Affinage

KLK7

Kallikrein-7 · UniProt P49862

Round 2 corrected
Length
253 aa
Mass
27.5 kDa
Annotated
2026-04-28
69 papers in source corpus 25 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KLK7 is a secreted chymotrypsin-like serine protease that functions as a central effector of epidermal desquamation and participates in extracellular proteolytic cascades in multiple tissues. In the stratum corneum, KLK7 is released from lamellar granules and directly cleaves the corneodesmosomal proteins corneodesmosin (CDSN) and desmocollin 1 (DSC1), with its activity gated by pH-dependent inhibition by LEKTI/SPINK5 fragments and by upstream activation of its proform by KLK5 (PMID:15140227, PMID:17596512, PMID:15675955). Beyond skin barrier homeostasis, KLK7 cleaves interferons, IL-10-family cytokines, mast cell chymase, IGFBP6, thrombospondin-1, and pro-MMP10, and its transcription is regulated by IL-13–ERK–EGR1, TNF, and NF-κB signaling axes (PMID:39655764, PMID:30705123, PMID:33276948, PMID:37672660). In disease contexts, KLK7 promotes inflammatory macrophage polarization and migration in adipose tissue, drives MAPK/ERK-dependent epithelial–mesenchymal transition in cancer, and participates in a KLK5/KLK7→KLK14→PAR-2/NF-κB protease cascade in cervical carcinogenesis (PMID:40154838, PMID:39991575, PMID:40753921).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1996 Medium

    Identification of KLK7 (SCCE) as a chymotrypsin-like serine protease of the stratum corneum established the molecular identity of the desquamation enzyme and placed it in a kallikrein gene cluster on 19q13.

    Evidence cDNA cloning and sequence homology analysis from human stratum corneum

    PMID:8898378

    Open questions at the time
    • no substrates identified
    • no in vitro enzymatic characterization
    • regulation unknown
  2. 2004 High

    Reconstituted cleavage assays resolved which corneodesmosomal targets KLK7 acts on directly (CDSN, DSC1 but not DSG1) and showed that KLK5 activates pro-KLK7, establishing a protease activation cascade driving desquamation.

    Evidence In vitro cleavage assays with recombinant and epidermal substrates at acidic pH; proform activation assays

    PMID:15140227

    Open questions at the time
    • in vivo confirmation of sequential activation not yet shown
    • cleavage site mapping not performed in this study
  3. 2005 High

    Subcellular imaging revealed that KLK7 resides in lamellar granules and is secreted after LEKTI, explaining how premature desquamation is prevented and why LEKTI loss (Netherton syndrome) leads to barrier failure.

    Evidence Confocal and immunoelectron microscopy of normal and Netherton syndrome skin biopsies

    PMID:15675955

    Open questions at the time
    • mechanism of secretion timing not defined
    • whether impaired secretion occurs in diseases other than Netherton syndrome unknown at this point
  4. 2007 High

    Kinetic characterization of LEKTI fragment–KLK interactions revealed pH-dependent release of active KLK5 (and differential inhibition of KLK7 and KLK14), providing the molecular gating mechanism that couples skin acidification to desquamation.

    Evidence Biochemical inhibition kinetics and pH-dependent binding/release assays with furin-processed LEKTI fragments

    PMID:17596512

    Open questions at the time
    • which specific LEKTI fragments are the dominant KLK7 inhibitors in vivo remains unclear
    • structural basis of pH-dependent release not determined
  5. 2017 High

    Comprehensive substrate-site profiling defined KLK7's chymotryptic specificity (hydrophobic P2-P1, hydrophilic P1'-P2') and showed that the canonical S195A active-site mutant retains residual activity, requiring a double catalytic-triad mutation for true inactivation.

    Evidence PICS mass spectrometry-based cleavage profiling; kinetic characterization of wild-type and active-site mutants

    PMID:28754951

    Open questions at the time
    • extended subsite cooperativity not fully modeled
    • no crystal structure of KLK7 with a substrate analog at this time
  6. 2017 High

    Adipose-tissue-specific Klk7 knockout demonstrated a non-skin role: KLK7 promotes weight gain, insulin resistance, and pro-inflammatory macrophage polarization under high-fat diet, establishing KLK7 as a metabolic regulator.

