UniProt functional annotation for Q9TY95



	UniProt functional annotation for Q9TY95

UniProt code: Q9TY95.

Organism: Plasmodium falciparum (isolate 3D7).

Taxonomy: Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida; Plasmodiidae; Plasmodium; Plasmodium (Laverania).

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}.

Subunit: May interact (via C-terminus) with PTKL (via SAM domain). {ECO:0000269|PubMed:31148576}.

Subunit: [p47]: Interacts (via C-terminus) with human VTN (via hemopexin repeat 2); may form heterotetramers of two VTN and SERA5 P47 heterodimers; the interaction may protect merozoites from phagocytosis by host monocytes; VTN glycosylation appears to be dispensable for the interaction. {ECO:0000250|UniProtKB:P69193}.

Subunit: [p50]: Monomer (PubMed:13679369, PubMed:25599609). Interacts with kinase CPK1/CDPK1 at the schizont stage (PubMed:29716996). {ECO:0000269|PubMed:13679369, ECO:0000269|PubMed:25599609, ECO:0000269|PubMed:29716996}.

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}.

Developmental stage: [Serine-repeat antigen protein 5]: Expressed during parasite asexual blood stages, specifically in late trophozoite and schizont stages (at protein level). {ECO:0000269|PubMed:18083098, ECO:0000269|PubMed:24769454, ECO:0000269|PubMed:25599609, ECO:0000269|PubMed:28683142, ECO:0000269|PubMed:29567995, ECO:0000269|PubMed:29716996}.

Developmental stage: [p50]: Produced during parasite asexual blood stages, specifically at the merozoite stage just prior to egress (at protein level). {ECO:0000269|PubMed:25599609, ECO:0000269|PubMed:29716996}.

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}.

Mass spectrometry: [p50]: Mass=52540.17; Method=Electrospray; Evidence={ECO:0000269|PubMed:25599609};

Disruption phenotype: Conditional knockout at the merozoite stage, does not cause any defect in schizont morphology, merozoite number and maturation initially. During the subsequent invasive cycle in host erythrocytes, merozoite replication is severely impaired due to a premature rupture of the parasitophorous vacuole and erythrocyte membranes resulting in an inefficient dispersal of released merozoites. {ECO:0000269|PubMed:28683142}.

Similarity: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE- ProRule:PRU10089, ECO:0000255|PROSITE-ProRule:PRU10090}.

Annotations taken from UniProtKB at the EBI.


Organism:		Plasmodium falciparum (isolate 3D7).
Taxonomy:		Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida; Plasmodiidae; Plasmodium; Plasmodium (Laverania).



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}.


Subunit:		May interact (via C-terminus) with PTKL (via SAM domain). {ECO:0000269\|PubMed:31148576}.
Subunit:		[p47]: Interacts (via C-terminus) with human VTN (via hemopexin repeat 2); may form heterotetramers of two VTN and SERA5 P47 heterodimers; the interaction may protect merozoites from phagocytosis by host monocytes; VTN glycosylation appears to be dispensable for the interaction. {ECO:0000250\|UniProtKB:P69193}.
Subunit:		[p50]: Monomer (PubMed:13679369, PubMed:25599609). Interacts with kinase CPK1/CDPK1 at the schizont stage (PubMed:29716996). {ECO:0000269\|PubMed:13679369, ECO:0000269\|PubMed:25599609, ECO:0000269\|PubMed:29716996}.
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}.
Developmental stage:		[Serine-repeat antigen protein 5]: Expressed during parasite asexual blood stages, specifically in late trophozoite and schizont stages (at protein level). {ECO:0000269\|PubMed:18083098, ECO:0000269\|PubMed:24769454, ECO:0000269\|PubMed:25599609, ECO:0000269\|PubMed:28683142, ECO:0000269\|PubMed:29567995, ECO:0000269\|PubMed:29716996}.
Developmental stage:		[p50]: Produced during parasite asexual blood stages, specifically at the merozoite stage just prior to egress (at protein level). {ECO:0000269\|PubMed:25599609, ECO:0000269\|PubMed:29716996}.
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}.
Mass spectrometry:		[p50]: Mass=52540.17; Method=Electrospray; Evidence={ECO:0000269\|PubMed:25599609};
Disruption phenotype:		Conditional knockout at the merozoite stage, does not cause any defect in schizont morphology, merozoite number and maturation initially. During the subsequent invasive cycle in host erythrocytes, merozoite replication is severely impaired due to a premature rupture of the parasitophorous vacuole and erythrocyte membranes resulting in an inefficient dispersal of released merozoites. {ECO:0000269\|PubMed:28683142}.
Similarity:		Belongs to the peptidase C1 family. {ECO:0000255\|PROSITE- ProRule:PRU10089, ECO:0000255\|PROSITE-ProRule:PRU10090}.