MSP1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005515 protein binding	IPI PMID:21175202 Proteome analysis reveals a large merozoite surface protein-...	MODIFY	Summary: Co-immunoprecipitation and mass spectrometry of merozoite lysates placed MSP1 in a large surface complex that includes the rhoptry proteins RhopH3 (Q8I395), RAP1 (Q8ILZ1) and CLAG9 (Q8I2G2); the p42 fragment interacts with RhopH3. Reason: The interactions are real, but GO:0005515 conveys no function. What this paper actually shows is MSP1 acting as the structural core of a large merozoite-surface complex that it holds together and that co-sheds with it, which is stated by GO:0140378 protein complex scaffold activity. MSP1 is an integral member of that complex, as the term requires, and partner-mapping work shows the partners contact defined MSP1 subunits rather than each other. Proposed replacements: protein complex scaffold activity Supporting Evidence: PMID:21175202 Proteomic analysis identified a major malaria surface protein, PfRhopH3 interacting with PfMSP-1(42). PMID:16940297 Both MSP-6(36) and MSP-7 bind only to MSP-1 subunits that are shed, but although MSP-6(36) contacts just subunit p38, MSP-7 interacts with p83, p30, and p38.
GO:0005515 protein binding	IPI PMID:22431641 Plasmodium falciparum merozoite surface protein 1 blocks the...	MODIFY	Summary: The shed 33 kDa fragment of MSP1 binds the human proinflammatory protein S100P (P25815) and blocks its activity on host monocytes and neutrophils. Reason: The interaction is directly demonstrated and the partner is identified, so the informative molecular function GO:0044548 S100 protein binding is available and replaces the uninformative generic term. The downstream claim that this suppresses host innate immunity rests on a single in vitro study and is not asserted as a process annotation here; it is raised under suggested_questions instead. Proposed replacements: S100 protein binding Supporting Evidence: PMID:22431641 the 33-kDa fragment of P. falciparum merozoite surface protein 1 (MSP1(33)), an abundant protein that is shed during red blood cell invasion, binds to the proinflammatory protein, S100P.
GO:0005515 protein binding	IPI PMID:25074930 The merozoite surface protein 1 complex is a platform for bi...	MODIFY	Summary: Surface plasmon resonance showed that the Duffy binding-like merozoite surface proteins MSPDBL1 (PF3D7_1035700) and MSPDBL2 bind the p83, p38 and p42 fragments of MSP1 and are thereby displayed on the merozoite surface. Reason: Correct and quantitatively characterised, but uninformative as a bare binding term. The paper's own conclusion is that MSP1 is the platform holding and displaying these peripheral partners, which is what GO:0140378 protein complex scaffold activity states; the same replacement is proposed for the other complex-forming protein-binding row. Proposed replacements: protein complex scaffold activity Supporting Evidence: PMID:25074930 We have shown that the peripheral merozoite surface proteins MSPDBL1 and MSPDBL2 are part of the large MSP1 complex.
GO:0005515 protein binding	IPI PMID:25157665 Human erythrocyte band 3 functions as a receptor for the sia...	MODIFY	Summary: MSP1-19 was shown to form a ternary complex with the rhoptry protein RhopH3 (PF3D7_0905400) and the 5ABC exofacial region of host band 3. Reason: The row is recorded as generic protein binding, but the interaction it comes from is MSP1-19 engaging the exofacial 5ABC segment of the host erythrocyte receptor band 3 (SLC4A1), with RhopH3 in the same complex. That is a host cell surface receptor binding activity (GO:0046789), independently established for MSP1-42/19 with band 3 and for the N-terminal region with glycophorin A, so the informative host-directed term replaces the generic one. Proposed replacements: host cell surface receptor binding Supporting Evidence: PMID:25157665 RhopH3 formed a complex with MSP119 and the 5ABC region of band 3, and a recombinant segment of RhopH3 inhibited parasite invasion in human erythrocytes. PMID:12692305 A major segment of the band 3 receptor (5ABC) bound to native MSP1(42) and blocked the interaction of native MSP1(42) with intact RBCs in vitro. PMID:25778531 Mapping of the binding domains established a direct interaction between malaria MSP1 and human GPA within a region of MSP1 known to potently inhibit P falciparum invasion of human RBCs.
