About Gene List

PF3D7_0617400 (VAR)

Genome location: Pf3D7_06_v3:722,377..731,499(-)

Genome classification: InternalHypervariable

Function and Localization

Product Description: erythrocyte membrane protein 1, PfEMP1

SignalP Peptide: N/A

# Transmembrane Domains: 1

EC Numbers: None

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0020002 host cell plasma membrane
Component GO:0020030 infected host cell surface knob
Function GO:0050839 cell adhesion molecule binding
Function GO:0046812 host cell surface 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 expressed 0.02 0.99
Trophozoite possibly expressed 0.03 0.98
Schizont expressed 0.06 0.96
Gametocyte possibly expressed 0.10 0.94

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0617400

Resistome Missense Mutations: E1946G, I1947F, D1950H, K1953Q, T2204I

Resistome Compounds with Missense Mutations: AN13762

Resistome # Samples with Disruptive Mutations: 2 (2 missense, 1 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Mutable in CDS

MIS: 1 | MFS: -0.531 | #Insertions: 3

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: C6KT15

"Best" AlphaFill ligand hit: 3PO (triphosphate, Local RMSD=0.27) with 5MZA (Global RMSD=2.94)

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: 1978

Non-coding: 362 | Synonymous: 473 | Nonsynonymous: 1131 | Stop Codon: 12

Protein Information

Protein Length: 2394 | Molecular Weight (kDa): 274.794

UniProt ID(s): A0A191VZ16, A0A191VZ35, A0A191VZD0, A0A5P1A005, A0A5P1A063, A0A5P1A0M8, A0A5P1A0Q1, A0A5P1A0T0, A0A5P1A163, A0A5P1A184, A0A5P1A1B1, A0A5P1A2R9, A0A5P1A2T7, A0A5P1A3D9, A1KQT2, A3R6R9, A3R6S0, C6KT15, P90580, Q26030, Q8T5G0, Q94657, Q95W83

PDB ID(s): None

Isoelectric Point: 6.46

Protein Domain Annotations:

Source Family ID Description
InterPro IPR004258 Duffy-binding-like domain
InterPro IPR008602 Duffy-antigen binding
InterPro IPR029210 Plasmodium falciparum erythrocyte membrane protein-1, N-terminal segment
InterPro IPR029211 Plasmodium falciparum erythrocyte membrane protein 1, acidic terminal segment
InterPro IPR041480 Cysteine-rich interdomain region 1 gamma
PFam PF03011 Duffy-binding-like domain
PFam PF05424 Duffy-antigen binding
PFam PF15445 Plasmodium falciparum erythrocyte membrane protein 1, acidic terminal segment
PFam PF15447 Plasmodium falciparum erythrocyte membrane protein-1, N-terminal segment
PFam PF18562 Cysteine-rich interdomain region 1 gamma
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
11316367 Variant antigens of Plasmodium falciparum encoded by the var multigenic familyare multifunctional macromolecules. Nogueira PA, Wunderlich G, Pereira da Silva LH 10.1016/s0923-2508(01)01184-6
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/
12368867 Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. Hall N, Pain A, ..., Barrell BG 10.1038/nature01095
16267556 A protein interaction network of the malaria parasite Plasmodium falciparum. LaCount DJ, Vignali M, ..., Hughes RE 10.1038/nature04104
17562715 Structural basis for binding of Plasmodium falciparum erythrocyte membraneprotein 1 to chondroitin sulfate and placental tissue and the influence ofprotein polymorphisms on binding specificity. Beeson JG, Andrews KT, ..., Chai W 10.1074/jbc.M700231200
17895392 PfEMP1-DBL1alpha amino acid motifs in severe disease states of Plasmodiumfalciparum malaria. Normark J, Nilsson D, ..., Wahlgren M 10.1073/pnas.0610485104
18005727 Plasmodium falciparum erythrocyte membrane protein-1 specifically suppressesearly production of host interferon-gamma. D'Ombrain MC, Voss TS, ..., Schofield L 10.1016/j.chom.2007.06.012
18299339 The C-terminal segment of the cysteine-rich interdomain of Plasmodium falciparumerythrocyte membrane protein 1 determines CD36 binding and elicits antibodiesthat inhibit adhesion of parasite-infected erythrocytes. Mo M, Lee HC, ..., Preiser P 10.1128/IAI.00480-07
18785843 Antigenic variation in Plasmodium falciparum. Scherf A, Lopez-Rubio JJ, Riviere L 10.1146/annurev.micro.61.080706.093134
19374733 Structural insights into chondroitin sulphate A binding Duffy-binding-likedomains from Plasmodium falciparum: implications for intervention strategiesagainst placental malaria. Gill J, Chitnis CE, Sharma A 10.1186/1475-2875-8-67
20169064 Differential recognition of P. falciparum VAR2CSA domains by naturally acquiredantibodies in pregnant women from a malaria endemic area. Brolin KJ, Persson KE, ..., Chen Q 10.1371/journal.pone.0009230
20823248 Dual stage synthesis and crucial role of cytoadherence-linked asexual gene 9 inthe surface expression of malaria parasite var proteins. Goel S, Valiyaveettil M, ..., Gowda DC 10.1073/pnas.1002568107
21592998 Positive selection of Plasmodium falciparum parasites with multiple var2csa-typePfEMP1 genes during the course of infection in pregnant women. Sander AF, Salanti A, ..., Taylor DW 10.1093/infdis/jir168
22570492 Structural and functional insight into how the Plasmodium falciparum VAR2CSAprotein mediates binding to chondroitin sulfate A in placental malaria. Clausen TM, Christoffersen S, ..., Salanti A 10.1074/jbc.M112.348839
23980802 A molecular switch in the efficiency of translation reinitiation controlsexpression of var2csa, a gene implicated in pregnancy-associated malaria. Bancells C, Deitsch KW 10.1111/mmi.12379
26450557 Structure of the DBL3X-DBL4epsilon region of the VAR2CSA placental malaria vaccinecandidate: insight into DBL domain interactions. Gangnard S, Lewit-Bentley A, ..., Gamain B 10.1038/srep14868
28351419 New var reconstruction algorithm exposes high var sequence diversity in a singlegeographic location in Mali. Dara A, Drabek EF, ..., Silva JC 10.1186/s13073-017-0422-4
32471507 Identification of a conserved var gene in different Plasmodium falciparumstrains. Dimonte S, Bruske EI, ..., Frank M 10.1186/s12936-020-03257-x