PLM5_PLAVS
ID PLM5_PLAVS Reviewed; 536 AA.
AC A5K302;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Plasmepsin V {ECO:0000303|PubMed:24983235};
DE Short=PvPMV {ECO:0000303|PubMed:24983235};
DE EC=3.4.23.- {ECO:0000269|PubMed:24983235, ECO:0000269|PubMed:26214367, ECO:0000269|PubMed:29800827};
DE AltName: Full=Plasmepsin 5 {ECO:0000305};
DE Flags: Precursor;
GN Name=PMV {ECO:0000303|PubMed:24983235};
GN ORFNames=PVX_116695 {ECO:0000312|EMBL:EDL45906.1};
OS Plasmodium vivax (strain Salvador I).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX NCBI_TaxID=126793 {ECO:0000312|Proteomes:UP000008333};
RN [1] {ECO:0000312|Proteomes:UP000008333}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Salvador I {ECO:0000312|Proteomes:UP000008333};
RX PubMed=18843361; DOI=10.1038/nature07327;
RA Carlton J.M., Adams J.H., Silva J.C., Bidwell S.L., Lorenzi H., Caler E.,
RA Crabtree J., Angiuoli S.V., Merino E.F., Amedeo P., Cheng Q.,
RA Coulson R.M.R., Crabb B.S., del Portillo H.A., Essien K., Feldblyum T.V.,
RA Fernandez-Becerra C., Gilson P.R., Gueye A.H., Guo X., Kang'a S.,
RA Kooij T.W.A., Korsinczky M., Meyer E.V.-S., Nene V., Paulsen I., White O.,
RA Ralph S.A., Ren Q., Sargeant T.J., Salzberg S.L., Stoeckert C.J.,
RA Sullivan S.A., Yamamoto M.M., Hoffman S.L., Wortman J.R., Gardner M.J.,
RA Galinski M.R., Barnwell J.W., Fraser-Liggett C.M.;
RT "Comparative genomics of the neglected human malaria parasite Plasmodium
RT vivax.";
RL Nature 455:757-763(2008).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ASP-80 AND ASP-313.
RX PubMed=24983235; DOI=10.1371/journal.pbio.1001897;
RA Sleebs B.E., Lopaticki S., Marapana D.S., O'Neill M.T., Rajasekaran P.,
RA Gazdik M., Guenther S., Whitehead L.W., Lowes K.N., Barfod L., Hviid L.,
RA Shaw P.J., Hodder A.N., Smith B.J., Cowman A.F., Boddey J.A.;
RT "Inhibition of Plasmepsin V activity demonstrates its essential role in
RT protein export, PfEMP1 display, and survival of malaria parasites.";
RL PLoS Biol. 12:e1001897-e1001897(2014).
RN [3] {ECO:0007744|PDB:4ZL4}
RP X-RAY CRYSTALLOGRAPHY (2.37 ANGSTROMS) OF 35-476 IN COMPLEX WITH INHIBITOR,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND DISULFIDE BONDS.
RX PubMed=26214367; DOI=10.1038/nsmb.3061;
RA Hodder A.N., Sleebs B.E., Czabotar P.E., Gazdik M., Xu Y., O'Neill M.T.,
RA Lopaticki S., Nebl T., Triglia T., Smith B.J., Lowes K., Boddey J.A.,
RA Cowman A.F.;
RT "Structural basis for plasmepsin V inhibition that blocks export of malaria
RT proteins to human erythrocytes.";
RL Nat. Struct. Mol. Biol. 22:590-596(2015).
RN [4] {ECO:0007744|PDB:6C4G}
RP X-RAY CRYSTALLOGRAPHY (2.39 ANGSTROMS) OF 35-476 IN COMPLEX WITH INHIBITOR,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND DISULFIDE BONDS.
RX PubMed=29800827; DOI=10.1016/j.ejmech.2018.05.022;
RA Nguyen W., Hodder A.N., de Lezongard R.B., Czabotar P.E., Jarman K.E.,
RA O'Neill M.T., Thompson J.K., Jousset Sabroux H., Cowman A.F., Boddey J.A.,
RA Sleebs B.E.;
RT "Enhanced antimalarial activity of plasmepsin V inhibitors by modification
RT of the P2 position of PEXEL peptidomimetics.";
RL Eur. J. Med. Chem. 154:182-198(2018).
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:24983235). Specifically, cleaves after the leucine
CC residue in the RxLxE/Q/D (or RxLxxE) motif of exported proteins
CC including EMP1 (By similarity). Also, by regulating protein export,
CC plays an essential role in gametocyte development and thus parasite
CC transmission to the mosquito vector (By similarity).
CC {ECO:0000250|UniProtKB:Q8I6Z5, ECO:0000250|UniProtKB:W7JPD9,
CC ECO:0000269|PubMed:24983235}.
CC -!- ACTIVITY REGULATION: Inhibited by peptidomimetic inhibitors such as
CC WEHI-842. {ECO:0000269|PubMed:26214367, ECO:0000269|PubMed:29800827}.
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:24983235}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:Q8I6Z5}.
