Details for: KLK7

Gene ID: 5650

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: KLK7

Ensembl ID: ENSG00000169035

Description: kallikrein related peptidase 7

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • stem cell CL0000034
    CSI 4.18
    rCSI 4.03%
    PRS 97.78
  • epithelial cell CL0000066
    CSI 3.27
    rCSI 5.03%
    PRS 92.83
  • keratinocyte CL0000312
    CSI 3.13
    rCSI 2.63%
    PRS 97.55
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.72
    rCSI 2.62%
    PRS 97.84
  • squamous epithelial cell CL0000076
    CSI 2.48
    rCSI 5.89%
    PRS 95.51
  • basal cell CL0000646
    CSI 1.85
    rCSI 2.47%
    PRS 97.19
  • epithelial cell of esophagus CL0002252
    CSI 0.56
    rCSI 5.5%
    PRS 95.95

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [KLK7](/details-gene/5650) (kallikrein related peptidase 7), also known as stratum corneum chymotryptic enzyme (SCCE), is a protein-coding gene located on chromosome 19q13.41. It encodes a secreted serine protease that is a member of the human tissue kallikrein family ([Link](https://doi.org/10.1016/s0378-1119(00)00280-8)). The primary function of [KLK7](/details-gene/5650) involves proteolysis, particularly in the degradation of the extracellular matrix and the regulation of epidermal homeostasis. Expression data highlight its profound significance in epithelial tissues, with particularly high expression in [keratinocytes](/details-cell/CL0000312) and other [squamous epithelial cells](/details-cell/CL0000076). Its enzymatic activity is crucial for the process of skin desquamation (shedding), and dysregulation of its function has been implicated in inflammatory skin diseases ([Link](https://doi.org/10.1046/j.0022-202x.2001.01684.x)). ## Cellular Roles and Expression Landscape The expression profile of [KLK7](/details-gene/5650) underscores its specialized role in epithelial biology. **Overall**, the gene shows its highest significance in cell types responsible for forming barrier tissues. It is a key marker for [stem cells](/details-cell/CL0000034) (CSI: 4.18), general [epithelial cells](/details-cell/CL0000066) (CSI: 3.27), and specifically [keratinocytes](/details-cell/CL0000312) (CSI: 3.13), the primary cell type of the epidermis. This is consistent with its initial characterization as a skin-specific protease involved in the shedding of the stratum corneum ([Link](https://doi.org/10.1016/s0021-9258(17)32185-3)). The gene's importance extends to other stratified epithelia, as evidenced by its high significance in [squamous epithelial cells](/details-cell/CL0000076) (CSI: 2.48) and [epithelial cells of the esophagus](/details-cell/CL0002252) (CSI: 0.56). Interestingly, it is also a significant marker in [fallopian tube secretory epithelial cells](/details-cell/CL4030006) (CSI: 2.72), suggesting a broader role in the turnover and maintenance of mucosal and secretory epithelial layers beyond the skin. The collective expression pattern points to [KLK7](/details-gene/5650) as a fundamental enzymatic component of tissues that require controlled cell shedding and extracellular matrix remodeling. ## Pathways and Molecular Function Functionally, [KLK7](/details-gene/5650) is annotated as a [serine-type endopeptidase](/details-go/GO:0004252) with chymotryptic specificity ([Link](https://doi.org/10.1006/bbrc.1995.1853)). Its molecular activity is central to the biological process of [proteolysis](/details-go/GO:0006508). This enzymatic function is deployed in several key physiological contexts, most notably [epidermis development](/details-go/GO:0008544) and the [degradation of the extracellular matrix](/details-pathway/R-HSA-1474228). Its role in the skin is well-defined by its participation in the [differentiation of keratinocytes in interfollicular epidermis](/details-pathway/R-HSA-9725554). As a secreted enzyme found in the [extracellular space](/details-go/GO:0005615) and within the [cornified envelope](/details-go/GO:0001533), [KLK7](/details-gene/5650) degrades proteins like desmocollin-1 and corneodesmosin, which are key components of the corneodesmosomes that hold skin cells together. This controlled degradation is essential for desquamation. Beyond the skin, its involvement in broader [extracellular matrix organization](/details-pathway/R-HSA-1474244) pathways suggests a role in tissue remodeling in other contexts. Additionally, it is implicated in the [positive regulation of antibacterial peptide production](/details-go/GO:0002803), pointing to a potential contribution to innate skin immunity. ## Research Directions The well-defined role of [KLK7](/details-gene/5650) in skin homeostasis and its dysregulation in disease present several avenues for future research. Its overexpression is known to cause excessive desquamation and barrier defects, leading to inflammatory conditions like chronic itchy dermatitis ([Link](https://doi.org/10.1046/j.0022-202x.2001.01684.x)). Furthermore, the identification of specific splice variants in epithelial ovarian cancer suggests its potential as a biomarker in malignancy ([Link](https://pubmed.ncbi.nlm.nih.gov/12738725)). Based on the available data, several testable hypotheses can be proposed: 1. Inhibition of [KLK7](/details-gene/5650) protease activity via topical small-molecule inhibitors will restore skin barrier integrity and reduce inflammation in atopic dermatitis by preventing the premature breakdown of corneodesmosomes and limiting the generation of pro-inflammatory signals. 2. The high expression of [KLK7](/details-gene/5650) in [fallopian tube secretory epithelial cells](/details-cell/CL4030006) suggests its activity is critical for reproductive processes, such as embryo implantation or gamete transport. Its dysregulation may therefore contribute to certain forms of female infertility. 3. Given its function in ECM degradation, tumor-specific splice variants of [KLK7](/details-gene/5650) in ovarian cancer actively contribute to tumor cell invasion and metastasis by remodeling the peritoneal extracellular matrix, creating a pathway for cancer cell dissemination. To test the first hypothesis regarding atopic dermatitis, a compelling experiment could be designed. A murine model of atopic dermatitis (e.g., MC903-induced or filaggrin-deficient) could be treated with a highly specific topical inhibitor of [KLK7](/details-gene/5650). The therapeutic effect would be evaluated by measuring key parameters of skin barrier function, such as transepidermal water loss (TEWL), alongside histological assessment of epidermal structure and immune cell infiltration. Furthermore, proteomic analysis of skin samples could be used to confirm that the inhibitor prevents the degradation of specific [KLK7](/details-gene/5650) substrates like desmocollin-1. Given that [KLK7](/details-gene/5650) is a secreted protease with overactivity linked to pathology, it represents a promising therapeutic target for **inhibition**. Its extracellular location makes it readily accessible to topical or systemic drugs. The development of specific inhibitors could be beneficial for inflammatory skin diseases characterized by a compromised skin barrier, such as Netherton syndrome and atopic dermatitis. In the context of cancer, its role in ECM degradation makes it a potential target to prevent metastasis, although the risk of off-target effects would need to be carefully evaluated.