    Evidence Conditional Cre-lox KO in mouse adipose tissue with metabolic phenotyping and macrophage flow cytometry

    PMID:28932870

    Open questions at the time
    • direct adipose substrates of KLK7 not identified
    • mechanism linking protease activity to macrophage polarization unresolved
  7. 2019 High

    Quantitative degradomics expanded the KLK7 substrate repertoire beyond corneodesmosomes to ECM remodeling mediators (pro-MMP10 activation, IGFBP6, thrombospondin-1 cleavage) in ovarian cancer secretomes, linking KLK7 to invasion and matrix turnover.

    Evidence qPROTOMAP and TAILS quantitative proteomics in OVMZ6 and SKOV3 ovarian cancer cells with biochemical validation

    PMID:30705123

    Open questions at the time
    • in vivo relevance of each novel substrate not confirmed
    • catalytic efficiency for individual substrates not fully quantified
  8. 2020 High

    Identification of the IL-13–ERK1/2–EGR1 transcriptional axis controlling KLK7 promoter activity explained how Th2 inflammation upregulates KLK7 in atopic dermatitis skin.

    Evidence Promoter-reporter assay with EBS point mutation, EGR1 knockdown, Egr1 KO mouse AD model, ERK inhibitor epistasis in keratinocytes

    PMID:33276948

    Open questions at the time
    • whether other Th2 cytokines (IL-4, IL-31) use the same promoter element is unknown
    • chromatin-level regulation not examined
  9. 2022 High

    Therapeutic proof-of-concept was achieved with inhibitory anti-KLK5/KLK7 bispecific antibodies that restored skin barrier integrity and reduced inflammation in Netherton syndrome and AD mouse models, confirming KLK5 and KLK7 as co-drivers of skin inflammatory disease.

    Evidence Antibody engineering; mouse NS and AD models; X-ray crystallography of KLK5–Fab complex revealing allosteric inhibition

    PMID:36516271

    Open questions at the time
    • structural basis of antibody–KLK7 interaction not resolved (only KLK5–Fab crystallized)
    • human clinical efficacy unknown
  10. 2024 High

    Discovery of KLK7-mediated hydrolysis of interferons (IFN-α, -β, -γ), IL-10-family cytokines, and mast cell chymase broadened KLK7's functional scope to immune modulation and revealed that KLK7 undergoes autolytic inactivation at two specific loops.

    Evidence In vitro cleavage assays with active-site variants and protease-specific inhibitors; substrate identification by protein BLAST

    PMID:39655764

    Open questions at the time
    • physiological relevance of cytokine cleavage in vivo not demonstrated
    • whether autolysis is a regulatory mechanism or artifact at high concentrations not resolved
  11. 2025 Medium

    Multiple 2025 studies extended KLK7's disease roles: a KLK5/KLK7→KLK14→PAR-2/NF-κB cascade drives HPV-dependent cervical carcinogenesis, macrophage-specific KLK7 promotes inflammatory polarization/migration in obese adipose tissue, KLK7 drives MAPK/ERK-dependent EMT in thyroid cancer, and KLK7 overexpression enhances peritoneal dissemination in colorectal cancer.

    Evidence KLK5/KLK7 double-KO mice with RNA-seq and pathway reporters; macrophage-specific Klk7 KO with HFD; KLK7 siRNA with ERK/EMT readouts in thyroid cancer; KLK7 overexpression xenograft peritoneal metastasis model

    PMID:39991575 PMID:40154838 PMID:40753921 PMID:41335524

    Open questions at the time
    • direct KLK7 substrates mediating EMT, macrophage migration, and peritoneal dissemination not individually identified
    • KLK7 versus KLK5 individual contributions hard to deconvolute in double-KO cervical cancer model
  12. 2026 High

    Structure-guided development of potent (<100 nM) KLK7 inhibitors identified Ala190 in the S1 pocket as the key selectivity determinant and confirmed chemokine cleavage and moesin upregulation as functional downstream outputs of KLK7 catalytic activity.

