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VOLUME NINETY ONE

ADVANCES IN
PARASITOLOGY
 SERIES EDITOR
D. ROLLINSON
Life Sciences Department
The Natural History Museum,
London, UK
d.rollinson@nhm.ac.uk
EDITORIAL BOARD
T. J. C. ANDERSON
Department of Genetics, Texas
Biomedical Research Institute,
San Antonio, TX, USA
M. G. BASÁÑEZ
Professor of Neglected Tropical
Diseases, Department of Infectious
Disease Epidemiology, Faculty of
Medicine (St Mary’s Campus),
Imperial College London,
London, UK
S. BROOKER
Wellcome Trust Research Fellow
and Professor, London School of
Hygiene and Tropical Medicine,
Faculty of Infectious and Tropical,
Diseases, London, UK
R. B. GASSER
Department of Veterinary Science,
The University of Melbourne,
Parkville, Victoria, Australia
N. HALL
School of Biological Sciences,
Biosciences Building, University of
Liverpool, Liverpool, UK
J. KEISER
Head, Helminth Drug
Development Unit, Department
of Medical Parasitology and
Infection Biology, Swiss Tropical
and Public Health Institute, Basel,
Switzerland
J. R. STOTHARD
Department of Parasitology
Liverpool School of Tropical
Medicine Liverpool, UK
russell.stothard@lstmed.ac.uk
R. C. OLIVEIRA
Centro de Pesquisas Rene Rachou/
CPqRR - A FIOCRUZ em Minas
Gerais, Rene Rachou Research
Center/CPqRR - The Oswaldo Cruz
Foundation in the State of Minas
Gerais-Brazil, Brazil
R. E. SINDEN
Immunology and Infection
Section, Department of Biological
Sciences, Sir Alexander Fleming
Building, Imperial College of
Science, Technology and
Medicine, London, UK
D. L. SMITH
Johns Hopkins Malaria Research
Institute & Department of
Epidemiology, Johns Hopkins
Bloomberg School of Public Health,
Baltimore, MD, USA
R. C. A. THOMPSON
Head, WHO Collaborating Centre
for the Molecular Epidemiology
of Parasitic Infections, Principal
Investigator, Environmental
Biotechnology CRC (EBCRC), School
of Veterinary and Biomedical
Sciences, Murdoch University,
Murdoch, WA, Australia
X.-N. ZHOU
Professor, Director, National
Institute of Parasitic Diseases,
Chinese Center for Disease Control
and Prevention, Shanghai, People’s
Republic of China
VOLUME NINETY ONE

ADVANCES IN
PARASITOLOGY
Edited by

D. ROLLINSON
Life Sciences Department
The Natural History Museum
London, UK

J.R. STOTHARD
Department of Parasitology
Liverpool School of Tropical Medicine
Liverpool, UK

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CONTRIBUTORS

Amy Abruzzi
Edward J. Bloustein School of Planning and Public Policy, Rutgers University,
New Brunswick, NJ, USA
Sukaina B. Alikhan
U.S. Fund for UNICEF, New York, NY, USA
Jason P. Andras
Zoological Institute, University of Basel, Basel, Switzerland; Department of Biological
Sciences, Mount Holyoke College, South Hadley, MA, USA
Frida Ben-Ami
Department of Zoology, George S. Wise Faculty of Life Sciences, Tel Aviv University,
Tel Aviv, Israel
Brian M. Cooke
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department
of Microbiology, Monash University, VIC, Australia
Ross L. Coppel
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department
of Microbiology, Monash University, VIC, Australia
David Duneau
Zoological Institute, University of Basel, Basel, Switzerland; Department Ecologie et
Diversité Biologique, University Paul Sabatier-Toulouse III, Toulouse, France
Louis Du Pasquier
Zoological Institute, University of Basel, Basel, Switzerland
Dieter Ebert
Zoological Institute, University of Basel, Basel, Switzerland
Bernard Fried
Lafayette College, Easton, PA, USA
Robin B. Gasser
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville,
VIC, Australia
Geoffrey N. Gobert
Molecular Parasitology Laboratory, Infectious Diseases Division, QIMR Berghofer Medical
Research Institute, Brisbane, QLD, Australia
Catherine A. Gordon
Molecular Parasitology Laboratory, Infectious Diseases Division, QIMR Berghofer Medical
Research Institute, Brisbane, QLD, Australia

ix j
x Contributors

Darren J. Gray
Research School of Population Health, The Australian National University, Canberra, ACT,
Australia
Matthew D. Hall
Zoological Institute, University of Basel, Basel, Switzerland; Monash University, School of
Biological Sciences, Clayton Campus, Melbourne, VIC, Australia
Anja Joachim
Institute of Parasitology, Department of Pathobiology, University of Veterinary Medicine
Vienna, Vienna, Austria
Malcolm K. Jones
Molecular Parasitology Laboratory, Infectious Diseases Division, QIMR Berghofer Medical
Research Institute, Brisbane, QLD, Australia; School of Veterinary Science, University of
Queensland, Brisbane, QLD, Australia
Pasi K. Korhonen
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville,
VIC, Australia
Pepijn Luijckx
Zoological Institute, University of Basel, Basel, Switzerland; Department of Ecology &
Evolutionary Biology, University of Toronto, Toronto, ON, Canada
Donald P. McManus
Molecular Parasitology Laboratory, Infectious Diseases Division, QIMR Berghofer Medical
Research Institute, Brisbane, QLD, Australia
Narla Mohandas
New York Blood Center, New York, NY, USA
Martina Ondrovics
Institute of Parasitology, Department of Pathobiology, University of Veterinary Medicine
Vienna, Vienna, Austria
Nicholas I. Proellocks
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department
of Microbiology, Monash University, VIC, Australia
Neil D. Young
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville,
VIC, Australia
Xing-Quan Zhu
State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary
Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy
of Agricultural Sciences, Lanzhou, Gansu Province, PR China
 CHAPTER ONE

Malaria Parasite Proteins and

Their Role in Alteration of the
Structure and Function of Red
Blood Cells
Nicholas I. Proellocks*, Ross L. Coppel*, Narla Mohandasx,
Brian M. Cooke*, 1
*Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of
Microbiology, Monash University, VIC, Australia
x
New York Blood Center, New York, NY, USA
1
Corresponding author: E-mail: brian.cooke@monash.edu

