P4548_PLAF7
ID P4548_PLAF7 Reviewed; 448 AA.
AC Q8I6T1; A0A5K1K917;
DT 18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 25-MAY-2022, entry version 77.
DE RecName: Full=Gametocyte surface protein P45/48;
DE Flags: Precursor;
GN Name=PF45/48; Synonyms=PFS45-48, PFS45/48;
GN ORFNames=PF13_0247, PF3D7_1346700;
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368867; DOI=10.1038/nature01095;
RA Hall N., Pain A., Berriman M., Churcher C.M., Harris B., Harris D.,
RA Mungall K.L., Bowman S., Atkin R., Baker S., Barron A., Brooks K.,
RA Buckee C.O., Burrows C., Cherevach I., Chillingworth C., Chillingworth T.,
RA Christodoulou Z., Clark L., Clark R., Corton C., Cronin A., Davies R.M.,
RA Davis P., Dear P., Dearden F., Doggett J., Feltwell T., Goble A.,
RA Goodhead I., Gwilliam R., Hamlin N., Hance Z., Harper D., Hauser H.,
RA Hornsby T., Holroyd S., Horrocks P., Humphray S., Jagels K., James K.D.,
RA Johnson D., Kerhornou A., Knights A., Konfortov B., Kyes S., Larke N.,
RA Lawson D., Lennard N., Line A., Maddison M., Mclean J., Mooney P.,
RA Moule S., Murphy L., Oliver K., Ormond D., Price C., Quail M.A.,
RA Rabbinowitsch E., Rajandream M.A., Rutter S., Rutherford K.M., Sanders M.,
RA Simmonds M., Seeger K., Sharp S., Smith R., Squares R., Squares S.,
RA Stevens K., Taylor K., Tivey A., Unwin L., Whitehead S., Woodward J.R.,
RA Sulston J.E., Craig A., Newbold C., Barrell B.G.;
RT "Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.";
RL Nature 419:527-531(2002).
RN [3]
RP INTERACTION WITH PF230.
RX PubMed=1380124; DOI=10.1016/0166-6851(92)90013-a;
RA Kumar N., Wizel B.;
RT "Further characterization of interactions between gamete surface antigens
RT of Plasmodium falciparum.";
RL Mol. Biochem. Parasitol. 53:113-120(1992).
RN [4]
RP PRODUCTION OF RECOMBINANT PROTEIN.
RX PubMed=18332422; DOI=10.1073/pnas.0800459105;
RA Outchkourov N.S., Roeffen W., Kaan A., Jansen J., Luty A., Schuiffel D.,
RA van Gemert G.J., van de Vegte-Bolmer M., Sauerwein R.W., Stunnenberg H.G.;
RT "Correctly folded Pfs48/45 protein of Plasmodium falciparum elicits malaria
RT transmission-blocking immunity in mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:4301-4305(2008).
RN [5]
RP PRODUCTION OF RECOMBINANT PROTEIN.
RX PubMed=19623257; DOI=10.1371/journal.pone.0006352;
RA Chowdhury D.R., Angov E., Kariuki T., Kumar N.;
RT "A potent malaria transmission blocking vaccine based on codon harmonized
RT full length Pfs48/45 expressed in Escherichia coli.";
RL PLoS ONE 4:E6352-E6352(2009).
RN [6] {ECO:0007744|PDB:6H5N}
RP X-RAY CRYSTALLOGRAPHY (3.23 ANGSTROMS) OF 293-428 IN COMPLEX WITH ANTIBODY,
RP BIOTECHNOLOGY, AND DISULFIDE BONDS.
RX PubMed=30237518; DOI=10.1038/s41467-018-06340-9;
RA Lennartz F., Brod F., Dabbs R., Miura K., Mekhaiel D., Marini A.,
RA Jore M.M., Soegaard M.M., Joergensen T., de Jongh W.A., Sauerwein R.W.,
RA Long C.A., Biswas S., Higgins M.K.;
RT "Structural basis for recognition of the malaria vaccine candidate Pfs48/45
RT by a transmission blocking antibody.";
RL Nat. Commun. 9:3822-3822(2018).
RN [7] {ECO:0007744|PDB:6E62, ECO:0007744|PDB:6E63}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 291-428 IN COMPLEX WITH ANTIBODY,
RP DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-303.
RX PubMed=30367064; DOI=10.1038/s41467-018-06742-9;
RA Kundu P., Semesi A., Jore M.M., Morin M.J., Price V.L., Liang A., Li J.,
RA Miura K., Sauerwein R.W., King C.R., Julien J.P.;
RT "Structural delineation of potent transmission-blocking epitope I on
RT malaria antigen Pfs48/45.";
RL Nat. Commun. 9:4458-4458(2018).
CC -!- FUNCTION: Gametocyte surface protein required for male fertility.
CC {ECO:0000250|UniProtKB:Q4YSU6}.
CC -!- SUBUNIT: Heterodimer; heterodimerizes with PF230.
CC {ECO:0000269|PubMed:1380124}.
CC -!- SUBCELLULAR LOCATION: Cell surface {ECO:0000250|UniProtKB:Q4YSU6}. Cell
CC membrane {ECO:0000250|UniProtKB:Q4YSU6}; Lipid-anchor, GPI-anchor
CC {ECO:0000250|UniProtKB:Q4YSU6}. Note=Present on the surface of male and
CC female gametocytes. {ECO:0000250|UniProtKB:Q4YSU6}.
CC -!- BIOTECHNOLOGY: Promising transmission-blocking vaccine candidate:
CC targeting the protein would prevent transmission of the parasite
CC decreasing the malaria burden. However, efforts to produce full length
CC recombinant protein in a functional conformation is difficult.
CC Different approaches have been tested to produce a recombinant protein
CC with display of its transmission-blocking epitopes.
CC {ECO:0000305|PubMed:18332422, ECO:0000305|PubMed:19623257,
CC ECO:0000305|PubMed:30237518}.
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DR EMBL; AL844509; VWP77780.1; -; Genomic_DNA.
DR RefSeq; XP_001350181.1; XM_001350145.1.
DR PDB; 6E62; X-ray; 2.70 A; A/P=291-428.
DR PDB; 6E63; X-ray; 2.60 A; A/P=291-428.
DR PDB; 6H5N; X-ray; 3.23 A; A/D=293-428.
DR PDBsum; 6E62; -.
DR PDBsum; 6E63; -.
DR PDBsum; 6H5N; -.
DR AlphaFoldDB; Q8I6T1; -.
DR SMR; Q8I6T1; -.
DR STRING; 5833.PF13_0247; -.
DR PRIDE; Q8I6T1; -.
DR ABCD; Q8I6T1; 2 sequenced antibodies.
DR EnsemblProtists; CAD52590; CAD52590; PF3D7_1346700.
DR GeneID; 814212; -.
DR KEGG; pfa:PF3D7_1346700; -.
DR VEuPathDB; PlasmoDB:PF3D7_1346700; -.
DR HOGENOM; CLU_611777_0_0_1; -.
DR InParanoid; Q8I6T1; -.
DR OMA; VLKYPHK; -.
DR PhylomeDB; Q8I6T1; -.
DR Proteomes; UP000001450; Chromosome 13.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR Gene3D; 2.60.40.2860; -; 2.
DR InterPro; IPR010884; 6_CYS_dom.
DR InterPro; IPR038160; 6_CYS_dom_sf.
DR Pfam; PF07422; s48_45; 2.
DR SMART; SM00970; s48_45; 2.
DR PROSITE; PS51701; 6_CYS; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; Glycoprotein; GPI-anchor;
KW Lipoprotein; Malaria; Membrane; Reference proteome; Repeat; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..426
FT /note="Gametocyte surface protein P45/48"
FT /id="PRO_0000423560"
FT PROPEP 427..448
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000423561"
FT DOMAIN 45..182
FT /note="6-Cys 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01038"
FT DOMAIN 294..426
FT /note="6-Cys 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01038"
FT LIPID 426
FT /note="GPI-anchor amidated aspartate"
FT /evidence="ECO:0000255"
FT CARBOHYD 50
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 303
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30367064"
FT DISULFID 49..71
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01038"
FT DISULFID 102..156
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01038"
FT DISULFID 298..327
FT /evidence="ECO:0000269|PubMed:30237518,
FT ECO:0000269|PubMed:30367064, ECO:0007744|PDB:6E62,
FT ECO:0007744|PDB:6E63, ECO:0007744|PDB:6H5N"
FT DISULFID 344..412
FT /evidence="ECO:0000269|PubMed:30237518,
FT ECO:0000269|PubMed:30367064, ECO:0007744|PDB:6E62,
FT ECO:0007744|PDB:6E63, ECO:0007744|PDB:6H5N"
FT DISULFID 352..410
FT /evidence="ECO:0000269|PubMed:30237518,
FT ECO:0000269|PubMed:30367064, ECO:0007744|PDB:6E62,
FT ECO:0007744|PDB:6E63, ECO:0007744|PDB:6H5N"
FT STRAND 295..299
FT /evidence="ECO:0007829|PDB:6E63"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:6E62"
FT STRAND 310..313
FT /evidence="ECO:0007829|PDB:6E63"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:6E62"
FT STRAND 324..331
FT /evidence="ECO:0007829|PDB:6E63"
FT STRAND 334..351
FT /evidence="ECO:0007829|PDB:6E63"
FT TURN 352..354
FT /evidence="ECO:0007829|PDB:6E63"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:6E63"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:6E62"
FT HELIX 372..376
FT /evidence="ECO:0007829|PDB:6E63"
FT STRAND 381..388
FT /evidence="ECO:0007829|PDB:6E63"
FT STRAND 391..400
FT /evidence="ECO:0007829|PDB:6E63"
FT STRAND 406..414
FT /evidence="ECO:0007829|PDB:6E63"
FT STRAND 417..425
FT /evidence="ECO:0007829|PDB:6E63"
SQ SEQUENCE 448 AA; 51486 MW; 63EF9EAB5CC7B013 CRC64;
MMLYISAKKA QVAFILYIVL VLRIISGNND FCKPSSLNSE ISGFIGYKCN FSNEGVHNLK
PDMRERRSIF CTIHSYFIYD KIRLIIPKKS SSPEFKILPE KCFQKVYTDY ENRVETDISE
LGLIEYEIEE NDTNPNYNER TITISPFSPK DIEFFCFCDN TEKVISSIEG RSAMVHVRVL
KYPHNILFTN LTNDLFTYLP KTYNESNFVS NVLEVELNDG ELFVLACELI NKKCFQEGKE
KALYKSNKII YHKNLTIFKA PFYVTSKDVN TECTCKFKNN NYKIVLKPKY EKKVIHGCNF
SSNVSSKHTF TDSLDISLVD DSAHISCNVH LSEPKYNHLV GLNCPGDIIP DCFFQVYQPE
SEELEPSNIV YLDSQINIGD IEYYEDAEGD DKIKLFGIVG SIPKTTSFTC ICKKDKKSAY
MTVTIDSAYY GFLAKTFIFL IVAILLYI
