| IED ID | IndEnz0002008749 |
| Enzyme Type ID | protease008749 |
| Protein Name |
Serine-repeat antigen protein 5 EC 3.4.22.- 111 kDa antigen Serine protease SERA5 p126 Cleaved into: p47 SER36 ; p56; p50; p18; p25n; p25c |
| Gene Name | SERA5 PFB0340c |
| Organism | Plasmodium falciparum (isolate 3D7) |
| Taxonomic Lineage | cellular organisms Eukaryota Sar Alveolata Apicomplexa Aconoidasida Haemosporida (haemosporidians) Plasmodiidae Plasmodium Plasmodium (Laverania) Plasmodium falciparum Plasmodium falciparum (isolate 3D7) |
| Enzyme Sequence | MKSYISLFFILCVIFNKNVIKCTGESQTGNTGGGQAGNTGGDQAGSTGGSPQGSTGASPQGSTGASPQGSTGASQPGSSEPSNPVSSGHSVSTVSVSQTSTSSEKQDTIQVKSALLKDYMGLKVTGPCNENFIMFLVPHIYIDVDTEDTNIELRTTLKKTNNAISFESNSGSLEKKKYVKLPSNGTTGEQGSSTGTVRGDTEPISDSSSSSSSSSSSSSSSSSSSSSSSSSSSESLPANGPDSPTVKPPRNLQNICETGKNFKLVVYIKENTLILKWKVYGETKDTTENNKVDVRKYLINEKETPFTNILIHAYKEHNGTNLIESKNYAIGSDIPEKCDTLASNCFLSGNFNIEKCFQCALLVEKENKNDVCYKYLSEDIVSKFKEIKAETEDDDEDDYTEYKLTESIDNILVKMFKTNENNDKSELIKLEEVDDSLKLELMNYCSLLKDVDTTGTLDNYGMGNEMDIFNNLKRLLIYHSEENINTLKNKFRNAAVCLKNVDDWIVNKRGLVLPELNYDLEYFNEHLYNDKNSPEDKDNKGKGVVHVDTTLEKEDTLSYDNSDNMFCNKEYCNRLKDENNCISNLQVEDQGNCDTSWIFASKYHLETIRCMKGYEPTKISALYVANCYKGEHKDRCDEGSSPMEFLQIIEDYGFLPAESNYPYNYVKVGEQCPKVEDHWMNLWDNGKILHNKNEPNSLDGKGYTAYESERFHDNMDAFVKIIKTEVMNKGSVIAYIKAENVMGYEFSGKKVQNLCGDDTADHAVNIVGYGNYVNSEGEKKSYWIVRNSWGPYWGDEGYFKVDMYGPTHCHFNFIHSVVIFNVDLPMNNKTTKKESKIYDYYLKASPEFYHNLYFKNFNVGKKNLFSEKEDNENNKKLGNNYIIFGQDTAGSGQSGKESNTALESAGTSNEVSERVHVYHILKHIKDGKIRMGMRKYIDTQDVNKKHSCTRSYAFNPENYEKCVNLCNVNWKTCEEKTSPGLCLSKLDTNNECYFCYV |
| Enzyme Length | 997 |
| Uniprot Accession Number | Q9TY95 |
| Absorption | |
| Active Site | ACT_SITE 762; /evidence=ECO:0000255|PROSITE-ProRule:PRU10089; ACT_SITE 787; /evidence=ECO:0000255|PROSITE-ProRule:PRU10090 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.22.- |
| Enzyme Function | FUNCTION: Plays an essential role during the asexual blood stage development by controlling the kinetics of merozoite egress from host erythrocytes (PubMed:25599609, PubMed:28683142). Specifically, prevents premature rupture of the parasitophorous vacuole and host erythrocyte membranes (PubMed:28683142). {ECO:0000269|PubMed:25599609, ECO:0000269|PubMed:28683142}.; FUNCTION: [p47]: May prevent merozoite phagocytosis by host monocytes via interaction with host VTN at the merozoite surface (By similarity). Plays a role in parasite growth (By similarity). {ECO:0000250|UniProtKB:P69193}.; FUNCTION: [p50]: Protease activity is controversial (PubMed:25599609). Has been shown in a number of studies to have protease activity towards a synthetic peptide in vitro (PubMed:13679369, PubMed:24769454, PubMed:29716996). Has also been shown to lack protease activity towards a synthetic peptide in vitro (PubMed:25599609). {ECO:0000269|PubMed:13679369, ECO:0000269|PubMed:24769454, ECO:0000269|PubMed:25599609, ECO:0000269|PubMed:29716996}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Beta strand (12); Chain (7); Compositional bias (1); Disulfide bond (6); Glycosylation (3); Helix (10); Modified residue (3); Mutagenesis (4); Propeptide (1); Region (5); Signal peptide (1); Site (5); Turn (2) |
| Keywords | 3D-structure;Cell membrane;Direct protein sequencing;Disulfide bond;Glycoprotein;Hydrolase;Malaria;Membrane;Phosphoprotein;Protease;Reference proteome;Secreted;Serine protease;Signal;Zymogen |
