Genome location: Pf3D7_04_v3:1,075,910..1,077,829(+)
Genome classification: Core
Product Description: cysteine-rich protective antigen
SignalP Peptide: MIIPFHKKFISFFQIVLVVLLLCRSINC
# Transmembrane Domains: 0
EC Numbers: None
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0046658 | anchored component of plasma membrane |
| Component | GO:0045177 | apical part of cell |
| Component | GO:0009986 | cell surface |
| Component | GO:0043655 | host extracellular space |
| Component | GO:0016021 | integral component of membrane |
| Component | GO:0020009 | microneme |
| Component | GO:0032991 | protein-containing complex |
| Function | GO:0005515 | protein binding |
| Process | GO:0044409 | entry into host |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | expressed | N/A | N/A |
| Ring | not expressed | 0.08 | 0.96 |
| Trophozoite | possibly expressed | 0.02 | 0.99 |
| Schizont | expressed | 0.25 | 0.86 |
| Gametocyte | not expressed | 0.03 | 0.98 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0423800
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.248 | MFS: -2.623 | #Insertions: 0
PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_1113400)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IFM8
"Best" AlphaFill ligand hit: COA (coenzyme a, Local RMSD=7.10) with 5KTC (Global RMSD=15.46)
No associated EC numbersNo evidence of orthology to BindingDB entries
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 2 | 20 | 11 | 18 |
| disruptive | 12 | 34 | 25 | 37 |
| missense | 11 | 34 | 24 | 32 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 41 | 17 | 24 |
| disruptive | 21 | 71 | 36 | 90 |
| missense | 20 | 60 | 30 | 57 |
PlasmoDB Total SNPs: 123
Non-coding: 103 | Synonymous: 10 | Nonsynonymous: 10 | Stop Codon: 0
Protein Length: 362 | Molecular Weight (kDa): 42.776
UniProt ID(s): A0A2S1Q7P0, A0A2S1Q7P5, A0A2S1Q7Q4, Q8IFM8
PDB ID(s): 5EZN, 5EZO, 5TIH, 5TIK, 6MPV, 7PHV, 7PHW, 7PI2, 7PI3, 7PI7, 8CDD, 8CDE
Isoelectric Point: 5.31
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR041396 | Cysteine-rich protective antigen 6 bladed domain |
| PFam | PF18638 | Cysteine-rich protective antigen 6 bladed domain |
| Superfamily | N/A | N/A |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 20037583 | Transcriptional profiling of growth perturbations of the human malaria parasitePlasmodium falciparum. | Hu G, Cabrera A, ..., Bozdech Z | 10.1038/nbt.1597 |
| 22593616 | Passive immunoprotection of Plasmodium falciparum-infected mice designates theCyRPA as candidate malaria vaccine antigen. | Dreyer AM, Matile H, ..., Pluschke G | 10.4049/jimmunol.1103177 |
| 25583518 | Multiprotein complex between the GPI-anchored CyRPA with PfRH5 and PfRipr iscrucial for Plasmodium falciparum erythrocyte invasion. | Reddy KS, Amlabu E, ..., Gaur D | https://pubmed.ncbi.nlm.nih.gov/25583518/ |
| 27374406 | Essential Role of the PfRh5/PfRipr/CyRPA Complex during Plasmodium falciparumInvasion of Erythrocytes. | Volz JC, Yap A, ..., Cowman AF | 10.1016/j.chom.2016.06.004 |
| 28195530 | Structural basis for inhibition of erythrocyte invasion by antibodies to Plasmodium falciparum protein Cy RPA | Chen L, Xu Y, ..., Cowman AF | 10.7554/eLife.21347 |
| 30542156 | Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex. | Wong W, Huang R, ..., Cowman AF | 10.1038/s41586-018-0779-6 |
| 32900802 | The Structure of the Cysteine-Rich Domain of Plasmodium falciparum P113Identifies the Location of the RH5 Binding Site | Campeotto I, Galaway F, ..., Wright GJ | 10.1128/mBio.01566-20 |
