About Gene List

PF3D7_0304600 (CSP)

Genome location: Pf3D7_03_v3:221,112..223,145(-)

Genome classification: Core

Function and Localization

Product Description: circumsporozoite (CS) protein

SignalP Peptide: MMRKLAILSVSSFLFVEA

# Transmembrane Domains: 1

EC Numbers: None

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0046658 anchored component of plasma membrane
Component GO:0009986 cell surface
Component GO:0030430 host cell cytoplasm
Component GO:0042025 host cell nucleus
Function GO:0043395 heparan sulfate proteoglycan binding
Function GO:0046812 host cell surface binding
Function GO:0005515 protein binding
Process GO:0044409 entry into host
Process GO:0035891 exit from host cell

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 expressed 0.02 0.99
Trophozoite expressed 0.05 0.97
Schizont expressed 0.01 0.99
Gametocyte expressed 0.07 0.96

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0304600

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS *tentative

MIS: 0.962 | MFS: -2.132 | #Insertions: 0

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PBANKA_0403200)

Modification: Mutated | RMgm-5235

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: M1V0B0

"Best" AlphaFill ligand hit: No AlphaFill hits

No associated EC numbers

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_532775

No human ortholog(s)

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 6 8 3 13
disruptive 44 24 10 31
missense 39 16 7 18

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 8 13 9 18
disruptive 56 32 20 51
missense 44 19 11 31

PlasmoDB Total SNPs: 187

Non-coding: 20 | Synonymous: 119 | Nonsynonymous: 48 | Stop Codon: 0

Protein Information

Protein Length: 397 | Molecular Weight (kDa): 42.646

UniProt ID(s): A0A2L1CF52, A0A2L1CF88, C6FGZ3, C6FH27, C6FHG7, M1V060, M1V0A3, M1V0B0, M1V0C4, M1V0E0, M1V9I4, M1VFN9, M1VKZ2, P02893, Q5EIJ9, Q5EIK2, Q5EIK8, Q5EIL3, Q5EIL5, Q5EIL8, Q5R2L2, Q7K740, Q8I9G5, Q8I9J3, Q8I9J4

PDB ID(s): 3VDJ, 3VDK, 3VDL, 6BQB, 6MB3, 6MHG, 7LKB, 7LKG, 7RQQ, 7RQR, 7RXI, 7RXJ, 7RXL, 7RXP, 7S0X, 7UFQ, 8DYT, 8EK1, 8EKA, 8EKF

Isoelectric Point: 5.18

Protein Domain Annotations:

Source Family ID Description
InterPro IPR000884 Thrombospondin type-1 (TSP1) repeat
InterPro IPR003067 Plasmodium circumsporozoite protein
InterPro IPR036383 Thrombospondin type-1 (TSP1) repeat superfamily
PFam PF00090 Thrombospondin type-1 (TSP1) repeat
Superfamily SSF82895 Thrombospondin type-1 (TSP1) repeat superfamily