    Evidence Medicinal chemistry; Ki measurement; T190A mutagenesis restoring inhibitor potency in murine Klk7; cell-based chemokine and moesin assays; ovarian cancer xenograft

    PMID:41855304

    Open questions at the time
    • no co-crystal structure of KLK7 with the inhibitor reported
    • in vivo pharmacokinetics and therapeutic window not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of direct KLK7 substrates mediating its pro-tumorigenic and metabolic effects, the physiological significance of cytokine and amyloid-β cleavage in vivo, structural characterization of KLK7–inhibitor and KLK7–antibody complexes, and the relative contributions of KLK7 versus other kallikreins in protease cascades across tissues.
  • no KLK7 crystal structure with a bound substrate or therapeutic antibody
  • in vivo substrate validation in non-skin contexts largely absent
  • whether autolysis is physiologically regulated remains unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016787 hydrolase activity 4
Localization
GO:0005576 extracellular region 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-168256 Immune System 2 GO:0016787 hydrolase activity 1
Partners
CDSNDSC1DSG1EGR1KLK14KLK5MMP10SPINK5

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 KLK7 (SCCE/hK7) was identified as a chymotrypsin-like serine protease expressed in the stratum corneum, responsible for the cell shedding (desquamation) process; the gene was localized to chromosome 19q13.3. cDNA cloning, sequence homology analysis, differential display Molecular medicine Medium 8898378
2000 KLK7 encodes a secreted chymotryptic serine protease (SCCE/hK7) whose expression is upregulated by estrogens and glucocorticoids in breast carcinoma cells (BT-474), and is expressed in brain, kidney, mammary and salivary glands in addition to skin; the gene maps to 19q13.3-q13.4 between KLK6 and KLK8. RT-PCR, Northern blot, genomic organization analysis, hormonal stimulation assays in BT-474 cells Gene Medium 10974542
2001 Antileukoprotease (ALP/SLPI) is co-expressed with KLK7 (SCCE) in ovarian tumors and has been identified as a specific inhibitor of KLK7 enzymatic activity. Northern blot, semi-quantitative PCR, immunohistochemistry; correlation of SCCE and ALP expression International journal of gynecological cancer Low 11906548
2004 KLK7 (SCCE/hK7) directly cleaves the corneodesmosomal proteins corneodesmosin (CDSN) and desmocollin 1 (DSC1) at acidic pH (mimicking stratum corneum pH), but cannot degrade desmoglein 1 (DSG1) alone; KLK5 (SCTE) activates the proform of KLK7 (pro-SCCE) and enables degradation of all three corneodesmosomal components including DSG1. Oligosaccharide residues on CDSN do not protect it from KLK7 proteolysis. In vitro protease cleavage assays with recombinant and epidermal forms of substrates at acidic pH; enzymatic deglycosylation experiments; SDS-PAGE analysis of cleavage products The Journal of investigative dermatology High 15140227
2005 KLK7 is localized to lamellar granules in the stratum granulosum separately from LEKTI, with LEKTI secreted earlier than KLK7 and KLK5; this spatial and temporal separation ensures LEKTI is present extracellularly before KLK7 is released, preventing premature desquamation. In Netherton syndrome skin lacking LEKTI, an abnormal split appears in the superficial stratum granulosum. Confocal laser scanning microscopy and immunoelectron microscopy of normal and Netherton syndrome skin biopsies The Journal of investigative dermatology High 15675955
2006 Multiple KLK family members including KLK7 participate in desquamation through cleavage of desmoglein 1 (within cadherin repeats, Ca2+-binding sites, and juxtamembrane region) and are regulated by LEKTI fragments; KLK7 digests the ectodomain of desmoglein 1 in vitro. KLK7 was not significantly inhibited by secretory leukocyte protease inhibitor (SLPI) or elafin in contrast to earlier reports. In vitro protease digestion assays with recombinant desmoglein 1 ectodomain; Ki measurements with recombinant LEKTI fragments; SDS-PAGE The Journal of biological chemistry High 17158887
