About Gene List

PF3D7_0302500 (CLAG3.1)

Genome location: Pf3D7_03_v3:134,486..141,185(+)

Genome classification: Core

Function and Localization

Product Description: cytoadherence linked asexual protein 3.1

SignalP Peptide: MVSFFKTPIFILIIFLYLNEKVIC

# Transmembrane Domains: 0

EC Numbers: None

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:1903561 extracellular vesicle
Component GO:0030430 host cell cytoplasm
Component GO:0020002 host cell plasma membrane
Component GO:0005634 nucleus
Component GO:0020008 rhoptry
Function GO:0003723 RNA binding
Function GO:0005253 anion channel activity
Function GO:0050839 cell adhesion molecule binding
Function GO:0005515 protein binding
Process GO:0020035 cytoadherence to microvasculature, mediated by symbiont protein

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

Stage LR class MCA mean MCA prop. zeros
Sporozoite possibly expressed N/A N/A
Ring expressed 0.19 0.91
Trophozoite expressed 0.16 0.92
Schizont expressed 1.77 0.57
Gametocyte expressed 0.09 0.95

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0302500

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: -2.547 | #Insertions: 2

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1400600)

  • Relative Growth Rate: 0.28 ± 0.27
  • Confidence: 4.02

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: O77310

"Best" AlphaFill ligand hit: No AlphaFill hits

No associated EC numbers

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_149547

No human ortholog(s)

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 29 11 2 9
disruptive 62 22 17 33
missense 29 18 12 27

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 33 16 0 11
disruptive 69 41 19 48
missense 33 31 15 35

PlasmoDB Total SNPs: 698

Non-coding: 210 | Synonymous: 262 | Nonsynonymous: 226 | Stop Codon: 0

Protein Information

Protein Length: 1417 | Molecular Weight (kDa): 167.242

UniProt ID(s): A0A1W6IZJ1, A0A1W6IZJ5, B0M155, B0M162, O77310, Q4AE85

PDB ID(s): None

Isoelectric Point: 7.17

Protein Domain Annotations:

Source Family ID Description
InterPro IPR005553 Cytoadherence-linked asexual protein
PFam PF03805 Cytoadherence-linked asexual protein
Superfamily N/A N/A