| 35782147 | Expanding the Malaria Antibody Toolkit: Development and Characterisation ofPlasmodium falciparum RH5, CyRPA, and CSP Recombinant Human MonoclonalAntibodies | Nacer A, Kivi G, ..., Bowyer PW | 10.3389/fcimb.2022.901253 |
| 34828264 | Genetic Diversity of Plasmodium vivax Cysteine-Rich Protective Antigen (PvCyRPA)in Field Isolates from Five Different Areas of the Brazilian Amazon | Bitencourt Chaves L, Guimaraes GO, ..., Lima-Junior JDC | 10.3390/genes12111657 |
| 35177602 | Heterotypic interactions drive antibody synergy against a malaria vaccinecandidate | Ragotte RJ, Pulido D, ..., Draper SJ | 10.1038/s41467-022-28601-4 |
| 34162366 | The Plasmodium falciparum Rh5 invasion protein complex reveals an excess of rarevariant mutations | Ndwiga L, Osoti V, ..., Ochola-Oyier LI | 10.1186/s12936-021-03815-x |
| 32989463 | Antibody Combinations Targeting the Essential Antigens CyRPA, RH5, and MSP-119Potently Neutralize Plasmodium falciparum Clinical Isolates From India andAfrica | Singh H, Mian SY, ..., Gaur D | 10.1093/infdis/jiaa608 |
| 32313230 | Antibodies against a short region of PfRipr inhibit Plasmodium falciparummerozoite invasion and PfRipr interaction with Rh5 and SEMA7A | Nagaoka H, Kanoi BN, ..., Takashima E | 10.1038/s41598-020-63611-6 |
| 32678144 | Bliss' and Loewe's additive and synergistic effects in Plasmodium falciparumgrowth inhibition by AMA1-RON2L, RH5, RIPR and CyRPA antibody combinations | Azasi Y, Gallagher SK, ..., Miura K | 10.1038/s41598-020-67877-8 |
| 34305923 | Identification and Immune Assessment of T Cell Epitopes in Five Plasmodiumfalciparum Blood Stage Antigens to Facilitate Vaccine Candidate Selection andOptimization | Kotraiah V, Phares TW, ..., Noe AR | 10.3389/fimmu.2021.690348 |
| 36211427 | Process development and preclinical evaluation of a major Plasmodium falciparumblood stage vaccine candidate, Cysteine-Rich Protective Antigen (CyRPA) | Somanathan A, Mian SY, ..., Chauhan VS | 10.3389/fimmu.2022.1005332 |
| 38123677 | The PfRCR complex bridges malaria parasite and erythrocyte during invasion | Farrell B, Alam N, ..., Higgins MK | 10.1038/s41586-023-06856-1 |
| 32359873 | The RH5-CyRPA-Ripr Complex as a Malaria Vaccine Target | Ragotte RJ, Higgins MK, Draper SJ | 10.1016/j.pt.2020.04.003 |
| 33379267 | Plasmodium vivax Cysteine-Rich Protective Antigen Polymorphism at Exon-1 ShowsRecombination and Signatures of Balancing Selection | Gonzalez-Ceron L, Cebrian-Carmona J, ..., Garrido-Cardenas JA | 10.3390/genes12010029 |
| 38406638 | Limited genetic variations of the Rh5-CyRPA-Ripr invasion complex in Plasmodiumfalciparum parasite population in selected malaria-endemic regions, Kenya | Waweru H, Kanoi BN, ..., Gitaka J | 10.3389/fitd.2023.1102265 |
| 35197516 | Enhancing neutralization of Plasmodium falciparum using a novel monoclonalantibody against the rhoptry-associated membrane antigen | Knudsen AS, Walker MR, ..., Barfod L | 10.1038/s41598-022-06921-1 |
| 36761022 | Plasmodium sporozoites require the protein B9 to invade hepatocytes | Fernandes P, Loubens M, ..., Silvie O | 10.1016/j.isci.2023.106056 |
| 34694918 | Plasmodium falciparum Cysteine-Rich Protective Antigen (CyRPA) Elicits DetectableLevels of Invasion-Inhibitory Antibodies during Natural Infection in Humans | Mian SY, Somanathan A, ..., Gaur D | 10.1128/IAI.00377-21 |
| 34447381 | Strain-Dependent Inhibition of Erythrocyte Invasion by Monoclonal AntibodiesAgainst Plasmodium falciparum CyRPA | Knudsen AS, Bjornsson KH, ..., Barfod L | 10.3389/fimmu.2021.716305 |
| 36396942 | PCRCR complex is essential for invasion of human erythrocytes by Plasmodiumfalciparum | Scally SW, Triglia T, ..., Cowman AF | 10.1038/s41564-022-01261-2 |