About Gene List

PF3D7_1200600 (VAR2CSA)

Genome location: Pf3D7_12_v3:45,887..58,295(-)

Genome classification: SubtelomericHypervariable

Function and Localization

Product Description: erythrocyte membrane protein 1, PfEMP1

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: None

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0020036 Maurer's cleft
Component GO:0020002 host cell plasma membrane
Component GO:0020030 infected host cell surface knob
Function GO:0001791 IgM binding
Function GO:0050839 cell adhesion molecule binding
Function GO:0035373 chondroitin sulfate proteoglycan binding
Function GO:0046789 host cell surface receptor binding
Function GO:0005515 protein binding
Process GO:0020033 antigenic variation
Process GO:0098609 cell-cell adhesion
Process GO:0020035 cytoadherence to microvasculature, mediated by symbiont protein
Process GO:0020013 modulation by symbiont of host erythrocyte aggregation

Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):

Stage LR class MCA mean MCA prop. zeros
Sporozoite not expressed N/A N/A
Ring possibly expressed 1.08 0.67
Trophozoite not expressed 0.39 0.85
Schizont not expressed 0.25 0.88
Gametocyte not expressed 0.18 0.91

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1200600

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: Mutable in CDS

MIS: 1 | MFS: -1.899 | #Insertions: 3

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: N/A

"Best" AlphaFill ligand hit: No AlphaFill hits

No associated EC numbers

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_104345

No human ortholog(s)

Genetic Variation

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

No passing variants found

PlasmoDB Total SNPs: 3256

Non-coding: 687 | Synonymous: 481 | Nonsynonymous: 2063 | Stop Codon: 25

Protein Information

Protein Length: 3056 | Molecular Weight (kDa): 355.245

UniProt ID(s): A0A0K2JPB4, A0A0K2JPK8, A0A0K2JPM4, A0A0K2JPN0, A0A5P1A070, A0A5P1A0B4, A0A5P1A0C9, A0A5P1A0D4, A0A5P1A0H1, A0A5P1A166, A0A5P1A1E1, A0A5P1A1R9, A0A5P1A207, A0A5P1A217, A0A5P1A243, A0A5P1A2A4, A0A6B9HE73, A7KYF0, A7KYF1, A7KYF2, A7KYF3, A7KYF5, A7KYF6, A7KYF7, A7KYF9, Q6UDW3, Q6UDW7, Q6UDW9, Q8I639

PDB ID(s): 2WAU, 7FAP, 7FAS

Isoelectric Point: 7.28

Protein Domain Annotations:

Source Family ID Description
InterPro IPR004258 Duffy-binding-like domain
InterPro IPR008602 Duffy-antigen binding
InterPro IPR029211 Plasmodium falciparum erythrocyte membrane protein 1, acidic terminal segment
InterPro IPR032761 Plasmodium falciparum erythrocyte membrane protein 1, N-terminal
PFam PF03011 Duffy-binding-like domain
PFam PF05424 Duffy-antigen binding
PFam PF15445 Plasmodium falciparum erythrocyte membrane protein 1, acidic terminal segment
PFam PF15448 Plasmodium falciparum erythrocyte membrane protein 1, N-terminal
Superfamily SSF140924 N/A