GO:0005576 extracellular region	EXP PMID:12692305 Band 3 is a host receptor binding merozoite surface protein ...	KEEP AS NON CORE	Summary: Native MSP1-42 and recombinant MSP1-19/MSP1-38 were studied as soluble, released ectodomain products binding host band 3 outside the parasite. Reason: MSP1 genuinely occupies the extracellular space as the shed ectodomain complex, so the term is correct and as precise as the evidence allows. It is not the core location, which is the merozoite surface (plasma membrane), so it is kept as non-core rather than accepted as core. Supporting Evidence: PMID:12692305 A major segment of the band 3 receptor (5ABC) bound to native MSP1(42) and blocked the interaction of native MSP1(42) with intact RBCs in vitro.
GO:0005576 extracellular region	EXP PMID:14630931 A co-ligand complex anchors Plasmodium falciparum merozoites...	KEEP AS NON CORE	Summary: Native MSP1-42 was isolated as part of a soluble co-ligand complex with MSP9 that engages the erythrocyte band 3 receptor at the merozoite-erythrocyte interface. Reason: Consistent with the other extracellular-region rows: the shed/released MSP1 complex is extracellular, a real but peripheral aspect of the protein's localisation compared with its GPI-anchored surface pool. Supporting Evidence: PMID:14630931 Native MSP9 and MSP1(42), the two ligands binding to the 5ABC receptor, existed as a stable complex.
GO:0005576 extracellular region	EXP PMID:16322767 Molecular identification of a malaria merozoite surface shed...	KEEP AS NON CORE	Summary: Identification of PfSUB2 as the merozoite surface sheddase demonstrated that the MSP1 ectodomain complex is proteolytically released from the parasite surface during invasion. Reason: Supports the extracellular pool of MSP1. Note that in this paper MSP1 is the substrate, not the protease, so the reference supports localisation only and no peptidase activity should be inferred for MSP1. Supporting Evidence: PMID:16322767 Erythrocyte invasion by merozoites of the malaria parasite Plasmodium falciparum requires the shedding of ectodomain components of two essential surface proteins, called MSP1 and AMA1.
GO:0005576 extracellular region	EXP PMID:17097159 Extensive proteolytic processing of the malaria parasite mer...	KEEP AS NON CORE	Summary: MSP7-derived fragments were shown to be shed together with MSP1 fragments as a protein complex during erythrocyte invasion. Reason: Documents the shed, extracellular form of the MSP1 complex; correct but peripheral to the core surface localisation. Supporting Evidence: PMID:17097159 these two derivatives are shed as part of the protein complex with MSP1 fragments during erythrocyte invasion.
GO:0005576 extracellular region	EXP PMID:25074930 The merozoite surface protein 1 complex is a platform for bi...	KEEP AS NON CORE	Summary: Recombinant MSP1 fragments and the MSP1 complex were characterised as soluble extracellular species displaying MSPDBL1/MSPDBL2 for erythrocyte binding. Reason: Consistent with the other extracellular-region rows for the shed complex. Supporting Evidence: PMID:25074930 This demonstrates that the MSP1 complex acts as a platform for display of MSPDBL1 and MSPDBL2 on the merozoite surface for binding to receptors on the erythrocyte and invasion.
GO:0005576 extracellular region	EXP PMID:29511044 Protein-protein interaction studies reveal the Plasmodium fa...	KEEP AS NON CORE	Summary: Recombinant extracellular MSP1 fragments (PfMSP-1-65, PfMSP-1-19) were used to map the interactions of the released MSP1 complex with other merozoite surface proteins and with erythrocytes. Reason: Supports the extracellular/ectodomain pool; correct but not the core location. Supporting Evidence: PMID:29511044 PfMSP-165 interacted strongly with PfMSP-3, PfMSP-6, PfMSP-7, and PfMSP-9, whereas PfMSP-119 did not interact with any of these proteins.
