PLM5_PLAFO
ID PLM5_PLAFO Reviewed; 590 AA.
AC W7JPD9;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 52.
DE RecName: Full=Plasmepsin V {ECO:0000303|PubMed:31851913};
DE EC=3.4.23.- {ECO:0000305|PubMed:31851913};
DE AltName: Full=Plasmepsin 5 {ECO:0000305};
DE Flags: Precursor;
GN Name=PMV {ECO:0000303|PubMed:31851913};
GN ORFNames=CK202_2868 {ECO:0000312|EMBL:PKC47229.1},
GN PFNF54_04321 {ECO:0000312|EMBL:EWC86768.1};
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|Proteomes:UP000232684};
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 FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=31851913; DOI=10.1016/j.celrep.2019.11.073;
RA Jennison C., Lucantoni L., O'Neill M.T., McConville R., Erickson S.M.,
RA Cowman A.F., Sleebs B.E., Avery V.M., Boddey J.A.;
RT "Inhibition of Plasmepsin V Activity Blocks Plasmodium falciparum
RT Gametocytogenesis and Transmission to Mosquitoes.";
RL Cell Rep. 29:3796-3806.e4(2019).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32069391; DOI=10.1021/acsinfecdis.9b00460;
RA Polino A.J., Nasamu A.S., Niles J.C., Goldberg D.E.;
RT "Assessment of Biological Role and Insight into Druggability of the
RT Plasmodium falciparum Protease Plasmepsin V.";
RL ACS Infect. Dis. 6:738-746(2020).
CC -!- FUNCTION: During the asexual blood stage, plays an essential role in
CC the export of several proteins into the host erythrocytes by cleaving
CC the pentameric localization motif RxLxE/Q/D (termed Plasmodium export
CC element (PEXEL)) located downstream of the N-terminal secretory signal
CC sequence (PubMed:32069391). Specifically, cleaves after the leucine
CC residue in the RxLxE/Q/D (or RxLxxE) motif of exported proteins
CC including RESA, EMP2, EMP3, KAHRP, RIF/Rifin and STEVOR (By
CC similarity). Also, by regulating protein export, plays an essential
CC role in gametocyte development and thus parasite transmission to the
CC mosquito vector (PubMed:31851913). {ECO:0000250|UniProtKB:Q8I6Z5,
CC ECO:0000269|PubMed:31851913, ECO:0000269|PubMed:32069391}.
CC -!- SUBUNIT: Component of a complex composed of SPC25 and PMV; the
CC interaction is mediated via the transmembrane domains. The complex
CC interacts with the SEC61 channel-forming translocon complex and is
CC involved in the recognition and import of PEXEL motif-containing
CC proteins into the ER for subsequent export.
CC {ECO:0000250|UniProtKB:Q8I6Z5}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:31851913}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:Q8I6Z5}. Note=During gametogenesis, localizes to
CC the perinuclear ER in stage I-II gametocytes, and relocalizes towards
CC the cell periphery as the ER redistributes in the cell in stage III-IV
CC gametocytes. {ECO:0000269|PubMed:31851913}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage including
CC during the ring stage and then in trophozoites (at protein level)
CC (PubMed:31851913). Expressed in all 5 gametocyte stages
CC (PubMed:31851913). {ECO:0000269|PubMed:31851913}.
CC -!- DOMAIN: The transmembrane domain is essential for localization to the
CC endoplasmic reticulum. {ECO:0000250|UniProtKB:Q8I6Z5}.
CC -!- PTM: It is not clear if the zymogen has a cleavable propeptide (By
CC similarity). In vitro, appears to be cleaved between Asn-80 and Ala-81
CC (By similarity). Cleavage of the putative propeptide is dispensable for
CC catalytic activity (By similarity). {ECO:0000250|UniProtKB:Q8I6Z5}.
CC -!- DISRUPTION PHENOTYPE: During the asexual blood stage, causes a
CC developmental arrest between the ring and trophozoite stages and
CC impairs export of ring-infected erythrocyte surface antigen RESA.
CC {ECO:0000269|PubMed:32069391}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family.
CC {ECO:0000255|RuleBase:RU000454}.
CC -!- CAUTION: It is unclear if PMV is glycosylated as other members of the
CC same enzyme family, ie. PMI and PMII, are not. {ECO:0000305}.