Associated Publications

PMID Title Authors DOI/Link
9230440 P. falciparum rosetting mediated by a parasite-variant erythrocyte membraneprotein and complement-receptor 1. Rowe JA, Moulds JM, Newbold CI, Miller LH 10.1038/40888
9291676 Knob proteins in falciparum malaria. Sharma YD https://pubmed.ncbi.nlm.nih.gov/9291676/
9786187 A recombinant peptide based on PfEMP-1 blocks and reverses adhesion ofmalaria-infected red blood cells to CD36 under flow. Cooke BM, Nicoll CL, Baruch DI, Coppel RL 10.1046/j.1365-2958.1998.01040.x
11420100 Molecules on the surface of the Plasmodium falciparum infected erythrocyte andtheir role in malaria pathogenesis and immune evasion. Craig A, Scherf A https://pubmed.ncbi.nlm.nih.gov/11420100/
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
16025132 A single member of the Plasmodium falciparum var multigene family determinescytoadhesion to the placental receptor chondroitin sulphate A. Viebig NK, Gamain B, ..., Scherf A 10.1038/sj.embor.7400466
18785843 Antigenic variation in Plasmodium falciparum. Scherf A, Lopez-Rubio JJ, Riviere L 10.1146/annurev.micro.61.080706.093134
27556547 Placental Sequestration of Plasmodium falciparum Malaria Parasites Is Mediated bythe Interaction Between VAR2CSA and Chondroitin Sulfate A on Syndecan-1. Ayres Pereira M, Mandel Clausen T, ..., Salanti A 10.1371/journal.ppat.1005831
31631203 A network-based approach reveals novel invasion and Maurer's clefts-relatedproteins in Plasmodium falciparum. Das D, Krishnan SR, Roy A, Bulusu G 10.1039/c9mo00124g
34718641 An Invariant Protein That Colocalizes With VAR2CSA on Plasmodiumfalciparum-Infected Red Cells Binds to Chondroitin Sulfate A. Keitany GJ, Jenkins BJ, ..., Duffy PE 10.1093/infdis/jiab550
37435892 Malaria Biomimetic for Tumor Targeted Drug Delivery Pihl J, Clausen TM, ..., Salanti A 10.1021/acsnano.3c01910
37569448 Raman Spectroscopy Combined with Malaria Protein for Early Capture andRecognition of Broad-Spectrum Circulating Tumor Cells Liu X, Zhang Y, ..., Yang J 10.3390/ijms241512072
37828011 Cryo-electron microscopy of IgM-VAR2CSA complex reveals IgM inhibits binding ofPlasmodium falciparum to Chondroitin Sulfate A Akhouri RR, Goel S, Skoglund U 10.1038/s41467-023-41838-x
37515848 Are high avidity antibodies to Plasmodium falciparum antigens preferentiallytransferred across the placenta of premature and term babies? Kayatani AKK, Bobbili N, ..., Taylor DW 10.1016/j.placenta.2023.07.011
37932470 Aotus nancymaae model predicts human immune response to the placental malariavaccine candidate VAR2CSA Doritchamou J, Nielsen MA, ..., Duffy PE 10.1038/s41684-023-01274-2
37414792 Detecting temporal and spatial malaria patterns from first antenatal care visits Pujol A, Brokhattingen N, ..., Mayor A 10.1038/s41467-023-39662-4
38285967 Correction: A conformational epitope in placental malaria vaccine antigen VAR2CSA: What does it teach us? Doritchamou JYA, Renn JP, Hviid L, Duffy PE 10.1371/journal.ppat.1011503
37754682 Associations between prenatal malaria exposure, maternal antibodies at birth, andmalaria susceptibility during the first year of life in Burkina Faso Natama HM, Moncunill G, ..., Dobano C 10.1128/iai.00268-23
37396303 A conserved epitope in VAR2CSA is targeted by a cross-reactive antibodyoriginating from Plasmodium vivax Duffy binding protein Iyamu U, Vinals DF, ..., Yanow SK 10.3389/fcimb.2023.1202276
37091678 Anti-phosphatidylserine antibody levels are low in multigravid pregnant women ina malaria-endemic area in Nigeria, and do not correlate with anti-VAR2CSAantibodies Fasanya A, Mohammed N, ..., Persson KEM 10.3389/fcimb.2023.1130186
37575395 VAR2CSA Ectodomain Labeling in Plasmodium falciparum Infected Red Blood Cells andAnalysis via Flow Cytometry Carmo OMS, Dixon MWA 10.21769/BioProtoc.4725
38117828 Mechanical forces control the valency of the malaria adhesin VAR2CSA by exposingcryptic glycan binding sites Roessner R, Michelarakis N, Grater F, Aponte-Santamaria C 10.1371/journal.pcbi.1011726
38270586 A novel computational pipeline for var gene expression augments the discovery ofchanges in the Plasmodium falciparum transcriptome during transition from in vivoto short-term in vitro culture Andradi-Brown C, Wichers-Misterek JS, ..., Bachmann A 10.7554/eLife.87726
38274790 Acquisition of antibodies that block Plasmodium falciparum adhesion to placentalreceptor chondroitin sulfate A with increasing gravidity in Malian women Mahamar A, Traore M, ..., Fried M 10.3389/fimmu.2023.1330962
38405848 Chromatin structure and var2csa - a tango in regulation of var gene expression inthe human malaria parasite, Plasmodium falciparum? Lenz T, Zhang X, ..., Le Roch KG 10.1101/2024.02.13.580059
37156765 Plasmodium falciparum has evolved multiple mechanisms to hijack humanimmunoglobulin M Ji C, Shen H, ..., Xiao J 10.1038/s41467-023-38320-z
38437239 Structure-guided design of VAR2CSA-based immunogens and a cocktail strategy for aplacental malaria vaccine Ma R, Salinas ND, ..., Tolia NH 10.1371/journal.ppat.1011879
37228009 A conformational epitope in placental malaria vaccine antigen V AR2CSA: What doesit teach us? Doritchamou JYA, Renn JP, Hviid L, Duffy PE 10.1371/journal.ppat.1011370