KLK7 (kallikrein-related peptidase 7)

2009-05-01   Ying Dong  , John Lai  , Judith A Clements  

Hormone Dependent Cancer Program, Institute of Health, Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, Australia

Identity

HGNC
LOCATION
19q13.41
IMAGE
Atlas Image
LEGEND
Genomic and protein structure of the KLK7 gene. The KLK7 gene is classically comprised of 5 coding exons (red boxes, classic numerals) and 4 intervening introns with a conserved intron phase pattern (I, II, I, 0). A non-coding exon and untranslated regions are shown in yellow. Also shown is the classical transcription initiation site (TIS) and corresponding translation start site (ATG1). An exon 1 deleted transcript has also been identified which would potentially result in the use of an alternative translation start site (ATG2). The numbering for the amino acid residues of the catalytic triad (His70, Asp112, Ser205) are relative to the full-length protein starting from ATG1.
LOCUSID
ALIAS
PRSS6,SCCE,hK7
FUSION GENES

DNA/RNA

Description

The gene encompasses 6.509 kb of gDNA.

Transcription

Five variant mRNA transcripts have been identified. These include transcripts using different 5 untranslated regions (UTRs) including exon 1 deletions, and transcripts using different 3UTR regions. Using rapid amplification of cDNA ends (RACE) different KLK7 5UTR sequences were identified from RNA extracted from pancreas, skin and ovarian cells, suggesting the expression of tissue specific KLK7 transcripts.

Pseudogene

Not identified.

Proteins

Description

Full-length KLK7 (253 amino acids) has a secretion signal (pre-) peptide (22 amino acids), followed by an activation (pro-) peptide (7 amino acids) and the mature chain (224 amino acids) with 1 potential N-linked glycosylation site. The catalytic triad of His70, Asp112 and Ser205 (relative to ATG1) is conserved and is essential for proteolytic activity. After synthesis as a KLK7 full-length protein, the signal peptide is then cleaved and pro-KLK7 (zymogen) is subsequently secreted from the cell. On activation, the propeptide is removed and the zymogen becomes the mature active enzyme. KLK7 can complex with antileukoprotease (secretory leukocyte protease inhibitor), elafin, Lympho-epithelial Kazal type inhibitor (LEKTI) fragments, and a member of a2-macroglobulin (a2M) protease inhibitor family, a2-macroglobulin-like 1 (a2ML1).
X-ray structures of recombinant full-length KLK7 from E. coli and insect cells have been solved, from which the most distinguishing features of KLK7 are the short 70-80 loop and the unique S1 pocket, which prefers P1 Tyr residues. KLK7 displays a unique chymotrypsin-like specificity for Tyr, which is preferred at P2. In addition, KLK7 exhibits large positively charged surface patches, representing putative exosites for prime side substrate recognition.
Similar to several other KLKs and based on the binding of metal to histidine such as His99, the KLK7 activity is inhibited by Zn++ and Cu++ at low micromolar concentrations. KLK7 induced degradation of corneodesmosin and desmocollin 1 with similar efficiency in acidic (pH 5.6) and neutral (pH 7.2) conditions. KLK7 activity is modulated by water content in stratum corneum as KLK7 activity increased significantly in an environment of high relative humidity. KLK7 also demonstrated a tolerance to water restriction suggesting that it may be adapted to function in the water-restricted stratum corneum. Thus, relative humidity modulates desquamation by its effect upon KLK7 activity, possibly other desquamatory hydrolases and adapted KLK7 function in water-deplete skin.
An N-terminal truncated KLK7 isoform (181 amino acids) initiating from the putative ATG2 would not have the pre-pro-region and 43 amino acids from the N-terminus of full-length KLK7. The histidine which is part of the catalytic triad is also omitted which would result in a proteolytic inactive protein. The presence of this isoform has not yet been confirmed in human tissues or biological fluids.

