CSP_PLABA
ID CSP_PLABA Reviewed; 340 AA.
AC P23093; A0A509AF96;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 2.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=Circumsporozoite protein {ECO:0000303|PubMed:2183186};
DE Short=CS {ECO:0000250|UniProtKB:P06915};
DE Short=PbCSP {ECO:0000303|PubMed:33253113};
DE Contains:
DE RecName: Full=Circumsporozoite protein C-terminus {ECO:0000305};
DE Flags: Precursor;
GN Name=CSP {ECO:0000303|PubMed:2183186}; ORFNames=PBANKA_0403200;
OS Plasmodium berghei (strain Anka).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Vinckeia).
OX NCBI_TaxID=5823;
RN [1] {ECO:0000312|EMBL:CAA35608.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND REPEATS.
RC STRAIN=ANKA clone 2.34L {ECO:0000312|EMBL:CAA35608.1};
RX PubMed=2183186; DOI=10.1093/nar/18.2.376;
RA Lockyer M.J., Davies C.S., Suhrbier A., Sinden R.E.;
RT "Nucleotide sequence of the Plasmodium berghei circumsporozoite protein
RT gene from the ANKA clone 2.34L.";
RL Nucleic Acids Res. 18:376-376(1990).
RN [2] {ECO:0000312|Proteomes:UP000074855}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ANKA {ECO:0000312|Proteomes:UP000074855};
RX PubMed=25359557; DOI=10.1186/s12915-014-0086-0;
RA Otto T.D., Bohme U., Jackson A.P., Hunt M., Franke-Fayard B.,
RA Hoeijmakers W.A., Religa A.A., Robertson L., Sanders M., Ogun S.A.,
RA Cunningham D., Erhart A., Billker O., Khan S.M., Stunnenberg H.G.,
RA Langhorne J., Holder A.A., Waters A.P., Newbold C.I., Pain A., Berriman M.,
RA Janse C.J.;
RT "A comprehensive evaluation of rodent malaria parasite genomes and gene
RT expression.";
RL BMC Biol. 12:86-86(2014).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND BIOTECHNOLOGY.
RX PubMed=6985745; DOI=10.1126/science.6985745;
RA Yoshida N., Nussenzweig R.S., Potocnjak P., Nussenzweig V., Aikawa M.;
RT "Hybridoma produces protective antibodies directed against the sporozoite
RT stage of malaria parasite.";
RL Science 207:71-73(1980).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DOMAIN, AND
RP MUTAGENESIS OF 317-CYS--ASN-340.
RX PubMed=16207248; DOI=10.1111/j.1462-5822.2005.00579.x;
RA Wang Q., Fujioka H., Nussenzweig V.;
RT "Mutational analysis of the GPI-anchor addition sequence from the
RT circumsporozoite protein of Plasmodium.";
RL Cell. Microbiol. 7:1616-1626(2005).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND PROTEOLYTIC
RP CLEAVAGE.
RX PubMed=15630135; DOI=10.1084/jem.20040989;
RA Coppi A., Pinzon-Ortiz C., Hutter C., Sinnis P.;
RT "The Plasmodium circumsporozoite protein is proteolytically processed
RT during cell invasion.";
RL J. Exp. Med. 201:27-33(2005).
RN [6]
RP FUNCTION, DEVELOPMENTAL STAGE, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=18005753; DOI=10.1016/j.chom.2007.10.002;
RA Coppi A., Tewari R., Bishop J.R., Bennett B.L., Lawrence R., Esko J.D.,
RA Billker O., Sinnis P.;
RT "Heparan sulfate proteoglycans provide a signal to Plasmodium sporozoites
RT to stop migrating and productively invade host cells.";
RL Cell Host Microbe 2:316-327(2007).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DOMAIN, PROTEOLYTIC
RP CLEAVAGE, AND MUTAGENESIS OF 25-ASN--PRO-93 AND 89-LYS--PRO-93.
RX PubMed=21262960; DOI=10.1084/jem.20101488;
RA Coppi A., Natarajan R., Pradel G., Bennett B.L., James E.R., Roggero M.A.,
RA Corradin G., Persson C., Tewari R., Sinnis P.;
RT "The malaria circumsporozoite protein has two functional domains, each with
RT distinct roles as sporozoites journey from mosquito to mammalian host.";
RL J. Exp. Med. 208:341-356(2011).