Contents
1. Introduction 2
2. Trafficking of Parasite Proteins into the RBC 4
2.1 The PEXEL motif 27
2.1.1 Plasmepsin V-mediated PEXEL function 28
2.1.2 PI(3)P-mediated PEXEL function 29
2.2 PEXEL-negative exported proteins 30
2.3 The role of PTEX 32
2.4 Protein trafficking within iRBCs 33
2.4.1 Vesicle-mediated trafficking 34
2.4.2 Chaperones 34
2.4.3 MCs: an external Golgi? 36
3. Exported Parasite Proteins 37
3.1 MC-associated proteins 38
3.1.1 Skeleton-binding protein 1 38
3.1.2 Membrane-associated histidine-rich protein 1 39
3.1.3 Membrane-associated histidine-rich protein 2 39
3.1.4 Ring-exported protein 1 40
3.1.5 Ring-exported protein 2 42
3.1.6 Other less-well characterized proteins associated with MCs 42
3.1.7 Parasite proteins and the tubovesicular network 43
3.2 Parasite proteins in the RBC cytosol or at the RBC membrane skeleton 44
3.2.1 Knob-associated histidine-rich protein 44
3.2.2 P. falciparum erythrocyte membrane protein 3 45
3.2.3 P. falciparum antigen 332 46
3.2.4 Plasmodium helical interspersed sub-telomeric proteins 47
3.2.5 Ring-infected erythrocyte surface antigen 52
Advances in Parasitology, Volume 91
© 2016 Elsevier Ltd.
j
ISSN 0065-308X
http://dx.doi.org/10.1016/bs.apar.2015.09.002 All rights reserved. 1
2 Nicholas I. Proellocks et al.

3.2.6 Proteins containing DnaJ domains 53

3.2.7 Mature-parasite-infected erythrocyte surface antigen 55
3.2.8 FIKK kinases 56
3.2.9 P. falciparum proteins involved in trafficking of PfEMP1 58
3.2.10 Other less-well characterized exported proteins 59
3.3 Proteins exposed on the surface of infected RBCs 59
3.3.1 P. falciparum erythrocyte membrane protein 1 60
3.3.2 RIFINs 63
3.3.3 STEVOR 64
3.3.4 SURFINS 64
3.3.5 Glycophorin-binding proteins 65
3.3.6 Cytoadherence-linked asexual gene 66
3.3.7 Other less-well characterized putative iRBC surface proteins 67
3.3.8 Exported proteins of sexual stage parasites 68
4. Alteration of Host RBC Proteins during Malaria Infection 69
5. Conclusion 69
References 71

Abstract
Malaria, caused by Plasmodium spp., continues to be a major threat to human health
and a significant cause of socioeconomic hardship in many countries. Almost half of
the world’s population live in malaria-endemic regions and many of them suffer one
or more, often life-threatening episodes of malaria every year, the symptoms of which
are attributable to replication of the parasite within red blood cells (RBCs). In the case of
Plasmodium falciparum, the species responsible for most malaria-related deaths, para-
site replication within RBCs is accompanied by striking alterations to the morphological,
biochemical and biophysical properties of the host cell that are essential for the para-
sites’ survival. To achieve this, the parasite establishes a unique and extensive protein
export network in the infected RBC, dedicating at least 6% of its genome to the process.
Understanding the full gamut of proteins involved in this process and the mechanisms
by which P. falciparum alters the structure and function of RBCs is important both for a
more complete understanding of the pathogenesis of malaria and for development of
new therapeutic strategies to prevent or treat this devastating disease. This review fo-
cuses on what is currently known about exported parasite proteins, their interactions
with the RBC and their likely pathophysiological consequences.

1. INTRODUCTION
Malaria in humans, caused by Plasmodium spp., remains a major cause
of morbidity, mortality and socioeconomic hardship in many areas of the
world, particularly Africa, South America and Asia. Almost half of the
Malaria Parasite Proteins and the RBC 3

world’s population lives in malaria-endemic regions making the develop-

ment and implementation of effective intervention strategies a global health
priority (Noor et al., 2014; Sachs, 2002; Snow et al., 2005). All of the clinical
symptoms of malaria are attributable to replication of the malaria parasite
within red blood cells (RBCs) and vary in severity depending on the parasite
species and the immune status of the infected host. In the case of Plasmodium
falciparum, the malaria species responsible for the vast majority of malaria-
related deaths, serious clinical complications arise because parasite-infected
RBCs (iRBCs) sequester in the microvasculature of various organs (Beare
et al., 2006; Cooke et al., 2000).
Parasite replication within RBCs is accompanied by striking alterations
to the morphological, biochemical and biophysical properties of the
iRBC. These changes have been most extensively studied in the case of
P. falciparum and consequently this review will largely concentrate on this
species. Unlike normal RBCs, iRBCs are rigid and poorly deformable
and adhere to the vascular endothelium or to other infected or uninfected
RBCs (Cooke et al., 2001, 2004a, 2005). For the parasite, which must main-
tain the mechanical integrity of the host RBC under haemodynamic stress,
collect nutrients from the extracellular environment, avoid the host immune
system and escape destruction by the spleen, these structural and functional
modifications of RBCs appear to be essential for its survival in vivo. On the
other hand, for the infected human, accumulation of iRBCs in the micro-
vasculature, perturbation of blood flow or partial or complete obstruction of
blood vessels by rheologically abnormal iRBCs results in severe and often
fatal clinical complications. Sequestration of iRBCs within the microvascu-
lature of the brain, for example results in cerebral malaria which is associated
with w10e15% mortality rate in some areas of the world (von Seidlein
et al., 2012). Sequestration of infected and uninfected RBCs by the spleen
results in anaemia which on occasion is life threatening. An understanding of
the mechanisms by which P. falciparum alters the structure and function of
RBCs is essential for the future development of new therapeutic strategies
to prevent or treat this severe and devastating disease.
At the molecular level, RBC modifications are mediated by a subset of
proteins that are secreted by the parasite beyond its own plasma membrane,
and selectively trafficked to various locations in the iRBC (Cooke et al.,
2004a; Maier et al., 2009). Bioinformatic analysis of the genome of P. falcip-
arum parasites reveals that about 6% of its genome encodes proteins that are
destined for export into the RBC (Hiller et al., 2004; Marti et al., 2004).
While some of these proteins, as well as others involved in their export
4 Nicholas I. Proellocks et al.

and trafficking, have been identified and characterized, the process remains
poorly understood. This review focuses on the current state of our knowl-
edge of exported parasite proteins, their interactions with RBCs and their
likely role in the pathogenesis of falciparum malaria.

