CSP_PLACL
ID CSP_PLACL Reviewed; 378 AA.
AC P08675;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 71.
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 London).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX NCBI_TaxID=5831;
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 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 (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; M15101; AAA29537.1; -; Genomic_DNA.
DR PIR; A26255; OZZQAL.
DR AlphaFoldDB; P08675; -.
DR SMR; P08675; -.
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..355
FT /note="Circumsporozoite protein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000024524"
FT CHAIN ?..355
FT /note="Circumsporozoite protein C-terminus"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT /id="PRO_0000455481"
FT PROPEP 356..378
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455482"
FT REPEAT 99..104
FT /note="1-1"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 105..110
FT /note="1-2"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 111..116
FT /note="1-3"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 117..122
FT /note="1-4"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 123..128
FT /note="1-5"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 129..134
FT /note="1-6"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 135..140
FT /note="1-7"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 141..146
FT /note="1-8"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 147..152
FT /note="1-9"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 153..158
FT /note="1-10"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 159..164
FT /note="1-11"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 165..170
FT /note="1-12"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 171..176
FT /note="1-13"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 177..182
FT /note="1-14"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 183..188
FT /note="1-15"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 189..194
FT /note="1-16"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 195..200
FT /note="1-17"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 201..206
FT /note="1-18"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 212..222
FT /note="2-1"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 223..233
FT /note="2-2"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 234..244
FT /note="2-3"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 245..255
FT /note="2-4"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 256..266
FT /note="2-5"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 267..277
FT /note="2-6"
FT /evidence="ECO:0000305|PubMed:3802196"
FT DOMAIN 304..356
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 50..291
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 99..206
FT /note="18 X 6 AA tandem repeats of D-G-A-R-A-[EA]"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REGION 212..277
FT /note="6 X 11 AA tandem repeats of G-N-[QR]-[AE]-G-G-Q-A-G-
FT A-G"
FT /evidence="ECO:0000305|PubMed:3802196"
FT COMPBIAS 63..95
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 103..129
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 139..165
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 355
FT /note="GPI-anchor amidated cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 319
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P19597"
FT DISULFID 316..350
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT DISULFID 320..355
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
SQ SEQUENCE 378 AA; 37463 MW; 8295A913C36420C5 CRC64;
MKNFNLLAVS SILLVDLFPT HCGHNVDLSR AINLNGVSFN NVDASSLGAA QVRQSASRGR
GLGENPKNEE GADKQKKDEK KVEPKKPREN KLKQPPPADG ARAEDGARAE DGARAEDGAR
AEDGARAADG ARAADGARAA DGARAEDGAR AEDGARAEDG ARAADGARAA DGARAADGAR
AADGARAADG ARAADGARAA DGARAEDGAP AGNREGGQAG AGGNQAGGQA GAGGNQAGGQ
AGAGGNQAGG QAGAGGNQAG GQAGAGGNRA GGQAGAGDAG AGQGQNNEGA NMPNAKLVKE
YLDKIRSTIG VEWSPCTVTC GKGVRMRRKV SAANKKPEEL DVNDLETEVC TMDKCAGIFN
VVSNSLGLVI LLVLALFN