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). Cleavage of the putative propeptide is dispensable for
CC catalytic activity (By similarity). {ECO:0000250|UniProtKB:Q8I6Z5}.
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; AAKM01000004; EDL45906.1; -; Genomic_DNA.
DR RefSeq; XP_001615633.1; XM_001615583.1.
DR PDB; 4ZL4; X-ray; 2.37 A; A/B=35-476.
DR PDB; 6C4G; X-ray; 2.39 A; A=35-476.
DR PDBsum; 4ZL4; -.
DR PDBsum; 6C4G; -.
DR SMR; A5K302; -.
DR STRING; 126793.A5K302; -.
DR MEROPS; A01.075; -.
DR EnsemblProtists; EDL45906; EDL45906; PVX_116695.
DR GeneID; 5474931; -.
DR KEGG; pvx:PVX_116695; -.
DR VEuPathDB; PlasmoDB:PVX_116695; -.
DR InParanoid; A5K302; -.
DR OMA; CEGSQIS; -.
DR PhylomeDB; A5K302; -.
DR Proteomes; UP000008333; Chromosome 12.
DR Proteomes; UP000008333; Unassembled WGS sequence.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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; 1.
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; 2.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aspartyl protease; Disulfide bond; Endoplasmic reticulum;
KW Hydrolase; Membrane; Protease; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..34
FT /evidence="ECO:0000255"
FT CHAIN 35..536
FT /note="Plasmepsin V"
FT /evidence="ECO:0000255"
FT /id="PRO_5002684980"
FT TOPO_DOM 35..492
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q8I6Z5"
FT TRANSMEM 493..513
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 514..536
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8I6Z5"
FT DOMAIN 62..462
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT REGION 244..264
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 245..263
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 80
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 313
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT DISULFID 90..172
FT /evidence="ECO:0000269|PubMed:26214367,
FT ECO:0000269|PubMed:29800827, ECO:0007744|PDB:4ZL4,
FT ECO:0007744|PDB:6C4G"
FT DISULFID 93..96
FT /evidence="ECO:0000269|PubMed:26214367,
FT ECO:0000269|PubMed:29800827, ECO:0007744|PDB:4ZL4,
FT ECO:0007744|PDB:6C4G"
FT DISULFID 117..128
FT /evidence="ECO:0000269|PubMed:26214367,
FT ECO:0000269|PubMed:29800827, ECO:0007744|PDB:4ZL4,
FT ECO:0007744|PDB:6C4G"
FT DISULFID 122..133
FT /evidence="ECO:0000269|PubMed:26214367,
FT ECO:0000269|PubMed:29800827, ECO:0007744|PDB:4ZL4,
FT ECO:0007744|PDB:6C4G"
FT DISULFID 220..466
FT /evidence="ECO:0000269|PubMed:26214367,
FT ECO:0000269|PubMed:29800827, ECO:0007744|PDB:4ZL4,
FT ECO:0007744|PDB:6C4G"
FT DISULFID 337..382
FT /evidence="ECO:0000269|PubMed:26214367,
FT ECO:0000269|PubMed:29800827, ECO:0007744|PDB:4ZL4,
FT ECO:0007744|PDB:6C4G"
FT DISULFID 391..427
FT /evidence="ECO:0000269|PubMed:26214367,
FT ECO:0000269|PubMed:29800827, ECO:0007744|PDB:4ZL4,
FT ECO:0007744|PDB:6C4G"
FT MUTAGEN 80
FT /note="D->A: Loss of catalytic activity; when associated
FT with A-313."
FT /evidence="ECO:0000269|PubMed:24983235"
FT MUTAGEN 313
FT /note="D->A: Loss of catalytic activity; when associated
FT with A-80."
FT /evidence="ECO:0000269|PubMed:24983235"
SQ SEQUENCE 536 AA; 60916 MW; 59503FD4DC874BA0 CRC64;
MVGASLGPPG RGSLSRLIRL VICVLTLCAL SVQGRSESTE GHSKDLLYKY KLYGDIDEYA
YYFLDIDIGT PEQRISLILD TGSSSLSFPC AGCKNCGVHM ENPFNLNNSK TSSILYCENE
ECPFKLNCVK GKCEYMQSYC EGSQISGFYF SDVVSVVSYN NERVTFRKLM GCHMHEESLF
LYQQATGVLG MSLSKPQGIP TFVNLLFDNA PQLKQVFTIC ISENGGELIA GGYDPAYIVR
RGGSKSVSGQ GSGPVSESLS ESGEDPQVAL REAEKVVWEN VTRKYYYYIK VRGLDMFGTN
MMSSSKGLEM LVDSGSTFTH IPEDLYNKLN YFFDILCIQD MNNAYDVNKR LKMTNESFNN
PLVQFDDFRK SLKSIIAKEN MCVKIVDGVQ CWKYLEGLPD LFVTLSNNYK MKWQPHSYLY
KKESFWCKGI EKQVNNKPIL GLTFFKNRQV IFDIQKNRIG FVDANCPSHP THTRPRTYNE
YKRKDNIFLK IPFFYLYSLF VVFALSVLLS LVFYVRRLYH MEYSPLPSEG KAPADA