2. TRAFFICKING OF PARASITE PROTEINS

INTO THE RBC
During the blood stage of malaria infection, the parasite invades, ma-
tures and replicates in RBCs over a period of 24e72 h, depending on the
parasite species. RBCs are atypical eukaryotic cells in that they do not contain
any of the organelles necessary for de novo protein synthesis or components
for protein trafficking. To survive in this resource-poor cellular environment,
essentially a membrane-bound ‘corpuscle’ of aqueous haemoglobin, the
parasite must establish its own network of protein trafficking machinery
and extensively embellish the corpuscular architecture. This complex process
involves the export of a large number of parasite proteins to the RBC
(Tables 1e5). The mechanism by which parasite proteins are exported has
been the subject of considerable research, debate and controversy over the
past few years. All species of malaria parasites export proteins into their
host RBC; however, from the evidence amassed so far, P. falciparum builds
the most elaborate export pathways and exports the greatest number of
parasite-encoded proteins. Construction of this export machinery begins
immediately after the parasite has invaded the RBC. Recent evidence sug-
gests that of the parasites invasion-related organelles, the rhoptry contains
components that build the parasitophorous vacuolar membrane (PVM)
and parasitophorous vacuole (PV) in which the parasite resides for the dura-
tion of its lifetime in RBCs as well as proteins that are directly exported into
the iRBC, such as the RhopH complex of proteins (Riglar et al., 2013;
Zuccala et al., 2012). Shortly after rhoptry contents are released during the
initial stages of parasite invasion, proteins are expelled from another parasite
organelle, the dense granules, that contain components required for later
export of parasite proteins (Bullen et al., 2012; Riglar et al., 2013). These
early stages of establishing a protein trafficking infrastructure are critical for
the survival of the parasite as protein export begins very early in the parasites’
life cycle, with the Ring-Exported Surface Antigen (RESA) being exported
to RBC membrane within 12 min after invasion (Riglar et al., 2013). Sub-
sequently, export of numerous, functionally diverse proteins into the RBC
then continues throughout the parasite’s life cycle until the RBC is finally
Table 1 Exported proteins in P. falciparum blood-stage parasites

Malaria Parasite Proteins and the RBC

Protein name Gene id Localization Comments References

SBP1 PF3D7_0501300 (PFE0065w) Maurer’s clefts Binds to the RBC membrane Blisnick et al. (2000),
skeleton; involved in Cooke et al. (2006),
PfEMP1 trafficking Maier et al. (2007)
MAHRP1 PF3D7_1370300 (MAL 13P1.413) Maurer’s clefts Involved in Pf EMP1 Spycher et al. (2003,
trafficking 2008)
MAHRP2 PF3D7_1353200 (PF13_0276) Maurer’s clefts - Involved in the formation of Pachlatko et al. (2010)
tethers tethers
REX1 PF3D7_0935900 (PFI1735c) Maurer’s clefts Required for formation of Dixon et al. (2008,
Maurer’s clefts; involved in 2011), Hanssen et al.
Pf EMP1 trafficking (2008a), Hawthorne
et al. (2004)
REX2 PF3D7_0936000 (PFI1740c) Maurer’s clefts Integral membrane protein in Haase et al. (2009),
Maurer’s clefts; unknown Spielmann et al.
function (2006)
Pf PTP1 PF3D7_0202200 (PFB0106c) Maurer’s clefts and Required for formation of Maier et al. (2008), Rug
iRBC Maurer’s clefts; involved in et al. (2014)
cytoplasm PfEMP1 and STEVOR
trafficking to Maurer’s clefts
Pf MC-2TM PF3D7_0114100 (PFA0680c) Maurer’s clefts Two transmembrane domains; Sam-Yellowe et al.
PF3D7_0101300 (PFA0065w) subfamily of STEVOR; (2004), Tsarukyanova
PF3D7_0222100 (PFB0985c) unknown function et al. (2009)
PF3D7_0221500 (PFB0960c)
PF3D7_0324100 (PFC1080c)
PF3D7_0601200 (PFF0060w)
PF3D7_ 0631400 (MAL6P1.15)
PF3D7_0701600 (MAL7P1.5)

5
(Continued)
Table 1 Exported proteins in P. falciparum blood-stage parasitesdcont'd

6
Protein name Gene id Localization Comments References
PF3D7_0713100 (MAL7P1.58)
PF3D7_0700800 (MAL8P1.213)
PF3D7_1039700 (PF10_0390)
PF3D7_1101700 (PF11_0025)
PF3D7_1100800 (PF11_0014)
PCRMPs PF3D7_0911300 (PFI0550w) Maurer’s clefts; Expressed throughout the Thompson et al. (2007)
PF3D7_0718300 (MAL7P1.92) sporozoite parasite’s life cycle;
PF3D7_1208200 (PFL0410w) surface unknown function
PF3D7_1475400 (PF14_0722)
Sec31p PF3D7_0214100 (PFB0640c) Maurer’s clefts Vesicle trafficking Adisa et al. (2001)
Sec23p PF3D7_0822600 (PF08_0036) Maurer’s clefts Vesicle trafficking Wickert et al. (2003a)
Sar1p PF3D7_0416800 (PFD0810w) Maurer’s clefts Vesicle trafficking Albano et al. (1999)
Pf NSF PF3D7_0303000 (PFC0140c) iRBC cytosol, Vesicle fusion component Hayashi et al. (2001)
possible Maurer’s
clefts
Pf J23 PF3D7_1001900 (PF10_0023) Maurer’s clefts Unknown function Vincensini et al. (2005)
ETRAMP PF3D7_0202500 (PFB0120w) iRBC periphery; Small proteins expressed at Birago et al. (2003),
PF3D7_0423700 (PFD1120c) parasite plasma different times throughout Spielmann et al.
PF3D7_0532100 (PFE1590w) membrane (PPM); the RBC cycle; unknown (2003)
PF3D7_0829600 (MAL8P1.6) parasitophorous function

Nicholas I. Proellocks et al.