2007 LEKTI is processed by furin into multiple single- and multi-domain fragments (D1, D5, D6, D8-D11, D9-D15); these fragments specifically and differentially inhibit KLK5, KLK7, and KLK14 but not other serine proteases tested. The KLK5-LEKTI(D8-D11) interaction is rapid, tight, and functionally irreversible; crucially, acidic pH (as found in the superficial stratum corneum) causes release of active KLK5 from the inhibitory complex, providing a pH-dependent gating mechanism for KLK-mediated corneodesmosomal cleavage. Biochemical inhibition kinetics; furin cleavage assays; pH-dependent binding/release assays; functional protease activity assays on KLK5, KLK7, KLK14 Molecular biology of the cell High 17596512
2008 KLK5 and KLK7 generate tissue-specific (pancreas) transcripts driven by alternative promoters distinct from those used in skin or ovary; immunohistochemistry localizes both enzymes predominantly to acinar cells of the exocrine pancreas, suggesting roles in digestion. Northern blot of 19 normal human tissues; in silico promoter analysis; immunohistochemistry; RT-PCR Biological chemistry Medium 18163887
2012 Combined overexpression of KLK4, KLK5, KLK6, and KLK7 in ovarian cancer cells (OV-MZ-6) downregulates α5β1 and αvβ3 integrin expression, reduces cell adhesion to vitronectin and fibronectin, and confers paclitaxel resistance (not carboplatin resistance) through reduced apoptotic stimuli; this resistance is independent of MEK1/2 signaling. Stable transfection; quantitative gene and protein expression; confocal microscopy; cell adhesion assays; chemosensitivity assays; MEK inhibitor (U0126) epistasis Gynecologic oncology Medium 22964375
2014 KLK7 overexpression in HT29 colon cancer cells increases cell proliferation in vitro and tumor growth in vivo; KLK7 protein is aberrantly expressed and secreted in colon cancer tissues and cell lines but absent in normal colonic epithelium. Stable transfection with KLK7 expression plasmid; CCK-8 proliferation assay; subcutaneous xenograft in nude mice; Ki-67 staining; Western blot; immunofluorescence Biological chemistry Medium 25153388
2016 In atopic dermatitis lesional skin, KLK7 secretion from lamellar granules is impaired despite increased total KLK7 protein levels, resulting in ineffective KLK activation and abnormal corneodesmosin degradation; concurrently, LEKTI expression is upregulated as a compensatory mechanism to prevent further barrier dysfunction. Western blot analysis of stratum corneum; in situ zymography on tape-stripped corneocytes; immunostaining; electron microscopy of lamellar granules The Journal of investigative dermatology Medium 27769847
2017 Adipose tissue-specific Klk7 knockout mice (ATKlk7-/-) show less weight gain, preferential subcutaneous adipose expansion, improved insulin sensitivity, higher energy expenditure, reduced pro-inflammatory cytokine expression, and increased anti-inflammatory M2 macrophages in epididymal adipose tissue under high-fat diet. KLK7 deficiency alters adipokine secretion including reduced circulating leptin. Conditional gene targeting (Cre-lox) in adipose tissue; metabolic phenotyping (glucose tolerance, insulin sensitivity); flow cytometry for macrophage polarization; cytokine expression analysis Cellular and molecular life sciences High 28932870
2017 KLK7 exhibits chymotryptic-like cleavage preferences with preference for hydrophobic residues at P2-P1 (non-prime) subsites and hydrophilic residues in prime subsites (P1'-P2'); single S195A active-site mutant retains residual catalytic activity, requiring double mutation (S195A + D102N) to achieve true catalytic inactivity. PICS (Proteomic Identification of Cleavage Sites) mass spectrometry-based approach using human proteome-derived peptide libraries; kinetic characterization of wild-type and catalytic triad mutants (kcat/KM determination) Scientific reports High 28754951
