Genome location: Pf3D7_10_v3:28,490..36,164(+)
Genome classification: SubtelomericHypervariable
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:0020002 | host cell plasma membrane |
| Component | GO:0020030 | infected host cell surface knob |
| Function | GO:0050839 | cell adhesion molecule binding |
| Function | GO:0046789 | host cell surface receptor 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 | expressed | N/A | N/A |
| Ring | expressed | 0.04 | 0.98 |
| Trophozoite | expressed | 0.01 | 1.00 |
| Schizont | expressed | 0.05 | 0.97 |
| Gametocyte | expressed | 0.02 | 0.99 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1000100
Resistome Missense Mutations: D625N, D625E, R1434S, S1435R, G1436R, R1438T, G1440R, K1449N, K1451E, E1452K, E1452D, E1452A, D1455N, I1457M, G1461S, D2151N
Resistome Compounds with Missense Mutations: AN13762, MMV024101
Resistome # Samples with Disruptive Mutations: 6 (5 missense, 3 "interesting" missense)
Zhang Phenotype: Mutable in CDS
MIS: 1 | MFS: -1.853 | #Insertions: 1
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IK37
"Best" AlphaFill ligand hit: 3PO (triphosphate, Local RMSD=1.23) with 5MZA (Global RMSD=8.52)
No associated EC numbersNo evidence of orthology to BindingDB entries
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
No passing variants found
PlasmoDB Total SNPs: 2652
Non-coding: 417 | Synonymous: 638 | Nonsynonymous: 1580 | Stop Codon: 17
Protein Length: 2241 | Molecular Weight (kDa): 252.331
UniProt ID(s): A0A0F6P8U9, A0A5P1A0Y2, A0A5P1A147, A0A5P1A172, A0A5P1A2Z3, Q8IK37
PDB ID(s): None
Isoelectric Point: 5.04
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 | SSF101967 | N/A |
| Superfamily | SSF140924 |
| 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/ |
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 15692070 | Trafficking of the major virulence factor to the surface of transfected P.falciparum-infected erythrocytes. | Knuepfer E, Rug M, ..., Cowman AF | 10.1182/blood-2004-12-4666 |
| 15973412 | Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protectagainst malaria. | Fairhurst RM, Baruch DI, ..., Wellems TE | 10.1038/nature03631 |
| 17311092 | Dissection of the role of PfEMP1 and ICAM-1 in the sensing ofPlasmodium-falciparum-infected erythrocytes by natural killer cells. | Baratin M, Roetynck S, ..., Ugolini S | 10.1371/journal.pone.0000228 |
| 18785843 | Antigenic variation in Plasmodium falciparum. | Scherf A, Lopez-Rubio JJ, Riviere L | 10.1146/annurev.micro.61.080706.093134 |
| 18844973 | CD36 selection of 3D7 Plasmodium falciparum associated with severe childhoodmalaria results in reduced VAR4 expression. | Magistrado PA, Staalsoe T, ..., Jensen AT | 10.1186/1475-2875-7-204 |
| 19119419 | An upstream open reading frame controls translation of var2csa, a gene implicatedin placental malaria. | Amulic B, Salanti A, ..., Deitsch KW | 10.1371/journal.ppat.1000256 |
| 19389407 | Ectopic recombination of a malaria var gene during mitosis associated with analtered var switch rate. | Duffy MF, Byrne TJ, ..., Brown GV | 10.1016/j.jmb.2009.04.032 |
| 19690615 | Multiple var2csa-type PfEMP1 genes located at different chromosomal loci occur inmany Plasmodium falciparum isolates. | Sander AF, Salanti A, ..., Arnot DE | 10.1371/journal.pone.0006667 |
