SUB1_PLAFO
ID SUB1_PLAFO Reviewed; 688 AA.
AC W7K9M0;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 49.
DE RecName: Full=Subtilisin-like protease 1 {ECO:0000303|PubMed:29074774};
DE EC=3.4.21.62 {ECO:0000250|UniProtKB:Q8I0V0};
DE Flags: Precursor;
GN Name=SUB1 {ECO:0000303|PubMed:29074774};
GN ORFNames=CK202_3597 {ECO:0000312|EMBL:PKC45911.1},
GN PFNF54_00901 {ECO:0000312|EMBL:EWC90279.1};
OS Plasmodium falciparum (isolate NF54).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5843 {ECO:0000312|Proteomes:UP000030673};
RN [1] {ECO:0000312|Proteomes:UP000030673}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NF54 {ECO:0000312|Proteomes:UP000030673};
RG The Broad Institute Genome Sequencing Platform;
RG The Broad Institute Genome Sequencing Center for Infectious Disease;
RA Neafsey D., Cheeseman I., Volkman S., Adams J., Walker B., Young S.K.,
RA Zeng Q., Gargeya S., Fitzgerald M., Haas B., Abouelleil A., Alvarado L.,
RA Arachchi H.M., Berlin A.M., Chapman S.B., Dewar J., Goldberg J., Griggs A.,
RA Gujja S., Hansen M., Howarth C., Imamovic A., Larimer J., McCowan C.,
RA Murphy C., Neiman D., Pearson M., Priest M., Roberts A., Saif S., Shea T.,
RA Sisk P., Sykes S., Wortman J., Nusbaum C., Birren B.;
RT "The Genome Sequence of Plasmodium falciparum NF54.";
RL Submitted (FEB-2013) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|Proteomes:UP000232684}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NF54 {ECO:0000312|EMBL:PKC45911.1};
RA Bryant J.M., Baumgarten S., Scheidig-Benatar C., Scherf A.;
RT "Plasmodium falciparum NF54 genome assembly.";
RL Submitted (NOV-2017) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=29074774; DOI=10.1126/science.aan1478;
RA Nasamu A.S., Glushakova S., Russo I., Vaupel B., Oksman A., Kim A.S.,
RA Fremont D.H., Tolia N., Beck J.R., Meyers M.J., Niles J.C., Zimmerberg J.,
RA Goldberg D.E.;
RT "Plasmepsins IX and X are essential and druggable mediators of malaria
RT parasite egress and invasion.";
RL Science 358:518-522(2017).
CC -!- FUNCTION: Serine protease which plays an essential role in merozoite
CC invasion of and egress from host erythrocytes by processing and
CC activating various merozoite surface and parasitophorous vacuole
CC proteins. Mediates the proteolytic maturation of serine proteases
CC SERA4, SERA5 and SERA6 just prior to merozoite egress. Prior to
CC merozoite egress, cleaves merozoite surface proteins MSP1, MSP6 and
CC MSP7, which form the MSP1/6/7 complex, and thereby may prime the
CC parasite cell surface for invasion of fresh erythrocytes. Prior to
CC merozoite egress, cleaves MSRP2 converting it to MSRP2 p25 form, and
CC RAP1 converting it to RAP1 p67 form. {ECO:0000250|UniProtKB:Q8I0V0}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins with broad specificity for peptide
CC bonds, and a preference for a large uncharged residue in P1.
CC Hydrolyzes peptide amides.; EC=3.4.21.62;
CC Evidence={ECO:0000250|UniProtKB:Q8I0V0};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:O61142};
CC Note=Binds 3 Ca(2+) ions per subunit. {ECO:0000250|UniProtKB:O61142};
CC -!- ACTIVITY REGULATION: p54 and probably p47 forms are inhibited by the
CC non-covalent interaction with the cleaved propeptide (By similarity).
CC Inhibited by subtilisin propeptide-like protein SUB1-ProM (By
CC similarity). {ECO:0000250|UniProtKB:Q8I0V0}.
CC -!- SUBUNIT: Heterodimer between p54 form and propeptide p31; the
CC interaction inhibits p54 catalytic activity.
CC {ECO:0000250|UniProtKB:O61142}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q8I0V0}.
CC Parasitophorous vacuole lumen {ECO:0000250|UniProtKB:Q8I0V0}. Note=At
CC the schizont stage, in merozoites, localizes to dense secretory
CC granules called exonemes (PubMed:29074774). Just prior to egress
CC secreted into the parasitophorous vacuole (By similarity).
CC {ECO:0000250|UniProtKB:Q8I0V0, ECO:0000269|PubMed:29074774}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the parasite blood stage,
CC specifically in schizonts (at protein level).
CC {ECO:0000269|PubMed:29074774}.
CC -!- PTM: The propeptide (p31) is cleaved, probably by autocatalysis, during
CC the transport to or in the Golgi apparatus, and remains non-covalently
CC associated with the p54 form as an inhibitor. p54 is further cleaved
CC into the p45 form (By similarity). This cleavage is likely occurring in
CC the exoneme prior to egress and is mediated by PMX/plasmepsin X
CC (PubMed:29074774). {ECO:0000250|UniProtKB:O61142,
CC ECO:0000269|PubMed:29074774}.