2019 In-depth proteomic analysis identified 16 novel putative KLK7 substrates in ovarian cancer cell secretome, including direct activation of pro-MMP10, hydrolysis of IGFBP6, and cleavage of thrombospondin 1 generating a potentially bioactive N-terminal fragment; MMP2 and IGFBP3 were confirmed as established substrates. KLK7-cleaved substrates are enriched in cell adhesion, extracellular matrix remodeling, and cell migration pathways. qPROTOMAP (SILAC-coupled proteomic topography); TAILS (Terminal Amine Isotopic Labeling of Substrates) for exact cleavage site determination; biochemical validation of selected substrates Molecular & cellular proteomics High 30705123
2019 KLK7 is a direct target of miR-326 (negatively regulated); in a Parkinson's disease mouse model, KLK7 expression is elevated and activates the MAPK signaling pathway (p38, ERK, JNK, caspase-3), promoting dopaminergic neuron apoptosis; silencing KLK7 or overexpressing miR-326 reduces MAPK pathway activation and neuronal apoptosis. PD mouse model; miR-326 mimic/inhibitor treatment; siRNA-KLK7 knockdown; luciferase reporter assay (miR-326/KLK7 3'UTR); measurement of dopamine metabolites; MAPK pathway protein analysis by Western blot Journal of molecular neuroscience Medium 31270675
2020 IL-13 induces KLK7 transcription in keratinocytes via the ERK1/2 MAPK pathway activating the transcription factor EGR-1, which binds directly to an EGR-1-binding sequence (EBS) in the KLK7 promoter; point mutation of the EBS abolishes IL-13-induced KLK7 promoter activity; EGR1 knockout mice show reduced KLK7 expression in AD-like skin lesions. Promoter luciferase reporter assay with EBS point mutation; EGR-1 ChIP (implied by direct binding); shRNA knockdown of EGR1; Egr1 knockout mouse model of AD-like dermatitis; ERK inhibitor epistasis Biochemical and biophysical research communications High 33276948
2021 A quenched phosphonate activity-based probe (KLK7-qABP) was developed that specifically detects active (but not inactive) KLK7 in vitro, providing a tool to monitor KLK7 enzymatic activity. Synthesis of mixed alkyl aryl phosphonate probe; in vitro activity-based protein profiling against recombinant KLK7 Organic & biomolecular chemistry Medium 34308939
2022 Inhibitory antibodies against KLK5 and KLK7 protect against skin inflammation in mouse models of Netherton syndrome and atopic dermatitis; combined anti-KLK5/7 bispecific antibody promotes skin barrier integrity and reduces inflammation. Crystal structure of KLK5 bound to the inhibitory Fab revealed allosteric inhibition distal to the active site, demonstrating a non-active-site inhibition mechanism for kallikrein-family proteases. Antibody discovery and engineering; mouse NS and AD models; skin barrier integrity assays; inflammation markers; X-ray crystallography of KLK5-Fab complex Science translational medicine High 36516271
2023 KLK7 expression in keratinocytes is regulated by TNF signaling; inhibition of KLK7 expression decreases proinflammatory responses to TNF in keratinocytes, placing KLK7 downstream of TNF in psoriatic inflammation. KLK7 siRNA knockdown in keratinocytes; TNF stimulation assays; measurement of proinflammatory cytokine responses; pharmacogenetic study with functional validation The British journal of dermatology Medium 37672660
2024 KLK7 undergoes autolysis at two sites in the 170 and 99 loops (chymotrypsinogen numbering), leading to loss of enzymatic activity; KLK7 cleaves and inactivates mast cell chymase; KLK7 hydrolyzes multiple cytokines including IFN-α, IFN-β, IFN-γ, IL-28A/IFN-λ2, IL-20, IL-22, and IL-27 (predominantly interferon and IL-10 families). Protease-specific inhibitors; active-site variants; in vitro cleavage assays; protein BLAST for substrate identification; activity measurements post-cleavage Biological chemistry High 39655764
