CSP_PLAKU
ID CSP_PLAKU Reviewed; 351 AA.
AC P04922;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Circumsporozoite protein {ECO:0000303|PubMed:4023712};
DE Short=CS {ECO:0000303|PubMed:4023712};
DE Contains:
DE RecName: Full=Circumsporozoite protein C-terminus {ECO:0000305};
DE Flags: Precursor;
GN Name=CSP {ECO:0000250|UniProtKB:P23093};
OS Plasmodium knowlesi (strain nuri).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX NCBI_TaxID=5852;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM, AND REPEATS.
RX PubMed=4023712; DOI=10.1126/science.4023712;
RA Sharma S., Svec P., Mitchell G.H., Godson G.N.;
RT "Diversity of circumsporozoite antigen genes from two strains of the
RT malarial parasite Plasmodium knowlesi.";
RL Science 229:779-782(1985).
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:4023712}.
CC -!- SIMILARITY: Belongs to the plasmodium circumsporozoite protein family.
CC {ECO:0000305}.
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DR EMBL; M11031; AAA29540.1; -; Genomic_DNA.
DR PIR; A26253; OZZQKU.
DR AlphaFoldDB; P04922; -.
DR SMR; P04922; -.
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..328
FT /note="Circumsporozoite protein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455496"
FT CHAIN ?..328
FT /note="Circumsporozoite protein C-terminus"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT /id="PRO_0000455497"
FT PROPEP 329..351
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455498"
FT REPEAT 101..109
FT /note="1"
FT /evidence="ECO:0000305|PubMed:4023712"
FT REPEAT 110..118
FT /note="2"
FT /evidence="ECO:0000305|PubMed:4023712"
FT REPEAT 119..127
FT /note="3"
FT /evidence="ECO:0000305|PubMed:4023712"
FT REPEAT 128..136
FT /note="4"
FT /evidence="ECO:0000305|PubMed:4023712"
FT REPEAT 137..145
FT /note="5"
FT /evidence="ECO:0000305|PubMed:4023712"
FT REPEAT 146..154
FT /note="6"
FT /evidence="ECO:0000305|PubMed:4023712"
FT REPEAT 155..163
FT /note="7"
FT /evidence="ECO:0000305|PubMed:4023712"
FT REPEAT 164..172
FT /note="8"
FT /evidence="ECO:0000305|PubMed:4023712"
FT REPEAT 173..181
FT /note="9"
FT /evidence="ECO:0000305|PubMed:4023712"
FT REPEAT 182..190
FT /note="10"
FT /evidence="ECO:0000305|PubMed:4023712"
FT REPEAT 191..199
FT /note="11"
FT /evidence="ECO:0000305|PubMed:4023712"
FT REPEAT 200..208
FT /note="12"
FT /evidence="ECO:0000305|PubMed:4023712"
FT REPEAT 209..217
FT /note="13"
FT /evidence="ECO:0000305|PubMed:4023712"
FT REPEAT 218..226
FT /note="14"
FT /evidence="ECO:0000305|PubMed:4023712"
FT DOMAIN 277..329
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 50..266
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 93..97
FT /note="Region I; contains the proteolytic cleavage site"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT REGION 101..226
FT /note="14 X 9 AA tandem repeats of A-A-G-A-[GR]-G-E-Q-P"
FT /evidence="ECO:0000305|PubMed:4023712"
FT COMPBIAS 60..94
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 328
FT /note="GPI-anchor amidated cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 292
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P19597"
FT DISULFID 289..323
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT DISULFID 293..328
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
SQ SEQUENCE 351 AA; 34782 MW; A85E87A152E6485B CRC64;
MKNFILLAVS SILLVDLLPT HFEHNVDLSR AINVNGVSFN NVDTSSLGAA QVRQSASRGR
GLGEKPKEGA DKEKKKEKEK EKEEEPKKPN ENKLKQPEQP AAGAGGEQPA AGAGGEQPAA
GAGGEQPAAG ARGEQPAAGA GGEQPAAGAG GEQPAAGAGG EQPAAGAGGE QPAAGAGGEQ
PAAGARGEQP AAGAGGEQPA AGAGGEQPAA GARGEQPAAG AGGEQPAPAP RREQPAPGAV
AGDGARGGNA GAGKGQGQNN QGANVPNEKV VNDYLHKIRS SVTTEWTPCS VTCGNGVRIR
RKGHAGNKKA EDLTMDDLEV EACVMDKCAG IFNVVSNSLG LVILLVLALF N