GO:0005576 extracellular region	IDA PMID:21175202 Proteome analysis reveals a large merozoite surface protein-...	KEEP AS NON CORE	Summary: Components of the MSP1-associated complex were detected directly in parasite culture supernatant, consistent with shedding of the complex into the extracellular medium. Reason: Direct detection of the shed complex outside the parasite; the claim is correct, and is kept non-core for the same reason as the other extracellular-region rows. Supporting Evidence: PMID:21175202 We could also identify many of these proteins in culture supernatant, suggesting the shedding of the complex.
GO:0005576 extracellular region	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic mapping of the UniProt "Secreted" subcellular-location term, which UniProt assigns on the basis of the experimental shedding papers. Reason: Reinforces the experimentally supported extracellular rows rather than adding an independent claim; kept with the same (non-core) status as those rows for consistency. Supporting Evidence: PMID:16322767 Erythrocyte invasion by merozoites of the malaria parasite Plasmodium falciparum requires the shedding of ectodomain components of two essential surface proteins, called MSP1 and AMA1.
GO:0005774 vacuolar membrane	EXP PMID:18769730 Formation of the food vacuole in Plasmodium falciparum: a po...	KEEP AS NON CORE	Summary: Immunofluorescence and immuno-electron microscopy showed that after invasion the GPI-anchored MSP1-19 fragment is endocytosed and persists at the membrane of the parasite's digestive (food) vacuole, colocalising there with CRT, throughout intraerythrocytic development. Reason: The localisation is real and directly observed by two independent methods (immunofluorescence against CRT, and immuno-electron microscopy), so it is not removed or marked over-annotated. But it is not a core location. MSP1 is a GPI-anchored merozoite surface protein, and what reaches this membrane is only the p19 remnant, carried there passively by endocytic uptake of the surface coat after invasion; the authors themselves present a functional role as a possibility rather than a finding ("a potential role", "it may play a significant role"), and UniProt flags it ECO:0000305 Probable. On current evidence this is the post-invasion fate of the surface pool, not a site where MSP1 is known to act, so the term is kept as a non-core location. The term is also as precise as GO allows: there is no "food vacuole membrane" term, and inventing one on this evidence is not warranted. Supporting Evidence: PMID:18769730 The food vacuole is marked by the presence of both MSP1(19) and the chloroquine resistance transporter (CRT) as components of the vacuolar membrane.
GO:0005774 vacuolar membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic mapping of the UniProt "Vacuole membrane" location, which UniProt assigns from the same food-vacuole imaging study. Reason: Reinforces the experimental vacuolar-membrane row and makes no separate claim, so it takes the same non-core status for the same reason: this is where the p19 remnant ends up after invasion, not an established site of MSP1 action. Supporting Evidence: PMID:18769730 This protein is the first marker for the biogenesis of the food vacuole; it is rapidly endocytosed into small vacuoles in the ring stage, which coalesce to form the single food vacuole containing hemozoin, and persists into the discarded residual body.
GO:0005886 plasma membrane	EXP PMID:1694225 A single fragment of a malaria merozoite surface protein rem...	ACCEPT	Summary: Classic demonstration that the MSP1-derived polypeptide complex coats the merozoite surface and that one small fragment stays attached to the parasite surface during invasion. Reason: The merozoite plasma membrane (parasite surface) is the core location of MSP1 and is directly demonstrated here; nothing more specific is warranted for this particular evidence, since the GPI-anchoring chemistry comes from a different study. Supporting Evidence: PMID:1694225 A complex of polypeptides derived from a precursor is present on the surface of the malaria merozoite. PMID:1694225 During erythrocyte invasion only a small fragment from this complex is retained on the parasite surface and carried into the newly infected red cell.
GO:0005886 plasma membrane	EXP PMID:18769730 Formation of the food vacuole in Plasmodium falciparum: a po...	ACCEPT	Summary: Metabolic labelling and imaging confirmed MSP1-19 on the merozoite surface before its post-invasion internalisation to the food vacuole. Reason: Directly supports the core surface (plasma membrane) localisation of the GPI-anchored fragment. Supporting Evidence: PMID:18769730 Following a second proteolytic cleavage during merozoite invasion of the red blood cell, most of the protein is shed from the surface except for the C-terminal 19-kDa fragment (MSP1(19)), which is still attached to the merozoite via its GPI-anchor.
