PLM4_PLAFX
ID PLM4_PLAFX Reviewed; 449 AA.
AC Q17SB3; A0A0L7K6M7;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 2.
DT 03-AUG-2022, entry version 64.
DE RecName: Full=Plasmepsin IV {ECO:0000303|PubMed:11782538};
DE EC=3.4.23.39 {ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:16452306};
DE AltName: Full=Plasmepsin 4 {ECO:0000303|PubMed:16784823};
DE Flags: Precursor;
GN Name=PMIV {ECO:0000303|PubMed:11782538};
GN ORFNames=PFHG_00463 {ECO:0000312|EMBL:KOB58715.1};
OS Plasmodium falciparum (isolate HB3).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=137071 {ECO:0000312|Proteomes:UP000054289};
RN [1] {ECO:0000312|EMBL:AAW71462.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-448.
RC STRAIN=D6 {ECO:0000312|EMBL:AAW71462.1}, and
RC HB3 {ECO:0000312|EMBL:AAW71461.1};
RX PubMed=16784823; DOI=10.1016/j.gene.2006.02.029;
RA Barry A.E., Leliwa-Sytek A., Man K., Kasper J.M., Hartl D.L., Day K.P.;
RT "Variable SNP density in aspartyl-protease genes of the malaria parasite
RT Plasmodium falciparum.";
RL Gene 376:163-173(2006).
RN [2] {ECO:0000312|Proteomes:UP000054289}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=HB3 {ECO:0000312|Proteomes:UP000054289};
RG The Broad Institute Genome Sequencing Platform;
RA Volkman S.K., Neafsey D.E., Dash A.P., Chitnis C.E., Hartl D.L.,
RA Young S.K., Zeng Q., Koehrsen M., Alvarado L., Berlin A., Borenstein D.,
RA Chapman S.B., Chen Z., Engels R., Freedman E., Gellesch M., Goldberg J.,
RA Griggs A., Gujja S., Heilman E.R., Heiman D.I., Howarth C., Jen D.,
RA Larson L., Mehta T., Neiman D., Park D., Pearson M., Roberts A., Saif S.,
RA Shea T., Shenoy N., Sisk P., Stolte C., Sykes S., Walk T., White J.,
RA Yandava C., Haas B., Henn M.R., Nusbaum C., Birren B.;
RT "Annotation of Plasmodium falciparum HB3.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND PROTEOLYTIC
RP CLEAVAGE.
RX PubMed=11782538; DOI=10.1073/pnas.022630099;
RA Banerjee R., Liu J., Beatty W., Pelosof L., Klemba M., Goldberg D.E.;
RT "Four plasmepsins are active in the Plasmodium falciparum food vacuole,
RT including a protease with an active-site histidine.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:990-995(2002).
RN [4] {ECO:0000305}
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=12850260; DOI=10.1016/s0166-6851(03)00119-1;
RA Banerjee R., Francis S.E., Goldberg D.E.;
RT "Food vacuole plasmepsins are processed at a conserved site by an acidic
RT convertase activity in Plasmodium falciparum.";
RL Mol. Biochem. Parasitol. 129:157-165(2003).
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PROTEOLYTIC CLEAVAGE,
RP AND MUTAGENESIS OF ASP-155 AND ASP-335.
RX PubMed=16452306; DOI=10.1093/jb/mvj018;
RA Kim Y.M., Lee M.H., Piao T.G., Lee J.W., Kim J.H., Lee S., Choi K.M.,
RA Jiang J.H., Kim T.U., Park H.;
RT "Prodomain processing of recombinant plasmepsin II and IV, the aspartic
RT proteases of Plasmodium falciparum, is auto- and trans-catalytic.";
RL J. Biochem. 139:189-195(2006).
CC -!- FUNCTION: During the asexual blood stage, catalyzes the cleavage of
CC denatured host hemoglobin (Hb) or globins (PubMed:11782538,
CC PubMed:16452306). Digestion of host Hb is an essential step which
CC provides the parasite with amino acids for protein synthesis, and
CC regulates osmolarity (Probable). {ECO:0000269|PubMed:11782538,
CC ECO:0000269|PubMed:16452306, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of the bonds linking certain hydrophobic residues
CC in hemoglobin or globin. Also cleaves small molecules substrates such
CC as Ala-Leu-Glu-Arg-Thr-Phe-|-Phe(NO2)-Ser-Phe-Pro-Thr.; EC=3.4.23.39;
CC Evidence={ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:16452306};
CC -!- ACTIVITY REGULATION: Inhibited by pepstatin A.
CC {ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:16452306}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 5.4. {ECO:0000269|PubMed:11782538};
CC -!- SUBUNIT: Component of the hemozoin formation complex (HFC) composed of
CC falcipain 2, plasmepsins PMII, PMIII/HAP and PMIV, heme detoxifying
CC protein HDP and falcilysin FLN. The HFC complex is involved in
CC hemoglobin degradation and detoxification of heme in the food vacuole
CC during the asexual blood stage. {ECO:0000250|UniProtKB:Q8IM16}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type II
CC membrane protein {ECO:0000305}. Vacuole lumen
CC {ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:12850260}. Note=In
CC trophozoites, localizes to the digestive (or food) vacuole, an acidic
CC vacuole where host hemoglobin is digested.