Expression

Full-length KLK7 protein was originally purified in human skin and named stratum corneum chymotryptic enzyme (SCCE, hSCCE). KLK7 cDNA was originally isolated from a keratinocyte derived library and designated PRSS6. Although Northern blot analyses have shown that KLK7 mRNA is predominantly localised to skin and pancreas, more sensitive RT-PCR experiments have shown that brain, kidney, ovary, bone, breast, endometrium, spinal cord, lung, prostate tissue and salivary tissue express KLK7 mRNA at low to modest levels. High KLK7 mRNA has been detected in malignancies of ovary, breast, lung and brain.
KLK7 protein has been detected by ELISA in a wide range of tissues at low (adrenal, bladder, cervix, fallopian tube, kidney, lung, lymph node, muscle, ovary, salivary gland, small intestine, spinal cord, spleen, thyroid gland, tonsil, trachea and vagina) to high (oesophagus, heart, liver and skin) levels. Modest levels of KLK7 protein have also been detected in human body fluid, such as, seminal plasma, breast milk, ovarian cancer ascites, salivary and cervicovaginal fluid.
In normal skin, KLK7 is expressed in late epidermal differentiation and found at all sites of epithelial cornification. Consequently, KLK7 is used as a marker for terminal epidermal differentiation. In normal epidermis, KLK7 was detected in a population of dendritic cells and in high suprabasal keratinocytes. KLK7 was also found in reconstructed human epidermis and its expression was suppressed by retinoic acid. An increased expression of KLK7 was found in suprabasal cells in orthokeratotic and parakeratotic areas of the lesions of oral lichen planus (an inflammatory disease) and benign oral keratosis (a non-inflammatory disease).
High KLK7 protein levels have been detected in the tissues of lung, breast, ovarian and squamous cervical cancers, oral squamous cell carcinoma and cervical adenocarcinoma tissues from patients. However, KLK7 is down regulated in cancerous prostate tissues compared to normal prostate tissues. KLK7, along with KLK6 and KLK10, is decreased in cerebrospinal fluid of frontotemporal dementia patients.

Localisation

Full-length KLK7 is localised intracellularly in the cytoplasm prior to secretion. KLK7 protein is co-localised with KLK5 in skin and acinar cells of the pancreas by immunohistochemical staining.
The putative N-terminal truncated KLK7-181 isoform is potentially not secreted as it does not have a signal peptide, and cellular localisation remains to be determined.

Function

To date, the major biological functions of KLK7 are associated with the skin and related epithelial tissues, such as hair follicles, oral mucosa and glandular lobules. KLK7 is involved in keratinization, stratum corneum formation, and turnover/desquamation of the skin through the degradation of cell adhesion glycoproteins, such as corneodesmosin, desmocollin 1 and plakoglobin. KLK7 has also been shown to cleave insulin B chain, degrade fibronectin, fibrinogen and interleukin 1beta (IL-1b), as well as activate pro-IL-1b. KLK7 and KLK5 can control activation of the human cathelicidin precursor protein, hCAP18, implying their ability to control innate immune defence.
An in vitro study showed that UVB radiation can increase KLK7 and KLK5 expression at both mRNA and protein levels in keratinocyte (HaCat) cells. In the epidermis, the major inhibitor of KLK7, antileukoprotease (secretory leukocyte protease inhibitor) is produced by keratinocytes and can inhibit detachment of corneocytes from human plantar callus in vitro, while a weaker KLK7 inhibitor, elafin (skin-derived antileukoprotease), can reduce the shedding of corneocytes. Established epidermal mouse models overexpressing KLK7 have been shown to develop chronic itchy dermatitis. Further characterisation of these models also revealed epidermal hyperproliferation, decreased skin barrier function, and decreased expression of MHC II antigen in keratinocytes. These data provide an in vivo pathophysiological foundation that KLK7 plays an important role in skin, such as listed those below.
KLK cascade activation systems have been described. KLK7 is activated by KLK5 and KLK12. KLK7 activates other members of the kallikrein-related peptidase family including KLK1, KLK2, prostate specific antigen (PSA/KLK3) and KLK9.
The function of the putative N-terminal truncated KLK7 remains to be established.

Homology

At the protein level, KLK7 shares 28% (KLK12), 33% (KLK9), 36% (KLK10, 11), 37% (KLK1, KLK3/PSA), 38% (KLK2, KLK5, KLK6, KLK13), 40% (KLK8), 41% (KLK14), 43% (KLK4) and 42.6% (KLK15) sequence homology with other members of the kallikrein-related peptidase family.

Mutations

Germinal

An AACC insertion in the 3UTR of the KLK7 gene has been found, which altered the common allele AACC to the rare allele AACCAACC. This insertion was found to be associated with atopic dermatitis.

