CSP_PLARE
ID CSP_PLARE Reviewed; 388 AA.
AC P26694;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=Circumsporozoite protein {ECO:0000303|PubMed:2016283};
DE Short=CS {ECO:0000303|PubMed:2016283};
DE Contains:
DE RecName: Full=Circumsporozoite protein C-terminus {ECO:0000305};
DE Flags: Precursor;
GN Name=CSP {ECO:0000250|UniProtKB:P23093};
OS Plasmodium reichenowi.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5854;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM, AND REPEATS.
RX PubMed=2016283; DOI=10.1016/s0021-9258(20)89552-0;
RA Lal A.A., Goldman I.F.;
RT "Circumsporozoite protein gene from Plasmodium reichenowi, a chimpanzee
RT malaria parasite evolutionarily related to the human malaria parasite
RT Plasmodium falciparum.";
RL J. Biol. Chem. 266:6686-6689(1991).
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:2016283}.
CC -!- SIMILARITY: Belongs to the plasmodium circumsporozoite protein family.
CC {ECO:0000305}.
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DR EMBL; M60972; AAA29561.1; -; Genomic_DNA.
DR PIR; A39756; A39756.
DR AlphaFoldDB; P26694; -.
DR SMR; P26694; -.
DR VEuPathDB; PlasmoDB:PRCDC_0303900; -.
DR VEuPathDB; PlasmoDB:PRG01_0308000; -.
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..18
FT /evidence="ECO:0000255"
FT CHAIN 19..365
FT /note="Circumsporozoite protein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000024533"
FT CHAIN ?..365
FT /note="Circumsporozoite protein C-terminus"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT /id="PRO_0000455501"
FT PROPEP 366..388
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455502"
FT REPEAT 120..123
FT /note="1"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 124..127
FT /note="2"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 128..131
FT /note="3"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 132..135
FT /note="4"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 136..139
FT /note="5"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 140..143
FT /note="6"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 144..147
FT /note="7"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 148..151
FT /note="8"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 152..155
FT /note="9"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 156..159
FT /note="10"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 160..163
FT /note="11"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 164..167
FT /note="12"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 168..171
FT /note="13"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 172..175
FT /note="14"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 176..179
FT /note="15"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 180..183
FT /note="16"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 184..187
FT /note="17"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 188..191
FT /note="18"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 192..195
FT /note="20"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 196..199
FT /note="21"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 200..203
FT /note="22"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 204..207
FT /note="23"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 208..211
FT /note="24"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 212..215
FT /note="25"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 216..219
FT /note="26"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 220..223
FT /note="27"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 224..227
FT /note="28"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 228..231
FT /note="29"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 232..235
FT /note="30"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 236..239
FT /note="31"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 240..243
FT /note="32"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 244..247
FT /note="33"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 248..251
FT /note="34"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 252..255
FT /note="35"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 256..259
FT /note="36"
FT /evidence="ECO:0000305|PubMed:2016283"
FT REPEAT 260..263
FT /note="37"
FT /evidence="ECO:0000305|PubMed:2016283"
FT DOMAIN 313..366
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 71..302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 104..111
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 112..116
FT /note="Region I; contains the proteolytic cleavage site"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT REGION 120..263
FT /note="37 X 4 AA tandem repeats of N-[AV]-[ND]-P"
FT /evidence="ECO:0000305|PubMed:2016283"
FT COMPBIAS 117..298
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 365
FT /note="GPI-anchor amidated cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 328
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P19597"
FT DISULFID 325..360
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT DISULFID 329..365
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
SQ SEQUENCE 388 AA; 42245 MW; C031EEFBE2E35604 CRC64;
MMRKLAILSV SSFLFVEALF QEYQCYGSSS NTRVLNELNY DNAGTNLYNE LEMNYYGKQE
NWYSLKKNSR SLGENDDADN GDADNGDEGI DENRRHRNKE GKEKLKKPKH NKLKQPGNDN
VDPNANPNVD PNANPNVDPN ANPNVDPNAN PNVDPNANPN VNPNANPNVD PNANPNVNPN
ANPNVNPNAN PNVNPNANPN ANPNANPNAN PNANPNANPN ANPNANPNAN PNANPNANPN
ANPNANPNAN PNANPNANPN ANPNRNNEAN GQGHNKPNDQ NRNVNENANA NNAGRNNNNE
EPSDKHIEEF LKQIQNNLST EWSPCSVTCG NGIQVRIKPG SAGKPKDQLD YENDLEKKIC
KMEKCSSVFN VVNSSIGLIM VLSFLFLN
