CSP_PLAFO
ID CSP_PLAFO Reviewed; 397 AA.
AC P19597; Q25798;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Circumsporozoite protein {ECO:0000303|PubMed:2671723};
DE Short=CS {ECO:0000303|PubMed:2671723};
DE Short=PfCSP {ECO:0000303|PubMed:32451496};
DE Contains:
DE RecName: Full=Circumsporozoite protein C-terminus {ECO:0000305};
DE Flags: Precursor;
GN Name=CSP {ECO:0000303|PubMed:32451496};
OS Plasmodium falciparum (isolate NF54).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5843;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2668895; DOI=10.1093/nar/17.14.5854;
RA Campbell J.R.;
RT "DNA sequence of the gene encoding a Plasmodium falciparum malaria
RT candidate vaccine antigen.";
RL Nucleic Acids Res. 17:5854-5854(1989).
RN [2]
RP SEQUENCE REVISION.
RA Campbell J.R.;
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1346766; DOI=10.1016/0014-4894(92)90043-a;
RA Davis J.R., Cortese J.F., Herrington D.A., Murphy J.R., Clyde D.F.,
RA Thomas A.W., Baqar S., Cochran M.A., Thanassi J., Levine M.M.,
RA Hackett C.S.;
RT "Plasmodium falciparum: in vitro characterization and human infectivity of
RT a cloned line.";
RL Exp. Parasitol. 74:159-168(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM, AND REPEATS.
RX PubMed=2671723; DOI=10.1016/0166-6851(89)90121-7;
RA Caspers P., Gentz R., Matile H., Pink J.R., Sinigaglia F.;
RT "The circumsporozoite protein gene from NF54, a Plasmodium falciparum
RT isolate used in malaria vaccine trials.";
RL Mol. Biochem. Parasitol. 35:185-190(1989).
RN [5]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND GLYCOSYLATION AT THR-337.
RX PubMed=27128092; DOI=10.1371/journal.ppat.1005606;
RA Swearingen K.E., Lindner S.E., Shi L., Shears M.J., Harupa A., Hopp C.S.,
RA Vaughan A.M., Springer T.A., Moritz R.L., Kappe S.H., Sinnis P.;
RT "Interrogating the Plasmodium Sporozoite Surface: Identification of
RT Surface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP
RT by Mass Spectrometry-Based Proteomics.";
RL PLoS Pathog. 12:e1005606-e1005606(2016).
RN [6]
RP GLYCOSYLATION AT THR-337.
RX PubMed=28916755; DOI=10.1038/s41467-017-00571-y;
RA Lopaticki S., Yang A.S.P., John A., Scott N.E., Lingford J.P.,
RA O'Neill M.T., Erickson S.M., McKenzie N.C., Jennison C., Whitehead L.W.,
RA Douglas D.N., Kneteman N.M., Goddard-Borger E.D., Boddey J.A.;
RT "Protein O-fucosylation in Plasmodium falciparum ensures efficient
RT infection of mosquito and vertebrate hosts.";
RL Nat. Commun. 8:561-561(2017).
RN [7] {ECO:0007744|PDB:6B0S}
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 310-374 IN COMPLEX WITH ANTIBODY
RP 1710, AND BIOTECHNOLOGY.
RX PubMed=29167197; DOI=10.1084/jem.20170869;
RA Scally S.W., Murugan R., Bosch A., Triller G., Costa G., Mordmuller B.,
RA Kremsner P.G., Sim B.K.L., Hoffman S.L., Levashina E.A., Wardemann H.,
RA Julien J.P.;
RT "Rare PfCSP C-terminal antibodies induced by live sporozoite vaccination
RT are ineffective against malaria infection.";
RL J. Exp. Med. 215:63-75(2018).
