About Gene List

PF3D7_0424200 (RH4)

Genome location: Pf3D7_04_v3:1,085,641..1,091,369(-)

Genome classification: Core

Function and Localization

Product Description: reticulocyte binding protein homologue 4

SignalP Peptide: MNKNILWITFFYFLFFLLDMYQGNDA

# Transmembrane Domains: 2

EC Numbers: None

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0045177 apical part of cell
Component GO:0020008 rhoptry
Function GO:0008201 heparin binding
Function GO:0046789 host cell surface receptor 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 not expressed N/A N/A
Ring not expressed 0.66 0.80
Trophozoite not expressed 0.07 0.96
Schizont expressed 0.29 0.89
Gametocyte not expressed 0.06 0.97

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0424200

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

MIS: 0.12 | MFS: -2.964 | #Insertions: 0

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: C0H496

"Best" AlphaFill ligand hit: UDP (uridine-5'-diphosphate, Local RMSD=0.02) with 5H60 (Global RMSD=17.97)

No associated EC numbers

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_533485

No human ortholog(s)

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 10 49 36 79
disruptive 74 177 111 271
missense 42 147 100 226

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 15 105 52 83
disruptive 108 372 179 354
missense 65 298 156 271

PlasmoDB Total SNPs: 181

Non-coding: 25 | Synonymous: 80 | Nonsynonymous: 76 | Stop Codon: 0

Protein Information

Protein Length: 1716 | Molecular Weight (kDa): 205.847

UniProt ID(s): A0A159SJR8, A0A159SJU8, A0A159SJV5, A0A159SJW5, A0A159SJW8, A0A159SKE7, A0A159SLJ4, A0A159SLK1, A0A161F2L4, A0A164KFX7, A0A2S1Q7L8, A0A2S1Q7M1, A0A346RD93, A0A346RD99, A0A346RDC4, A0A346RDC7, C0H496, Q8MWH2, Q8MWP1, Q8MWP2, U6C8F2, U6C8T1, U6C8U7, U6C974

PDB ID(s): None

Isoelectric Point: 7.37

Protein Domain Annotations:

Source Family ID Description
InterPro N/A N/A
PFam N/A N/A
Superfamily N/A N/A

Associated Publications

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
16123303 Molecular mechanism for switching of P. falciparum invasion pathways into humanerythrocytes. Stubbs J, Simpson KM, ..., Cowman AF 10.1126/science.1115257
17971435 Recombinant Plasmodium falciparum reticulocyte homology protein 4 binds toerythrocytes and blocks invasion. Gaur D, Singh S, ..., Miller LH 10.1073/pnas.0708772104
19307208 Antibodies to reticulocyte binding protein-like homologue 4 inhibit invasion ofPlasmodium falciparum into human erythrocytes. Tham WH, Wilson DW, ..., Cowman AF 10.1128/IAI.00048-09
20855594 Complement receptor 1 is the host erythrocyte receptor for Plasmodium falciparumPfRh4 invasion ligand. Tham WH, Wilson DW, ..., Cowman AF 10.1073/pnas.1008151107
23028883 The Plasmodium falciparum erythrocyte invasion ligand Pfrh4 as a target offunctional and protective human antibodies against malaria. Reiling L, Richards JS, ..., Beeson JG 10.1371/journal.pone.0045253
24212193 Analyses of interactions between heparin and the apical surface proteins ofPlasmodium falciparum. Kobayashi K, Takano R, ..., Kato K 10.1038/srep03178
24214979 Using mutagenesis and structural biology to map the binding site for thePlasmodium falciparum merozoite protein PfRh4 on the human immune adherencereceptor. Park HJ, Guariento M, ..., Atkinson JP 10.1074/jbc.M113.520346
26324715 Characterization of Inhibitors and Monoclonal Antibodies That Modulate theInteraction between Plasmodium falciparum Adhesin PfRh4 with Its ErythrocyteReceptor Complement Receptor 1. Lim NT, Harder MJ, ..., Tham WH 10.1074/jbc.M115.657171
27244695 Identification of a reticulocyte-specific binding domain of Plasmodium vivaxreticulocyte-binding protein 1 that is homologous to the PfRh4erythrocyte-binding domain. Han JH, Lee SK, ..., Han ET 10.1038/srep26993
38132622 Demonstration of RNAi Yeast Insecticide Activity in Semi-Field Larvicide andAttractive Targeted Sugar Bait Trials Conducted on Aedes and Culex Mosquitoes Stewart ATM, Mysore K, ..., Duman-Scheel M 10.3390/insects14120950
37653544 Recent increase in low complexity polygenomic infections and sialicacid-independent invasion pathways in Plasmodium falciparum from Western Gambia Nganyewo NN, Bojang F, ..., Amambua-Ngwa A 10.1186/s13071-023-05929-4