KLK2 (Kallikrein Related Peptidase 2): A Prostate-Specific Biomarker and Signaling Modulator
Comprehensive genomic, proteomic, and clinical insights into KLK2, a key member of the kallikrein family with implications in prostate cancer diagnosis and therapy.
Gene Information Card
| Symbol | KLK2 |
|---|---|
| Full Name | Kallikrein Related Peptidase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 3817 ncbi.nlm.nih.gov/gene/3817 |
| Ensembl ID | ENSG00000167751 |
| UniProt ID | P20151 |
| OMIM ID | 147960 |
| HGNC ID | 6364 |
| Aliases | hK2, KLK2A, kallikrein 2, tissue kallikrein 2 |
Description
KLK2 encodes kallikrein-related peptidase 2 (hK2), a serine protease predominantly expressed in the prostate epithelium. It is a member of the kallikrein family, which includes prostate-specific antigen (PSA/KLK3). hK2 is involved in the cleavage of pro-PSA to active PSA and plays roles in semen liquefaction and extracellular matrix remodeling. Its expression is largely androgen-regulated, and it serves as a serum biomarker for prostate cancer, often used in combination with PSA for diagnostic and prognostic purposes. KLK2 has also been implicated in tumor progression and metastasis through modulation of growth factor signaling and angiogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate Cancer | Overexpression of KLK2 in prostate tissue leads to increased hK2 levels in serum; hK2 can activate pro-PSA and modulate tumor microenvironment via proteolysis of extracellular matrix components, promoting invasion and metastasis. | ClinVar, COSMIC, multiple studies |
| Benign Prostatic Hyperplasia (BPH) | Elevated KLK2 expression in hyperplastic prostate tissue contributes to increased serum hK2 levels, though to a lesser extent than in cancer; used in differential diagnosis. | ClinVar, literature |
| Prostatic Intraepithelial Neoplasia (PIN) | KLK2 expression is elevated in PIN lesions, suggesting early involvement in prostate carcinogenesis. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Prostate | High (nTPM ~ 5000) | High |
| Salivary Gland | Low (nTPM ~ 5) | Low |
| Breast | Low (nTPM ~ 1) | Low |
| Testis | Low (nTPM ~ 0.5) | Low |
| Other tissues | Not detected | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| LNCaP (prostate cancer) | High | Androgen-responsive; KLK2 expression is induced by androgens. |
| PC-3 (prostate cancer) | Low | Androgen-independent; low KLK2 expression. |
| DU145 (prostate cancer) | Low | Androgen-independent; low KLK2 expression. |
| 22Rv1 (prostate cancer) | Moderate | Androgen-responsive; moderate KLK2 expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.79G>A (p.Asp27Asn) | Missense | Rare (0.1% in population) | May affect protein stability or activity; clinical significance uncertain. |
| c.245C>T (p.Thr82Met) | Missense | Rare (0.05% in population) | Potential impact on substrate specificity; not well characterized. |
| c.356G>A (p.Arg119His) | Missense | Rare (0.02% in population) | Located in catalytic domain; may alter enzymatic activity. |
| c.457C>T (p.Arg153Cys) | Missense | Rare (0.01% in population) | Potential disulfide bond disruption; functional impact unknown. |
Mutation functional classification
Loss of Function (LOF)
No well-documented loss-of-function mutations in KLK2 have been reported. Given its role as a protease, complete loss may be compensated by other kallikreins.
Gain of Function (GOF)
Some missense variants may alter substrate specificity or activity, potentially enhancing proteolytic activity, but no definitive gain-of-function mutations have been established.
Dominant Negative (DN)
No evidence for dominant-negative effects; KLK2 functions as a secreted protease, and mutations are unlikely to exert dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • serine-type endopeptidase activity | • protein binding |
| • peptidase activity | • extracellular space |
| • proteolysis | • regulation of cell proliferation |
| • androgen receptor signaling pathway |
Pathways
• Kallikrein-kinin system
• Prostate cancer pathway
• Androgen receptor signaling
• Proteolytic processing of PSA
Protein Summary
Kallikrein-related peptidase 2 (hK2) is a 261-amino acid serine protease with a trypsin-like specificity. It is synthesized as a preproenzyme and processed to an active form. hK2 is primarily secreted by prostate epithelial cells and is present in seminal plasma. It plays a role in the cleavage of pro-PSA to active PSA, contributing to semen liquefaction. hK2 also degrades extracellular matrix components such as fibronectin and laminin, facilitating tumor invasion. Its expression is regulated by androgens via androgen response elements in the promoter. hK2 is a valuable biomarker for prostate cancer, and its measurement in serum improves the specificity of PSA testing. Additionally, hK2 has been explored as a target for immunotherapy and drug delivery.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLK2 Knockout HEK293 Cell Line | EDJ-KQ2036 | Human | 3817 | Details Get a Quote |
| KLK2 Knockout HeLa Cell Line | EDJ-KQ53742 | Human | 3817 | Details Get a Quote |
| KLK2 Knockout A-549 Cell Line | EDJ-KQ62218 | Human | 3817 | Details Get a Quote |
| KLK2 Knockout HCT 116 Cell Line | EDJ-KQ70703 | Human | 3817 | Details Get a Quote |
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