PF3D7_0936100 (PFI1745c) vacuolar
PF3D7_1001500 (PF10_0019) membrane (PVM);
PF3D7_1033200 (PF10_0323) Maurer’s clefts
PF3D7_1016900 (PF10_0164)
PF3D7_1102700 (PF11_0039)
PF3D7_1102800 (PF11_0040)
PF3D7_1240100 (PFL1945c)
 PF3D7_1302200 (PF13_0012)

Malaria Parasite Proteins and the RBC

PF3D7_1401400 (PF14_0016)
PF3D7_1476100 (PF14_0729)
PF07_0007 PF3D7_0702400 Maurer’s clefts; Unknown function Heiber et al. (2013),
iRBC cytosol Oehring et al. (2012)
PF07_0008 PF3D7_0702500 Maurer’s clefts; Unknown function Heiber et al. (2013)
iRBC cytosol
PF08_0003 PF3D7_0830500 Maurer’s clefts Unknown function; Heiber et al. (2013)
tryptophan/threonine-rich
antigen
PF11_0505 PF3D7_1148900 Maurer’s clefts Unknown function Heiber et al. (2013)
PF14_0045 PF3D7_1404800 iRBC cytoplasm Unknown function Heiber et al. (2013)
PF08_0004 PF3D7_0830400 Maurer’s clefts Unknown function Heiber et al. (2013)
PF08_0005 PF3D7_0830300 Maurer’s clefts Unknown function Heiber et al. (2013)
PFF0090w PF3D7_0601900 Maurer’s clefts Unknown function Heiber et al. (2013)
PFL0065w PF3D7_1201300 Maurer’s clefts Unknown function; suggested Frech and Chen (2013),
to be part of the ETRAMP Heiber et al. (2013)
family
PFL2515c PF3D7_1252300 Maurer’s clefts Unknown function Heiber et al. (2013)
MSRP5 PF3D7_1334300 (PF13_0191) iRBC cytosol; Unknown function; Heiber et al. (2013)
external face of the MSP7-related protein
PVM
MSRP6 PF3D7_1334500 (PF13_0192) Maurer’s clefts Unknown function; Heiber et al. (2013)
MSP7-related protein
SEMP1 PF3D7_0702400 (PF07_0007) Maurer’s clefts Unknown function Dietz et al. (2014)
MSRP7 PF3D7_1334700 (PF13_0194) iRBC cytoplasm; Unknown function; Heiber et al. (2013)
external face of the MSP7-related protein
PVM
EVP1 PF3D7_0410000 (PFD0495c) TVN Involved in lipid dynamics Tamez et al. (2008)

7
in the TVN
(Continued)
Table 1 Exported proteins in P. falciparum blood-stage parasitesdcont'd
Protein name Gene id
TVN-JP1 PF3D7_0310400 (PFC0435w)
PfEMP1 Multigene family (w60 copies)
RIFIN Multigene family (w200 copies)
STEVOR Multigene family (w30 copies)
SURFIN PF3D7_0113100 (PFA0625w)
PF3D7_0113600 (PFA0650w)
PF3D7_0115000 (PFA0725w)
PF3D7_0402200 (PFD0100c)
PF3D7_0424400 (PFD1160w)
PF3D7_0800700 (MAL8P1.162)
PF3D7_0830800 (PF08_0002)
PF3D7_081100 (MAL8P1.1)
PF3D7_1301800 (PF13_0074)
PF3D7_1477600 (PF14_0747)
8
Localization Comments References
TVN Possibly required for van Ooij et al. (2008)
formation of the TVN
iRBC surface Bind to multiple host cell
expressed receptors; key
mediator of virulence
iRBC surface Two sub-groups. RIFIN A Cheng et al. (1998),
(involved in antigenic Fernandez et al.
variation) and RIFIN B (1999), Kyes et al.
(localizes to the PV; (1999), Petter et al.
unknown function) (2007)
iRBC surface Clonally expressed on the Cheng et al. (1998),
iRBC surface; involved in Niang et al. (2009),
antigenic variation and Sanyal et al. (2012)
regulation of iRBC
membrane mechanical
properties
iRBC and merozoite Unknown function Winter et al. (2005)
surface
Nicholas I. Proellocks et al.

GBP130 PF3D7_1016300 (PF10_0159)
(GBPH) PF3D7_1301200 (PF13_0010)
PF3D7_1401000 (PF14_0010)
PF3D7_1462300 (PF14_0593)
CLAG PF3D7_0220800 (PFB0935w)
PF3D7_0302200 (PFC0110w)
PF3D7_0302500 (PFC0120w)
PF3D7_0831600 (MAL7P1.229)
PF3D7_0935800 (PFI1730w)
PHISTa See PHIST Table
PHISTb See PHIST Table
PHISTc See PHIST Table
RESA PF3D7_0102200 (PFA0110w)
KAHRP PF3D7_0202000 (PFB0100c)
iRBC surface Binds to glycophorin;
involved in altered RBC
membrane rigidity;
GBHP-2 is essential
Rhoptries, Part of the RhopH complex; Gardiner et al. (2004),
transferred to possible alternative
newly invaded functions once in the iRBC;
iRBC membrane roles in cytoadhesion and
and surface nutrient uptake (new
exposed permeability pathway
NPP); represent a possible
novel group of rhoptry
proteins localizing to the
iRBC following invasion
iRBC membrane Involved in altering RBC
membrane mechanical
properties; required for
stabilization of spectrin and
the iRBC membrane under
heat stress
iRBC membrane; Essential for knob formation
knobs and anchoring PfEMP1 at
knobs and iRBC membrane
skeleton
Malaria Parasite Proteins and the RBC
Maier et al. (2008),
Nolte et al. (1991),
Perkins (1988)
Kaneko et al. (2001,
2005), Ling et al.
(2004), Nguitragool
et al. (2011, 2014),
Trenholme et al.
(2000)
Sargeant et al. (2006)
Sargeant et al. (2006)
Sargeant et al. (2006)
Maier et al. (2008), Pei
et al. (2007a),
Sargeant et al. (2006),
Silva et al. (2005)
Magowan et al. (2000),
Rug et al. (2006),
Waller et al. (1999,
2002)
(Continued)
9
Table 1 Exported proteins in P. falciparum blood-stage parasitesdcont'd
Protein name Gene id Localization Comments References

10
PfEMP3 PF3D7_0201900 (PFB0095c) iRBC membrane Binds to spectrin at the iRBC Waller et al. (2007),
membrane skeleton Waterkeyn et al.
(2000)
Pf332 PF3D7_1149000 (PF11_0507) Maurer’s clefts; Dual role; decrease of iRBC Glenister et al. (2009),
iRBC membrane membrane rigidity and role Hinterberg et al.
in adhesion; binds to actin at (1994), Hodder et al.
the iRBC membrane (2009), Mattei and
skeleton Scherf (1992), Waller
et al. (2010)
DnaJs/Hsp40 See Table 4 Botha et al. (2007),
Sargeant et al. (2006)
MESA PF3D7_0500800 (PFE0040c) iRBC membrane Binds to protein 4.1R at the Bennett et al. (1997),
(PfEMP2) skeleton RBC membrane skeleton; Black et al. (2008),
unknown function Waller et al. (2003)
FIKK Kinases See Table 5 Schneider and
Mercereau-Puijalon
(2005), Ward et al.
(2004)
hyp1 e hyp17 60e70 members Unknown No known function; some Frech and Chen (2013),
gene families members have been Silvestrini et al. (2010)

