Q9Y006 · PLM3_PLAFX

Function

function

During the asexual blood stage, catalyzes the cleavage of denatured host hemoglobin (Hb) or globins (PubMed:11782538).
Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable)

Caution

Unlike other plasmepsins, one of the two catalytic aspartates, Asp-157, is replaced with histidine; however, the protein is catalytic active (PubMed:11782538).
Unlikely to act as a serine protease (By similarity).
His-157 may stabilizes the catalysis and Asp-337 may act as both an acid and a base during catalysis (By similarity).
It is unclear if PMIII is glycosylated as other members of the same enzyme family, ie. PMI and PMII, are not.

Catalytic activity

  • Hydrolysis of the bonds linking certain hydrophobic residues in hemoglobin or globin. Also cleaves small molecules substrates such as Ala-Leu-Glu-Arg-Thr-Phe-|-Phe(NO2)-Ser-Phe-Pro-Thr.
    EC:3.4.23.39 (UniProtKB | ENZYME | Rhea)

Activity regulation

Dimerization causes loss of catalytic activity (By similarity).
Inhibited by pepstatin A (PubMed:11782538).

pH Dependence

Optimum pH is 5.7.

Features

Showing features for active site.

TypeIDPosition(s)Description
Active site337

GO annotations

AspectTerm
Cellular Componentfood vacuole
Cellular Componentmembrane
Cellular Componentvacuolar lumen
Molecular Functionaspartic-type endopeptidase activity
Biological Processacquisition of nutrients from host
Biological Processproteolysis

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Plasmepsin III
  • EC number
  • Alternative names
    • Histo-aspartic protease
    • Plasmepsin 3

Gene names

    • Name
      PMIII
    • Synonyms
      HAP
    • ORF names
      PFHG_00466

Organism names

  • Taxonomic identifier
  • Strains
    • 7G8
    • D6
    • HB3
    • MUZ12
    • W2
  • Taxonomic lineage
    Eukaryota > Sar > Alveolata > Apicomplexa > Aconoidasida > Haemosporida > Plasmodiidae > Plasmodium > Plasmodium (Laverania)

Accessions

  • Primary accession
    Q9Y006
  • Secondary accessions
    • A0A0L7K5R8

Proteomes

Organism-specific databases

Subcellular Location

Membrane
; Single-pass type II membrane protein
Vacuole lumen
Note: In trophozoites, localizes to the digestive (or food) vacuole, an acidic vacuole where host hemoglobin is digested.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-37Cytoplasmic
Transmembrane38-58Helical; Signal-anchor for type II membrane protein
Topological domain59-451Lumenal

Keywords

Phenotypes & Variants

PTM/Processing

Features

Showing features for propeptide, chain, disulfide bond.

TypeIDPosition(s)Description
PropeptidePRO_00004533801-123
ChainPRO_0000453381124-451Plasmepsin III
Disulfide bond170↔175
Disulfide bond372↔408

Post-translational modification

Proteolytically cleaved into the soluble active mature form by cysteine proteases in the digestive vacuole of trophozoites (PubMed:12850260).
Proteolysis requires an acidic environment (By similarity).
Transprocessing may serve as an alternate activation system (Probable)

Keywords

Expression

Developmental stage

Expressed during the asexual blood stage; expression begins in trophozoites and continues in schizonts (at protein level).

Interaction

Subunit

Probable homodimer; in the zymogen form (PubMed:32385863).
Monomer; in the active form (PubMed:11782538, PubMed:32385863).
Acidification disrupts homodimerization (PubMed:32385863).
Component of the hemozoin formation complex (HFC) composed of falcipains FP2A and/or FP2B, plasmepsins PMII, PMIII/HAP and PMIV, heme detoxifying protein HDP and falcilysin FLN (By similarity).
The HFC complex is involved in hemoglobin degradation and detoxification of heme in the food vacuole during the asexual blood stage (By similarity).

Chemistry

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain139-446Peptidase A1

Sequence similarities

Belongs to the peptidase A1 family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    451
  • Mass (Da)
    51,693
  • Last updated
    1999-11-01 v1
  • Checksum
    D9ED8C4A066B2154
MNLTIKEEDFTNTFMKNEESFNTFRVTKVKRWNAKRLFKILFVTVFIVLAGGFSYYIFENFVFQKNRKINHIIKTSKYSTVGFNIENSYDRLMKTIKEHKLKNYIKESVKLFNKGLTKKSYLGSEFDNVELKDLANVLSFGEAKLGDNGQKFNFLFHTASSNVWVPSIKCTSESCESKNHYDSSKSKTYEKDDTPVKLTSKAGTISGIFSKDLVTIGKLSVPYKFIEMTEIVGFEPFYSESDVDGVFGLGWKDLSIGSIDPYIVELKTQNKIEQAVYSIYLPPENKNKGYLTIGGIEERFFDGPLNYEKLNHDLMWQVDLDVHFGNVSSKKANVILDSATSVITVPTEFFNQFVESASVFKVPFLSLYVTTCGNTKLPTLEYRSPNKVYTLEPKQYLEPLENIFSALCMLNIVPIDLEKNTFVLGDPFMRKYFTVYDYDNHTVGFALAKNL

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict451in Ref. 3; KOB58718

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY878730
EMBL· GenBank· DDBJ
AAW71454.1
EMBL· GenBank· DDBJ
Genomic DNA
AY878731
EMBL· GenBank· DDBJ
AAW71455.1
EMBL· GenBank· DDBJ
Genomic DNA
AY878732
EMBL· GenBank· DDBJ
AAW71456.1
EMBL· GenBank· DDBJ
Genomic DNA
AY878733
EMBL· GenBank· DDBJ
AAW71457.1
EMBL· GenBank· DDBJ
Genomic DNA
AY878734
EMBL· GenBank· DDBJ
AAW71458.1
EMBL· GenBank· DDBJ
Genomic DNA
AJ009990
EMBL· GenBank· DDBJ
CAB40630.1
EMBL· GenBank· DDBJ
Genomic DNA
CH671923
EMBL· GenBank· DDBJ
KOB58718.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

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