CSP_PLAVB
ID CSP_PLAVB Reviewed; 378 AA.
AC P08677;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Circumsporozoite protein {ECO:0000303|PubMed:2414847};
DE Short=CS {ECO:0000303|PubMed:2414847};
DE Contains:
DE RecName: Full=Circumsporozoite protein C-terminus {ECO:0000305};
DE Flags: Precursor;
GN Name=CSP {ECO:0000250|UniProtKB:P23093};
OS Plasmodium vivax (strain Belem).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX NCBI_TaxID=31273;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM, AND REPEATS.
RX PubMed=2414847; DOI=10.1126/science.2414847;
RA Arnot D.E., Barnwell J.W., Tam J.P., Nussenzweig V., Nussenzweig R.S.,
RA Enea V.;
RT "Circumsporozoite protein of Plasmodium vivax: gene cloning and
RT characterization of the immunodominant epitope.";
RL Science 230:815-818(1985).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=3054880; DOI=10.1073/pnas.85.21.8102;
RA Arnot D.E., Barnwell J.W., Stewart M.J.;
RT "Does biased gene conversion influence polymorphism in the circumsporozoite
RT protein-encoding gene of Plasmodium vivax?";
RL Proc. Natl. Acad. Sci. U.S.A. 85:8102-8106(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:2414847}.
CC -!- SIMILARITY: Belongs to the plasmodium circumsporozoite protein family.
CC {ECO:0000305}.
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DR EMBL; M11926; AAA29526.1; -; Genomic_DNA.
DR EMBL; J02751; AAA29529.1; ALT_SEQ; Genomic_DNA.
DR PIR; A26256; OZZQAV.
DR PDB; 7RLV; X-ray; 2.20 A; P/Q/R=150-167.
DR PDB; 7RLW; X-ray; 2.54 A; P/R=249-266.
DR PDB; 7RLX; X-ray; 1.97 A; P=222-239.
DR PDB; 7RLY; X-ray; 2.67 A; P/Q/R=214-230.
DR PDB; 7RLZ; X-ray; 2.27 A; P/R=258-275.
DR PDBsum; 7RLV; -.
DR PDBsum; 7RLW; -.
DR PDBsum; 7RLX; -.
DR PDBsum; 7RLY; -.
DR PDBsum; 7RLZ; -.
DR AlphaFoldDB; P08677; -.
DR SMR; P08677; -.
DR PRIDE; P08677; -.
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 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasm; Disulfide bond; Glycoprotein;
KW GPI-anchor; 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_0000024535"
FT CHAIN ?..355
FT /note="Circumsporozoite protein C-terminus"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT /id="PRO_0000455505"
FT PROPEP 356..378
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455506"
FT REPEAT 95..103
FT /note="1"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 104..112
FT /note="2"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 113..121
FT /note="3"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 122..130
FT /note="4"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 131..139
FT /note="5"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 140..148
FT /note="6"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 149..157
FT /note="7"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 158..166
FT /note="8"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 167..175
FT /note="9"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 176..184
FT /note="10"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 185..193
FT /note="11"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 194..202
FT /note="12"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 203..211
FT /note="13"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 212..220
FT /note="14"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 221..229
FT /note="15"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 230..238
FT /note="16"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 239..247
FT /note="17"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 248..256
FT /note="18"
FT /evidence="ECO:0000305|PubMed:2414847"
FT REPEAT 257..265
FT /note="19"
FT /evidence="ECO:0000305|PubMed:2414847"
FT DOMAIN 304..356
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 51..295
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 95..265
FT /note="19 X 9 AA tandem repeats of [PA]-G-D-R-A-[DA]-G-Q-P"
FT /evidence="ECO:0000305|PubMed:2414847"
FT COMPBIAS 62..104
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 279..293
FT /note="Polar 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"
FT CONFLICT 36
FT /note="G -> E (in Ref. 1; AAA29526)"
FT /evidence="ECO:0000305"
FT CONFLICT 96
FT /note="G -> R (in Ref. 1; AAA29526)"
FT /evidence="ECO:0000305"
FT CONFLICT 295
FT /note="E -> A (in Ref. 1; AAA29526)"
FT /evidence="ECO:0000305"
FT CONFLICT 328
FT /note="R -> S (in Ref. 1; AAA29526)"
FT /evidence="ECO:0000305"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:7RLV"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:7RLY"
FT TURN 224..227
FT /evidence="ECO:0007829|PDB:7RLY"
FT HELIX 229..231
FT /evidence="ECO:0007829|PDB:7RLX"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:7RLZ"
SQ SEQUENCE 378 AA; 37800 MW; C84B5BED05E3C9ED CRC64;
MKNFILLAVS SILLVDLFPT HCGHNVDLSK AINLNGVNFN NVDASSLGAA HVGQSASRGR
GLGENPDDEE GDAKKKKDGK KAEPKNPREN KLKQPGDRAD GQPAGDRADG QPAGDRADGQ
PAGDRAAGQP AGDRADGQPA GDRADGQPAG DRADGQPAGD RADGQPAGDR AAGQPAGDRA
AGQPAGDRAD GQPAGDRAAG QPAGDRADGQ PAGDRAAGQP AGDRADGQPA GDRAAGQPAG
DRAAGQPAGD RAAGQPAGDR AAGQPAGNGA GGQAAGGNAG GGQGQNNEGA NAPNEKSVKE
YLDKVRATVG TEWTPCSVTC GVGVRVRRRV NAANKKPEDL TLNDLETDVC TMDKCAGIFN
VVSNSLGLVI LLVLALFN