RN [8] {ECO:0007744|PDB:6O23, ECO:0007744|PDB:6O24, ECO:0007744|PDB:6O25, ECO:0007744|PDB:6O26, ECO:0007744|PDB:6O28, ECO:0007744|PDB:6O29, ECO:0007744|PDB:6O2A, ECO:0007744|PDB:6O2B, ECO:0007744|PDB:6O2C, ECO:0007744|PDB:6ULE, ECO:0007744|PDB:6ULF}
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 261-272 IN COMPLEX WITH
RP ANTIBODIES, FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=32451496; DOI=10.1038/s41591-020-0881-9;
RA Murugan R., Scally S.W., Costa G., Mustafa G., Thai E., Decker T.,
RA Bosch A., Prieto K., Levashina E.A., Julien J.P., Wardemann H.;
RT "Evolution of protective human antibodies against Plasmodium falciparum
RT circumsporozoite protein repeat motifs.";
RL Nat. Med. 26:1135-1145(2020).
CC -!- FUNCTION: Essential sporozoite protein (PubMed:32451496). In the
CC mosquito vector, required for sporozoite development in the oocyst,
CC migration through the vector hemolymph and entry into the vector
CC salivary glands (By similarity). In the vertebrate host, required for
CC sporozoite migration through the host dermis and infection of host
CC hepatocytes (PubMed:32451496). Binds to highly sulfated heparan sulfate
CC proteoglycans (HSPGs) on the surface of host hepatocytes (By
CC similarity). {ECO:0000250|UniProtKB:P23093,
CC ECO:0000269|PubMed:32451496}.
CC -!- FUNCTION: [Circumsporozoite protein C-terminus]: In the vertebrate
CC host, binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on
CC the surface of host hepatocytes and is required for sporozoite invasion
CC of the host hepatocytes. {ECO:0000250|UniProtKB:P23093}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27128092};
CC Lipid-anchor, GPI-anchor {ECO:0000255}. Cytoplasm
CC {ECO:0000250|UniProtKB:P23093}. Note=Localizes to the cytoplasm and the
CC cell membrane in oocysts at day 6 post infection and then gradually
CC distributes over the entire cell surface of the sporoblast and the
CC budding sporozoites. {ECO:0000250|UniProtKB:P23093}.
CC -!- DEVELOPMENTAL STAGE: Expressed in sporozoites (at protein level).
CC {ECO:0000269|PubMed:27128092}.
CC -!- DOMAIN: The N-terminus is involved in the initial binding to heparan
CC sulfate proteoglycans (HSPGs) on the surface of host hepatocytes (By
CC similarity). The N-terminus masks the TSP type-1 (TSR) domain which
CC maintains the sporozoites in a migratory state, enabling them to
CC complete their journey to the salivary gland in the mosquito vector and
CC then to the host liver. The unmasking of the TSP type-1 (TSR) domain
CC when the sporozoite interacts with the host hepatocyte also protects
CC sporozoites from host antibodies (By similarity).
CC {ECO:0000250|UniProtKB:P23093, ECO:0000250|UniProtKB:Q7K740}.
CC -!- DOMAIN: The TSP type-1 (TSR) domain is required for sporozoite
CC development and invasion. CSP has two conformational states, an
CC adhesive conformation in which the TSP type-1 (TSR) domain is exposed
CC and a nonadhesive conformation in which the TSR is masked by the N-
CC terminus. TSR-exposed conformation occurs during sporozoite development
CC in the oocyst in the mosquito vector and during host hepatocyte
CC invasion. TSR-masked conformation occurs during sporozoite migration
CC through the hemolymph to salivary glands in the mosquito vector and in
CC the host dermis. {ECO:0000250|UniProtKB:P23093}.
CC -!- DOMAIN: The GPI-anchor is essential for cell membrane localization and
CC for sporozoite formation inside the oocyst.
CC {ECO:0000250|UniProtKB:P23093}.
