Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
LEKTI, a novel 15-domain type of human serine proteinase inhibitor.
LEKTI proteolytic processing in human primary keratinocytes, tissue distribution and defective expression in Netherton syndrome.
LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum.
Consequences of C-terminal domains and N-terminal signal peptide deletions on LEKTI secretion, stability, and subcellular distribution.
LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction.
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Furin-generated LEKTI fragments inhibit KLK5, KLK7 and KLK14; binding to KLK5 is tight and released at acidic pH.
"We demonstrated that pH variations govern this interaction, leading to the release of active KLK5 from the complex at acidic pH."
Inhibition of serine proteinases plasmin, trypsin, subtilisin A, cathepsin G, and elastase by LEKTI: a kinetic analysis.
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Recombinant full-length LEKTI inhibits several serine proteinases but not chymotrypsin or cysteine proteinases.
"rLEKTI did not inhibit the cysteine proteinase papain or cathepsin K, L, or S."
hK5 and hK7, two serine proteinases abundant in human skin, are inhibited by LEKTI domain 6.
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LEKTI domain 6 inhibits KLK5 and KLK7.
"LEKTI domain 6 is a potent inhibitor of hK5 and hK7, whereas LEKTI domain 15 exhibits inhibitory activity on plasmin."
New role for LEKTI in skin barrier formation: label-free quantitative proteomic identification of caspase 14 as a novel target for the protease inhibitor LEKTI.
Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome.
SPINK5, the defective gene in netherton syndrome, encodes multiple LEKTI isoforms derived from alternative pre-mRNA processing.
Homologous proteins with different folds: the three-dimensional structures of domains 1 and 6 of the multiple Kazal-type inhibitor LEKTI.
Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity.
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Spink5-null mice show desmoglein 1 degradation from kallikrein-like hyperactivity and loss of skin barrier.
"LEKTI deficiency causes abnormal desmosome cleavage in the upper granular layer through degradation of desmoglein 1"
Lethal, neonatal ichthyosis with increased proteolytic processing of filaggrin in a mouse model of Netherton syndrome.
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Spink5 R820X mice have lethal barrier failure and increased profilaggrin processing.
"revealed a substantial increase in the proteolytic processing of profilaggrin into its constituent filaggrin monomers"
Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome.
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In LEKTI deficiency, free KLK5 activates PAR2 and drives TSLP-mediated inflammation.
"unregulated kallikrein (KLK) 5 directly activates proteinase-activated receptor 2"
Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin.
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Spink5-deficient mouse epidermis has increased cathelicidin-dependent antimicrobial activity.
"Epidermal extracts of these animals show a significant increase in antimicrobial activity compared with controls"
Serine protease activity and residual LEKTI expression determine phenotype in Netherton syndrome.
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In Netherton patients, residual LEKTI inversely correlates with serine protease activity and disease severity.
"The magnitude of SP activation correlated with both the barrier defect and clinical severity, and inversely with residual LEKTI expression."
Dissociation of the SPINK5:KLK5 complex at low pH
SPINK5(490-624) binds KLK5
SPINK5 PANTHER 19 tree placement