RN [8] {ECO:0007744|PDB:6X8P, ECO:0007744|PDB:6X8Q, ECO:0007744|PDB:6X8S, ECO:0007744|PDB:6X8U}
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 181-196 IN COMPLEX WITH ANTIBODY
RP 3D11, REPEATS, BIOTECHNOLOGY, AND POLYMORPHISM.
RX PubMed=33253113; DOI=10.7554/elife.59018;
RA Kucharska I., Thai E., Srivastava A., Rubinstein J.L., Pomes R.,
RA Julien J.P.;
RT "Structural ordering of the Plasmodium berghei circumsporozoite protein
RT repeats by inhibitory antibody 3D11.";
RL Elife 9:0-0(2020).
CC -!- FUNCTION: Essential sporozoite protein (PubMed:6985745,
CC PubMed:15630135, PubMed:16207248, PubMed:18005753, PubMed:21262960). In
CC the mosquito vector, required for sporozoite development in the oocyst,
CC migration through the vector hemolymph and entry into the vector
CC salivary glands (PubMed:16207248, PubMed:21262960). In the vertebrate
CC host, required for sporozoite migration through the host dermis and
CC infection of host hepatocytes (PubMed:6985745, PubMed:15630135,
CC PubMed:18005753, PubMed:21262960). Binds to highly sulfated heparan
CC sulfate proteoglycans (HSPGs) on the surface of host hepatocytes
CC (PubMed:18005753). {ECO:0000269|PubMed:15630135,
CC ECO:0000269|PubMed:16207248, ECO:0000269|PubMed:18005753,
CC ECO:0000269|PubMed:21262960, ECO:0000269|PubMed:6985745}.
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:0000269|PubMed:18005753,
CC ECO:0000269|PubMed:21262960}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15630135,
CC ECO:0000269|PubMed:16207248, ECO:0000269|PubMed:21262960,
CC ECO:0000269|PubMed:6985745}; Lipid-anchor, GPI-anchor
CC {ECO:0000305|PubMed:16207248}. Cytoplasm {ECO:0000269|PubMed:16207248}.
CC Note=Localizes to the cytoplasm and the cell membrane in oocysts at day
CC 6 post infection and then gradually distributes over the entire cell
CC surface of the sporoblast and the budding sporozoites.
CC {ECO:0000269|PubMed:16207248}.
CC -!- DEVELOPMENTAL STAGE: Expressed in sporozoites (at protein level)
CC (PubMed:16207248, PubMed:15630135, PubMed:18005753, PubMed:21262960,
CC PubMed:6985745). In the mosquito vector, expression begins in the
CC oocyst 8 days post-infection (at protein level) (PubMed:16207248).
CC {ECO:0000269|PubMed:15630135, ECO:0000269|PubMed:16207248,
CC ECO:0000269|PubMed:18005753, ECO:0000269|PubMed:21262960,
CC ECO:0000269|PubMed:6985745}.
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 (PubMed:21262960). The unmasking of the TSP
CC type-1 (TSR) domain when the sporozoite interacts with the host
CC hepatocyte also protects sporozoites from host antibodies
CC (PubMed:21262960). {ECO:0000250|UniProtKB:Q7K740,
CC ECO:0000269|PubMed:21262960}.
CC -!- DOMAIN: The TSP type-1 (TSR) domain is required for sporozoite
CC development and invasion (PubMed:21262960). CSP has two conformational
CC states, an adhesive conformation in which the TSP type-1 (TSR) domain
CC is exposed and a nonadhesive conformation in which the TSR is masked by
CC the N-terminus (PubMed:21262960). TSR-exposed conformation occurs
CC during sporozoite development in the oocyst in the mosquito vector and
CC during host hepatocyte invasion (PubMed:21262960). TSR-masked
CC conformation occurs during sporozoite migration through the hemolymph
CC to salivary glands in the mosquito vector and in the host dermis
CC (PubMed:21262960). {ECO:0000269|PubMed:21262960}.
CC -!- DOMAIN: The GPI-anchor is essential for cell membrane localization and
CC for sporozoite formation inside the oocyst.
CC {ECO:0000269|PubMed:16207248}.
