CSP_PLABE
ID CSP_PLABE Reviewed; 339 AA.
AC P06915; Q25648; Q25649;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=Circumsporozoite protein {ECO:0000303|PubMed:2432395};
DE Short=CS {ECO:0000303|PubMed:2432395};
DE Contains:
DE RecName: Full=Circumsporozoite protein C-terminus {ECO:0000305};
DE Flags: Precursor;
GN Name=CSP {ECO:0000250|UniProtKB:P23093};
OS Plasmodium berghei.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Vinckeia).
OX NCBI_TaxID=5821;
RN [1] {ECO:0000312|EMBL:AAA29577.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DEVELOPMENTAL STAGE, AND REPEATS.
RC STRAIN=NK65 {ECO:0000312|EMBL:AAA29577.1};
RX PubMed=2432395; DOI=10.1128/mcb.6.11.3965-3972.1986;
RA Eichinger D.J., Arnot D.E., Tam J.P., Nussenzweig V., Enea V.;
RT "Circumsporozoite protein of Plasmodium berghei: gene cloning and
RT identification of the immunodominant epitopes.";
RL Mol. Cell. Biol. 6:3965-3972(1986).
RN [2] {ECO:0000312|EMBL:AAA29541.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NK65 {ECO:0000312|EMBL:AAA29541.1};
RX PubMed=2406593; DOI=10.1016/0166-6851(90)90018-h;
RA Lanar D.E.;
RT "Sequence of the circumsporozoite gene of Plasmodium berghei ANKA clone and
RT NK65 strain.";
RL Mol. Biochem. Parasitol. 39:151-154(1990).
RN [3] {ECO:0000312|EMBL:AAA29531.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 61-339.
RX PubMed=3556207; DOI=10.1016/0014-4894(87)90176-7;
RA Weber J.L., Egan J.E., Lyon J.A., Wirtz R.A., Charoenvit Y., Maloy W.L.,
RA Hockmeyer W.T.;
RT "Plasmodium berghei: cloning of the circumsporozoite protein gene.";
RL Exp. Parasitol. 63:295-300(1987).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=NK65 {ECO:0000269|PubMed:9002517};
RX PubMed=9002517; DOI=10.1038/385336a0;
RA Menard R., Sultan A.A., Cortes C., Altszuler R., van Dijk M.R., Janse C.J.,
RA Waters A.P., Nussenzweig R.S., Nussenzweig V.;
RT "Circumsporozoite protein is required for development of malaria
RT sporozoites in mosquitoes.";
RL Nature 385:336-340(1997).
CC -!- FUNCTION: Essential sporozoite protein (PubMed:9002517). 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 (PubMed:9002517). In the vertebrate host, required for
CC sporozoite migration through the host dermis and infection of host
CC hepatocytes (By similarity). 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:9002517}.
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:0000250|UniProtKB:P23093};
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 sporozites.
CC {ECO:0000269|PubMed:2432395}.
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:0000250|UniProtKB:P19597}.
CC -!- POLYMORPHISM: The sequence of the repeats varies across Plasmodium
CC species and strains. {ECO:0000250|UniProtKB:P23093}.
CC -!- DISRUPTION PHENOTYPE: Following infection of the vector mosquito, the
CC number and size of oocysts in midgut are normal; however, oocysts
CC display a highly vacuolated structure and fail to produce sporozoites.
CC {ECO:0000269|PubMed:9002517}.
CC -!- SIMILARITY: Belongs to the plasmodium circumsporozoite protein family.
CC {ECO:0000305}.
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DR EMBL; M14135; AAA29577.1; -; Genomic_DNA.
DR EMBL; M25445; AAA29531.1; -; Genomic_DNA.
DR EMBL; M28887; AAA29541.1; -; Genomic_DNA.
DR PIR; A44948; OZZQMB.
DR PDB; 6X87; EM; 3.20 A; X=26-317.