Nicholas I. Proellocks et al.

detected in gametocytes
PfHsp70x PF3D7_0831700 (MAL7P1.228) J-Dots; iRBC Interacts with the exported K€ulzer et al. (2012)
cytoplasm type II DnaJs, possible role
in PfEMP1 trafficking
REX3 PF3D7_0936300 (PFI1755c) iRBC cytoplasm; Unknown function Maier et al. (2008),
detected in Silvestrini et al.
gametocytes (2010), Spielmann
et al. (2006)
REX4 PF3D7_0936400 (PFI1760w) iRBC cytoplasm; Unknown function Silvestrini et al. (2010),

Malaria Parasite Proteins and the RBC

detected in Spielmann et al.
gametocytes (2006)
PF14_0758 PF3D7_1478600 iRBC cytoplasm Involved in PfEMP1 Boddey and Cowman
(PfPTP3) trafficking and decreasing (2013), Maier et al.
membrane rigidity (2008)
MAL7P1.171 PF3D7_0730900 Unknown Involved in PfEMP1 Boddey and Cowman
(PfPTP4) trafficking and increasing (2013), Ikadai et al.
membrane rigidity; (2013), Maier et al.
disruption of the gene arrest (2008)
development of
gametocytes at stage I
PF10_0025 PF3D7_1002100 Unknown Involved in PfEMP1 Boddey and Cowman
(PfPTP5) trafficking and increasing (2013), Maier et al.
membrane rigidity (2008)
PF13_0076 PF3D7_1302000 Unknown Involved in PfEMP1 Boddey and Cowman
(PfPTP6) trafficking (2013), Maier et al.
(2008)
HRP2 PF3D7_0831800 (MAL7P1.231) iRBC cytosol Role in haem detoxification Papalexis et al. (2001),
Sullivan et al. (1996)
HRP3 PF3D7_1372200 (MAL13P1.480) Unknown Unknown function Rock et al. (1987)
GARP PF3D7_0113000 (PFA0620c) Unknown Unknown function Maier et al. (2008),
Triglia et al. (1988)
PIESP1 PF3D7_0310400 (PFC0435w) iRBC surface Essential; unknown function Florens et al. (2004),
Maier et al. (2008)
PIESP2/PfE60 PF3D7_0501200 (PFE0060w) iRBC surface or Unknown function Florens et al. (2004),
Maurer’s clefts Maier et al. (2008),
Vincensini et al.
(2005)

11
(Continued)
Table 1 Exported proteins in P. falciparum blood-stage parasitesdcont'd

12
Protein name Gene id Localization Comments References
LSA3 PF3D7_0220000 (PFB0915w) Hepatocyte surface; Unknown function; expressed Aidoo et al. (2000),
unknown in the in the RBC and liver stage; Guerin-Marchand
iRBC liver stage vaccine candidate et al. (1987), Maier
et al. (2008), Moyano
et al. (2007),
Silvestrini et al. (2010)
PfAARP1 PF3D7_1233600 (PFL1620w) iRBC membrane Unknown function Barale et al. (1997b)
PfAARP2 PF3D7_0106700 (PFA0330w) iRBC cytosol Unknown function Barale et al. (1997a)
PfGCN20 PF3D7_1121700 (PF11_0225) iRBC cytosol Unknown function Bozdech et al. (1998)
PfTKL2 PF3D7_1121300 (PF11_0220) IRBC cytosol in Active kinase, also secreted Abdi et al. (2013)
close proximity to beyond the iRBC
membrane
PF07_0087 PF3D7_0721100 Unknown Expressed in trophozoites; Silvestrini et al. (2010)
unknown function
PF11_0508 PF3D7_1149100.1/ Unknown Expressed in trophozoites; Silvestrini et al. (2010)
PF3D7_1149100.2 unknown function
PF13_0275 PF3D7_1353100 Unknown Expressed in trophozoites; Silvestrini et al. (2010)
unknown function
PFA0210c PF3D7_0104200 Unknown Expressed in trophozoites; Silvestrini et al. (2010)
unknown function

Nicholas I. Proellocks et al.

PFC0085c PF3D7_0301700 Unknown Expressed in trophozoites; Silvestrini et al. (2010)
unknown function
PFE0050w PF3D7_0501000 Unknown Expressed in trophozoites; Silvestrini et al. (2010)
unknown function
GEXP03 PF3D7_1429600 (PF14_0275) Unknown Expressed in early gametocytes Silvestrini et al. (2010)
GEXP13 PF3D7_0831300 (MAL8P1.205) Unknown Expressed in early gametocytes Silvestrini et al. (2010)
 Malaria Parasite Proteins and the RBC
GEXP14 PF3D7_1133400 (PF11_0038) Unknown Expressed in early gametocytes Silvestrini et al. (2010)
GEXP16 PF3D7_1407800 (PF14_0075) Unknown Expressed in early gametocytes Silvestrini et al. (2010)
GEXP18 PF3D7_0402400 (PFD0115c) Unknown Expressed in early gametocytes Silvestrini et al. (2010)
GEXP19 PF3D7_0111400 (PFA0550w) Unknown Expressed in early gametocytes Silvestrini et al. (2010)
GEXP22 PF3D7_0935500 (PFI1715w) Unknown Expressed in early gametocytes Silvestrini et al. (2010)
PFA0225w PF3D7_0104400 Unknown Expressed in mature Silvestrini et al. (2010)
gametocytes
MDR5 PF3D7_1339900 (PF13_0218) Unknown Putative ABC transporter Silvestrini et al. (2010)
(MDR family); expressed in
mature gametocytes
PF13_0317 PF3D7_1360000 Unknown Expressed in mature Silvestrini et al. (2010)
gametocytes
FP1 PF3D7_1458000 (PF14_0553) Unknown cysteine proteinase falcipain 1; Silvestrini et al. (2010)
expressed in mature
gametocytes
PFE1615c PF3D7_0532600 Unknown Expressed in gametocytes; Ikadai et al. (2013)
possible role in
gametocytogenesis
PfPI3K PF3D7_0515300 (PFE0765w) Food vacuole; PM/ Type III phosphatidylinositol Vaid et al. (2010)
PVM; iRBC 3-kinase, catalyses
cytosol formation of PI(3)P, PI(3,4)
P2 and PI(3,4,5)P3; found
in multiple locations
including the periphery of
the iRBC; involved in
haemoglobin uptake
Abbreviations: RBC, Red Blood Cell; PV, Parasitophorous Vacuole; PVM, Parasitophorous Vacuolar Membrane; TVN, Tubovesicular Network.

