ID CSP_PLAMA Reviewed; 429 AA.
AC P13815;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 13-SEP-2023, entry version 73.
DE RecName: Full=Circumsporozoite protein {ECO:0000303|PubMed:3054537};
DE Short=CS {ECO:0000250|UniProtKB:P02893};
DE Contains:
DE RecName: Full=Circumsporozoite protein C-terminus {ECO:0000305};
DE Flags: Precursor;
GN Name=CSP {ECO:0000303|PubMed:3054537};
OS Plasmodium malariae.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX NCBI_TaxID=5858;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM, AND REPEATS.
RX PubMed=3054537; DOI=10.1016/0166-6851(88)90099-0;
RA Lal A.A., la Cruz V.F., Campbell G.H., Procell P.M., Collins W.E.,
RA McCutchan T.F.;
RT "Structure of the circumsporozoite gene of Plasmodium malariae.";
RL Mol. Biochem. Parasitol. 30:291-294(1988).
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:3054537}.
CC -!- SIMILARITY: Belongs to the plasmodium circumsporozoite protein family.
CC {ECO:0000305}.
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DR EMBL; J03992; AAA29557.1; -; Genomic_DNA.
DR PIR; A54504; A54504.
DR AlphaFoldDB; P13815; -.
DR SMR; P13815; -.
DR GlyCosmos; P13815; 1 site, No reported glycans.
DR VEuPathDB; PlasmoDB:PmUG01_08051600; -.
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:0098552; C:side of membrane; IEA:UniProtKB-KW.
DR Gene3D; 2.20.100.10; Thrombospondin type-1 (TSP1) repeat; 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; TSP-1 type 1 repeat; 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..20
FT /evidence="ECO:0000255"
FT CHAIN 21..406
FT /note="Circumsporozoite protein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000024532"
FT CHAIN ?..406
FT /note="Circumsporozoite protein C-terminus"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT /id="PRO_0000455499"
FT PROPEP 407..429
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455500"
FT REPEAT 110..113
FT /note="1"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 114..117
FT /note="2"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 118..121
FT /note="3"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 122..125
FT /note="4"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 126..129
FT /note="5"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 130..133
FT /note="6"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 134..137
FT /note="7"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 138..141
FT /note="8"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 142..145
FT /note="9"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 146..149
FT /note="10"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 150..153
FT /note="11"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 154..157
FT /note="12"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 158..161
FT /note="13"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 162..165
FT /note="14"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 166..169
FT /note="15"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 170..173
FT /note="16"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 174..177
FT /note="17"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 178..181
FT /note="18"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 182..185
FT /note="20"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 186..189
FT /note="21"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 190..193
FT /note="22"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 194..197
FT /note="23"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 198..201
FT /note="24"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 202..205
FT /note="25"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 206..209
FT /note="26"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 210..213
FT /note="27"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 214..217
FT /note="28"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 218..221
FT /note="29"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 222..225
FT /note="30"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 226..229
FT /note="31"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 230..233
FT /note="32"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 234..237
FT /note="33"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 238..241
FT /note="34"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 242..245
FT /note="35"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 246..249
FT /note="36"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 250..253
FT /note="37"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 254..257
FT /note="38"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 258..261
FT /note="39"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 262..265
FT /note="40"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 266..269
FT /note="41"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 270..273
FT /note="42"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 274..277
FT /note="43"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 278..281
FT /note="44"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 282..285
FT /note="45"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 286..289
FT /note="46"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 290..293
FT /note="47"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 294..297
FT /note="48"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 298..301
FT /note="49"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 302..305
FT /note="50"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 306..309
FT /note="51"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REPEAT 310..313
FT /note="52"
FT /evidence="ECO:0000305|PubMed:3054537"
FT DOMAIN 355..407
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 72..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 87..92
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 97..101
FT /note="Region I; contains the proteolytic cleavage site"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT REGION 110..313
FT /note="52 X 4 AA tandem repeats of N-[AD]-A-G"
FT /evidence="ECO:0000305|PubMed:3054537"
FT REGION 307..347
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 79..104
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 316..343
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 406
FT /note="GPI-anchor amidated cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 370
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P19597"
FT DISULFID 367..401
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT DISULFID 371..406
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
SQ SEQUENCE 429 AA; 41596 MW; 3629D641D1C0BB7E CRC64;
MKKLSVLAIS SFLIVDFLFP GYHHNSNSTK SRNLSELCYN NVDTKLFNEL EVRYSTNQDH
FYNYNKTIRL LNENNNEKDG NVTNERKKKP TKAVENKLKQ PPGDDDGAGN DAGNDAGNDA
GNAAGNAAGN AAGNAAGNAA GNAAGNAAGN AAGNAAGNAA GNDAGNAAGN AAGNAAGNAA
GNAAGNDAGN AAGNAAGNAA GNAAGNAAGN AAGNAAGNAA GNAAGNAAGN DAGNAAGNAA
GNAAGNAAGN AAGNAAGNAA GNAAGNAAGN AAGNAAGNAA GNAAGNAAGN AAGNAAGNAA
GNAAGNAAGN AAGNEKAKNK DNKVDANTNK KDNQEENNDS SNGPSEEHIK NYLESIRNSI
TEEWSPCSVT CGSGIRARRK VGAKNKKPAE LVLSDLETEI CSLDKCSSIF NVVSNSLGIV
LVLVLILFH
//