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 (PubMed:15630135, PubMed:18005753, PubMed:21262960). Cleavage is
CC triggered by the sporozoite contact with highly sulfated heparan
CC sulfate proteoglycans (HSPGs) present on the host hepatocyte cell
CC surface (PubMed:18005753). 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 (PubMed:15630135, PubMed:18005753,
CC PubMed:21262960). Cleavage is dispensable for sporozoite development in
CC the oocyst, motility and for traversal of host and vector cells
CC (PubMed:21262960). {ECO:0000269|PubMed:15630135,
CC ECO:0000269|PubMed:18005753, ECO:0000269|PubMed:21262960}.
CC -!- PTM: O-glycosylated; maybe by POFUT2. {ECO:0000250|UniProtKB:P19597}.
CC -!- POLYMORPHISM: The sequence of the repeats varies across Plasmodium
CC species and strains. {ECO:0000269|PubMed:33253113}.
CC -!- BIOTECHNOLOGY: Antibodies against the central repeats (repeats 1), such
CC as 3D11, can neutralize infection in the mouse host and thus may be a
CC candidate for the design of vaccine against Plasmodium species that
CC infect human. {ECO:0000269|PubMed:33253113,
CC ECO:0000269|PubMed:6985745}.
CC -!- SIMILARITY: Belongs to the plasmodium circumsporozoite protein family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X17606; CAA35608.1; -; Genomic_DNA.
DR EMBL; LK023119; VUC54256.1; -; Genomic_DNA.
DR PIR; S07873; OZZQBK.
DR PDB; 6X8P; X-ray; 2.27 A; P=117-132.
DR PDB; 6X8Q; X-ray; 1.60 A; P=157-172.
DR PDB; 6X8S; X-ray; 1.55 A; P=133-148.
DR PDB; 6X8U; X-ray; 1.55 A; P=181-196.
DR PDBsum; 6X8P; -.
DR PDBsum; 6X8Q; -.
DR PDBsum; 6X8S; -.
DR PDBsum; 6X8U; -.
DR AlphaFoldDB; P23093; -.
DR SMR; P23093; -.
DR STRING; 5821.PBANKA_040320; -.
DR VEuPathDB; PlasmoDB:PBANKA_0403200; -.
DR eggNOG; ENOG502RVPU; Eukaryota.
DR OMA; LEMEACT; -.
DR Proteomes; UP000074855; Chromosome 4.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; IDA:UniProtKB.
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:0044650; P:adhesion of symbiont to host cell; IMP:UniProtKB.
DR GO; GO:0085017; P:entry into host cell by a symbiont-containing vacuole; IMP:UniProtKB.
DR GO; GO:0075294; P:positive regulation by symbiont of entry into host; IDA:UniProtKB.
DR GO; GO:0044129; P:positive regulation of development of symbiont in host; IMP:UniProtKB.
DR GO; GO:0051094; P:positive regulation of developmental process; 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; Reference proteome; Repeat;
KW Signal; Sporozoite.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..317
FT /note="Circumsporozoite protein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000024518"
FT CHAIN ?..317
FT /note="Circumsporozoite protein C-terminus"
FT /evidence="ECO:0000269|PubMed:21262960"
FT /id="PRO_0000455468"
FT PROPEP 318..340
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455469"
FT REPEAT 94..101
FT /note="1-1"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REPEAT 102..109
FT /note="1-2"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REPEAT 110..117
FT /note="1-3"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REPEAT 118..125
FT /note="1-4"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REPEAT 126..133
FT /note="1-5"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REPEAT 134..141
FT /note="1-6"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REPEAT 142..149
FT /note="1-7"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REPEAT 150..157
FT /note="1-8"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REPEAT 158..165
FT /note="1-9"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REPEAT 166..173
FT /note="1-10"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REPEAT 174..181
FT /note="1-11"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REPEAT 182..189
FT /note="1-12"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REPEAT 190..197
FT /note="1-13"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REPEAT 198..201
FT /note="1-14; half-length"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REPEAT 207..208
FT /note="2-1"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 209..210
FT /note="2-2"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 211..212
FT /note="2-3; approximate"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 213..214
FT /note="2-4"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 215..216
FT /note="2-5"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 217..218
FT /note="2-6"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 219..220
FT /note="2-7"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 221..222
FT /note="2-8"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 223..224
FT /note="2-9"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 225..226
FT /note="2-10"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 227..228
FT /note="2-11"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 229..230
FT /note="2-12"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 231..232
FT /note="2-13; approximate"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 233..234
FT /note="2-14"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 235..236
FT /note="2-15"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 237..238
FT /note="2-16"
FT /evidence="ECO:0000305|PubMed:2183186"
FT REPEAT 239..240
FT /note="2-17; approximate"
FT /evidence="ECO:0000305|PubMed:2183186"
FT DOMAIN 267..318
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 69..254
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 79..86
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 89..93
FT /note="Region I; contains the proteolytic cleavage site"
FT /evidence="ECO:0000269|PubMed:21262960"
FT REGION 94..201
FT /note="14 X 8 AA tandem repeats of P-[PA]-P-P-N-[PA]-N-D"
FT /evidence="ECO:0000305|PubMed:33253113"
FT REGION 207..240
FT /note="17 X 2 AA approximate tandem repeats of P-Q"
FT /evidence="ECO:0000305|PubMed:2183186"
FT COMPBIAS 71..89
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 90..238
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 239..254
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 317
FT /note="GPI-anchor amidated cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 282
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P19597"
FT DISULFID 279..312
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT DISULFID 283..317
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT MUTAGEN 25..93
FT /note="Missing: Constitutive exposure of the TSP type-1
FT (TSR) domain. No defect in cell membrane localization.