2025 KLK5 and KLK7 drive HPV-dependent cervical carcinogenesis; their absence ameliorates the HPV phenotype through modulation of KLK14 activation; KLK14 then activates PAR-2-dependent RhoA and NF-κB signaling pathways to exert pro-tumorigenic effects, placing KLK7 upstream of KLK14 activation in a protease cascade governing cervical carcinogenesis. Genetically engineered mice (KLK5/KLK7 double knockout); bulk RNA-seq; reporter assays for RhoA and NF-κB; human cervical biopsy expression analysis Translational oncology Medium 40753921
2025 KLK7 in macrophages promotes inflammatory macrophage polarization and migration in visceral adipose tissue during obesity; macrophage-specific KLK7 knockout (KLK7MKO) reduces pro-inflammatory gene expression, restricts macrophage migration by increasing cell adhesion, and decreases immune cell infiltration into epididymal adipose tissue of HFD-fed mice. Macrophage-specific conditional KLK7 knockout (Cre-lox); HFD mouse model; flow cytometry for macrophage subsets; inflammatory gene expression analysis; cell adhesion assays; correlation with human visceral adipose tissue transcriptomics (n=1143) Metabolism: clinical and experimental High 40154838
2025 KLK7 promotes epithelial-mesenchymal transition (EMT) in papillary thyroid cancer cells via the MAPK/ERK pathway; silencing KLK7 reduces ERK1/2 phosphorylation, suppresses EMT markers, and decreases proliferation, migration, and invasion in vitro and in vivo. KLK7 siRNA knockdown; immunohistochemistry; growth curve analysis; Western blot for ERK1/2 phosphorylation and EMT markers; nude mouse xenograft model Journal of Cancer Medium 39991575
2025 KLK7 overexpression in colorectal cancer cells enhances peritoneal dissemination in vivo; in vitro, it increases proliferation, migration, spheroid formation, adhesion to ECM proteins, and upregulates moesin (MSN) and integrin subunits, indicating cytoskeletal remodeling and altered matrix interactions. Stable KLK7 overexpression; xenograft peritoneal metastasis mouse model; Peritoneal Cancer Index scoring; in vitro migration, adhesion, spheroid assays; gene expression analysis FEBS open bio Medium 41335524
2025 NMDA receptor signaling in astrocytes negatively regulates KLK7 mRNA expression through NF-κB; inhibition of NF-κB signaling increases KLK7 expression in astrocytes and promotes degradation of amyloid-β (Aβ), identifying KLK7 as an astrocyte-derived Aβ-degrading protease; in vivo NF-κB inhibitor injection upregulates Klk7 and reduces Aβ levels. NMDA receptor antagonist (memantine) and NF-κB inhibitor treatment of astrocytes; KLK7 expression analysis; Aβ degradation assays; in vivo mouse model with NF-κB inhibitor injection and Aβ measurement bioRxivpreprint Medium
2025 Loss of store-operated Ca2+ entry (SOCE) via Stim1/2 knockout in mouse epidermis leads to elevated Klk7 levels and increased chymotrypsin-like serine protease activity, accompanied by alterations in desmoglein 1 and hyperkeratosis; this places SOCE/Ca2+ signaling upstream of KLK7 activity in epidermal barrier maintenance. Epithelial-specific Stim1/2 conditional knockout mice; RNA-seq; transepidermal water loss measurement; in situ protease activity assays; immunofluorescence for Dsg1 bioRxivpreprint Medium
2026 Substrate-analog and non-peptide inhibitors of KLK7 with Ki values <100 nM were developed; a key determinant of inhibitor selectivity is alanine at position 190 in the S1 pocket. KLK7 inhibition blocks chemokine cleavage and moesin gene upregulation by KLK7, confirming these as functional downstream activities; mutating T190A in murine Klk7 restored human-inhibitor potency, validating a species-adapted model. Medicinal chemistry synthesis; Ki measurement; KLK7 crystal structure-guided design; site-directed mutagenesis (T190A); cell-based assays for chemokine cleavage and moesin upregulation; ovarian cancer xenograft mouse model Biological chemistry High 41855304