CC -!- PTM: During host cell invasion, proteolytically cleaved at the cell
CC membrane in the region I by a papain-like cysteine protease of parasite
CC origin. Cleavage is triggered by the sporozoite contact with highly
CC sulfated heparan sulfate proteoglycans (HSPGs) present on the host
CC hepatocyte cell surface. Cleavage exposes the TSP type-1 (TSR) domain
CC and is required for productive invasion of host hepatocytes but not for
CC adhesion to the host cell membrane. Cleavage is dispensable for
CC sporozoite development in the oocyst, motility and for traversal of
CC host and vector cells. {ECO:0000250|UniProtKB:P23093}.
CC -!- PTM: O-glycosylated; maybe by POFUT2. {ECO:0000269|PubMed:27128092,
CC ECO:0000269|PubMed:28916755}.
CC -!- POLYMORPHISM: The sequence of the repeats varies across Plasmodium
CC species and strains. {ECO:0000269|PubMed:2671723}.
CC -!- BIOTECHNOLOGY: CSP immunodominant B cell epitopes are primarily located
CC in the central repeats (PubMed:29167197, PubMed:32451496). Antibodies
CC against CSP and particularly against the central repeats can neutralize
CC infection at the pre-liver stage and thus makes CSP an attractive
CC candidate for the development of vaccines (PubMed:32451496). CSP C-
CC terminus is less efficient at eliciting antibodies. These antibodies
CC are less efficient at neutralizing infections (PubMed:29167197,
CC PubMed:32451496). {ECO:0000269|PubMed:29167197,
CC ECO:0000269|PubMed:32451496}.
CC -!- SIMILARITY: Belongs to the plasmodium circumsporozoite protein family.
CC {ECO:0000305}.
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DR EMBL; X15363; CAA33421.1; -; Genomic_DNA.
DR EMBL; M83886; AAA29521.1; -; Genomic_DNA.
DR EMBL; M22982; AAA29527.1; -; Genomic_DNA.
DR PIR; S05428; S05428.
DR PDB; 6B0S; X-ray; 1.95 A; C=310-374.
DR PDB; 6O23; X-ray; 2.00 A; E=253-272.
DR PDB; 6O24; X-ray; 1.40 A; I=261-272.
DR PDB; 6O25; X-ray; 2.90 A; D/H/L=261-272.
DR PDB; 6O26; X-ray; 1.80 A; C=289-302.
DR PDB; 6O28; X-ray; 1.93 A; E/F=95-109.
DR PDB; 6O29; X-ray; 2.40 A; C/D=101-116.
DR PDB; 6O2A; X-ray; 2.15 A; F/G/K/L=193-204.
DR PDB; 6O2B; X-ray; 2.10 A; F/G/K/L=117-128.
DR PDB; 6O2C; X-ray; 2.02 A; C=261-272.
DR PDB; 6ULE; X-ray; 2.55 A; I=253-272.
DR PDB; 6ULF; X-ray; 1.70 A; P=193-204.
DR PDB; 6VLN; X-ray; 1.63 A; P=117-128.
DR PDBsum; 6B0S; -.
DR PDBsum; 6O23; -.
DR PDBsum; 6O24; -.
DR PDBsum; 6O25; -.
DR PDBsum; 6O26; -.
DR PDBsum; 6O28; -.
DR PDBsum; 6O29; -.
DR PDBsum; 6O2A; -.
DR PDBsum; 6O2B; -.
DR PDBsum; 6O2C; -.
DR PDBsum; 6ULE; -.
DR PDBsum; 6ULF; -.
DR PDBsum; 6VLN; -.
DR AlphaFoldDB; P19597; -.
DR SMR; P19597; -.
DR PRIDE; P19597; -.
DR ABCD; P19597; 8 sequenced antibodies.
DR VEuPathDB; PlasmoDB:PfNF54_030009700; -.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0031233; C:intrinsic component of external side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0085017; P:entry into host cell by a symbiont-containing vacuole; IMP:UniProtKB.
DR Gene3D; 2.20.100.10; -; 1.
DR InterPro; IPR003067; Crcmsprzoite.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR Pfam; PF00090; TSP_1; 1.
DR PRINTS; PR01303; CRCMSPRZOITE.
DR SMART; SM00209; TSP1; 1.