Implicated in

Entity name
Endocrine related cancers
Disease
It has been postulated that KLK7 plays a role in endocrine related cancers given its (a) dysregulated expression in cancerous tissues compared to normal tissues, (b) regulation by hormones, such as, oestradiol, progestins and glucocorticoids and (c) potential roles in degradation of cell-cell adhesion proteins, extracellular matrix (ECM) proteins and activation of other proteases and growth factors.
Entity name
Epithelial ovarian carcinoma (EOC)
Disease
Kallikrein 7 is highly expressed in serous EOC at both the mRNA and protein levels, and high KLK7 mRNA expression is associated with poorly differentiated, late clinical stage ovarian carcinomas and the volume of residual tumour after surgery. Upregulated KLK7 protein was detected in EOC patient sera and tumour cytosols using ELISA, and in EOC tissue sections using immunohistochemistry and a quantitative automated in situ immunofluorescence-based protein analysis. At the mRNA level, both KLK7 and its exon 1 deleted short KLK7 transcripts were detected in serous EOC cells, while none or only KLK7 short transcript was found in normal ovarian epithelial cells. In addition, a coordinated expression pattern and co-localisation of KLK7 and KLK5 were found in serous EOC cells suggesting a proteolytic cascade between them. Co-overexpression of KLK4, KLK5, KLK6 and KLK7 in ovarian cancer cells (OV-MZ-6) led to increased invasion in vitro and resulted in increased tumour burden in nude mice. A coordinated expression of KLK7 and protease inhibitor antileukoprotease was also found in EOC cells. Of interest, the 110-139 amino acid region of the KLK7 protein incorporates multiple CD8+ CTL and CD4+ helper T cell epitopes, and represents an attractive target antigen for immunotherapy of ovarian cancer.
Prognosis
EOC patients with KLK7 mRNA or protein expression in their tumours had a significantly shorter disease-free survival time than those with KLK7 negative tumours. KLK7 is an independent unfavourable predictor of disease-free and overall survival for patients with low grade cancers. KLK7 has been shown to increase specificity for diagnosis and prognosis of EOC in conjunction with other biomarkers, such as CA125, HE4 and B7-H4.
Entity name
Breast cancer
Disease
KLK7 gene expression was significantly lower in tumour tissues from early stage (I/II) breast cancer patients and tumour cells with progesterone receptors.
Prognosis
Two groups have reported conflicting data regarding the prognoses for breast cancer patients and KLK7 expressing tumours. One study found that breast cancer patients with KLK7 positive tumours have relatively shorter disease-free survival and overall survival than patients with KLK7 negative tumours. However, another study reported that breast cancer patients with KLK7 expressing tumours have favourable outcomes compared to those with KLK7 negative tumours.
Entity name
Cervical cancer
Disease
In a study of 18 cervical cancer cell lines (10 primary and 8 established cell lines) and 8 normal cervical keratinocyte cell lines, KLK7 mRNA expression was detected in the cancer cells (5/10 primary and 4/8 established lines) but not in any of the normal cervical keratinocytes. Interestingly, all five patients, who harbour KLK7 positive tumours that were used to establish the primary cell lines, were found to have metastatic involvement of the pelvic tumour draining lymph nodes. In the same study, tumour restricted expression of KLK7 was confirmed by immunohistochemistry staining in 4 of the 5 primary squamous cervical tumours, and 1 of the 4 primary adenocarcinomas, but none of the normal cervical epithelial cells. Another immunohistochemical study showed a significantly higher expression of KLK7 in cervical adenocarcinomas compared to normal endocervical glands.
Entity name
Pancreatic cancer
Disease
KLK7 is expressed in normal pancreas at mRNA and protein levels, and KLK7 protein is localised in acinar cells of the pancreas by immunohistochemical staining. KLK7 is overexpressed in pancreatic adenocarcinomas at both the mRNA and protein levels. KLK7 expression was also observed in neoplastic cells of all tumours examined using immunohistochemistry with moderate-to-intense staining in 16 of the 23 tumours examined. Only 2 of the 13 nonmalignant tissue specimens displayed moderate KLK7 staining, whereas the remaining specimens showed weak immunoreactivity. In pancreatic cancer cells, KLK7 was shown to i) cleave desmoglein 2, ii) cleave E-cadherin and the ECM protein, fibronectin, iii) enhance urokinase-type plasminogen activator receptor shedding, and iv) reduce cell aggregation and adhesion to vitronectin to promote pancreatic cancer invasion.
Entity name
Oral squamous cell carcinoma (OSCC)
Disease
