dpy-31

id: A8Q2D1
gene_symbol: dpy-31
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:6279
  label: Brugia malayi
description: >-
  Bm-DPY-31 (nematode astacin NAS-35) is a secreted, zinc-dependent
  metalloendopeptidase of the astacin (M12A peptidase) family, structurally
  related to vertebrate BMP-1/tolloid procollagen C-proteinases. The mature
  enzyme has a multidomain architecture comprising an N-terminal signal peptide
  and propeptide (zymogen), a catalytic astacin/peptidase M12A domain bearing
  the HExxH zinc-binding motif and a downstream zinc-coordinating residue, an
  EGF-like domain, and a C-terminal CUB domain. It binds one catalytic zinc ion
  per subunit and cleaves the C-terminal (carboxyl) propeptide of procollagens
  to generate mature collagen, acting as a procollagen C-proteinase. In
  nematodes this activity is required for processing and assembly of cuticular
  collagens, and the orthologous gene is essential for cuticle integrity and the
  molting cycle; loss of function causes body-morphology and cuticle defects.
  The enzyme is widely conserved across free-living and parasitic nematodes and
  is inhibited by hydroxamate-based metalloprotease inhibitors such as
  marimastat, making it of interest as a nematode-specific anthelmintic target.
alternative_products:
- name: dpy-31a {ECO:0000303|PubMed:19883650}
  id: A8Q2D1-1
- name: dpy-31b {ECO:0000303|PubMed:19883650}
  id: A8Q2D1-2
  sequence_note: VSP_059217
existing_annotations:
- term:
    id: GO:0004222
    label: metalloendopeptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Core molecular function. DPY-31 is an astacin/M12A family zinc
      metalloendopeptidase (EC 3.4.24.-) with a catalytic astacin domain
      carrying the HExxH zinc-binding motif and an experimentally demonstrated
      proteolytic activity (cleaving procollagen C-termini; PubMed:19883650) that
      is blocked by metalloprotease inhibitors (PubMed:26546217). This specific
      endopeptidase term is well supported and preferred over the more general
      'metallopeptidase activity'.
    action: ACCEPT
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Consistent with UniProt annotation that DPY-31 is secreted; the protein
      has an N-terminal signal peptide and acts on procollagens in the
      extracellular/cuticular compartment. This is a general but accurate
      localization term and represents the correct compartment of action.
    action: ACCEPT
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      Accurate but high-level: proteolysis is the generic process parent of the
      specific endopeptidase molecular function already captured by GO:0004222.
      Retained as a true but non-core process annotation; the informative
      content is the metalloendopeptidase activity and the cuticle/molting role.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0008237
    label: metallopeptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      This is the more general parent of GO:0004222 'metalloendopeptidase
      activity', which is also annotated and is the more specific, correct
      molecular function for this endopeptidase. Marked as over-annotated in
      favor of the specific endopeptidase term.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Core supporting molecular function. The astacin catalytic domain binds one
      catalytic zinc ion per subunit via the HExxH motif (His306, His310,
      His316) with Glu307 as the catalytic acid/base, as required for
      metalloendopeptidase activity. Well supported by sequence/structure and
      family conservation.
    action: ACCEPT
- term:
    id: GO:0018996
    label: molting cycle, collagen and cuticulin-based cuticle
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Core biological role. DPY-31/NAS-35 processes cuticular procollagens to
      mature collagens, an activity required for cuticle formation and the
      molting cycle in nematodes; the C. elegans ortholog is essential and its
      loss produces cuticle/morphology defects (PubMed:19883650). Strongly
      supported by family function and ortholog phenotypes; retained as a core
      process annotation.
    action: ACCEPT
core_functions:
- description: >-
    Zinc-dependent metalloendopeptidase (astacin/M12A family, procollagen
    C-proteinase) that cleaves the C-terminal propeptide of procollagens to
    generate mature cuticular collagens, acting in the secreted/extracellular
    compartment and required for cuticle formation and the molting cycle.
  molecular_function:
    id: GO:0004222
    label: metalloendopeptidase activity
  supported_by:
  - reference_id: PMID:19883650
  - reference_id: PMID:26546217
  locations:
  - id: GO:0005576
    label: extracellular region
- description: >-
    Binds the catalytic zinc ion required for the astacin metalloendopeptidase
    active site (HExxH motif).
  molecular_function:
    id: GO:0008270
    label: zinc ion binding
  supported_by:
  - reference_id: PMID:19883650
  - reference_id: PMID:26546217
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:19883650
  title: >-
    Collagen processing and cuticle formation is catalysed by the astacin
    metalloprotease DPY-31 in free-living and parasitic nematodes.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Cited in the UniProt record (reference [1]) for FUNCTION and catalytic
      activity of Brugia malayi DPY-31/NAS-35; establishes DPY-31 as the astacin
      procollagen C-proteinase required for cuticle collagen processing across
      free-living and parasitic nematodes. PubMed-verified title; no cached
      full text in publications/, so claims anchored to UniProt evidence codes
      (ECO:0000269) rather than direct quotation.
- id: PMID:26546217
  title: >-
    Identification and activity of inhibitors of the essential nematode-specific
    metalloprotease DPY-31.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Cited in the UniProt record (reference [3]) for catalytic activity and
      activity regulation; reports hydroxamate/marimastat inhibition of DPY-31,
      supporting its identity as a druggable zinc metalloprotease and
      nematode-specific target. PubMed-verified title; no cached full text, so
      not used for verbatim supporting_text.