13
14 Nicholas I. Proellocks et al.

Table 2 Protein interactions at the iRBC membrane skeleton

Binding
constants
Interacting proteins Kd (mM) References

MESA/protein 4.1 0.63e1.25 Bennett et al. (1997), Waller et al. (2003)

KAHRP/ankyrin 1.3e8.3 Magowan et al. (2000), Weng et al. (2014)
KAHRP/PfEMP1 0.01e13.0 Oh et al. (2000), Waller et al. (1999, 2002)
KAHRP/actin NQ Kilejian et al. (1991), Oh et al. (2000)
KAHRP/a spectrin 0.0018 Kilejian et al. (1991), Oh et al. (2000),
Pei et al. (2005)
PfEMP1/actin 0.04 Oh et al. (2000)
PfEMP1/a spectrin NQ Oh et al. (2000)
PfEMP3/actin NQ Waller et al. (2007)
PfEMP3/a spectrin 0.07 Pei et al. (2007b), Waller et al. (2007)
Pf332/Actin 0.4 Waller et al. (2010)
PHIST/PfEMP1 w150 Mayer et al. (2012)
PF10_0378 (MEC)/ NQ Kilili and LaCount (2011)
Protein 4.1
SBP1/a spectrin NQ Blisnick et al. (2000)
RESA/b spectrin 0.00088 Pei et al. (2007a)
Kd is the dissociation constant. NQ is not quantified.

lysed and multiple new parasites are released. In general, exported parasite
proteins are directed into the parasites’ secretory pathway, usually by the
presence of N-terminal signal sequences (Hiller et al., 2004; Marti et al.,
2004); however, in some cases, the presence of a C-terminal transmembrane
domain is also required (Gr€uring et al., 2012; Saridaki et al., 2009). Once pro-
teins are directed into the parasite’s endoplasmic reticulum (ER) and enter
the secretory pathway, they are then committed for export into the RBC
by the recognition and cleavage of a signature sequence at the N-terminus
of the protein, termed the Plasmodium EXport ELement (PEXEL) or the
Vacuolar Transport Signal (VTS) (Hiller et al., 2004; Marti et al., 2004).
The proteins are then trafficked into the PV, by a yet unidentified mecha-
nism, and then directed to a transporter in the PVM, termed Plasmodium
translocon of exported proteins (PTEX) (de Koning-Ward et al., 2009),
where they are first unfolded before being translocated across the PVM
into the RBC cytosol (Gehde et al., 2009; Gr€ uring et al., 2012), then onto
their final cellular destination. Several mechanisms for this final step of the
trafficking process have been proposed and include vesicle transport, trans-
port in soluble complexes and chaperone-mediated transport (K€ ulzer et al.,
2010; McMillan et al., 2013; Saridaki et al., 2009) (Figure 1).
Table 3 P. falciparum exported proteins containing a PHIST domain

Malaria Parasite Proteins and the RBC

PHIST Gene id PEXEL Comments References
PHISTa
PF3D7_0402000 (PFD0090c) RNLSE Localizes to the PMV; interacts Maier et al. (2008), Parish
with a sub-population of 4.1R; et al. (2013), Sargeant
unknown function et al. (2006)
PF3D7_1478000 (PF14_0752) RNLTE Up-regulated in highly Mok et al. (2007), Sargeant
cytoadherent clones of 3D7 et al. (2006)
PF3D7_1253300 (PFL2565w) RNLAQ Only other PHISTa with Sargeant et al. (2006)
detectable transcript in asexual
3D7 blood-stage parasites
PF3D7_0102000 (PFA0100c) Negative Sargeant et al. (2006)
PF3D7_0424900 (PFD1185w) RNLVQ Sargeant et al. (2006)
PF3D7_0425300 (PFD1210w) Negative Sargeant et al. (2006)
PF3D7_0425400 (PFD1215w) RNLVQ Sargeant et al. (2006)
PF3D7_0601700 (MAL6P1.21) RNLSE Pseudogene Sargeant et al. (2006)
PF3D7_0819500 (MAL8P1.63) RKNIE Sargeant et al. (2006)
ACBP1 PF3D7_1001100.1/ Negative Two annotated genes in the same Frech and Chen (2013),
PF3D7_1001100.2 (PF10_0014/ location, representing different Sargeant et al. (2006)
PF10_0015) isoforms of acyl-CoA-binding
protein 1 (ACBP1)
PF3D7_1001300 (PF10_0017) RTLSE Sargeant et al. (2006)
PF3D7_1100600 (PF11_0012) Negative Pseudogene Sargeant et al. (2006)
PF3D7_1149700 (PF11_0514) Negative Sargeant et al. (2006)
PF3D7_1253100 (PFL2555w) RNLCE Sargeant et al. (2006)
PF3D7_1253900 (PFL2595w) RNLSE Psuedogene Sargeant et al. (2006)
PF3D7_1301100 (MAL13P1.11) RNLSE Pseudogene Sargeant et al. (2006)

15
(Continued)
Table 3 P. falciparum exported proteins containing a PHIST domaindcont'd
PHIST Gene id PEXEL Comments References

16
PF3D7_1301500 (MAL13P1.59) Negative Sargeant et al. (2006)
PF3D7_1372000 (MAL13P1.470) RNLSE Sargeant et al. (2006)
PF3D7_1400900 (PF14_0009) RNLSE Pseudogene Sargeant et al. (2006)
Pfg14.748 PF3D7_1477700 (PF14_0748) Negative Expressed and localized to the PV Eksi et al. (2005), Sargeant
in gametocytes et al. (2006), Silvestrini
et al. (2010)
PF3D7_1478500 (PF14_0757) RNLSE Pseudogene Sargeant et al. (2006)
PF3D7_1479200 (PF14_0763) RNLVQ Sargeant et al. (2006)
PF3D7_1479300 (PF14_0764) RNLSE Pseudogene Sargeant et al. (2006)
Pfg14.744 PF3D7_1477300 (PF14_0744) RSLSE Localized to the iRBC in Eksi et al. (2005), Frech and
gametocytes Chen (2013), Silvestrini
et al. (2010)
Pfg14.745 PF3D7_1477400 (PF14_0745) RSVND Expressed in gametocytes Eksi et al. (2005), Frech and
Chen (2013), Silvestrini
et al. (2010)
GEXP13 PF3D7_0831300 (MAL8P1.205) RKLSE Expressed in gametocytes Frech and Chen (2013),
Silvestrini et al. (2010)
PHISTb
PfD80 PF3D7_0401800 (PFD0080c) RNLSE Essential; possibly integral Maier et al. (2008), Pease et

Nicholas I. Proellocks et al.