Associated Publications

PMID Title Authors DOI/Link
8006589 Structural and functional properties of region II-plus of the malariacircumsporozoite protein. Sinnis P, Clavijo P, ..., Nussenzweig V 10.1084/jem.180.1.297
8478608 Malaria circumsporozoite protein binds to heparan sulfate proteoglycansassociated with the surface membrane of hepatocytes. Frevert U, Sinnis P, ..., Nussenzweig V 10.1084/jem.177.5.1287
10448855 The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum. Bowman S, Lawson D, ..., Barrell BG 10.1038/22964
12244064 Function of region I and II adhesive motifs of Plasmodium falciparumcircumsporozoite protein in sporozoite motility and infectivity. Tewari R, Spaccapelo R, ..., Crisanti A 10.1074/jbc.M208453200
12368867 Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. Hall N, Pain A, ..., Barrell BG 10.1038/nature01095
15691125 A survey of the Th2R and Th3R allelic variants in the circumsporozoite proteingene of P. falciparum parasites from western Thailand. Kumkhaek C, Phra-ek K, ..., Khusmith S https://pubmed.ncbi.nlm.nih.gov/15691125/
16148140 Are extensive T cell epitope polymorphisms in the Plasmodium falciparumcircumsporozoite antigen, a leading sporozoite vaccine candidate, selected byimmune pressure? Kumkhaek C, Phra-Ek K, ..., Snounou G 10.4049/jimmunol.175.6.3935
16565072 Major histocompatibility complex and T cell interactions of a universal T cellepitope from Plasmodium falciparum circumsporozoite protein. Parra-Lopez C, Calvo-Calle JM, ..., Stern LJ 10.1074/jbc.M511571200
16603573 Identification and stoichiometry of glycosylphosphatidylinositol-anchoredmembrane proteins of the human malaria parasite Plasmodium falciparum. Gilson PR, Nebl T, ..., Crabb BS 10.1074/mcp.M600035-MCP200
17597060 Mosquito heparan sulfate and its potential role in malaria infection andtransmission. Sinnis P, Coppi A, ..., Linhardt RJ 10.1074/jbc.M704698200
17981117 Plasmodium circumsporozoite protein promotes the development of the liver stagesof the parasite. Singh AP, Buscaglia CA, ..., Nussenzweig V 10.1016/j.cell.2007.09.013
19460323 Natural selection maintains a stable polymorphism at the circumsporozoite proteinlocus of Plasmodium falciparum in a low endemic area. Putaporntip C, Jongwutiwes S, Hughes AL 10.1016/j.meegid.2009.02.006
19633296 Structure of the Plasmodium falciparum circumsporozoite protein, a leadingmalaria vaccine candidate. Plassmeyer ML, Reiter K, ..., Narum DL 10.1074/jbc.M109.013706
22912873 Genetic variation in the Plasmodium falciparum circumsporozoite protein in Indiaand its relevance to RTS,S malaria vaccine. Zeeshan M, Alam MT, ..., Sharma YD 10.1371/journal.pone.0043430
23144750 Protective antibody and CD8+ T-cell responses to the Plasmodium falciparumcircumsporozoite protein induced by a nanoparticle vaccine. Kaba SA, McCoy ME, ..., Lanar DE 10.1371/journal.pone.0048304
23399449 A chemiluminescent-western blot assay for quantitative detection of Plasmodiumfalciparum circumsporozoite protein. Kumar S, Zheng H, ..., Kumar N 10.1016/j.jim.2013.02.001
24983460 An unstable Th epitope of P. falciparum fosters central memory T cells andanti-CS antibody responses. Parra-Lopez CA, Bernal-Estevez D, ..., Stern LJ 10.1371/journal.pone.0100639
26169272 Reversible Conformational Change in the Plasmodium falciparum CircumsporozoiteProtein Masks Its Adhesion Domains. Herrera R, Anderson C, ..., Narum DL 10.1128/IAI.02676-14
27007512 Malaria sporozoite protein expression enhances baculovirus-mediated gene transferto hepatocytes. Tamura T, Kawabata C, ..., Yoshida S 10.1002/jgm.2879
28759593 Proteogenomic analysis of the total and surface-exposed proteomes of Plasmodiumvivax salivary gland sporozoites. Swearingen KE, Lindner SE, ..., Mikolajczak SA https://pubmed.ncbi.nlm.nih.gov/28759593/
33600048 Fluorescent tagging of Plasmodium circumsporozoite protein allows imaging ofsporozoite formation but blocks egress from oocysts. Singer M, Frischknecht F 10.1111/cmi.13321
33852850 Avid binding by B cells to the Plasmodium circumsporozoite protein repeatsuppresses responses to protective subdominant epitopes. Chatterjee D, Lewis FJ, ..., Cockburn IA 10.1016/j.celrep.2021.108996
34507066 Live attenuated rubella vectors expressing Plasmodium falciparum circumsporozoiteprotein (Pf-CSP) provide a novel malaria vaccine platform in the rhesus macaque. Virnik K, Zhou W, ..., Berkower I 10.1016/j.bbrc.2021.08.052
36841398 Genetic variations of Plasmodium falciparum circumsporozoite protein and theimpact on interactions with human immunoproteins and malaria vaccine efficacy. Dieng CC, Ford CT, ..., Lo E 10.1016/j.meegid.2023.105418