Source papers

Stage 0 corpus · 69 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2004 Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. The Journal of investigative dermatology 366 15140227
2007 LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction. Molecular biology of the cell 237 17596512
2006 A potential role for multiple tissue kallikrein serine proteases in epidermal desquamation. The Journal of biological chemistry 213 17158887
1996 A novel protease homolog differentially expressed in breast and ovarian cancer. Molecular medicine (Cambridge, Mass.) 194 8898378
2006 Proteinase-activated receptors, targets for kallikrein signaling. The Journal of biological chemistry 193 16885167
1997 Molecular cloning of a novel trypsin-like serine protease (neurosin) preferentially expressed in brain. Biochimica et biophysica acta 156 9003450
2002 Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system. The Journal of biological chemistry 149 11983703
1997 Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from Alzheimer's disease brain. The Journal of biological chemistry 139 9312124
2003 Alpha-synuclein degradation by serine protease neurosin: implication for pathogenesis of synucleinopathies. Human molecular genetics 132 12928483
2003 Characterization of the enzymatic activity of human kallikrein 6: Autoactivation, substrate specificity, and regulation by inhibitors. Biochemical and biophysical research communications 124 12878203
2013 Low CSF levels of both α-synuclein and the α-synuclein cleaving enzyme neurosin in patients with synucleinopathy. PloS one 118 23308173
2005 LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum. The Journal of investigative dermatology 116 15675955
2006 A comprehensive nomenclature for serine proteases with homology to tissue kallikreins. Biological chemistry 110 16800724
2002 Activity of a newly identified serine protease in CNS demyelination. Brain : a journal of neurology 108 12023317
2004 Human kallikrein 6 degrades extracellular matrix proteins and may enhance the metastatic potential of tumour cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 100 15557757
2003 Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers. Clinical cancer research : an official journal of the American Association for Cancer Research 94 12738725
2005 Clinical significance of human kallikrein gene 6 messenger RNA expression in colorectal cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 92 15837738
2005 Substrate specificity of human kallikrein 6: salt and glycosaminoglycan activation effects. The Journal of biological chemistry 89 16321973
1999 Molecular characterization of zyme/protease M/neurosin (PRSS9), a hormonally regulated kallikrein-like serine protease. Genomics 89 10610719
2000 Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region. Gene 87 11054574
2020 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. Cell reports 79 32814053
2018 Long noncoding RNA NEAT1 regulate papillary thyroid cancer progression by modulating miR-129-5p/KLK7 expression. Journal of cellular physiology 79 29319165
2006 Human colostrum: identification of minor proteins in the aqueous phase by proteomics. Proteomics 77 16502470
2009 A tumor-protective role for human kallikrein-related peptidase 6 in breast cancer mediated by inhibition of epithelial-to-mesenchymal transition. Cancer research 76 19383923
2001 The spectrum of human kallikrein 6 (zyme/protease M/neurosin) expression in human tissues as assessed by immunohistochemistry. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 76 11668196
2000 The KLK7 (PRSS6) gene, encoding for the stratum corneum chymotryptic enzyme is a new member of the human kallikrein gene family - genomic characterization, mapping, tissue expression and hormonal regulation. Gene 72 10974542
2003 Role of kallikrein enzymes in the central nervous system. Clinica chimica acta; international journal of clinical chemistry 69 12589961
2002 The structure of human prokallikrein 6 reveals a novel activation mechanism for the kallikrein family. The Journal of biological chemistry 69 12016211
2010 Extracellular neurosin degrades α-synuclein in cultured cells. Neuroscience research 67 20403393
2005 Clinicopathologic and biological significance of kallikrein 6 overexpression in human gastric cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 65 16203767
2002 Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker. British journal of cancer 63 12232761
2008 Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk. The Journal of allergy and clinical immunology 55 18774391
2005 KLK5 and KLK7, two members of the human tissue kallikrein family, are differentially expressed in lung cancer. Biochemical and biophysical research communications 44 15766562
2022 Dual antibody inhibition of KLK5 and KLK7 for Netherton syndrome and atopic dermatitis. Science translational medicine 43 36516271
2009 Clinical significance of kallikrein-related peptidase 7 (KLK7) in colorectal cancer. Thrombosis and haemostasis 39 19350120