cDNA microarray analysis revealed that KLK5, KLK7, KLK8 and KLK10 were upregulated in tumour samples versus normal controls. RT-qPCR analysis confirmed that KLK7 mRNA was most differentially regulated with a 5.3-fold increase, while 2.8-, 4.0- and 3.5-fold increases were observed for KLK5, KLK8, and KLK10, respectively. Immunohistochemical analysis demonstrated strong reactivity for all 4 KLK proteins in both orthotopic murine tumours and human OSCC tissues.
Entity name
Lung cancer
Disease
KLK7 mRNA levels are decreased in adenocarcinoma compared to matched nonmalignant lung tissue. Similarly, sera of patients with non-small cell lung cancer (NSCLC) have lower protein levels of KLK7, KLK5, KLK8, KLK10 and KLK12 than those from normal subjects. However, a study has reported intense cytoplasmic staining for KLK7, KLK5, KLK6 and KLK8 in 40-90% of squamous cell carcinomas, small cell carcinomas and carcinoid tumours while 20% of tumour cells had intense nuclear staining for KLK7, KLK5 and KLK8.
Entity name
Brain tumours
Disease
RT-qPCR analysis showed that KLK7 mRNA expression in intracranial tumours was associated with shorter overall survival than those tumours with no KLK7 expression from a survival analysis study of 73 patients with intracranial tumours. Overexpression of KLK7 protein by cultivated brain tumour cells significantly enhanced the invasive potential in a Matrigel invasion assay.
Entity name
Colon cancer
Disease
One study using a semi-quantitative RT-PCR method showed that the KLK7 gene is up-regulated in colon cancer and its expression predicts poor prognosis for colon cancer patients.
Entity name
Skin disorders
Note
A majority of studies have concentrated on the concomitant functions of KLK7 and KLK5 in normal human skin and a number of skin disorders given its (a) high expression in pathological conditions compared to normal skin samples, (b) cleavage/degradation of intercellular adhesive glycoproteins and (c) potential of activation and degradation of cytokines, such as interleukin 1beta (IL-1b).
Entity name
Netherton syndrome (NS)
Disease
NS is a rare but severe inherited disorder that presents the three following characteristics with varying degrees of severity of their symptoms. 1) Ichthyosiform erythroderma - inflamed, red, scaly skin and trichorrhexis invaginata ("bamboo hair"). 2) Short, brittle, lustreless hair and atopic diathesis. 3) Predisposition to allergy problems.
NS patients have mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene, encoding the protease inhibitor LEKTI (lympho-epithelial Kazal-type related inhibitor). Early studies using mouse models revealed that SPINK5-deficient mice mimic NS through degradation of desmoglein 1 by epidermal protease. The pathophysiological processes in the skin and epithelial related tissues of NS patients result from the lack of functional LEKTI protease inhibitor and consequently the over-degradation of corneodesmosomal cadherins by KLK7, KLK5 and KLK14.
The SPINK5 gene is localised chromosome 5. SPINK5 mutations introduce premature termination codons in LEKTI transcripts and lead to the production of truncated LEKTI forms that lack several inhibitory domains. NS is an autosomal recessive condition.
Entity name
Atopic dermatitis (AD)
Disease
AD is a chronic inflammatory and allergic skin disorder. Multifactorial studies have suggested that both genetic and environmental factors contribute to AD development. A study comprising 103 AD patients and 261 matched controls revealed a significant association between the rare AACCAACC allele in the 3UTR of KLK7 with AD. However, another group found that the AACCAACC allele was not associated with AD in a cohort of 99 patients and 189 controls. Nevertheless, patients with the AACCAACC allele have increased KLK7 protease activity resulting in premature breakdown of corneodesmosomes, and leading to impairment of the epidermal barrier. Furthermore, acute eczematous lesions and clinically unaffected skin can further increase production of KLK7 and epidermal barrier functions are damaged through environmental interactions, such as washing with soap and detergents, or long-term application of corticosteroids. A combination of the above factors leads to a defective skin barrier and increases the risk of allergen penetration and succeeding inflammatory reaction. By ELISA, KLK7 levels were found to be elevated in the stratum corneum of AD patients, and KLK7 in the serum significantly correlated with eosinophil counts in the blood of AD patients, indicative of the body under an allergic condition.
Entity name
Psoriasis
Disease
A number of early studies reported that the chymotrypsin-like activity in stratum corneum was slightly elevated in psoriasis, but KLK7 serum levels did not differ between normal volunteers and patients with psoriasis. It has been confirmed that KLK7 protein levels were similar between non-lesional and lesional skin extracts, but increased amounts of desmoglein 1, plakoglobin and high molecular weight fragments of desmocollin 1 were detected in the lesional skin, suggesting an involvement of other proteases.

