About Gene List

PF3D7_1302200 (UIS3)

Genome location: Pf3D7_13_v3:123,360..124,429(-)

Genome classification: Core

Function and Localization

Product Description: protein UIS3

SignalP Peptide: N/A

# Transmembrane Domains: 2

EC Numbers: None

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0020005 symbiont-containing vacuole membrane
Function GO:0005515 protein binding

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 not expressed 0.21 0.90
Trophozoite not expressed 0.04 0.98
Schizont not expressed 0.04 0.97
Gametocyte not expressed 0.12 0.93

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1302200

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: -1.583 | #Insertions: 1

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PBANKA_1400800)

Modification: Disrupted | RMgm-4988

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IEU1

"Best" AlphaFill ligand hit: PTY (phosphatidylethanolamine, Local RMSD=0.14) with 2VWA (Global RMSD=0.47)

No associated EC numbers

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_532346

No human ortholog(s)

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 7 10 3 3
disruptive 6 17 9 24
missense 6 14 9 21

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 8 13 10 10
disruptive 9 43 20 56
missense 9 35 17 34

PlasmoDB Total SNPs: 50

Non-coding: 30 | Synonymous: 12 | Nonsynonymous: 8 | Stop Codon: 0

Protein Information

Protein Length: 229 | Molecular Weight (kDa): 26.831

UniProt ID(s): Q8IEU1, Q9NFU2, Q9NFU4

PDB ID(s): 2VWA

Isoelectric Point: 9.67

Protein Domain Annotations:

Source Family ID Description
InterPro IPR006389 Early transcribed membrane protein (ETRAMP)
InterPro IPR021626 Plasmodium falciparum UIS3 membrane protein
PFam PF09716 Early transcribed membrane protein (ETRAMP)
PFam PF11567 Plasmodium falciparum UIS3 membrane protein
Superfamily N/A N/A

Associated Publications

PMID Title Authors DOI/Link
12686607 etramps, a new Plasmodium falciparum gene family coding for developmentallyregulated and highly charged membrane proteins located at the parasite-host cellinterface. Spielmann T, Fergusen DJ, Beck HP 10.1091/mbc.e02-04-0240
29109477 Plasmodium UIS3 sequesters host LC3 to avoid elimination by autophagy inhepatocytes. Real E, Rodrigues L, ..., Mota MM 10.1038/s41564-017-0054-x
18466298 Targeted deletion of SAP1 abolishes the expression of infectivity factorsnecessary for successful malaria parasite liver infection Aly AS, Mikolajczak SA, ..., Kappe SH 10.1111/j.1365-2958.2008.06271.x
15922944 Genetically modified Plasmodium highlights the potential of whole parasitevaccine strategies Good MF 10.1016/j.it.2005.04.005
23169100 Evidence from NMR interaction studies challenges the hypothesis of direct lipidtransfer from L-FABP to malaria sporozoite protein UIS3 Favretto F, Assfalg M, Molinari H, D'Onofrio M 10.1002/pro.2194
21787828 Comparative efficacy of pre-erythrocytic whole organism vaccine strategiesagainst the malaria parasite Friesen J, Matuschewski K 10.1016/j.vaccine.2011.07.034
33214643 Disrupting Plasmodium UIS3-host LC3 interaction with a small molecule causesparasite elimination from host cells Setua S, Enguita FJ, ..., Mota MM 10.1038/s42003-020-01422-1
31936739 Synthetic DNA Vaccines Adjuvanted with pIL-33 Drive Liver-Localized T Cells andProvide Protection from Plasmodium Challenge in a Mouse Model Reeder SM, Reuschel EL, ..., Aly ASI 10.3390/vaccines8010021
35214758 An Attenuated HSV-1-Derived Malaria Vaccine Expressing Liver-Stage ExportedProteins Induces Sterilizing Protection against Infectious Sporozoite Challenge Rider PJF, Kamil M, ..., Aly ASI 10.3390/vaccines10020300
28031267 Assessment of the Plasmodium falciparum Preerythrocytic Antigen UIS3 as aPotential Candidate for a Malaria Vaccine Longley RJ, Halbroth BR, ..., Spencer AJ 10.1128/IAI.00641-16
27241521 Protective efficacy and safety of liver stage attenuated malaria parasites Kumar H, Sattler JM, ..., Frischknecht F 10.1038/srep26824
17303141 L-FABP is a critical host factor for successful malaria liver stage development Mikolajczak SA, Jacobs-Lorena V, ..., Kappe SH 10.1016/j.ijpara.2007.01.002
23840634 The ETRAMP family member SEP2 is expressed throughout Plasmodium berghei lifecycle and is released during sporozoite gliding motility Curra C, Di Luca M, ..., Ponzi M 10.1371/journal.pone.0067238
33771680 Plasmodium UIS3 avoids host cell-autonomous exclusion that requires GABARAPs butnot LC3 and autophagy Pradipta A, Bando H, ..., Yamamoto M 10.1016/j.parint.2021.102335
17624848 Protracted sterile protection with Plasmodium yoelii pre-erythrocytic geneticallyattenuated parasite malaria vaccines is independent of significant liver-stagepersistence and is mediated by CD8+ T cells Tarun AS, Dumpit RF, ..., Kappe SH 10.1086/519742
22004696 Immunization with genetically attenuated P52-deficient Plasmodium bergheisporozoites induces a long-lasting effector memory CD8+ T cell response in theliver Douradinha B, van Dijk M, ..., Epiphanio S 10.1186/1476-8518-9-6
18577521 Crystal structure of soluble domain of malaria sporozoite protein UIS3 in complexwith lipid Sharma A, Yogavel M, ..., Sharma A 10.1074/jbc.M801946200
17591958 Genetically attenuated Plasmodium berghei liver stages persist and elicit sterileprotection primarily via CD8 T cells Mueller AK, Deckert M, ..., Schluter D 10.2353/ajpath.2007.060792
19214236 Conserved protective mechanisms in radiation and genetically attenuated uis3(-)and uis4(-) Plasmodium sporozoites Kumar KA, Baxter P, ..., Nussenzweig V 10.1371/journal.pone.0004480
30067422 Plasmodium protein UIS3 protects the parasite from autophagy clearance Yao Z, Klionsky DJ 10.1080/15548627.2018.1483671
17624847 Genetically attenuated Plasmodium berghei liver stages induce sterile protractedprotection that is mediated by major histocompatibility complex Class I-dependentinterferon-gamma-producing CD8+ T cells Jobe O, Lumsden J, ..., Krzych U 10.1086/519743