, ECO:0000269|PubMed:9722575}.; PTM: The disulfide bond between Cys-523 and Cys-536 acts as a redox-sensitive disulfide switch (PubMed:24785947). The oxidized form is required for catalytic activity (PubMed:24785947). {ECO:0000269|PubMed:24785947}.; PTM: The relevance of N-glycosylation is not clear. In an insect expression system, SUB1 glycosylation appears to affect its processing into the active mature form suggesting that SUB1 may not be N-glycosylated in parasites. {ECO:0000269|PubMed:10617661}. |
| Signal Peptide | SIGNAL 1..25; /evidence=ECO:0000305|PubMed:10617661 |
| Structure 3D | X-ray crystallography (2) |
| Cross Reference PDB | 4LVN; 4LVO; |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 77,875 |
| Kinetics | |
| Metal Binding | METAL 340; /note="Calcium 1"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 383; /note="Calcium 1"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 394; /note="Calcium 2"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 394; /note="Calcium 3"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 398; /note="Calcium 2; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 401; /note="Calcium 2; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 402; /note="Calcium 3"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 403; /note="Calcium 2"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 404; /note="Calcium 3"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 406; /note="Calcium 3"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 408; /note="Calcium 3; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 410; /note="Calcium 2"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 411; /note="Calcium 3"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 441; /note="Calcium 1; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 444; /note="Calcium 1"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 446; /note="Calcium 1; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO"; METAL 448; /note="Calcium 1; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:24785947, ECO:0007744|PDB:4LVN, ECO:0007744|PDB:4LVO" |
| Rhea ID | |
| Cross Reference Brenda |