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DR EMBL; KE123862; EWC86768.1; -; Genomic_DNA.
DR EMBL; NYMT01000007; PKC47229.1; -; Genomic_DNA.
DR SMR; W7JPD9; -.
DR PRIDE; W7JPD9; -.
DR EnsemblProtists; EWC86768; EWC86768; PFNF54_04321.
DR VEuPathDB; PlasmoDB:PfNF54_130028900; -.
DR OMA; CEGSQIS; -.
DR Proteomes; UP000030673; Unassembled WGS sequence.
DR Proteomes; UP000232684; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031227; C:intrinsic component of endoplasmic reticulum membrane; IMP:UniProtKB.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0032527; P:protein exit from endoplasmic reticulum; IMP:UniProtKB.
DR GO; GO:0016485; P:protein processing; IMP:UniProtKB.
DR CDD; cd06096; Plasmepsin_5; 1.
DR Gene3D; 2.40.70.10; -; 2.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR033121; PEPTIDASE_A1.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR InterPro; IPR033866; Plasmepsin_5.
DR InterPro; IPR032861; TAXi_N.
DR PANTHER; PTHR47966; PTHR47966; 2.
DR Pfam; PF00026; Asp; 1.
DR Pfam; PF14543; TAXi_N; 1.
DR PRINTS; PR00792; PEPSIN.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 1.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 1: Evidence at protein level;
KW Aspartyl protease; Coiled coil; Disulfide bond; Endoplasmic reticulum;
KW Hydrolase; Membrane; Protease; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..?
FT /evidence="ECO:0000305"
FT CHAIN ?..590
FT /note="Plasmepsin V"
FT /id="PRO_0000453928"
FT TOPO_DOM 1..544
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q8I6Z5"
FT TRANSMEM 545..565
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 566..590
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8I6Z5"
FT DOMAIN 100..514
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT REGION 282..316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 33..81
FT /evidence="ECO:0000255"
FT ACT_SITE 118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 365
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT DISULFID 128..211
FT /evidence="ECO:0000250|UniProtKB:A5K302"
FT DISULFID 131..134
FT /evidence="ECO:0000250|UniProtKB:A5K302"
FT DISULFID 155..166
FT /evidence="ECO:0000250|UniProtKB:A5K302"
FT DISULFID 160..171
FT /evidence="ECO:0000250|UniProtKB:A5K302"
FT DISULFID 259..518
FT /evidence="ECO:0000250|UniProtKB:A5K302"
FT DISULFID 389..434
FT /evidence="ECO:0000250|UniProtKB:A5K302"
FT DISULFID 443..479
FT /evidence="ECO:0000250|UniProtKB:A5K302"
SQ SEQUENCE 590 AA; 68480 MW; E0108FA9E9C38832 CRC64;
MNNYFLRKEN FFILFCFVFV SIFFVSNVTI IKCNNVENKI DNVGKKIENV GKKIGDMENK
NDNVENKNDN VGNKNDNVKN ASSDLYKYKL YGDIDEYAYY FLDIDIGKPS QRISLILDTG
SSSLSFPCNG CKDCGIHMEK PYNLNYSKTS SILYCNKSNC PYGLKCVGNK CEYLQSYCEG
SQIYGFYFSD IVTLPSYNNK NKISFEKLMG CHMHEESLFL HQQATGVLGF SLTKPNGVPT
FVDLLFKHTP SLKPIYSICV SEHGGELIIG GYEPDYFLSN QKEKQKMDKS DNNSSNKGNV
SIKLKNNDKN DDEENNSKDV IVSNNVEDIV WQAITRKYYY YIKIYGLDLY GTNIMDKKEL
DMLVDSGSTF THIPENIYNQ INYYLDILCI HDMTNIYEIN KRLKLTNESL NKPLVYFEDF
KTALKNIIQN ENLCIKIVDG VQCWKSLENL PNLYITLSNN YKMIWKPSSY LYKKESFWCK
GLEKQVNNKP ILGLTFFKNK QVIFDLQQNQ IAFIESKCPS NLTSSRPRTF NEYREKENIF
LKVSYINLYC LWLLLALTIL LSLILYVRKM FYMDYFPLSD QNKSPIQEST