| 19730749 | Differential, positional-dependent transcriptional response of antigenicvariation (var) genes to biological stress in Plasmodium falciparum. | Rosenberg E, Ben-Shmuel A, ..., Pollack Y | 10.1371/journal.pone.0006991 |
| 20403153 | The kinetics of antibody binding to Plasmodium falciparum VAR2CSA PfEMP1 antigenand modelling of PfEMP1 antigen packing on the membrane knobs. | Joergensen LM, Salanti A, ..., Arnot DE | 10.1186/1475-2875-9-100 |
| 20410497 | IgM, Fc mu Rs, and malarial immune evasion. | Czajkowsky DM, Salanti A, ..., Pleass RJ | 10.4049/jimmunol.1000203 |
| 21402930 | Structure of a Plasmodium falciparum PfEMP1 rosetting domain reveals a role forthe N-terminal segment in heparin-mediated rosette inhibition. | Juillerat A, Lewit-Bentley A, ..., Bentley GA | 10.1073/pnas.1018692108 |
| 21573138 | Investigating the host binding signature on the Plasmodium falciparum PfEMP1protein family. | Janes JH, Wang CP, ..., Smith JD | 10.1371/journal.ppat.1002032 |
| 21696460 | Genetic ablation of a Maurer's cleft protein prevents assembly of the Plasmodiumfalciparum virulence complex. | Dixon MW, Kenny S, ..., Tilley L | 10.1111/j.1365-2958.2011.07740.x |
| 22249178 | Structural analysis of the Plasmodium falciparum erythrocyte membrane protein 1(PfEMP1) intracellular domain reveals a conserved interaction epitope. | Mayer C, Slater L, ..., Vakonakis I | 10.1074/jbc.M111.330779 |
| 22272280 | T-cell responses to the DBLalpha-tag, a short semi-conserved region of the Plasmodiumfalciparum membrane erythrocyte protein 1. | Gitau EN, Tuju J, ..., Urban BC | 10.1371/journal.pone.0030095 |
| 22347496 | Sequence polymorphism, segmental recombination and toggling amino acid residueswithin the DBL3X domain of the VAR2CSA placental malaria antigen. | Talundzic E, Shah S, ..., Peterson DS | 10.1371/journal.pone.0031565 |
| 22533832 | Evidence for in vitro and in vivo expression of the conserved VAR3 (type 3)plasmodium falciparum erythrocyte membrane protein 1. | Wang CW, Lavstsen T, ..., Turner L | 10.1186/1475-2875-11-129 |
| 22807674 | Structural basis for the ABO blood-group dependence of Plasmodium falciparumrosetting. | Vigan-Womas I, Guillotte M, ..., Mercereau-Puijalon O | 10.1371/journal.ppat.1002781 |
| 23209327 | A novel domain cassette identifies Plasmodium falciparum PfEMP1 proteins bindingICAM-1 and is a target of cross-reactive, adhesion-inhibitory antibodies. | Bengtsson A, Joergensen L, ..., Jensen AT | 10.4049/jimmunol.1202578 |
| 23475702 | Nuclear pores and perinuclear expression sites of var and ribosomal DNA genescorrespond to physically distinct regions in Plasmodium falciparum. | Guizetti J, Martins RM, ..., Scherf A | 10.1128/EC.00023-13 |
| 24343658 | Rosetting Plasmodium falciparum-infected erythrocytes bind to human brainmicrovascular endothelial cells in vitro, demonstrating a dual adhesion phenotypemediated by distinct P. falciparum erythrocyte membrane protein 1 domains. | Adams Y, Kuhnrae P, ..., Rowe JA | 10.1128/IAI.01233-13 |
| 24760153 | Kinetics of B cell responses to Plasmodium falciparum erythrocyte membraneprotein 1 in Ghanaian women naturally exposed to malaria parasites. | Ampomah P, Stevenson L, ..., Hviid L | 10.4049/jimmunol.1400325 |