PF3D7_0402100 (PFD0095c)
PF3D7_0424600 (PFD1170c)
membrane protein; localizes
to iRBC membrane; highly
phosphorylated
RKLYHE Expressed in trophozoites;
essential; contains a MEC
domain binds to IOVs
RILSE Involved in knob formation;
membrane associated
al. (2013), Sargeant et al.
(2006), Tarr et al. (2014),
Vincensini et al. (2005)
Kilili and LaCount (2011),
Maier et al. (2008),
Sargeant et al. (2006),
Silvestrini et al. (2010)
Florens et al. (2004), Maier
et al. (2008), Sargeant
 et al. (2006), Tarr et al.

Malaria Parasite Proteins and the RBC

(2014)
GEXP02 PF3D7_1102500 (PF11_0037) RNLYE Expressed in gametocytes; Maier et al. (2008),
unknown function Sargeant et al. (2006),
Silvestrini et al. (2010)
PF3D7_1401600 (PF14_0018) RSLYE Involved in iRBC increasing Kilili and LaCount (2011),
membrane rigidity; contains a Maier et al. (2008),
MEC domain Sargeant et al. (2006)
PF3D7_1201000 (PFL0050c) RILSS Membrane associated; two Florens et al. (2004), Maier
PHISTb domains et al. (2008), Sargeant
et al. (2006)
PfG174 PF3D7_0731300 (MAL7P1.174) RILSE Expressed in gametocytes; Maier et al. (2008),
unknown function Sargeant et al. (2006),
Vincensini et al. (2005)
PF3D7_0936900 (PFI1785w) RILSE Up-regulated in women with Sargeant et al. (2006),
pregnancy-associated malaria; Tuikue Ndam et al.
psuedogene (2008)
PF3D7_1252800 (PFL2540w) RILCT Contains a MEC domain Kilili and LaCount (2011),
Sargeant et al. (2006)
PF3D7_0601500 (PFF0075c) Negative Contains two MEC domains Kilili and LaCount (2011),
Sargeant et al. (2006)
PF3D7_0631100 (PFF1510w) RNLSE Contains two MEC domains; Kilili and LaCount (2011),
binds IOVs Sargeant et al. (2006)
PF3D7_0902700 (PFI0130c) RNLHE Contains a MEC domain; Kilili and LaCount (2011),
pseudogene Sargeant et al. (2006)
PF3D7_0937000 (PFI1790w) Negative Contains a MEC domain; binds Kilili and LaCount (2011),
IOVs Sargeant et al. (2006)
(Continued)

17
Table 3 P. falciparum exported proteins containing a PHIST domaindcont'd
PHIST Gene id
PF3D7_0201600 (PFB0080c)
PF3D7_0424800 (PFD1180w)
PF3D7_0532300 (PFE1600w)
LyMP PF3D7_0532400 (PFE1605w)
PF3D7_0702100 (MAL7P1.7)
GEXP09 PF3D7_0831000 (MAL8P1.2)
PF3D7_1252700 (PFL2535w)
GEXP04 PF3D7_1372100 (MAL13P1.475)
PF3D7_1476200 (PF14_0731)
PF3D7_1476300 (PF14_0732)
PF3D7_1477500 (PF14_0746)
PHISTb + DnaJ
RESA PF3D7_0102200 (PFA0110w)
18
PEXEL Comments References
RNLSS Localizes to iRBC cytosol; Goel et al. (2014), Sargeant
possibly involved in regulation et al. (2006), Tarr et al.
of VAR2CSA expression (2014)
RILST Sargeant et al. (2006)
RNLCE Sargeant et al. (2006)
RKLCE Localizes to and associates with Oberli et al. (2014),
iRBC membrane skeleton; role Proellocks et al. (2014),
in cytoadhesion Sargeant et al. (2006)
RILIE Pseudogene Sargeant et al. (2006)
Negative Expressed in gametocytes Sargeant et al. (2006),
Silvestrini et al. (2010)
RTLFE Localizes to iRBC membrane Sargeant et al. (2006), Tarr
et al. (2014)
RSLLG Expressed in gametocytes Sargeant et al. (2006),
Silvestrini et al. (2010)
Negative Localizes to iRBC membrane Sargeant et al. (2006), Tarr
et al. (2014)
RKLYE Sargeant et al. (2006)
Negative Sargeant et al. (2006)
Nicholas I. Proellocks et al.
RNLYGE Localizes to the iRBC Maier et al. (2008), Pei
membrane; involved in et al. (2007a), Sargeant et
membrane mechanic and al. (2006), Silva et al.
required for the stabilization of (2005)
spectrin and the iRBC
membrane under heat stress
RESA-2 PF3D7_1149500 (PF11_0512) RNLYG Up-regulated in Clinical isolates; Daily et al. (2005), Maier et
truncation, does not express al. (2008), Sargeant et al.

Malaria Parasite Proteins and the RBC

DnaJ domain; unknown (2006)
function
RESA-like PF3D7_1149200 (PF11_0509) RNLYCE Essential; expressed in Maier et al. (2008),
trophozoites Sargeant et al. (2006),
Silvestrini et al. (2010)
RESA-like PF3D7_0201700 (PFB0085c) RQLSE Expressed in trophozoites; role in Maier et al. (2008),
increasing membrane rigidity Sargeant et al. (2006),
Silvestrini et al. (2010)
RESA-like PF3D7_0220100 (PFB0920w) Negative Involved in increasing iRBC Maier et al. (2008),
membrane rigidity and Sargeant et al. (2006)
cytoadhesion
RESA-like PF3D7_1038800 (PF10_0378) RKVCE Contains a MEC domain; binds Kilili and LaCount (2011),
IOVs and 4.1R Maier et al. (2008),
Sargeant et al. (2006)
RESA-like PF3D7_1201100 (PFL0055c) RYLCE Contains a MEC domain Kilili and LaCount (2011),
Sargeant et al. (2006)
PHISTc
PF3D7_0424000 (PFD1140w) RNLSE Unknown function Maier et al. (2008),
Sargeant et al. (2006)
GEXP05 PF3D7_0936600 (PFI1770w) RKLSE Originally described as PHISTb Frech and Chen (2013),
now reclassified as PHISTc; Sargeant et al. (2006),
expressed in gametocytes Silvestrini et al. (2010)
PF3D7_0936800 (PFI1780w) KSLSD Expressed in trophozoites; Maier et al. (2008), Mayer
essential; role in anchoring of et al. (2012), Sargeant
PfEMP1 et al. (2006), Silvestrini
et al. (2010)

