CSP_PLABR
ID CSP_PLABR Reviewed; 485 AA.
AC P14593;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 2.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Circumsporozoite protein {ECO:0000303|PubMed:2323391};
DE Short=CS {ECO:0000303|PubMed:2323391};
DE Contains:
DE RecName: Full=Circumsporozoite protein C-terminus {ECO:0000305};
DE Flags: Precursor;
GN Name=CSP {ECO:0000250|UniProtKB:P23093};
OS Plasmodium brasilianum.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX NCBI_TaxID=5824;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM, AND REPEATS.
RX PubMed=2323391; DOI=10.1016/0014-4894(90)90120-2;
RA di Giovanni L., Cochrane A.H., Enea V.;
RT "On the evolutionary history of the circumsporozoite protein in
RT plasmodia.";
RL Exp. Parasitol. 70:373-381(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 93-485.
RX PubMed=3128542; DOI=10.1016/s0021-9258(18)60590-3;
RA Lal A.A., la Cruz V.F., Collins W.E., Campbell G.H., Procell P.M.,
RA McCutchan T.F.;
RT "Circumsporozoite protein gene from Plasmodium brasilianum. Animal
RT reservoirs for human malaria parasites?";
RL J. Biol. Chem. 263:5495-5498(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:2323391}.
CC -!- SIMILARITY: Belongs to the plasmodium circumsporozoite protein family.
CC {ECO:0000305}.
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DR EMBL; J03203; AAA29553.1; -; Genomic_DNA.
DR PIR; A60610; A60610.
DR AlphaFoldDB; P14593; -.
DR SMR; P14593; -.
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..20
FT /evidence="ECO:0000255"
FT CHAIN 21..462
FT /note="Circumsporozoite protein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000024520"
FT CHAIN ?..462
FT /note="Circumsporozoite protein C-terminus"
FT /evidence="ECO:0000250|UniProtKB:P23093"
FT /id="PRO_0000455472"
FT PROPEP 463..485
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455473"
FT REPEAT 109..112
FT /note="1"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 113..116
FT /note="2"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 117..120
FT /note="3"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 121..124
FT /note="4"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 125..128
FT /note="5"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 129..132
FT /note="6"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 133..136
FT /note="7"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 137..140
FT /note="8"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 141..144
FT /note="9"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 145..148
FT /note="10"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 149..152
FT /note="11"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 153..156
FT /note="12"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 157..160
FT /note="13"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 161..164
FT /note="14"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 165..168
FT /note="15"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 169..172
FT /note="16"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 173..176
FT /note="17"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 177..180
FT /note="18"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 181..184
FT /note="19"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 185..188
FT /note="20"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 189..192
FT /note="21"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 193..196
FT /note="22"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 197..200
FT /note="23"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 201..204
FT /note="24"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 205..208
FT /note="25"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 209..212
FT /note="26"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 213..216
FT /note="27"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 217..220
FT /note="28"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 221..224
FT /note="29"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 225..228
FT /note="30"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 229..232
FT /note="31"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 233..236
FT /note="32"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 237..240
FT /note="33"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 241..244
FT /note="34"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 245..248
FT /note="35"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 249..252
FT /note="36"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 253..256
FT /note="37"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 257..260
FT /note="38"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 261..264
FT /note="39"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 265..268
FT /note="40"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 269..272
FT /note="41"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 273..276
FT /note="42"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 277..280
FT /note="43"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 281..284
FT /note="44"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 285..288
FT /note="45"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 289..292
FT /note="46"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 293..296
FT /note="47"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 297..300
FT /note="48"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 301..304
FT /note="49"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 305..308
FT /note="50"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 309..312
FT /note="51"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 313..316
FT /note="52"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 317..320
FT /note="53"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 321..324
FT /note="54"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 325..328
FT /note="55"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 329..332
FT /note="56"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 333..336
FT /note="57"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 337..340
FT /note="58"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 341..344
FT /note="59"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 345..348
FT /note="60"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 349..352
FT /note="61"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 353..356
FT /note="62"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 357..360
FT /note="63"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 361..364
FT /note="64"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REPEAT 365..368
FT /note="65"
FT /evidence="ECO:0000305|PubMed:2323391"
FT DOMAIN 411..463
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 72..122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 84..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 109..368
FT /note="65 X 4 AA tandem repeats of G-N-[AD]-[EA]"
FT /evidence="ECO:0000305|PubMed:2323391"
FT REGION 363..403
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 79..106
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 372..399
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 462
FT /note="GPI-anchor amidated cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 426
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P19597"
FT DISULFID 423..457
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
FT DISULFID 427..462
FT /evidence="ECO:0000250|UniProtKB:Q7K740"
SQ SEQUENCE 485 AA; 46201 MW; 6B95F75AEDF1CD00 CRC64;
MKKLSVLAIS SFLIVDFLFP GYHHNSNSTK SRNLSELCYN NVDTKLFNEL EVRYSTNQDH
FYNYNKTIRL LNENNNEKDG NVTNERKKKP TKAVENKLKQ PPGDDDDAGN DEGNDAGNDA
GNAAGNAAGN AAGNAAGNAA GNAAGNAAGN AAGNAAGNAA GNDAGNAAGN AAGNAAGNAA
GNAAGNAAGN AAGNAAGNAA GNAAGNDAGN AAGNAAGNAA GNAAGNAAGN AAGNDAGNAA
GNAAGNAAGN AAGNAAGNAA GNAAGNAAGN AAGNAAGNDA GNAAGNAAGN AAGNAAGNAA
GNAAGNAAGN AAGNAAGNAA GNAAGNAAGN AAGNAAGNAA GNAAGNAAGN AAGNAAGNAA
GNAAGNAAGN EKAKNKDNKV DANTNKKDNQ EENNDSSNGP SEEHIKNYLE SIRNSITEEW
SPCSVTCGSG IRARRKVDAK NKKPAELVLS DLETEICSLD KCSSIFNVVS NSLGIVLVLV
LILFH
