CSP_PLACC
ID CSP_PLACC Reviewed; 398 AA.
AC P08673;
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: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 Ceylon).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX NCBI_TaxID=5829;
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; M15103; AAA29533.1; -; Genomic_DNA.
DR PIR; C26255; OZZQAS.
DR AlphaFoldDB; P08673; -.
DR SMR; P08673; -.
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..23
FT /evidence="ECO:0000255"
FT CHAIN 24..375
FT /note="Circumsporozoite protein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000024522"
FT CHAIN ?..375
FT /note="Circumsporozoite protein C-terminus"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT /id="PRO_0000455476"
FT PROPEP 376..398
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455477"
FT REPEAT 97..105
FT /note="1-1"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 106..114
FT /note="1-2"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 115..123
FT /note="1-3"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 124..132
FT /note="1-4"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 133..141
FT /note="1-5"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 142..150
FT /note="1-6"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 151..159
FT /note="1-7"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 160..168
FT /note="1-8"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 169..177
FT /note="1-9"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 178..186
FT /note="1-10"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 187..195
FT /note="1-11"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 196..204
FT /note="1-12"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 205..213
FT /note="1-13"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 214..222
FT /note="1-14"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 223..231
FT /note="1-15"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 232..240
FT /note="1-16"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 241..257
FT /note="2-1"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 258..274
FT /note="2-2"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REPEAT 275..291
FT /note="2-3"
FT /evidence="ECO:0000305|PubMed:3802196"
FT DOMAIN 324..376
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 50..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 81..89
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 92..96
FT /note="Region I; contains the proteolytic cleavage site"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT REGION 97..240
FT /note="16 X 9 AA tandem repeats of A-G-N-N-A-A-[AG]-G-[EA]"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REGION 241..291
FT /note="3 X 17 AA tandem repeats of A-G-N-N-A-A-A-G-E-A-G-A-
FT G-G-A-G-[RG]"
FT /evidence="ECO:0000305|PubMed:3802196"
FT REGION 248..310
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 63..93
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 375
FT /note="GPI-anchor amidated cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 339
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P19597"
FT DISULFID 336..370
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT DISULFID 340..375
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
SQ SEQUENCE 398 AA; 37719 MW; 6DFA2E8A62ED05BF CRC64;
MKNFNLLAVS SILLVDLFRT QWGHNVHFSK AINLNGVSFN NVDASSLGAA QVRQSASRGR
GLGENPKNEE GADKPKKKDE KQVEPKKPRE NKLKQPAGNN AAAGEAGNNA AAGEAGNNAA
AGEAGNNAAA GEAGNNAAAG EAGNNAAAGE AGNNAAGGAA GNNAAGGEAG NNAAGGAAGN
NAAAGEAGNN AAGGEAGNNA AAGEAGNNAA GGAAGNNAAA GEAGNNAAAG AAGNNAAAGA
AGNNAAAGEA GAGGAGRAGN NAAAGEAGAG GAGRAGNNAA AGEAGAGGAG GNAGNKKAGD
AGQGQNNGGA NVPNVKLVKE YLDKIRSTIG VEWSPCSVTC GKGVRMRRKV NAANKKPEEL
DANDLETEVC TMDKCAGIFN VVSNSLGLVI LLVLALFN