| 24983235 | Inhibition of Plasmepsin V activity demonstrates its essential role in proteinexport, PfEMP1 display, and survival of malaria parasites. | Sleebs BE, Lopaticki S, ..., Boddey JA | 10.1371/journal.pbio.1001897 |
| 25064606 | The role of PfEMP1 adhesion domain classification in Plasmodium falciparumpathogenesis research. | Smith JD | 10.1016/j.molbiopara.2014.07.006 |
| 25703704 | Discovery of a novel and conserved Plasmodium falciparum exported protein that isimportant for adhesion of PfEMP1 at the surface of infected erythrocytes. | Nacer A, Claes A, ..., Mattei D | 10.1111/cmi.12430 |
| 26015475 | IgG antibodies to endothelial protein C receptor-binding cysteine-richinterdomain region domains of Plasmodium falciparum erythrocyte membrane protein1 are acquired early in life in individuals exposed to malaria. | Turner L, Lavstsen T, ..., Theander TG | 10.1128/IAI.00271-15 |
| 26094597 | Identification of the minimal binding region of a Plasmodium falciparum IgMbinding PfEMP1 domain. | Semblat JP, Ghumra A, ..., Rowe JA | 10.1016/j.molbiopara.2015.06.001 |
| 26222304 | Immunogenicity of the Plasmodium falciparum PfEMP1-VarO Adhesin: Induction ofSurface-Reactive and Rosette-Disrupting Antibodies to VarO Infected Erythrocytes. | Guillotte M, Juillerat A, ..., Mercereau-Puijalon O | 10.1371/journal.pone.0134292 |
| 26804201 | Global selection of Plasmodium falciparum virulence antigen expression by hostantibodies. | Abdi AI, Warimwe GM, ..., Bull PC | 10.1038/srep19882 |
| 26916885 | Plasmodium falciparum Plasmodium helical interspersed subtelomeric proteinscontribute to cytoadherence and anchor P. falciparum erythrocyte membrane protein1 to the host cell cytoskeleton. | Oberli A, Zurbrugg L, ..., Beck HP | 10.1111/cmi.12583 |
| 27907004 | In Vitro Variant Surface Antigen Expression in Plasmodium falciparum Parasitesfrom a Semi-Immune Individual Is Not Correlated with Var Gene Transcription. | Bruske EI, Dimonte S, ..., Frank M | 10.1371/journal.pone.0166135 |
| 28481333 | Regulation of PfEMP1-VAR2CSA translation by a Plasmodium translation-enhancingfactor. | Chan S, Frasch A, ..., Wahlgren M | 10.1038/nmicrobiol.2017.68 |
| 29349926 | Extracellular vesicles from early stage Plasmodium falciparum-infected red bloodcells contain PfEMP1 and induce transcriptional changes in human monocytes. | Sampaio NG, Emery SJ, ..., Eriksson EM | 10.1111/cmi.12822 |
| 29459671 | In silico guided reconstruction and analysis of ICAM-1-binding var genes fromPlasmodium falciparum. | Carrington E, Otto TD, ..., Craig AG | 10.1038/s41598-018-21591-8 |
| 30804381 | Cholesterol bound Plasmodium falciparum co-chaperone 'PFA0660w' complexes withmajor virulence factor 'PfEMP1' via chaperone 'PfHsp70-x'. | Behl A, Kumar V, ..., Mishra PC | 10.1038/s41598-019-39217-y |
| 31251748 | From genomic to LC-MS/MS evidence: Analysis of PfEMP1 in Benin malaria cases. | Kamaliddin C, Rombaut D, ..., Bertin GI | 10.1371/journal.pone.0218012 |
| 32732983 | In vitro selection for adhesion of Plasmodium falciparum-infected erythrocytes toABO antigens does not affect PfEMP1 and RIFIN expression. | van der Puije W, Wang CW, ..., Staalsoe T | 10.1038/s41598-020-69666-9 |
| 34035177 | Complement C1s cleaves Pf EMP1 at interdomain conserved sites inhibiting Plasmodium falciparum cytoadherence | Azasi Y, Low LM, ..., Miller LH | 10.1073/pnas.2104166118 |