DR PDBsum; 6X87; -.
DR AlphaFoldDB; P06915; -.
DR SMR; P06915; -.
DR VEuPathDB; PlasmoDB:PBANKA_0403200; -.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IEA:InterPro.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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; Repeat; Signal; Sporozoite.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..316
FT /note="Circumsporozoite protein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000024519"
FT CHAIN ?..316
FT /note="Circumsporozoite protein C-terminus"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT /id="PRO_0000455470"
FT PROPEP 317..339
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455471"
FT REPEAT 93..100
FT /note="1-1"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 101..108
FT /note="1-2"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 109..116
FT /note="1-3"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 117..124
FT /note="1-4"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 125..132
FT /note="1-5"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 133..140
FT /note="1-6"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 141..148
FT /note="1-7"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 149..156
FT /note="1-8"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 157..164
FT /note="1-9"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 165..172
FT /note="1-10"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 173..180
FT /note="1-11"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 181..188
FT /note="1-12"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 189..196
FT /note="1-13"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 197..200
FT /note="1-14; half-length"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 206..207
FT /note="2-1"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 208..209
FT /note="2-2"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 210..211
FT /note="2-3; approximate"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 212..213
FT /note="2-4"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 214..215
FT /note="2-5"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 216..217
FT /note="2-6"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 218..219
FT /note="2-7"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 220..221
FT /note="2-8"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 222..223
FT /note="2-9"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 224..225
FT /note="2-10"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 226..227
FT /note="2-11"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 228..229
FT /note="2-12"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 230..231
FT /note="2-13; approximate"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 232..233
FT /note="2-14"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 234..235
FT /note="2-15"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 236..237
FT /note="2-16"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REPEAT 238..239
FT /note="2-17; approximate"
FT /evidence="ECO:0000305|PubMed:2432395"
FT DOMAIN 266..317
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 71..253
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 78..85
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 88..92
FT /note="Region I; contains the proteolytic cleavage site"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT REGION 93..200
FT /note="14 X 8 AA tandem repeats of P-[PA]-P-P-N-[PA]-N-D"
FT /evidence="ECO:0000305|PubMed:2432395"
FT REGION 206..239
FT /note="17 X 2 AA approximate tandem repeats of P-Q"
FT /evidence="ECO:0000305|PubMed:2432395"
FT COMPBIAS 71..88
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 89..237
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 238..253
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 316
FT /note="GPI-anchor amidated cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 281
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P19597"
FT DISULFID 278..311
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT DISULFID 282..316
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT CONFLICT 69..73
FT /note="PMLRR -> ADAPEG (in Ref. 2; AAA29541 and 3;
FT AAA29531)"
FT /evidence="ECO:0000305"
FT CONFLICT 93..100
FT /note="Missing (in Ref. 3; AAA29531)"
FT /evidence="ECO:0000305"
FT CONFLICT 123..130
FT /note="Missing (in Ref. 2; AAA29541)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="P -> A (in Ref. 2; AAA29541 and 3; AAA29531)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 339 AA; 37138 MW; E8068A6D11D9551B CRC64;
MKKCTILVVA SLLLVNSLLP GYGQNKIIQA QRNLNELCYN EGNDNKLYHV LNSKNGKIYN
RNTVNRLLPM LRRKKNEKKN EKIERNNKLK QPPPPPNPND PPPPNPNDPP PPNPNDPPPP
NPNDPPPPNA NDPPPPNAND PAPPNANDPA PPNANDPAPP NANDPAPPNA NDPAPPNAND
PAPPNANDPP PPNPNDPAPP QGNNNPQPQP RPQPQPQPQP QPQPQPQPQP RPQPQPQPGG
NNNNKNNNND DSYIPSAEKI LEFVKQIRDS ITEEWSQCNV TCGSGIRVRK RKGSNKKAED
LTLEDIDTEI CKMDKCSSIF NIVSNSLGFV ILLVLVFFN
