CSP_PLAKH
ID CSP_PLAKH Reviewed; 363 AA.
AC P02894;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Circumsporozoite protein {ECO:0000303|PubMed:6313209};
DE Short=CS {ECO:0000303|PubMed:6313209};
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 H).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX NCBI_TaxID=5851;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM, AND REPEATS.
RX PubMed=6313209; DOI=10.1016/0092-8674(83)90538-x;
RA Ozaki L.S., Svec P., Nussenzweig R.S., Nussenzweig V., Godson G.N.;
RT "Structure of the plasmodium knowlesi gene coding for the circumsporozoite
RT protein.";
RL Cell 34:815-822(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 84-258.
RX PubMed=6193427; DOI=10.1038/305029a0;
RA Godson G.N., Ellis J., Svec P., Schlesinger D.H., Nussenzweig V.;
RT "Identification and chemical synthesis of a tandemly repeated immunogenic
RT region of Plasmodium knowlesi circumsporozoite protein.";
RL Nature 305:29-33(1983).
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:6313209}.
CC -!- SIMILARITY: Belongs to the plasmodium circumsporozoite protein family.
CC {ECO:0000305}.
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DR EMBL; K00822; AAA19699.1; -; Genomic_DNA.
DR EMBL; K00772; AAA29556.1; -; mRNA.
DR PIR; A90841; OZZQAK.
DR AlphaFoldDB; P02894; -.
DR SMR; P02894; -.
DR STRING; 5850.PKH_083560; -.
DR PRIDE; P02894; -.
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 2: Evidence at transcript level;
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..340
FT /note="Circumsporozoite protein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000024530"
FT CHAIN ?..340
FT /note="Circumsporozoite protein C-terminus"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT /id="PRO_0000455494"
FT PROPEP 341..363
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455495"
FT REPEAT 98..109
FT /note="1; approximate"
FT /evidence="ECO:0000305|PubMed:6313209"
FT REPEAT 110..121
FT /note="2"
FT /evidence="ECO:0000305|PubMed:6313209"
FT REPEAT 122..133
FT /note="3"
FT /evidence="ECO:0000305|PubMed:6313209"
FT REPEAT 134..145
FT /note="4"
FT /evidence="ECO:0000305|PubMed:6313209"
FT REPEAT 146..157
FT /note="5"
FT /evidence="ECO:0000305|PubMed:6313209"
FT REPEAT 158..169
FT /note="6"
FT /evidence="ECO:0000305|PubMed:6313209"
FT REPEAT 170..181
FT /note="7"
FT /evidence="ECO:0000305|PubMed:6313209"
FT REPEAT 182..193
FT /note="8"
FT /evidence="ECO:0000305|PubMed:6313209"
FT REPEAT 194..205
FT /note="9"
FT /evidence="ECO:0000305|PubMed:6313209"
FT REPEAT 206..217
FT /note="10"
FT /evidence="ECO:0000305|PubMed:6313209"
FT REPEAT 218..229
FT /note="11"
FT /evidence="ECO:0000305|PubMed:6313209"
FT REPEAT 230..241
FT /note="12"
FT /evidence="ECO:0000305|PubMed:6313209"
FT DOMAIN 289..341
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 48..278
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 98..241
FT /note="12 X 12 AA approximate tandem repeats of N-A-G-Q-P-
FT Q-A-Q-G-D-G-A"
FT /evidence="ECO:0000305|PubMed:6313209"
FT COMPBIAS 60..94
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 95..242
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 263..278
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 340
FT /note="GPI-anchor amidated cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 304
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P19597"
FT DISULFID 301..335
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT DISULFID 305..340
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
SQ SEQUENCE 363 AA; 36793 MW; 574DF4BD320A7955 CRC64;
MKNFILLAVS SILLVDLLPT HFEHNVDLSR AINVNGVSFN NVDTSSLGAQ QVRQSASRGR
GLGEKPKEGA DKEKKKEKGK EKEEEPKKPN ENKLKQPNEG QPQAQGDGAN AGQPQAQGDG
ANAGQPQAQG DGANAGQPQA QGDGANAGQP QAQGDGANAG QPQAQGDGAN AGQPQAQGDG
ANAGQPQAQG DGANAGQPQA QGDGANAGQP QAQGDGANAG QPQAQGDGAN AGQPQAQGDG
ANVPRQGRNG GGAPAGGNEG NKQAGKGQGQ NNQGANAPNE KVVNDYLHKI RSSVTTEWTP
CSVTCGNGVR IRRKAHAGNK KAEDLTMDDL EVEACVMDKC AGIFNVVSNS LGLVILLVLA
LFN