CC {ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:12850260}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage;
CC expression begins in mid to late trophozoites and continues in
CC schizonts (at protein level). {ECO:0000269|PubMed:11782538,
CC ECO:0000269|PubMed:12850260}.
CC -!- PTM: Proteolytically cleaved into the soluble active mature form by
CC cysteine proteases in the digestive vacuole of trophozoites (Probable).
CC Proteolysis requires an acidic environment (Probable)
CC (PubMed:16452306). Autoprocessing or transprocessing by other
CC plasmepsins such as PMII may serve as an alternate activation system
CC (PubMed:16452306). {ECO:0000269|PubMed:16452306,
CC ECO:0000305|PubMed:11782538, ECO:0000305|PubMed:12850260}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family.
CC {ECO:0000255|RuleBase:RU000454}.
CC -!- CAUTION: It is unclear if PMIV is glycosylated as other members of the
CC same enzyme family, ie. PMI and PMII, are not. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=KOB58715.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AY878737; AAW71461.1; -; Genomic_DNA.
DR EMBL; AY878738; AAW71462.1; -; Genomic_DNA.
DR EMBL; CH671923; KOB58715.1; ALT_SEQ; Genomic_DNA.
DR SMR; Q17SB3; -.
DR MEROPS; A01.059; -.
DR EnsemblProtists; KOB58715; KOB58715; PFHG_00463.
DR VEuPathDB; PlasmoDB:PF3D7_1407800; -.
DR VEuPathDB; PlasmoDB:Pf7G8-2_000483000; -.
DR VEuPathDB; PlasmoDB:Pf7G8_140013200; -.
DR VEuPathDB; PlasmoDB:PfCD01_140013500; -.
DR VEuPathDB; PlasmoDB:PfDd2_140012400; -.
DR VEuPathDB; PlasmoDB:PfGA01_140013500; -.
DR VEuPathDB; PlasmoDB:PfGB4_140014000; -.
DR VEuPathDB; PlasmoDB:PfGN01_140013100; -.
DR VEuPathDB; PlasmoDB:PfHB3_140013700; -.
DR VEuPathDB; PlasmoDB:PfIT_140014400; -.
DR VEuPathDB; PlasmoDB:PfKE01_140013100; -.
DR VEuPathDB; PlasmoDB:PfKH01_140013400; -.
DR VEuPathDB; PlasmoDB:PfKH02_140013700; -.
DR VEuPathDB; PlasmoDB:PfML01_140013300; -.
DR VEuPathDB; PlasmoDB:PfNF135_140013300; -.
DR VEuPathDB; PlasmoDB:PfNF166_140012000; -.
DR VEuPathDB; PlasmoDB:PfNF54_140012800; -.
DR VEuPathDB; PlasmoDB:PfSD01_140011300; -.
DR VEuPathDB; PlasmoDB:PfSN01_140015200; -.
DR VEuPathDB; PlasmoDB:PfTG01_140013200; -.
DR Proteomes; UP000054289; Unassembled WGS sequence.
DR GO; GO:0020020; C:food vacuole; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005775; C:vacuolar lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0044002; P:acquisition of nutrients from host; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd05471; pepsin_like; 1.
DR Gene3D; 2.40.70.10; -; 2.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR034164; Pepsin-like_dom.
DR InterPro; IPR033121; PEPTIDASE_A1.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR PANTHER; PTHR47966; PTHR47966; 1.
DR Pfam; PF00026; Asp; 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 Aspartyl protease; Disulfide bond; Hydrolase; Membrane; Protease;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Vacuole; Zymogen.
FT PROPEP 1..121
FT /evidence="ECO:0000305|PubMed:12850260"
FT /id="PRO_0000453384"
FT CHAIN 122..449
FT /note="Plasmepsin IV"
FT /id="PRO_0000453385"
FT TOPO_DOM 1..37
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 38..58
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 59..449
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT DOMAIN 137..444
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 155
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 335
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT DISULFID 168..173
FT /evidence="ECO:0000250|UniProtKB:Q8IM16"
FT DISULFID 370..406
FT /evidence="ECO:0000250|UniProtKB:Q8IM16"
FT MUTAGEN 155
FT /note="D->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:16452306"
FT MUTAGEN 335
FT /note="D->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:16452306"
SQ SEQUENCE 449 AA; 50991 MW; 96CFB8754F2AF12A CRC64;
MALTVKEEEF SNTLIKNASA FDRLKLGNLK NLKIQKKLQF LYLILFVLIT GVFFFFLIGN
FYSHRKLYQV IKNTKHTTIG FKIDRPHDKV LSSVLKNKLS TYVKESFKFF KSGYAQKGYL
GSENDSIELD DVANLMFYGE GQIGTNKQPF MFIFDTGSAN LWVPSVNCDS IGCSTKHLYD
ASASKSYEKD GTKVEISYGS GTVRGYFSKD VISLGDLSLP YKFIEVTDAD DLEPIYSGSE
FDGILGLGWK DLSIGSIDPV VVELKKQNKI DNALFTFYLP VHDKHVGYLT IGGIESDFYE
GPLTYEKLNH DLYWQIDLDI HFGKYVMQKA NAVVDSGTST ITAPTSFLNK FFTDMNVIKV
PFLPLYVTTC DNDDLPTLEF HSRNNKYTLE PEFYMDPLSD IDPALCMLYI LPVDIDDNTF
ILGDPFMRKY FTVFDYEKES VGFAVAKNL