GO:0005886 plasma membrane	EXP PMID:20735778 Regulated maturation of malaria merozoite surface protein-1 ...	ACCEPT	Summary: Analysis of ordered MSP1 maturation in transgenic parasites, in which MSP1 and its processing products were followed on the merozoite surface. Reason: Supports the core surface localisation; the same study shows that correctly timed maturation of this surface pool is required for blood-stage growth. Supporting Evidence: PMID:20735778 Merozoite surface protein-1 (MSP1), a prime malaria vaccine candidate and one of the most abundant components of the merozoite surface, is implicated in the ligand-receptor interactions leading to invasion.
GO:0005886 plasma membrane	EXP PMID:26468747 Processing of Plasmodium falciparum Merozoite Surface Protei...	ACCEPT	Summary: Study of surface-bound MSP1 and of merozoites engineered to lack surface MSP1, establishing the GPI-anchored surface pool as the functional one for egress. Reason: Core location, directly demonstrated, and functionally tied in the same paper to the spectrin-binding and egress role. Supporting Evidence: PMID:26468747 The most abundant merozoite surface component, a GPI-anchored protein called MSP1, is synthesized as an ∼200 kDa protein that in P. falciparum associates with at least two other peripheral proteins belonging to the MSP3 and MSP7 families (Kauth et al., 2006; Lin et al., 2014; Pachebat et al., 2001; Trucco et al., 2001).
GO:0005886 plasma membrane	IDA PMID:21175202 Proteome analysis reveals a large merozoite surface protein-...	ACCEPT	Summary: Surface labelling and immunoprecipitation from intact merozoites placed MSP1 and its partners on the merozoite surface at the schizont/merozoite stage. Reason: Reinforces the core surface localisation with direct evidence. Supporting Evidence: PMID:21175202 Plasmodium merozoite surface protein-1 (MSP-1) is an essential antigen for the merozoite invasion of erythrocytes.
GO:0005886 plasma membrane	IDA PMID:8992312 Structural analysis of the glycosyl-phosphatidylinositol mem...	ACCEPT	Summary: Biochemical dissection of the MSP1 membrane anchor established that MSP1 is held in the parasite membrane by a GPI anchor whose core glycan carries an additional alpha1-2 mannose. Reason: Correct: the paper confirms that MSP1 is held in the parasite plasma membrane. Its evidence additionally supports the more specific relationship (a GPI-anchored protein on the outer face of that membrane), which is added as a separate NEW row for GO:0031362 rather than by modifying this row, so that all plasma-membrane rows stay consistent. Supporting Evidence: PMID:8992312 In this report the identity of these GPI-anchors is confirmed by labelling with tritiated precursors and additionally by specific enzymatic and chemical treatments. PMID:18769730 which is still attached to the merozoite via its GPI-anchor.
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic mapping of the UniProt "Cell membrane" location, itself derived from the experimental surface-localisation studies. Reason: Agrees with the experimental plasma-membrane rows; kept for consistency with them. Supporting Evidence: PMID:26468747 The most abundant merozoite surface component, a GPI-anchored protein called MSP1, is synthesized as an ∼200 kDa protein that in P. falciparum associates with at least two other peripheral proteins belonging to the MSP3 and MSP7 families (Kauth et al., 2006; Lin et al., 2014; Pachebat et al., 2001; Trucco et al., 2001).
GO:0016020 membrane	IEA GO_REF:0000002	TOO GENERAL	Summary: InterPro2GO transfer from the MSP1 family signature IPR010901, asserting only that the protein is membrane-associated. Reason: True but uninformative: the plasma-membrane and vacuolar-membrane terms accepted elsewhere in this review already entail membrane. The signature is correct for the protein (an MSP1-family domain in a Plasmodium MSP1), so this is a judgement about the term's specificity, not about the mapping being wrong.