Associated Publications

PMID Title Authors DOI/Link
10448855 The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum. Bowman S, Lawson D, ..., Barrell BG 10.1038/22964
10737759 clag9: A cytoadherence gene in Plasmodium falciparum essential for binding ofparasitized erythrocytes to CD36. Trenholme KR, Gardiner DL, ..., Kemp DJ 10.1073/pnas.040561197
12368867 Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. Hall N, Pain A, ..., Barrell BG 10.1038/nature01095
15953647 Apical expression of three RhopH1/Clag proteins as components of the Plasmodiumfalciparum RhopH complex. Kaneko O, Yim Lim BY, ..., Torii M https://pubmed.ncbi.nlm.nih.gov/15953647/
16267556 A protein interaction network of the malaria parasite Plasmodium falciparum. LaCount DJ, Vignali M, ..., Hughes RE 10.1038/nature04104
21320181 Functional analysis of epigenetic regulation of tandem RhopH1/clag genes revealsa role in Plasmodium falciparum growth. Comeaux CA, Coleman BI, ..., Duraisingh MT 10.1111/j.1365-2958.2011.07572.x
21620134 Malaria parasite clag3 genes determine channel-mediated nutrient uptake byinfected red blood cells. Nguitragool W, Bokhari AA, ..., Desai SA 10.1016/j.cell.2011.05.002
23819786 Epigenetic switches in clag3 genes mediate blasticidin S resistance in malariaparasites. Mira-Martinez S, Rovira-Graells N, ..., Cortes A 10.1111/cmi.12162
27299521 Malaria Parasite CLAG3, a Protein Linked to Nutrient Channels, Participates inHigh Molecular Weight Membrane-Associated Complexes in the Infected Erythrocyte. Zainabadi K 10.1371/journal.pone.0157390
28252383 Plasmodium falciparum parasites deploy Rhop H2 into the host erythrocyte to obtainnutrients, grow and replicate Counihan NA, Chisholm SA, ..., de Koning-Ward TF 10.7554/eLife.23217
28944300 Proteomic analysis of extracellular vesicles from a Plasmodium falciparum Kenyanclinical isolate defines a core parasite secretome. Abdi A, Yu L, ..., Rayner J 10.12688/wellcomeopenres.11910.2
29739907 C LAG3 Self-Associates in Malaria Parasites and Quantitatively Determines Nutrient Uptake Channels at the Host Membrane Gupta A, Balabaskaran-Nina P, ..., Desai SA 10.1128/mBio.02293-17
30379851 Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. Briquet S, Ourimi A, ..., Vaquero C 10.1371/journal.pone.0205596
32069335 Complex nutrient channel phenotypes despite Mendelian inheritance in a Plasmodiumfalciparum genetic cross. Gupta A, Bokhari AAB, ..., Desai SA 10.1371/journal.ppat.1008363
32900800 Live-Cell F RET Reveals that Malaria Nutrient Channel Proteins C LAG3 and Rhop H2Remain Associated throughout Their Tortuous Trafficking Ahmad M, Manzella-Lapeira J, ..., Desai SA 10.1128/mBio.01354-20
33906926 Functional Characterization of the m(6)A-Dependent Translational Modulator PfYTH Sinha A, Baumgarten S, ..., Scherf A 10.1128/mBio.00661-21
35393572 RhopH2 and RhopH3 export enables assembly of the RhopH complex on P.falciparum-infected erythrocyte membranes. Pasternak M, Verhoef JMJ, ..., Cowman AF 10.1038/s42003-022-03290-3
28089547 Antibody profiles to wheat germ cell-free system synthesized Plasmodiumfalciparum proteins correlate with protection from symptomatic malaria in Uganda Kanoi BN, Takashima E, ..., Tsuboi T 10.1016/j.vaccine.2017.01.001
17175193 The Plasmodium falciparum RhopH2 promoter and first 24 amino acids are sufficientto target proteins to the rhoptries Ghoneim A, Kaneko O, Tsuboi T, Torii M 10.1016/j.parint.2006.11.001
30782998 Identification of Antimalarial Compounds That Require CLAG3 for Their Uptake byPlasmodium falciparum-Infected Erythrocytes Mira-Martinez S, Pickford AK, ..., Rosanas-Urgell A 10.1128/AAC.00052-19
21306446 Heterochromatin formation in bistable chromatin domains controls the epigeneticrepression of clonally variant Plasmodium falciparum genes linked to erythrocyteinvasion Crowley VM, Rovira-Graells N, Ribas de Pouplana L, Cortes A 10.1111/j.1365-2958.2011.07574.x
22028613 Positive selection on the Plasmodium falciparum clag2 gene encoding a componentof the erythrocyte-binding rhoptry protein complex Alexandre JS, Kaewthamasorn M, ..., Kaneko O 10.2149/tmh.2011-12
28419281 Expression of the Plasmodium falciparum Clonally Variant clag3 Genes in HumanInfections Mira-Martinez S, van Schuppen E, ..., Cortes A 10.1093/infdis/jix053
26202963 Deciphering the principles that govern mutually exclusive expression ofPlasmodium falciparum clag3 genes Rovira-Graells N, Crowley VM, ..., Cortes A 10.1093/nar/gkv730
25573429 A role for adaptor protein complex 1 in protein targeting to rhoptry organellesin Plasmodium falciparum Kaderi Kibria KM, Rawat K, ..., Malhotra P 10.1016/j.bbamcr.2014.12.030
34446549 Native structure of the RhopH complex, a key determinant of malaria parasitenutrient acquisition Ho CM, Jih J, ..., Zhou ZH 10.1073/pnas.2100514118
17676953 Epigenetic silencing of Plasmodium falciparum genes linked to erythrocyteinvasion Cortes A, Carret C, ..., Holder AA 10.1371/journal.ppat.0030107