Article Bibliography

Pubmed IDLast YearTitleAuthors
158672472005Definition of an immunogenic region within the ovarian tumor antigen stratum corneum chymotryptic enzyme.Bondurant KL et al
155169602004The emerging roles of human tissue kallikreins in cancer.Borgoño CA et al
156549742005A proteolytic cascade of kallikreins in the stratum corneum.Brattsand M et al
151402272004Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7.Caubet C et al
153076342004The tissue kallikrein family of serine proteases: functional roles in human disease and potential as clinical biomarkers.Clements JA et al
168151332006New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions.Cork MJ et al
186273432008Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7.Debela M et al
179091802007Chymotryptic specificity determinants in the 1.0 A structure of the zinc-inhibited human tissue kallikrein 7.Debela M et al
175965122007LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction.Deraison C et al
166281982006Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin- and chymotrypsin-like hyperactivity in Netherton syndrome.Descargues P et al
149726462004Altered kallikrein 7 and 10 concentrations in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia.Diamandis EP et al
127387252003Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers.Dong Y et al
181638872008Tissue-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.Dong Y et al
163076582005hK5 and hK7, two serine proteinases abundant in human skin, are inhibited by LEKTI domain 6.Egelrud T et al
81056131993Expression of stratum corneum chymotryptic enzyme in reconstructed human epidermis and its suppression by retinoic acid.Egelrud T et al
108849392000Desquamation in the stratum corneum.Egelrud T et al
186272992008Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier functions.Eissa A et al
106883772000Expression of stratum corneum chymotryptic enzyme in relation to other markers of epidermal differentiation in a skin explant model.Ekholm E et al
97792501998Expression of stratum corneum chymotryptic enzyme in human sebaceous follicles.Ekholm E et al
106201162000Stratum corneum tryptic enzyme in normal epidermis: a missing link in the desquamation process?Ekholm IE et al
183290422008Crystal structure of human epidermal kallikrein 7 (hK7) synthesized directly in its native state in E. coli: insights into the atomic basis of its inhibition by LEKTI domain 6 (LD6).Fernández IS et al
87029901996Antileukoprotease inhibits stratum corneum chymotryptic enzyme. Evidence for a regulative function in desquamation.Franzke CW et al
162989982006A novel protease inhibitor of the alpha2-macroglobulin family expressed in the human epidermis.Galliano MF et al
161177922005Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity.Hachem JP et al
118744832002Epidermal overexpression of stratum corneum chymotryptic enzyme in mice: a model for chronic itchy dermatitis.Hansson L et al
80347091994Cloning, expression, and characterization of stratum corneum chymotryptic enzyme. A skin-specific human serine proteinase.Hansson L et al
184892992006Effects of environmentally realistic levels of ozone on stratum corneum function.He QC et al
166275592006Quantitative reverse transcription-PCR assay for detection of mRNA encoding full-length human tissue kallikrein 7: prognostic relevance of KLK7 mRNA expression in breast cancer.Holzscheiter L et al
179898872007Analysis of SPINK 5, KLK 7 and FLG genotypes in a French atopic dermatitis cohort.Hubiche T et al
156759552005LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum.Ishida-Yamamoto A et al
128344832003Expression of stratum corneum chymotryptic enzyme in ichthyoses and squamoproliferative processes.Johnson B et al
173542282007Kallikrein 7 enhances pancreatic cancer cell invasion by shedding E-cadherin.Johnson SK et al
182095062008Genetic susceptibility to atopic dermatitis.Kiyohara C et al
175189922007Human tissue kallikrein expression in the stratum corneum and serum of atopic dermatitis patients.Komatsu N et al
129252132003Expression and localization of tissue kallikrein mRNAs in human epidermis and appendages.Komatsu N et al
158782402005A survey of alternative transcripts of human tissue kallikrein genes.Kurlender L et al
126337632003Prognostic value of quantitatively assessed KLK7 expression in ovarian cancer.Kyriakopoulou LG et al
191189812009Dichotomous effect of ultraviolet B on the expression of corneodesmosomal enzymes in human epidermal keratinocytes.Nin M et al
150404722004Epidermal hyperproliferation and decreased skin barrier function in mice overexpressing stratum corneum chymotryptic enzyme.Ny A et al
