ELANE encodes neutrophil elastase, a serine endopeptidase whose substrate cleavage contributes to antimicrobial defense and remodeling of proteins in neutrophils and extracellular material. Direct human-enzyme experiments establish cleavage of plasma proteins, cell-surface substrates, histones and other defense-related proteins. An interaction with a substrate or inhibitor is not automatically a separate receptor, signaling or structural function.
The official protein is a 267-aa precursor. The signal peptide spans residues 1–27, the annotated propeptide 28–29, and the chain feature 30–267. Historical purified preparations and the 1HNE structure include a 218-residue sequence mapping to residues 30–247 with a sequence discrepancy. These boundaries, glycoforms and experimental truncations are distinct from natural splice products; no additional natural splice form is inferred. Native sputum sourcing in the original structure paper is retained despite inconsistent deposition source-method metadata. PMID:2911584(https://pubmed.ncbi.nlm.nih.gov/2911584/) PMID:3550808(https://pubmed.ncbi.nlm.nih.gov/3550808/)
Human elastase directly fragments kininogens and thrombin-related substrates. The kininogen experiments separate the elastase reaction from subsequent kallikrein-dependent kinin release. The thrombin study separately demonstrates antimicrobial peptide activity; applying a derived peptide in a mouse infection experiment is not an ELANE perturbation. PMID:12887060(https://pubmed.ncbi.nlm.nih.gov/12887060/) PMID:20421939(https://pubmed.ncbi.nlm.nih.gov/20421939/)
The ecotin study measures bacterial survival after treatment with human elastase, providing direct antibacterial evidence rather than only a requirement inferred from a host knockout. Susceptibility depends on bacterial protection mechanisms and assay context. In the SPIN study, elastase processing of a bacterial inhibitor and MPO-dependent killing are separate steps. PMID:14705961(https://pubmed.ncbi.nlm.nih.gov/14705961/) PMID:29306874(https://pubmed.ncbi.nlm.nih.gov/29306874/)
NET formation includes direct work by ELANE: purified enzyme cleaves histones and promotes chromatin decondensation, while human neutrophil experiments place its release and nuclear translocation in a wider MPO-dependent response. This interpretation uses the combined evidence rather than treating an inhibitor with PR3 activity as uniquely specific. The current definition and exact synonyms of GO:0031452 include chromatin decondensation. The separate human-thrombus localization study establishes elastase-positive extracellular DNA structures but does not measure its catalytic activity in those specimens. PMID:20974816(https://pubmed.ncbi.nlm.nih.gov/20974816/) PMID:25066128(https://pubmed.ncbi.nlm.nih.gov/25066128/) PMID:32434865(https://pubmed.ncbi.nlm.nih.gov/32434865/)
GSDMD activation and GSDMB inactivation are distinct substrate reactions. A lytic-death result does not by itself establish all elements of a pyroptotic inflammatory response or ELANE-dependent cytokine maturation. The accepted non-core pathway annotation preserves direct ELANE catalysis while keeping that broader process limit explicit. PMID:29539421(https://pubmed.ncbi.nlm.nih.gov/29539421/) PMID:36899106(https://pubmed.ncbi.nlm.nih.gov/36899106/)
CD40 cleavage in gingival fibroblasts reduces CD40L-stimulated chemokine production, whereas elastase exposure in A549 cells increases IL-8 production. These are different stimulus and cell contexts, not a single contradictory response. The A549 and airway smooth-muscle studies remain at abstract-level access; no missing preparation or mechanistic details are supplied. PMID:12223522(https://pubmed.ncbi.nlm.nih.gov/12223522/) PMID:14730209(https://pubmed.ncbi.nlm.nih.gov/14730209/) PMID:15010259(https://pubmed.ncbi.nlm.nih.gov/15010259/)
The C5a study reports selective suppression of neutrophil responses by purified human leukocyte elastase. Its named alternate-agonist controls are explicit in the lysate/supernatant experiments; the purified-enzyme result is separately summarized as selective. Neither C5a nor its receptor is assigned as the cleaved substrate. Acute calcium-response inhibition leaves the steady-state homeostasis annotation unresolved. PMID:15140022(https://pubmed.ncbi.nlm.nih.gov/15140022/)
ECM-enriched tissue and marrow preparations contain target-specific ELANE peptide records. These support contextual association without establishing a structural matrix role or exclusive localization. A verified urinary-exosome target record is retained independently of an unresolved EPS-urine record whose supplemental target table was not recovered. Missing supplementary evidence is not evidence of contamination or biological absence. PMID:25037231(https://pubmed.ncbi.nlm.nih.gov/25037231/) PMID:28344315(https://pubmed.ncbi.nlm.nih.gov/28344315/) PMID:19056867(https://pubmed.ncbi.nlm.nih.gov/19056867/) PMID:23533145(https://pubmed.ncbi.nlm.nih.gov/23533145/)
One source-specific term is removed: the alpha2-plasmin-inhibitor interaction does not support protease binding, because the named partner is a protease inhibitor. The positive cleavage experiment is preserved. The responsible BHF-UCL source row is recorded as a structured term-check request without inventing a replacement specific binding term. PMID:6980881(https://pubmed.ncbi.nlm.nih.gov/6980881/)
Five source contexts remain uncertain: steady-state calcium homeostasis; ELANE-specific attribution of UVA-associated fibroblast activity; the EPS-urine exosome target record; direct fungal killing in a study whose measured killing assay uses bacteria; and ELANE-specific leukocyte rolling after a multi-protease inhibitor. These uncertainties do not assert absence of the corresponding biological functions.
The final source actions comprise 52 ACCEPT, 34 KEEP_AS_NON_CORE, 10 MODIFY, five UNDECIDED and one REMOVE. All 102 imported source objects and 104 raw contexts are preserved, including interacting-taxon differences omitted by the normal projection. There are no new annotation rows or publication quotations. Detailed access limits, public links and exact normal-cache hashes are in the source guide; database reconstruction is documented in the evidence results.
The single serine-endopeptidase core includes azurophil granule (GO:0042582), phagocytic vesicle (GO:0045335) and neutrophil extracellular trap (GO:0140644), alongside its existing extracellular, surface, cytosolic and nuclear contexts. Human granule fractionation and localization support the azurophil pool, with heterogeneous membrane/lumen patterns; this does not imply uniform topology or unrestricted substrate access. The phagocytic-vesicle assignment follows the curated human P08246 location record, whose cited primary paper remains abstract-only here. Human thrombus staining supports ELANE on extracellular NET DNA, without measuring catalytic activity in those specimens. These context-specific locations do not assert that every core process occurs in every compartment. PMID:20974816(https://pubmed.ncbi.nlm.nih.gov/20974816/) PMID:25066128(https://pubmed.ncbi.nlm.nih.gov/25066128/) UniProt P08246 PMID:10947984(https://pubmed.ncbi.nlm.nih.gov/10947984/) PMID:32434865(https://pubmed.ncbi.nlm.nih.gov/32434865/)
Proteolysis (GO:0006508) remains accepted in all four imported rows. The compact core represents the defining peptide-bond chemistry with serine-type endopeptidase activity (GO:0004252) and separately names the selected defense, matrix-disassembly and NET-formation contexts. Omitting the generic process from this summary does not deny participation or claim an ontology ancestor relationship between proteolysis and every listed process. The core is a synthesis rather than a second exhaustive annotation table; no annotation action, qualifier, processed-product boundary or source assertion changes.