GO:0085017 entry into host cell by a symbiont-containing vacuole	IDA PMID:21175202 Proteome analysis reveals a large merozoite surface protein-...	ACCEPT	Summary: MSP1 and its associated complex act at the merozoite-erythrocyte interface during invasion, which proceeds by formation of a parasitophorous vacuole around the entering merozoite; antibody and ligand-blocking experiments link MSP1-complex interactions to successful invasion. Reason: The correct host-directed branch for an apicomplexan invasion protein, and the right level of specificity: P. falciparum merozoites enter erythrocytes enclosed in a parasitophorous vacuole, which is exactly what this term describes. MSP1 does work in this process itself - it binds host band 3 and glycophorin A and displays the erythrocyte-binding MSPDBL/MSP6/MSP9 partners - rather than merely being required for it. Supporting Evidence: PMID:21175202 Plasmodium merozoite surface protein-1 (MSP-1) is an essential antigen for the merozoite invasion of erythrocytes. PMID:12692305 These findings suggest that the chymotrypsin-sensitive MSP1-band 3 interaction plays a role in a sialic acid-independent invasion pathway and reveal the function of MSP1 in the Plasmodium invasion of RBCs.
GO:0031362 anchored component of external side of plasma membrane	IDA	NEW	Summary: NEW: MSP1 is attached to the outer face of the parasite plasma membrane by a GPI anchor whose core glycan carries an extra alpha1-2 mannose, which is why the bulk of the protein is accessible to the surface sheddase SUB2 and to antibodies, while the GPI-anchored p19 fragment is retained on the invading merozoite. Reason: Refines the accepted plasma-membrane rows with the membrane relationship that the biochemistry actually establishes. GO:0031362 is a part_of descendant of GO:0005886, so it adds specificity without conflicting with those rows. Supporting Evidence: PMID:8992312 In this report the identity of these GPI-anchors is confirmed by labelling with tritiated precursors and additionally by specific enzymatic and chemical treatments. PMID:18769730 which is still attached to the merozoite via its GPI-anchor.
GO:0030507 spectrin binding	IDA	NEW	Summary: NEW: SUB1-processed MSP1 binds host erythrocyte spectrin directly; binding requires cleavage within the 38/42 region, and microscale thermophoresis gives nanomolar affinities for the MSP1-spectrin complex. Reason: This is the best-defined molecular activity of MSP1 and is absent from GOA. It is supported by two independent laboratories using orthogonal methods (cytoskeleton pulldowns with purified spectrin, and biophysical affinity measurement on the recombinant protein), and it is the activity that explains the egress phenotype. Supporting Evidence: PMID:26468747 Processing modifies the secondary structure of MSP1 and activates its capacity to bind spectrin, a molecular scaffold protein that is the major component of the host erythrocyte cytoskeleton. PMID:26468747 Cleaved rMSP1-Dwt bound exclusively to a Triton X-100-insoluble doublet migrating at the positions of α- and β-spectrin, the dominant components of the cytoskeleton (Figure 4F). PMID:34078606 MSP-1 also interacts with the erythrocyte cytoskeleton protein spectrin (24, 25) and plays a role in egress (25).
GO:0035891 exit from host cell	IMP	NEW	Summary: NEW: merozoites lacking surface-bound MSP1 show a severe egress defect, and parasites expressing an inefficiently processed MSP1 mutant egress late; the processed protein acts by engaging the host spectrin network to facilitate rupture of the host erythrocyte. Reason: MSP1 performs work in this process rather than merely being required for it: the protein itself binds and perturbs the host cytoskeletal lattice that must give way for rupture, and the processing event that creates the spectrin-binding form is what licenses egress. Genetic perturbation (loss of surface MSP1, and a processing-site mutant) plus the direct binding activity together support the term. GO:0035891 is the symbiont-side term for a parasite leaving its host cell, which is the correct branch for an intraerythrocytic parasite. Supporting Evidence: PMID:26468747 Parasites expressing an inefficiently processed MSP1 mutant show delayed egress, and merozoites lacking surface-bound MSP1 display a severe egress defect. PMID:26468747 Our results indicate that interactions between SUB1-processed merozoite surface MSP1 and the spectrin network of the erythrocyte cytoskeleton facilitate host erythrocyte rupture to enable parasite egress.

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

📄 View Raw YAML