CSP_PLASI
ID CSP_PLASI Reviewed; 386 AA.
AC Q03110;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=Circumsporozoite protein {ECO:0000303|PubMed:8426613};
DE Short=CS {ECO:0000303|PubMed:8426613};
DE Contains:
DE RecName: Full=Circumsporozoite protein C-terminus {ECO:0000305};
DE Flags: Precursor;
GN Name=CSP {ECO:0000250|UniProtKB:P23093};
OS Plasmodium simium.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium.
OX NCBI_TaxID=5859;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM, AND REPEATS.
RX PubMed=8426613; DOI=10.1016/0166-6851(93)90257-x;
RA Goldman I.F., Qari S.H., Millet P.G., Collins W.E., Lal A.A.;
RT "Circumsporozoite protein gene of Plasmodium simium, a Plasmodium vivax-
RT like monkey malaria parasite.";
RL Mol. Biochem. Parasitol. 57:177-180(1993).
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:8426613}.
CC -!- SIMILARITY: Belongs to the plasmodium circumsporozoite protein family.
CC {ECO:0000305}.
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DR EMBL; L05068; AAA29525.1; -; Genomic_DNA.
DR PIR; A48571; A48571.
DR AlphaFoldDB; Q03110; -.
DR SMR; Q03110; -.
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..363
FT /note="Circumsporozoite protein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000024534"
FT CHAIN ?..363
FT /note="Circumsporozoite protein C-terminus"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT /id="PRO_0000455503"
FT PROPEP 364..386
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455504"
FT REPEAT 96..104
FT /note="1"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 105..113
FT /note="2"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 114..122
FT /note="3"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 123..131
FT /note="4"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 132..140
FT /note="5"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 141..149
FT /note="6"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 150..158
FT /note="7"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 159..167
FT /note="8"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 168..176
FT /note="9"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 177..185
FT /note="10"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 186..194
FT /note="11"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 195..203
FT /note="12"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 204..212
FT /note="13"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 213..221
FT /note="14"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 222..230
FT /note="15"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 231..239
FT /note="16"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 240..248
FT /note="17"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 249..257
FT /note="18"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 258..266
FT /note="19"
FT /evidence="ECO:0000305|PubMed:8426613"
FT REPEAT 267..275
FT /note="20"
FT /evidence="ECO:0000305|PubMed:8426613"
FT DOMAIN 312..364
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 51..304
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 96..275
FT /note="20 X 9 AA tandem repeats of G-D-R-A-[AD]-G-Q-P-A"
FT /evidence="ECO:0000305|PubMed:8426613"
FT COMPBIAS 62..104
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 287..301
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 363
FT /note="GPI-anchor amidated cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 327
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P19597"
FT DISULFID 324..358
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT DISULFID 328..363
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
SQ SEQUENCE 386 AA; 38567 MW; A0097D4BDE5548DB CRC64;
MKNFILLAVS SILLVDLFPT HCGHNVDLSK AINLNGVNFN NVDASSLGAA HVGQSASRGR
GLGENPDDEE GDAKKKKDGK KAEPKNPREN KLKQPGDRAD GQPAGDRADG QPAGDRADGQ
PAGDRADGQP AGDRADGQPA GDRAAGQPAG DRADGQPAGD RADGQPAGDR AAGQPAGDRA
AGQPAGDRAD GQPAGDRADG QPAGDRADGQ PAGDRAAGQP AGDRAAGQPA GDRAAGQPAG
DRAAGQPAGD RAAGQPAGDR AAGQPAGDRA AGQPAGNGAG GQAAGGNAGG QGQNNEGANA
PNEKSVKEYL DKVRATVGTE WTPCSVTCGV GVRVRRRVNA ANKKPEDLTL NDLETDVCTM
DKCAGIFNVV SNSLGLVILL VLALFN
