CSP_PLACG
ID CSP_PLACG Reviewed; 401 AA.
AC P08674;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=Circumsporozoite protein {ECO:0000303|PubMed:3802196};
DE Short=CS {ECO:0000303|PubMed:3802196};
DE Contains:
DE RecName: Full=Circumsporozoite protein C-terminus {ECO:0000305};
DE Flags: Precursor;
GN Name=CSP {ECO:0000250|UniProtKB:P23093};
OS Plasmodium cynomolgi (strain Gombak).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX NCBI_TaxID=5830;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM, AND REPEATS.
RX PubMed=3802196; DOI=10.1016/0092-8674(87)90434-x;
RA Galinski M.R., Arnot D.E., Cochrane A.H., Barnwell J.W., Nussenzweig R.S.,
RA Enea V.;
RT "The circumsporozoite gene of the Plasmodium cynomolgi complex.";
RL Cell 48:311-319(1987).
CC -!- FUNCTION: Essential sporozoite protein (By similarity). In the mosquito
CC vector, required for sporozoite development in the oocyst, migration
CC through the vector hemolymph and entry into the vector salivary glands
CC (By similarity). In the vertebrate host, required for sporozoite
CC migration through the host dermis and infection of host hepatocytes (By
CC similarity). Binds to highly sulfated heparan sulfate proteoglycans
CC (HSPGs) on the surface of host hepatocytes (By similarity).
CC {ECO:0000250|UniProtKB:P02893, ECO:0000250|UniProtKB:P23093}.
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:P19597};
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 -!- 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 the TSP type-1 (TSR) domain when
CC 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: TSP type-1 (TSR) domain is required for sporozoite development
CC and invasion. CSP has two conformational states, an adhesive
CC conformation in which the TSP type-1 (TSR) domain is exposed and a
CC nonadhesive conformation in which the TSR is masked by the N-terminus.
CC TSR-exposed conformation occurs during sporozoite development in the
CC oocyst in the mosquito vector and during host hepatocyte invasion. TSR-
CC masked conformation occurs during sporozoite migration through the
CC hemolymph to salivary glands in the mosquito vector and in the host
CC 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 (By similarity). Cleavage is triggered by the sporozoite contact
CC with highly sulfated heparan sulfate proteoglycans (HSPGs) present on
CC the host hepatocyte cell surface (By similarity). Cleavage exposes the
CC TSP type-1 (TSR) domain and is required for productive invasion of host
CC hepatocytes but not for adhesion to the host cell membrane (By
CC similarity). Cleavage is dispensable for sporozoite development in the
CC oocyst, motility and for traversal of host and vector cells (By
CC similarity). {ECO:0000250|UniProtKB:P02893,
CC 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:0000269|PubMed:3802196}.
CC -!- SIMILARITY: Belongs to the plasmodium circumsporozoite protein family.
CC {ECO:0000305}.
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DR EMBL; M15100; AAA29536.1; -; Genomic_DNA.
DR PIR; E26255; OZZQAC.
DR AlphaFoldDB; P08674; -.
DR SMR; P08674; -.
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 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 3: Inferred from homology;
KW Cell membrane; Cytoplasm; Disulfide bond; Glycoprotein; GPI-anchor;
KW Lipoprotein; Malaria; Membrane; Repeat; Signal; Sporozoite.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..378
FT /note="Circumsporozoite protein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455478"
FT CHAIN ?..378
FT /note="Circumsporozoite protein C-terminus"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT /id="PRO_0000455479"
FT PROPEP 379..401
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455480"
FT REPEAT 98..108
FT /note="1"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 109..119
FT /note="2"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 120..130
FT /note="3"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 131..141
FT /note="4"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 142..152
FT /note="5"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 153..163
FT /note="6"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 164..174
FT /note="7"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 175..185
FT /note="8"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 186..196
FT /note="9"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 197..207
FT /note="10"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 208..218
FT /note="11"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 219..229
FT /note="12"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 230..240
FT /note="13"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 241..250
FT /note="14; truncated"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 251..260
FT /note="15; truncated"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 261..269
FT /note="16; truncated"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 270..278
FT /note="17; truncated"
FT /evidence="ECO:0000305|PubMed:3802196"
FT DOMAIN 327..379
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 45..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 80..88
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 91..95
FT /note="Region I; contains the proteolytic cleavage site"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT REGION 98..278
FT /note="17 X 11 AA tandem repeats of [DG]-G-A-A-A-A-G-G-G-G-
FT N"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REGION 132..240
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 268..311
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 62..96
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 378
FT /note="GPI-anchor amidated cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 342
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P19597"
FT DISULFID 339..373
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT DISULFID 343..378
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
SQ SEQUENCE 401 AA; 36664 MW; 57D666268238503E CRC64;
MKNFNLLAVS SILLVDLFPT HCGHNVDFSR GINLNGVSFN NVDASSHGAE QVRQSASRGR
GLGENPKDEG ADKPKKKDEK QVEPKKPREN KLKQPREDGA AAAGGGGNDG AAAAGGGGND
GAAAAGGGGN DGAAAAGGGG NDGAAAAGGG GNDGAAAAGG GGNDGAAAAG GGGNDGAAAA
GGGGNDGAAA AGGGGNDGAA AAGGGGNDGA AAAGGGGNGG AAAAGGGGND GAAAAGGGGN
DGAAAAGGGN GGAAAGGGGN GGAAAGGGNG GAAAGGGNNA RAGDQQPPAG GNKKAGEAGG
NAGAGQAQNN EAANVPNAKL VKEYLDKIRS TLGVEWSPCT VTCGKGVRMR RKVSAANKKP
EELDANDLET EVCTMDKCAG IFNVVSNSLR LVILLVLALF N