91888711997Formation of active IL-1 beta from pro-IL-1 beta catalyzed by stratum corneum chymotryptic enzyme in vitro.Nylander-Lundqvist E et al
187661802008Prediction of ovarian cancer prognosis and response to chemotherapy by a serum-based multiparametric biomarker panel.Oikonomopoulou K et al
176294062007Tissue kallikrein proteolytic cascade pathways in normal physiology and cancer.Pampalakis G et al
190858362009Multiple kallikrein (KLK 5, 7, 8, and 10) expression in squamous cell carcinoma of the oral cavity.Pettus JR et al
183165552008A multiparametric serum kallikrein panel for diagnosis of non-small cell lung carcinoma.Planque C et al
157665622005KLK5 and KLK7, two members of the human tissue kallikrein family, are differentially expressed in lung cancer.Planque C et al
168007442006Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases the malignant phenotype of ovarian cancer cells.Prezas P et al
171321072006The role of human tissue kallikreins 7 and 8 in intracranial malignancies.Prezas P et al
183259192008Human tissue kallikrein 7, a novel biomarker for advanced ovarian carcinoma using a novel in situ quantitative method of protein expression.Psyrri A et al
183432202008The extracellular matrix protein fibronectin is a substrate for kallikrein 7.Ramani VC et al
152971632004The serine protease stratum corneum chymotryptic enzyme (kallikrein 7) is highly overexpressed in squamous cervical cancer cells.Santin AD et al
163074832005Inhibition of human kallikreins 5 and 7 by the serine protease inhibitor lympho-epithelial Kazal-type inhibitor (LEKTI).Schechter NM et al
169169862006Unfavorable prognostic value of human kallikrein 7 quantified by ELISA in ovarian cancer cytosols.Shan SJ et al
175734182007Distribution of 15 human kallikreins in tissues and biological fluids.Shaw JL et al
119065482001Expression of the protease inhibitor antileukoprotease and the serine protease stratum corneum chymotryptic enzyme (SCCE) is coordinated in ovarian tumors.Shigemasa K et al
184600282008Alterations in the desquamation-related proteolytic cleavage of corneodesmosin and other corneodesmosomal proteins in psoriatic lesional epidermis.Simon M et al
181822442008Expression of kallikrein-related peptidases (KRP/hK5, 7, 6, 8) in subtypes of human lung carcinoma.Singh J et al
77942731995Primary substrate specificity of recombinant human stratum corneum chymotryptic enzyme.Skytt A et al
88002941996Association between expression of stratum corneum chymotryptic enzyme and pathological keratinization in human oral mucosa.Sondell B et al
92055001997In situ evidence that the population of Langerhans cells in normal human epidermis may be heterogeneous.Sondell B et al
75377771995Evidence that stratum corneum chymotryptic enzyme is transported to the stratum corneum extracellular space via lamellar bodies.Sondell B et al
146915842004Expression analysis of the human kallikrein 7 (KLK7) in breast tumors: a new potential biomarker for prognosis of breast carcinoma.Talieri M et al
193501202009Clinical significance of kallikrein-related peptidase 7 (KLK7) in colorectal cancer.Talieri M et al
168007302006Kallikrein-related peptidase (KLK) family mRNA variants and protein isoforms in hormone-related cancers: do they have a function?Tan OL et al
105704341999The stratum corneum chymotryptic enzyme that mediates shedding and desquamation of skin cells is highly overexpressed in ovarian tumor cells.Tanimoto H et al
154927842004Expression of human kallikrein 7 (hK7/SCCE) and its inhibitor antileukoprotease (ALP/SLPI) in uterine endocervical glands and in cervical adenocarcinomas.Tian X et al
151915432004Genetic association between an AACC insertion in the 3'UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis.Vasilopoulos Y et al
159697482005Ovarian cancer, the coagulation pathway, and inflammation.Wang X et al
117587902001Water modulation of stratum corneum chymotryptic enzyme activity and desquamation.Watkinson A et al
187743912008Analysis 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.Weidinger S et al
189760182008Expression of the serine protease kallikrein 7 and its inhibitor antileukoprotease is decreased in prostate cancer.Xuan Q et al
170122592006Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin.Yamasaki K et al
178231172007Activation profiles and regulatory cascades of the human kallikrein-related peptidases.Yoon H et al
127278432003Parallel overexpression of seven kallikrein genes in ovarian cancer.Yousef GM et al
109745422000The 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.Yousef GM et al
175984542007[Cloning and expression of the gene of chymotrypsin-like protease of human kallikrein-7 in Escherichia coli and isolation of recombinant protein].Zakabunin AI et al