Genular Protein ID: 4160931996

Symbol: KLK7_HUMAN

Name: Kallikrein-7

UniProtKB Accession Codes:

P49862 A8K0U5 Q8N5N9 Q8NFV7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 2 EMBL 10 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 13 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 12 PDBsum 12 PIR 1 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 2 RefSeq 4 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 8034709

Title: Cloning, expression, and characterization of stratum corneum chymotryptic enzyme. A skin-specific human serine proteinase.

PubMed ID: 8034709

DOI: 10.1016/s0021-9258(17)32185-3

PubMed ID: 10974542

Title: 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.

PubMed ID: 10974542

DOI: 10.1016/s0378-1119(00)00280-8

PubMed ID: 11054574

Title: Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region.

PubMed ID: 11054574

DOI: 10.1016/s0378-1119(00)00382-6

PubMed ID: 11874483

Title: Epidermal overexpression of stratum corneum chymotryptic enzyme in mice: a model for chronic itchy dermatitis.

PubMed ID: 11874483

DOI: 10.1046/j.0022-202x.2001.01684.x

PubMed ID: 12738725

Title: Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers.

PubMed ID: 12738725

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 7794273

Title: Primary substrate specificity of recombinant human stratum corneum chymotryptic enzyme.

PubMed ID: 7794273

DOI: 10.1006/bbrc.1995.1853

PubMed ID: 23370777

Title: Vaspin inhibits kallikrein 7 by serpin mechanism.

PubMed ID: 23370777

DOI: 10.1007/s00018-013-1258-8

PubMed ID: 17909180

Title: Chymotryptic specificity determinants in the 1.0 A structure of the zinc-inhibited human tissue kallikrein 7.

PubMed ID: 17909180

DOI: 10.1073/pnas.0707811104

PubMed ID: 18329042

Title: Crystal 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).

PubMed ID: 18329042

DOI: 10.1016/j.jmb.2008.01.089

Sequence Information:

  • Length: 253
  • Mass: 27525
  • Checksum: 2D68B6B15A76A668
  • Sequence:
    • MARSLLLPLQ ILLLSLALET AGEEAQGDKI IDGAPCARGS HPWQVALLSG NQLHCGGVLV 
NERWVLTAAH CKMNEYTVHL GSDTLGDRRA QRIKASKSFR HPGYSTQTHV NDLMLVKLNS 
QARLSSMVKK VRLPSRCEPP GTTCTVSGWG TTTSPDVTFP SDLMCVDVKL ISPQDCTKVY 
KDLLENSMLC AGIPDSKKNA CNGDSGGPLV CRGTLQGLVS WGTFPCGQPN DPGVYTQVCK 
FTKWINDTMK KHR

Genular Protein ID: 3227403073

Symbol: B4DHX9_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DHX9

Database IDs:

ARBA 1 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 3 Gene3D 1 InterPro 5 KEGG 1 MEROPS 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 3 PeptideAtlas 1 Pfam 1 ProteomicsDB 1 RefSeq 2 SMART 1 SUPFAM 1

Sequence Information:

  • Length: 140
  • Mass: 15217
  • Checksum: 2DD42803DA58FEA7
  • Sequence:
    • MLVKLNSQAR LSSMVKKVRL PSRCEPPGTT CTVSGWGTTT SPDVTFPSDL MCVDVKLISP 
QDCTKVYKDL LENSMLCAGI PDSKKNACNG DSGGPLVCRG TLQGLVSWGT FPCGQPNDPG 
VYTQVCKFTK WINDTMKKHR