DR SUPFAM; SSF82895; SSF82895; 1.
DR PROSITE; PS50092; TSP1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasm; Disulfide bond; Glycoprotein;
KW GPI-anchor; Lipoprotein; Malaria; Membrane; Repeat; Signal; Sporozoite.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..374
FT /note="Circumsporozoite protein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000024527"
FT CHAIN ?..374
FT /note="Circumsporozoite protein C-terminus"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT /id="PRO_0000455488"
FT PROPEP 375..397
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455489"
FT REPEAT 105..108
FT /note="1"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 109..112
FT /note="2"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 113..116
FT /note="3"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 117..120
FT /note="4"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 121..124
FT /note="5"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 125..128
FT /note="6"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 129..132
FT /note="7"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 133..136
FT /note="8"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 137..140
FT /note="9"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 141..144
FT /note="10"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 145..148
FT /note="11"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 149..152
FT /note="12"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 153..156
FT /note="13"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 157..160
FT /note="14"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 161..164
FT /note="15"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 165..168
FT /note="16"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 169..172
FT /note="17"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 173..176
FT /note="18"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 177..180
FT /note="19"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 181..184
FT /note="20"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 185..188
FT /note="21"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 189..192
FT /note="22"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 193..196
FT /note="23"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 197..200
FT /note="24"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 201..204
FT /note="25"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 205..208
FT /note="26"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 209..212
FT /note="27"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 213..216
FT /note="28"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 217..220
FT /note="29"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 221..224
FT /note="30"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 225..228
FT /note="31"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 229..232
FT /note="32"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 233..236
FT /note="33"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 237..240
FT /note="34"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 241..244
FT /note="35"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 245..248
FT /note="36"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 249..252
FT /note="37"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 253..256
FT /note="38"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 257..260
FT /note="39"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 261..264
FT /note="40"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 265..268
FT /note="41"
FT /evidence="ECO:0000305|PubMed:2671723"
FT REPEAT 269..272
FT /note="42"
FT /evidence="ECO:0000305|PubMed:2671723"
FT DOMAIN 322..375
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 69..313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 85..92
FT /note="Required for the binding to heparan sulfate
FT proteoglycans (HSPGs) on the surface of host hepatocytes"
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT REGION 93..97
FT /note="Region I; contains the proteolytic cleavage site"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT REGION 105..272
FT /note="42 X 4 AA tandem repeats of N-[AV]-[ND]-P"
FT /evidence="ECO:0000305|PubMed:2671723"
FT COMPBIAS 70..88
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 102..307
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 374
FT /note="GPI-anchor amidated cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 337
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000305|PubMed:27128092,
FT ECO:0000305|PubMed:28916755"
FT DISULFID 334..369
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT DISULFID 338..374
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT CONFLICT 194
FT /note="A -> ANPNANPNA (in Ref. 4; AAA29527)"
FT /evidence="ECO:0000305"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:6O28"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:6O29"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:6O2B"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:6O2B"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:6O2A"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:6O2C"
SQ SEQUENCE 397 AA; 42646 MW; 9E81146F59EBCEA3 CRC64;
MMRKLAILSV SSFLFVEALF QEYQCYGSSS NTRVLNELNY DNAGTNLYNE LEMNYYGKQE
NWYSLKKNSR SLGENDDGNN EDNEKLRKPK HKKLKQPADG NPDPNANPNV DPNANPNVDP
NANPNVDPNA NPNANPNANP NANPNANPNA NPNANPNANP NANPNANPNA NPNANPNANP
NANPNANPNA NPNANPNVDP NANPNANPNA NPNANPNANP NANPNANPNA NPNANPNANP
NANPNANPNA NPNANPNANP NANPNANPNA NPNKNNQGNG QGHNMPNDPN RNVDENANAN
SAVKNNNNEE PSDKHIKEYL NKIQNSLSTE WSPCSVTCGN GIQVRIKPGS ANKPKDELDY
ANDIEKKICK MEKCSSVFNV VNSSIGLIMV LSFLFLN