FT Sporozoite motility is reduced while its invasive ability
FT is enhanced. In the mosquito vector, produces between 50
FT and 100% more sporozoites in oocysts due to an increase in
FT budding from sporoblasts. Sporozoite egress from the oocyst
FT is normal; however, they adhere non-specifically throughout
FT the mosquito hemocoel resulting in a reduced number of
FT sporozoites reaching the salivary gland. In the mouse host,
FT enhanced infectivity when sporozoites are injected i.v.;
FT however, no liver infection when sporozoites are injected
FT i.d. due to their failure to exit the host dermis."
FT /evidence="ECO:0000269|PubMed:21262960"
FT MUTAGEN 89..93
FT /note="Missing: Impaired proteolytic processing. Prevents
FT exposure of the TSP type-1 (TSR) domain. No defect in cell
FT membrane localization. In the mosquito vector, oocyst
FT numbers, sporozoite development in oocysts, and sporozoite
FT egress from oocysts are normal. Invasion of salivary glands
FT is reduced by 15%. In the mouse host, sporozoite motility
FT is normal and host cell traversal ability is enhanced in
FT the host dermis. However, invasion of host hepatocytes is
FT reduced by 10-15-fold."
FT /evidence="ECO:0000269|PubMed:21262960"
FT MUTAGEN 317..340
FT /note="Missing: Probable loss of GPI-anchor. The number of
FT oocytes is normal in the mosquito gut following infection;
FT however, sporozoite budding process is defective and no
FT sporozoites are produced. In the oocyst, the inner membrane
FT complex (IMC) forms prematurely before the oocyst plasma
FT membrane is fully retracted. Also, the IMC is not
FT restricted to the sporozoite budding sites, extending
FT underneath the entire oocyst plasma membrane. CSP
FT processing is impaired and remains in the cytoplasm,
FT associated with the periphery of vesicles."
FT /evidence="ECO:0000269|PubMed:16207248"
FT CONFLICT 60
FT /note="N -> I (in Ref. 1; CAA35608)"
FT /evidence="ECO:0000305"
FT CONFLICT 82
FT /note="Missing (in Ref. 1; CAA35608)"
FT /evidence="ECO:0000305"
FT CONFLICT 93
FT /note="P -> PPPPPNPND (in Ref. 1; CAA35608)"
FT /evidence="ECO:0000305"
FT CONFLICT 167
FT /note="A -> P (in Ref. 1; CAA35608)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 340 AA; 37051 MW; 2578891FF7AA991D CRC64;
MKKCTILVVA SLLLVNSLLP GYGQNKSIQA QRNLNELCYN EGNDNKLYHV LNSKNGKIYN
RNTVNRLLAD APEGKKNEKK NEKIERNNKL KQPPPPPNPN DPPPPNPNDP PPPNPNDPPP
PNPNDPPPPN ANDPPPPNAN DPAPPNANDP APPNANDPAP PNANDPAPPN ANDPPPPNPN
DPAPPNANDP PPPNPNDPAP PQGNNNPQPQ PRPQPQPQPQ PQPQPQPQPQ PRPQPQPQPG
GNNNNKNNNN DDSYIPSAEK ILEFVKQIRD SITEEWSQCN VTCGSGIRVR KRKGSNKKAE
DLTLEDIDTE ICKMDKCSSI FNIVSNSLGF VILLVLVFFN