2012 Combined expression of KLK4, KLK5, KLK6, and KLK7 by ovarian cancer cells leads to decreased adhesion and paclitaxel-induced chemoresistance. Gynecologic oncology 38 22964375
2018 LncRNA FOXD2-AS1 accelerates the papillary thyroid cancer progression through regulating the miR-485-5p/KLK7 axis. Journal of cellular biochemistry 37 30456805
2016 Incomplete KLK7 Secretion and Upregulated LEKTI Expression Underlie Hyperkeratotic Stratum Corneum in Atopic Dermatitis. The Journal of investigative dermatology 36 27769847
2014 Kallikrein family proteases KLK6 and KLK7 are potential early detection and diagnostic biomarkers for serous and papillary serous ovarian cancer subtypes. Journal of ovarian research 35 25477184
2017 Ablation of kallikrein 7 (KLK7) in adipose tissue ameliorates metabolic consequences of high fat diet-induced obesity by counteracting adipose tissue inflammation in vivo. Cellular and molecular life sciences : CMLS 32 28932870
2014 Kallikrein-related peptidase 7 (KLK7) is a proliferative factor that is aberrantly expressed in human colon cancer. Biological chemistry 32 25153388
2001 Expression of the protease inhibitor antileukoprotease and the serine protease stratum corneum chymotryptic enzyme (SCCE) is coordinated in ovarian tumors. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32 11906548
2004 Expression of human kallikrein 7 (hK7/SCCE) and its inhibitor antileukoprotease (ALP/SLPI) in uterine endocervical glands and in cervical adenocarcinomas. Oncology reports 30 15492784
2019 MicroRNA-326 Inhibits Apoptosis and Promotes Proliferation of Dopaminergic Neurons in Parkinson's Disease Through Suppression of KLK7-Mediated MAPK Signaling Pathway. Journal of molecular neuroscience : MN 29 31270675
2019 Integration of Two In-depth Quantitative Proteomics Approaches Determines the Kallikrein-related Peptidase 7 (KLK7) Degradome in Ovarian Cancer Cell Secretome. Molecular & cellular proteomics : MCP 20 30705123
2008 Tissue-specific promoter utilisation of the kallikrein-related peptidase genes, KLK5 and KLK7, and cellular localisation of the encoded proteins suggest roles in exocrine pancreatic function. Biological chemistry 17 18163887
2020 EGR-1 acts as a transcriptional activator of KLK7 under IL-13 stimulation. Biochemical and biophysical research communications 13 33276948
2021 Generation of a quenched phosphonate activity-based probe for labelling the active KLK7 protease. Organic & biomolecular chemistry 11 34308939
2023 Mini-PBPK-Based Population Model and Covariate Analysis to Assess the Complex Pharmacokinetics and Pharmacodynamics of RO7449135, an Anti-KLK5/KLK7 Bispecific Antibody in Cynomolgus Monkeys. The AAPS journal 7 37353723
2023 Retrospective pharmacogenetic study of psoriasis highlights the role of KLK7 in tumour necrosis factor signalling. The British journal of dermatology 7 37672660
2025 The serine protease KLK7 promotes immune cell infiltration in visceral adipose tissue in obesity. Metabolism: clinical and experimental 6 40154838
2024 KLK7 expression in human tumors: a tissue microarray study on 13,447 tumors. BMC cancer 6 38961454
2017 Mass spectrometry-based determination of Kallikrein-related peptidase 7 (KLK7) cleavage preferences and subsite dependency. Scientific reports 6 28754951
2019 Molecular characteristics and association analysis with litter size trait for porcine KLK7 gene. Animal biotechnology 4 31006337
2016 Experiment research of cisplatin implants inhibiting transplantation tumor growth and regulating the expression of KLK7 and E-cad of tumor-bearing mice with gastric cancer. Asian Pacific journal of tropical medicine 4 27262076
2024 Increase of KLK7, cytokeratin 5/6, and elafin expression in head and neck squamous cell carcinoma compared with lung squamous cell carcinoma. Journal of histotechnology 3 38189409
2024 Analysis of kallikrein-related peptidase 7 (KLK7) autolysis reveals novel protease and cytokine substrates. Biological chemistry 3 39655764
2018 [The expression of KLK7 in pancreatic cancer and the effects on the biological behavior of pancreatic cancer cells]. Zhonghua wai ke za zhi [Chinese journal of surgery] 2 29779317
2025 KLK7 Involvement in Thyroid Papillary Carcinoma Cell Migration and Invasion by EMT via MAPK/ERK Pathways. Journal of Cancer 1 39991575
2025 KLK5 and KLK7 drive cervical carcinoma via KLK14-dependent RhoA and NF-κB pathways. Translational oncology 1 40753921
2025 KLK7 overexpression promotes an aggressive phenotype and facilitates peritoneal dissemination in colorectal cancer cells. FEBS open bio 1 41335524
2026 Development of kallikrein-related peptidase 7 (KLK7) inhibitors and use in a species-adapted model for ovarian cancer. Biological chemistry 0 41855304
2025 Significance of KLK7 expression, polymorphisms, and function in sheep horn growth. BMC genomics 0 39871127
2025 Detection of probable phytochemical inhibitors targeting kallikrein related peptidase 7 (KLK7) in ovarian cancer through molecular dynamics and virtual screening approaches. Scientific reports 0 41053179