Other Information

Locus ID:

NCBI: 5650
MIM: 604438
HGNC: 6368
Ensembl: ENSG00000169035

Variants:

dbSNP: 5650
ClinVar: 5650
TCGA: ENSG00000169035
COSMIC: KLK7

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000169035ENST00000304045Q6DTY1
ENSG00000169035ENST00000391807P49862
ENSG00000169035ENST00000391807A0A024R4H6
ENSG00000169035ENST00000593904M0QYU8
ENSG00000169035ENST00000595820P49862
ENSG00000169035ENST00000595820A0A024R4H6
ENSG00000169035ENST00000597707P49862

Expression (GTEx)

0
50
100
150
200
250
300

Pathways

PathwaySourceExternal ID
Extracellular matrix organizationREACTOMER-HSA-1474244
Degradation of the extracellular matrixREACTOMER-HSA-1474228

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
381894092024Increase of KLK7, cytokeratin 5/6, and elafin expression in head and neck squamous cell carcinoma compared with lung squamous cell carcinoma.0
381894092024Increase of KLK7, cytokeratin 5/6, and elafin expression in head and neck squamous cell carcinoma compared with lung squamous cell carcinoma.0
345259042022The Role of Kallikrein 7 in Tumorigenesis.3
345259042022The Role of Kallikrein 7 in Tumorigenesis.3
332769482021EGR-1 acts as a transcriptional activator of KLK7 under IL-13 stimulation.4
335889112021Identification of MFGE8 and KLK5/7 as mediators of breast tumorigenesis and resistance to COX-2 inhibition.11
332769482021EGR-1 acts as a transcriptional activator of KLK7 under IL-13 stimulation.4
335889112021Identification of MFGE8 and KLK5/7 as mediators of breast tumorigenesis and resistance to COX-2 inhibition.11
318839632020Kallikrein 7 Promotes Atopic Dermatitis-Associated Itch Independently of Skin Inflammation.19
323238432020Extracellular acidity‑induced expression of Kallikrein‑related peptidases 7 and 8 is involved in increased invasiveness of gastric cancer cells.4
318839632020Kallikrein 7 Promotes Atopic Dermatitis-Associated Itch Independently of Skin Inflammation.19
323238432020Extracellular acidity‑induced expression of Kallikrein‑related peptidases 7 and 8 is involved in increased invasiveness of gastric cancer cells.4
306448452019Crystal structures of the complex of a kallikrein inhibitor from Bauhinia bauhinioides with trypsin and modeling of kallikrein complexes.2
307051232019Integration of Two In-depth Quantitative Proteomics Approaches Determines the Kallikrein-related Peptidase 7 (KLK7) Degradome in Ovarian Cancer Cell Secretome.11
306448452019Crystal structures of the complex of a kallikrein inhibitor from Bauhinia bauhinioides with trypsin and modeling of kallikrein complexes.2

Citation

Ying Dong ; John Lai ; Judith A Clements

KLK7 (kallikrein-related peptidase 7)

Atlas Genet Cytogenet Oncol Haematol. 2009-05-01

Online version: http://atlasgeneticsoncology.org/gene/41087/haematological-explorer/gene-fusions/?id=41087