dpy-31

Gene 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.

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004222 metalloendopeptidase activity	IEA GO_REF:0000120	ACCEPT	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'.
GO:0005576 extracellular region	IEA GO_REF:0000044	ACCEPT	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.
GO:0006508 proteolysis	IEA GO_REF:0000002	KEEP AS NON CORE	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.
GO:0008237 metallopeptidase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	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.
GO:0008270 zinc ion binding	IEA GO_REF:0000002	ACCEPT	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.
GO:0018996 molting cycle, collagen and cuticulin-based cuticle	IEA GO_REF:0000120	ACCEPT	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.

Core Functions

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:

metalloendopeptidase activity

Cellular Locations:

extracellular region

Supporting Evidence:

Binds the catalytic zinc ion required for the astacin metalloendopeptidase active site (HExxH motif).