| Interact With | Q8I0V0 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Serine-repeat antigen protein 5]: Parasitophorous vacuole {ECO:0000269|PubMed:25599609, ECO:0000269|PubMed:28683142, ECO:0000269|PubMed:29716996, ECO:0000305|PubMed:18083098}. Note=Secreted in large amount into the parasitophorous vacuole. {ECO:0000305|PubMed:18083098}.; SUBCELLULAR LOCATION: [p18]: Secreted {ECO:0000250|UniProtKB:P69193}. Note=Secreted during merozoite egress from erythrocytes. {ECO:0000250|UniProtKB:P69193}.; SUBCELLULAR LOCATION: [p25n]: Secreted. Note=Secreted during merozoite egress from erythrocytes. {ECO:0000250|UniProtKB:P69193}.; SUBCELLULAR LOCATION: [p25c]: Secreted {ECO:0000250|UniProtKB:P69193}. Note=Secreted during merozoite egress from erythrocytes. {ECO:0000250|UniProtKB:P69193}.; SUBCELLULAR LOCATION: [p47]: Secreted {ECO:0000250|UniProtKB:P69193}. Cell membrane {ECO:0000269|PubMed:29567995}; Peripheral membrane protein {ECO:0000269|PubMed:29567995}; Extracellular side {ECO:0000250|UniProtKB:P69193}. Note=Secreted during merozoite egress from erythrocytes (By similarity). Colocalizes at the merozoite surface with human VTN (PubMed:29567995). {ECO:0000250|UniProtKB:P69193, ECO:0000269|PubMed:29567995}.; SUBCELLULAR LOCATION: [p50]: Secreted {ECO:0000269|PubMed:18083098, ECO:0000269|PubMed:25599609}. Note=Secreted during egress from host erythrocytes. {ECO:0000269|PubMed:25599609}.; SUBCELLULAR LOCATION: [p56]: Secreted {ECO:0000269|PubMed:18083098}. Note=Secreted during egress from host erythrocytes. {ECO:0000269|PubMed:25599609}. |
| Modified Residue | MOD_RES 183; /note=Phosphoserine; /evidence=ECO:0000269|PubMed:29716996; MOD_RES 549; /note=Phosphothreonine; by CPK1; /evidence=ECO:0000269|PubMed:29716996; MOD_RES 866; /note=Phosphoserine; /evidence=ECO:0000269|PubMed:29716996 |
| Post Translational Modification | PTM: [p50]: Phosphorylation by CPK1/CDPK1 increases SERA5 protease activity towards a synthetic peptide in vitro. {ECO:0000269|PubMed:29716996}.; PTM: Just prior to merozoite egress from host erythrocytes, proteolytically cleaved into multiple fragments (PubMed:18083098, PubMed:25599609, PubMed:24769454). Cleaved by SUB1 into p47 and p73, p73 is further cleaved by SUB1 into p56 and p18 and p56 is further processed into p50 by an unidentified protease (PubMed:25599609, PubMed:18083098). p47 remains covalently associated with p18 via disulfide bond (PubMed:25599609). p47 can be processed into p25n and p25c by SUB1 (PubMed:25599609, PubMed:18083098). p25c and p25n remain associated with p18 (PubMed:25599609). Proteolytic processing is essential for merozoite egress from host erythrocytes (PubMed:28683142). The cleavage of the propeptide to produce p50 is necessary for protease activity and to promote merozoite egress (PubMed:24769454). {ECO:0000269|PubMed:18083098, ECO:0000269|PubMed:24769454, ECO:0000269|PubMed:25599609, ECO:0000269|PubMed:28683142}. |
| Signal Peptide | SIGNAL 1..22; /evidence=ECO:0000269|PubMed:18083098 |
| Structure 3D | X-ray crystallography (5) |
| Cross Reference PDB | 2WBF; 3CH2; 3CH3; 6X42; 6X44; |
| Mapped Pubmed ID | 16267556; 32955133; |
| Motif | |
| Gene Encoded By | |
| Mass | 111,768 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |