SERA5_PLAFG
ID SERA5_PLAFG Reviewed; 989 AA.
AC P69192; P13823;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=Serine-repeat antigen protein 5 {ECO:0000305};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:Q9TY95};
DE AltName: Full=111 kDa antigen;
DE AltName: Full=Serine protease SERA5 {ECO:0000305};
DE AltName: Full=p126;
DE Contains:
DE RecName: Full=p47 {ECO:0000303|PubMed:1501648};
DE AltName: Full=SER36 {ECO:0000250|UniProtKB:P69193};
DE Contains:
DE RecName: Full=p56 {ECO:0000303|PubMed:1501648};
DE Contains:
DE RecName: Full=p50 {ECO:0000303|PubMed:1501648};
DE Contains:
DE RecName: Full=p18 {ECO:0000303|PubMed:1501648};
DE Contains:
DE RecName: Full=p25n {ECO:0000250|UniProtKB:Q9TY95};
DE Contains:
DE RecName: Full=p25c {ECO:0000250|UniProtKB:Q9TY95};
DE Flags: Precursor;
GN Name=SERA5 {ECO:0000303|PubMed:2651911};
OS Plasmodium falciparum (isolate FCR-3 / Gambia).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5838;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2651911; DOI=10.1016/0166-6851(89)90037-6;
RA Li W.-B., Bzik D.J., Horii T., Inselburg J.;
RT "Structure and expression of the Plasmodium falciparum SERA gene.";
RL Mol. Biochem. Parasitol. 33:13-26(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2847041; DOI=10.1016/0166-6851(88)90097-7;
RA Bzik D.J., Li W.-B., Horii T., Inselburg J.;
RT "Amino acid sequence of the serine-repeat antigen (SERA) of Plasmodium
RT falciparum determined from cloned cDNA.";
RL Mol. Biochem. Parasitol. 30:279-288(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-362.
RC STRAIN=FCR-3 / Gambia;
RX PubMed=2456465; DOI=10.1016/0166-6851(88)90127-2;
RA Horii T., Bzik D.J., Inselburg J.;
RT "Characterization of antigen-expressing Plasmodium falciparum cDNA clones
RT that are reactive with parasite inhibitory antibodies.";
RL Mol. Biochem. Parasitol. 30:9-18(1988).
RN [4]
RP PROTEIN SEQUENCE OF 23-27; 383-392 AND 879-883, DEVELOPMENTAL STAGE, AND
RP PROTEOLYTIC CLEAVAGE.
RX PubMed=1501648; DOI=10.1016/0166-6851(92)90010-h;
RA Debrabant A., Maes P., Delplace P., Dubremetz J.F., Tartar A., Camus D.;
RT "Intramolecular mapping of Plasmodium falciparum P126 proteolytic fragments
RT by N-terminal amino acid sequencing.";
RL Mol. Biochem. Parasitol. 53:89-95(1992).
RN [5]
RP SIMILARITY TO THIOL PROTEASES OF A DOMAIN.
RX PubMed=2671749; DOI=10.1038/340604a0;
RA Higgins D.G., McConnell D.J., Sharp P.M.;
RT "Malarial proteinase?";
RL Nature 340:604-604(1989).
RN [6]
RP SIMILARITY TO THIOL PROTEASES OF A DOMAIN.
RX PubMed=2682262; DOI=10.1038/342132b0;
RA Eakin A.E., Higaki J.N., McKerrow J.H., Craik C.S., Mottram J.C.,
RA Coombs G.H., North M.J.;
RT "Cysteine or serine proteinase?";
RL Nature 342:132-132(1989).
RN [7]
RP FUNCTION, DEVELOPMENTAL STAGE, AND BIOTECHNOLOGY.
RX PubMed=12244052; DOI=10.1074/jbc.m207145200;
RA Aoki S., Li J., Itagaki S., Okech B.A., Egwang T.G., Matsuoka H.,
RA Palacpac N.M., Mitamura T., Horii T.;
RT "Serine repeat antigen (SERA5) is predominantly expressed among the SERA
RT multigene family of Plasmodium falciparum, and the acquired antibody titers
RT correlate with serum inhibition of the parasite growth.";
RL J. Biol. Chem. 277:47533-47540(2002).
RN [8] {ECO:0007744|PDB:2MUG}
RP STRUCTURE BY NMR OF 901-920.
RX PubMed=16126320; DOI=10.1016/j.biochi.2005.07.006;
RA Patarroyo M.E., Salazar L.M., Cifuentes G., Lozano J.M., Delgado G.,
RA Rivera Z., Rosas J., Vargas L.E.;
RT "Protective cellular immunity against P. falciparum malaria merozoites is
RT associated with a different P7 and P8 residue orientation in the MHC-
RT peptide-TCR complex.";
RL Biochimie 88:219-230(2006).
CC -!- FUNCTION: Plays an essential role during the asexual blood stage
CC development by controlling the kinetics of merozoite egress from host
CC erythrocytes (By similarity). Specifically, prevents premature rupture
CC of the parasitophorous vacuole and host erythrocyte membranes (By
CC similarity). {ECO:0000250|UniProtKB:Q9TY95}.
CC -!- FUNCTION: [p47]: May prevent merozoite phagocytosis by host monocytes
CC via interaction with host VTN at the merozoite surface (By similarity).
CC Plays a role in parasite growth (PubMed:12244052).
CC {ECO:0000250|UniProtKB:P69193, ECO:0000269|PubMed:12244052}.
CC -!- SUBUNIT: May interact (via C-terminus) with PTKL (via SAM domain).
CC {ECO:0000250|UniProtKB:Q9TY95}.
CC -!- SUBUNIT: [p47]: Interacts (via C-terminus) with human VTN (via
CC hemopexin repeat 2); may form heterotetramers of two VTN and SERA5 P47
CC heterodimers; the interaction may protect merozoites from phagocytosis
CC by host monocytes; VTN glycosylation appears to be dispensable for the
CC interaction. {ECO:0000250|UniProtKB:P69193}.
CC -!- SUBUNIT: [p50]: Monomer. Interacts with kinase CPK1/CDPK1 at the
CC schizont stage. {ECO:0000250|UniProtKB:Q9TY95}.
CC -!- SUBCELLULAR LOCATION: [Serine-repeat antigen protein 5]:
CC Parasitophorous vacuole {ECO:0000250|UniProtKB:Q9TY95}. Note=Secreted
CC in large amount into the parasitophorous vacuole.
CC {ECO:0000250|UniProtKB:Q9TY95}.
CC -!- SUBCELLULAR LOCATION: [p18]: Secreted {ECO:0000250|UniProtKB:P69193}.
CC Note=Secreted during merozoite egress from erythrocytes.
CC {ECO:0000250|UniProtKB:P69193}.
CC -!- SUBCELLULAR LOCATION: [p25n]: Secreted {ECO:0000250|UniProtKB:Q9TY95}.
CC Note=Secreted during merozoite egress from erythrocytes.
CC {ECO:0000250|UniProtKB:P69193}.
CC -!- SUBCELLULAR LOCATION: [p25c]: Secreted {ECO:0000250|UniProtKB:P69193}.
CC Note=Secreted during merozoite egress from erythrocytes.
CC {ECO:0000250|UniProtKB:P69193}.
CC -!- SUBCELLULAR LOCATION: [p47]: Secreted {ECO:0000250|UniProtKB:P69193}.
CC Cell membrane {ECO:0000250|UniProtKB:Q9TY95}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q9TY95}; Extracellular side
CC {ECO:0000250|UniProtKB:P69193}. Note=Secreted during merozoite egress
CC from erythrocytes (By similarity). Colocalizes at the merozoite surface
CC with human VTN (By similarity). {ECO:0000250|UniProtKB:P69193,
CC ECO:0000250|UniProtKB:Q9TY95}.
CC -!- SUBCELLULAR LOCATION: [p50]: Secreted {ECO:0000250|UniProtKB:Q9TY95}.
CC Note=Secreted during egress from host erythrocytes.
CC {ECO:0000250|UniProtKB:Q9TY95}.
CC -!- SUBCELLULAR LOCATION: [p56]: Secreted {ECO:0000250|UniProtKB:Q9TY95}.
CC Note=Secreted during egress from host erythrocytes.
CC {ECO:0000250|UniProtKB:Q9TY95}.
CC -!- DEVELOPMENTAL STAGE: Expressed during parasite asexual blood stages,
CC specifically at the late trophozoite and schizont stages (at protein
CC level). {ECO:0000269|PubMed:12244052, ECO:0000269|PubMed:1501648}.
CC -!- PTM: [p50]: Phosphorylation by CPK1/CDPK1 increases SERA5 protease
CC activity towards a synthetic peptide in vitro.
CC {ECO:0000250|UniProtKB:Q9TY95}.
CC -!- PTM: Just prior to merozoite egress from host erythrocytes,
CC proteolytically cleaved into multiple fragments (PubMed:1501648).
CC Cleaved by SUB1 into p47 and p73, p73 is further cleaved by SUB1 into
CC p56 and p18 and p56 is further processed into p50 by an unidentified
CC protease (PubMed:1501648). p47 remains covalently associated with p18
CC via disulfide bond (By similarity). p47 can be processed into p25n and
CC p25c by SUB1 (By similarity). p25c and p25n remain associated with p18
CC (By similarity). Proteolytic processing is essential for merozoite
CC egress from host erythrocytes (By similarity). The cleavage of the
CC propeptide to produce p50 is necessary for protease activity and to
CC promote merozoite egress (By similarity).
CC {ECO:0000250|UniProtKB:Q9TY95, ECO:0000269|PubMed:1501648}.
CC -!- BIOTECHNOLOGY: [p47]: Potential candidate for the development of
CC parasite blood stage vaccines (PubMed:12244052). In vitro and in vivo,
CC induces antibodies capable of inhibiting parasite growth
CC (PubMed:12244052). {ECO:0000269|PubMed:12244052}.
CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU10089, ECO:0000255|PROSITE-ProRule:PRU10090}.
CC -!- CAUTION: In contrast to other serine-repeat antigen proteins (SERA) of
CC the peptidase C1 family, contains a serine residue at the position of
CC the canonical catalytic cysteine and has been shown to lack protease
CC activity (By similarity). However, other studies show that it has
CC protease activity towards synthetic peptides in vitro (By similarity).
CC {ECO:0000250|UniProtKB:Q9TY95}.
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DR EMBL; J04000; AAA16791.1; -; Genomic_DNA.
DR EMBL; X06427; CAA29734.1; -; mRNA.
DR EMBL; J03993; AAA29763.1; -; mRNA.
DR EMBL; M21323; AAA29488.1; -; mRNA.
DR PIR; A54505; A54505.
DR PIR; A54512; A54512.
DR PDB; 2MUG; NMR; -; A=901-920.
DR PDBsum; 2MUG; -.
DR AlphaFoldDB; P69192; -.
DR BMRB; P69192; -.
DR SMR; P69192; -.
DR MEROPS; C01.984; -.
DR PRIDE; P69192; -.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020003; C:symbiont-containing vacuole; IEA:UniProtKB-SubCell.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR025661; Pept_asp_AS.
DR InterPro; IPR025660; Pept_his_AS.
DR InterPro; IPR000668; Peptidase_C1A_C.
DR Pfam; PF00112; Peptidase_C1; 1.
DR SMART; SM00645; Pept_C1; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00640; THIOL_PROTEASE_ASN; 1.
DR PROSITE; PS00639; THIOL_PROTEASE_HIS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Hydrolase; Malaria; Membrane; Phosphoprotein; Protease;
KW Secreted; Signal; Thiol protease; Zymogen.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..989
FT /note="Serine-repeat antigen protein 5"
FT /id="PRO_0000026481"
FT CHAIN 23..382
FT /note="p47"
FT /evidence="ECO:0000269|PubMed:1501648"
FT /id="PRO_0000450191"
FT CHAIN 23..184
FT /note="p25n"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT /id="PRO_0000450192"
FT CHAIN 185..382
FT /note="p25c"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT /id="PRO_0000450193"
FT CHAIN 383..878
FT /note="p56"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT /id="PRO_0000450194"
FT CHAIN 383..834
FT /note="p50"
FT /evidence="ECO:0000269|PubMed:1501648"
FT /id="PRO_0000450195"
FT PROPEP 835..878
FT /note="Inhibition peptide"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT /id="PRO_0000450196"
FT CHAIN 879..989
FT /note="p18"
FT /evidence="ECO:0000269|PubMed:1501648"
FT /id="PRO_0000450197"
FT REGION 26..91
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 165..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 208..245
FT /note="Interaction with PTKL"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT REGION 365..382
FT /note="Interaction with host VTN"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT REGION 577..802
FT /note="Thiol protease-like"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT COMPBIAS 167..245
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 754
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10089"
FT ACT_SITE 779
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10090"
FT SITE 184..185
FT /note="Cleavage; by SUB1"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT SITE 382..383
FT /note="Cleavage; by SUB1"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT SITE 588
FT /note="Ancestral active site"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT SITE 834..835
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT SITE 878..879
FT /note="Cleavage; by SUB1"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT MOD_RES 167
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT MOD_RES 541
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT MOD_RES 858
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 820
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 437..489
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT DISULFID 559..564
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT DISULFID 573..602
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT DISULFID 585..628
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT DISULFID 619..664
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT DISULFID 747..801
FT /evidence="ECO:0000250|UniProtKB:Q9TY95"
FT VARIANT 178..191
FT /note="Missing (in an allele)"
FT CONFLICT 8
FT /note="F -> L (in Ref. 3; AAA29488)"
FT /evidence="ECO:0000305"
FT CONFLICT 44
FT /note="A -> T (in Ref. 3; CAA29734/AAA29488)"
FT /evidence="ECO:0000305"
FT CONFLICT 356..362
FT /note="EKENKND -> KKKKKGI (in Ref. 3; CAA29734)"
FT /evidence="ECO:0000305"
FT HELIX 902..919
FT /evidence="ECO:0007829|PDB:2MUG"
SQ SEQUENCE 989 AA; 111095 MW; E732960770C15F52 CRC64;
MKSYISLFFI LCVIFNKNVI KCTGESQTGN TGGGQAGNTV GDQAGSTGGS PQGSTGASQP
GSSEPSNPVS SGHSVSTVSV SQTSTSSEKQ DTIQVKSALL KDYMGLKVTG PCNENFIMFL
VPHIYIDVDT EDTNIELRTT LKETNNAISF ESNSGSLEKK KYVKLPSNGT TGEQGSSTGT
VRGDTEPISD SSSSSSSSSS SSSSSSSSSS SSSSSSSSSS SSSSSESLPA NGPDSPTVKP
PRNLQNICET GKNFKLVVYI KENTLIIKWK VYGETKDTTE NNKVDVRKYL INEKETPFTS
ILIHAYKEHN GTNLIESKNY ALGSDIPEKC DTLASNCFLS GNFNIEKCFQ CALLVEKENK
NDVCYKYLSE DIVSNFKEIK AETEDDDEDD YTEYKLTESI DNILVKMFKT NENNDKSELI
KLEEVDDSLK LELMNYCSLL KDVDTTGTLD NYGMGNEMDI FNNLKRLLIY HSEENINTLK
NKFRNAAVCL KNVDDWIVNK RGLVLPELNY DLEYFNEHLY NDKNSPEDKD NKGKGVVHVD
TTLEKEDTLS YDNSDNMFCN KEYCNRLKDE NNCISNLQVE DQGNCDTSWI FASKYHLETI
RCMKGYEPTK ISALYVANCY KGEHKDRCDE GSSPMEFLQI IEDYGFLPAE SNYPYNYVKV
GEQCPKVEDH WMNLWDNGKI LHNKNEPNSL DGKGYTAYES ERFHDNMDAF VKIIKTEVMN
KGSVIAYIKA ENVMGYEFSG KKVQNLCGDD TADHAVNIVG YGNYVNSEGE KKSYWIVRNS
WGPYWGDEGY FKVDMYGPTH CHFNFIHSVV IFNVDLPMNN KTTKKESKIY DYYLKASPEF
YHNLYFKNFN VGKKNLFSEK EDNENNKKLG NNYIIFGQDT AGSGQSGKES NTALESAGTS
NEVSERVHVY HILKHIKDGK IRMGMRKYID TQDVNKKHSC TRSYAFNPEN YEKCVNLCNV
NWKTCEEKTS PGLCLSKLDT NNECYFCYV