CC -!- PTM: The disulfide bond between Cys-521 and Cys-534 acts as a redox-
CC sensitive disulfide switch. The oxidized form is required for catalytic
CC activity. {ECO:0000250|UniProtKB:O61142}.
CC -!- PTM: The relevance of N-glycosylation is not clear. In an insect
CC expression system, SUB1 glycosylation appears to affect its processing
CC into the active mature form suggesting that SUB1 may not be N-
CC glycosylated in parasites. {ECO:0000250|UniProtKB:O61142}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family.
CC {ECO:0000255|RuleBase:RU003355}.
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DR EMBL; KE123753; EWC90279.1; -; Genomic_DNA.
DR EMBL; NYMT01000012; PKC45911.1; -; Genomic_DNA.
DR AlphaFoldDB; W7K9M0; -.
DR SMR; W7K9M0; -.
DR MEROPS; S08.012; -.
DR PRIDE; W7K9M0; -.
DR EnsemblProtists; EWC90279; EWC90279; PFNF54_00901.
DR VEuPathDB; PlasmoDB:PfNF54_050011800; -.
DR OMA; FKCIDYC; -.
DR Proteomes; UP000030673; Unassembled WGS sequence.
DR Proteomes; UP000232684; Unassembled WGS sequence.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd07473; Peptidases_S8_Subtilisin_like; 1.
DR Gene3D; 3.40.50.200; -; 1.
DR InterPro; IPR017314; Pept_S8A_PfSUB_1.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR InterPro; IPR023827; Peptidase_S8_Asp-AS.
DR InterPro; IPR022398; Peptidase_S8_His-AS.
DR InterPro; IPR023828; Peptidase_S8_Ser-AS.
DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR InterPro; IPR034204; PfSUB1-like_cat_dom.
DR InterPro; IPR041089; SUB1_ProdP9.
DR Pfam; PF00082; Peptidase_S8; 1.
DR Pfam; PF18213; SUB1_ProdP9; 1.
DR PIRSF; PIRSF037900; Subtilisin_rel_PfSUB_1; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF52743; SSF52743; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
DR PROSITE; PS00136; SUBTILASE_ASP; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 1: Evidence at protein level;
KW Calcium; Disulfide bond; Glycoprotein; Hydrolase; Metal-binding; Protease;
KW Reference proteome; Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..25
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT PROPEP 26..217
FT /note="Inhibition peptide"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT /id="PRO_0000450202"
FT CHAIN 218..688
FT /note="Subtilisin-like protease 1"
FT /evidence="ECO:0000255"
FT /id="PRO_5014109794"
FT DOMAIN 343..661
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT REGION 99..129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 264..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 303..332
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 106..125
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..330
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 372
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 428
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 606
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT BINDING 338
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 381
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 392
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 392
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 396
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 399
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 400
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 401
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 402
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 404
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 406
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 408
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 409
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 439
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 442
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 444
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT BINDING 446
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT SITE 217..218
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT SITE 243..244
FT /note="Cleavage; by PMX"
FT /evidence="ECO:0000250|UniProtKB:Q8I0V0"
FT SITE 249..250
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 261
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 317
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 322
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 488
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 501
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 520
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 603
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 675
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 369..479
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT DISULFID 458..475
FT /evidence="ECO:0000250|UniProtKB:O61142"
FT DISULFID 521..534
FT /evidence="ECO:0000250|UniProtKB:O61142"
SQ SEQUENCE 688 AA; 77647 MW; FACFEFB495AEF4F7 CRC64;
MMLNKKVVAL CTLTLHLFCI FLCLGKEVRS EENGKIQDDA KKIVSELRFL EKVEDVIEKS
NIGGNEVDAD ENSFNPDTEV PIEEIEEIKM RELKDVKEEK NKNDNHNNNN NNISSSSSSS
SNTFGEEKEE VSKKKKKLRL IVSENHATTP SFFQESLLEP DVLSFLESKG NLSNLKNINS
MIIELKEDTT DDELISYIKI LEEKGALIES DKLVSADNID ISGIKDAIRR GEENIDVNDY
KSMLEVENDA EDYDKMFGMF NESHAATSKR KRHSTNERGY DTFSSPSYKT YSKSDYLYDD
DNNNNNYYYS HSSNGHNSSS RNSSSSRSRP GKYHFNDEFR NLQWGLDLSR LDETQELINE
HQVMSTRICV IDSGIDYNHP DLKDNIELNL KELHGRKGFD DDNNGIVDDI YGANFVNNSG
NPMDDNYHGT HVSGIISAIG NNNIGVVGVD VNSKLIICKA LDEHKLGRLG DMFKCLDYCI
SRNAHMINGS FSFDEYSGIF NSSVEYLQRK GILFFVSASN CSHPKSSTPD IRKCDLSINA
KYPPILSTVY DNVISVANLK KNDNNNHYSL SINSFYSNKY CQLAAPGTNI YSTAPHNSYR
KLNGTSMAAP HVAAIASLIF SINPDLSYKK VIQILKDSIV YLPSLKNMVA WAGYADINKA
VNLAIKSKKT YINSNISNKW KKKSRYLH