19
(Continued)
Table 3 P. falciparum exported proteins containing a PHIST domaindcont'd
PHIST Gene id PEXEL Comments References

20
PfPTP2 PF3D7_0731100 (MAL7P1.172) RNLGE Localized to the Maurer’s clefts; Maier et al. (2008), Regev-
GEXP11 role in trafficking of PfEMP1 Rudzki et al. (2013),
from the clefts to the iRBC Sargeant et al. (2006),
membrane; expressed in Silvestrini et al. (2010)
gametocytes; involved in cell
ecell communication via
exosomes
PF3D7_0801000 (PF08_0137) Negative Expressed in trophozoites; Akinyi et al. (2012), Florens
membrane associated; et al. (2004), Sargeant et
homologue in Pv localizes to al. (2006), Silvestrini et
Schuffner’s dots al. (2010)
LSAP2 PF3D7_0202100 (PFB0105c) RKFAE Liver-stage protein localized to Sargeant et al. (2006), Siau
the periphery liver-stage et al. (2008)
parasites; minimal expression in
blood-stage schizonts
GEXP20 PF3D7_0219700 (PFB0900c) Negative Expressed in gametocytes Sargeant et al. (2006),
Silvestrini et al. (2010)
PF3D7_0219800 (PFB0905c) Negative Sargeant et al. (2006)
PF3D7_0532200 (PFE1595c) Negative Sargeant et al. (2006)
PF3D7_0830600 (MAL8P1.4) RILYE Sargeant et al. (2006)
PF3D7_1001700 (PF10_0021) KILCE Sargeant et al. (2006)

Nicholas I. Proellocks et al.

PF3D7_1001800 (PF10_0022) Negative Sargeant et al. (2006)
PF3D7_1016500 (PF10_0161) Negative Sargeant et al. (2006)
PF3D7_1016600 (PF10_0161a) Negative Sargeant et al. (2006)
PF3D7_1016700 (PF10_0162) Negative Sargeant et al. (2006)
PF3D7_1016800 (PF10_0163) RVLTE Sargeant et al. (2006)
GEXP12 PF3D7_1148700 (PF11_0503) RTLAS Expressed in gametocytes Sargeant et al. (2006),
Silvestrini et al. (2010)
PF3D7_1200900 (PFL0045c) KMLCE Sargeant et al. (2006)
Table 4 P. falciparum exported proteins containing a DnaJ domain

Malaria Parasite Proteins and the RBC

ATP
hydrolysis
DnaJ Gene id motif Comments References
Type II
PFA660 PF3D7_0113700 (PFA0660w) HDP J-Dots; interacts with PfHsp70x; possibly Botha et al. (2007), K€ ulzer
involved in trafficking of PfEMP1 et al. (2010, 2012), Sargeant
et al. (2006)
PFB90 PF3D7_0201800 (PFB0090c) HDP Possible J-Dots; expressed in trophozoites Botha et al. (2007), Sargeant
et al. (2006), Silvestrini et al.
(2010)
PFE55 PF3D7_0501100.1 (PFE0055c) HDP J-Dots; interacts with PfHsp70x; possibly Botha et al. (2007), K€ ulzer
involved in trafficking of PfEMP1 et al. (2010, 2012), Sargeant
et al. (2006)
Type III
PF3D7_0220100 (PFB0920w) HDP RESA-like (Table 3) Botha et al. (2007), Sargeant
et al. (2006)
PF3D7_1038800 (PF10_0378) HDP Contains a MEC domain; RESA-like Botha et al. (2007), Kilili and
(Table 3) LaCount (2011), Sargeant
et al. (2006)
PF3D7_1039100 (PF10_0381) HDP Contains a MEC domain; involved in Botha et al. (2007), Kilili and
knob formation LaCount (2011), Maier
et al. (2008), Sargeant et al.
(2006)
(Continued)

21
 22
Table 4 P. falciparum exported proteins containing a DnaJ domaindcont'd
ATP
hydrolysis
DnaJ Gene id motif Comments References
PF3D7_1149600 (PF11_0513) HDP Unknown function Botha et al. (2007), Maier et al.
(2008), Sargeant et al.
(2006)
PF3D7_1201100 (PFL0055c) HDP Contains a MEC domain; RESA-like Botha et al. (2007), Kilili and
(Table 3) LaCount (2011), Sargeant
et al. (2006)
Type IV
PF3D7_0102200 (PFA0110w) YPY RESA (Table 3) Botha et al. (2007), Sargeant
et al. (2006)
GEXP06 PF3D7_0114000 (PFA0675w) YPK RESA-like but does not contain a PHIST Botha et al. (2007), Kilili and
domain; contains a MEC domain; LaCount (2011), Sargeant
expressed in gametocytes et al. (2006), Silvestrini et al.
(2010)

Nicholas I. Proellocks et al.

PF3D7_0201700 (PFB0085c)
PF3D7_0220400 (PFB0925w)
NPE RESA-like (Table 3) Botha et al. (2007), Sargeant
et al. (2006)
HPE Contains a MEC domain; unknown Botha et al. (2007), Kilili and
function LaCount (2011), Maier
et al. (2008), Sargeant et al.
(2006)
 Malaria Parasite Proteins and the RBC
PF3D7_0500800 (PFE0040c) NPH MESA; binds to protein 4.1R Bennett et al. (1997), Black
et al. (2008), Botha et al.
(2007), Sargeant et al.
(2006), Waller et al. (2003)
PF3D7_1102200 (PF11_0034) FLD Contains a MEC domain; essential Botha et al. (2007), Kilili and
LaCount (2011), Maier
et al. (2008), Sargeant et al.
(2006)
PF3D7_1149200 (PF11_0509) YPP RESA-like (Table 3) Botha et al. (2007), Sargeant
et al. (2006)
PF3D7_1149500 (PF11_0512) YPI RESA-2 (Table 3) Botha et al. (2007), Sargeant
et al. (2006)
GECO PF3D7_1253000 (PFL2550w) YPK Gametocyte erythrocyte cytosolic protein; Botha et al. (2007), Maier et al.
unknown function (2008), Sargeant et al.
(2006)
PF3D7_1401100 (PF14_0013) YPK Botha et al. (2007), Sargeant
et al. (2006)

23
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