Alternative titles; symbols
HGNC Approved Gene Symbol: KLK6
Cytogenetic location: 19q13.41 Genomic coordinates (GRCh38) : 19:50,958,631-50,969,591 (from NCBI)
Anisowicz et al. (1996) used differential display PCR to identify a novel gene that was expressed in a primary breast cancer cell line, but not in the corresponding metastatic cell lines from the same patient. They cloned the full-length cDNA, which encoded a postulated protein of 244 amino acids that they termed 'protease M.' The protein sequence contained a serine protease domain and had high homology to the kallikreins (KLK1; 147910 and KLK2; 147960), trypsin-1 (PRSS1; 276000), and prostate-specific antigen (PSA; 176820). Northern blot analysis revealed that the PRSS9 mRNA was expressed in several primary tumors and cell lines from mammary, prostate, and ovarian cancers, but was not detected in any metastases of these cancers. Among normal tissues, a 1.7-kb message was detected in brain and kidney and a 1.2-kb message was detected in pancreas.
Little et al. (1997) cloned the PRSS9 cDNA, which they termed 'zyme,' using PCR of Alzheimer disease brain tissue. When zyme cDNA was coexpressed with the Alzheimer amyloid precursor protein (APP; 104760), amyloidogenic fragments were detected. Southern blot analysis failed to show definitive PRSS9 homologs in several other mammalian species, suggesting that zyme may have species specificity. Yamashiro et al. (1997) cloned a cDNA encoding PRSS9, which they called 'neurosin,' from a cDNA library prepared from a colon adenocarcinoma cell line.
Using RT-PCR, Gan et al. (2000) detected KLK6 expression in most of the 35 adult and fetal tissues examined.
Accumulation of insoluble alpha-synuclein (163890) aggregates in the brain is characteristic of Parkinson disease (PD; 168600), dementia with Lewy bodies (DLB; 127750), and multiple system atrophy. Iwata et al. (2003) found that the serine protease neurosin (kallikrein-6) degraded alpha-synuclein and colocalized with pathologic inclusions such as Lewy bodies and glial cytoplasmic inclusions. In cell lysates, neurosin prevented alpha-synuclein polymerization by reducing the amount of monomer and also by generating fragmented alpha-synucleins that themselves inhibited the polymerization. Upon cellular stress, neurosin was released from mitochondria to the cytosol, which resulted in the increase of degraded alpha-synuclein species. Downregulation of neurosin caused accumulation of alpha-synuclein within cultured cells. The authors concluded that neurosin may play a significant role in physiologic alpha-synuclein degradation and also in the pathogenesis of synucleinopathies.
Elliott et al. (2006) determined that the KLK6 gene contains 7 exons, the first 2 of which are noncoding.
Anisowicz et al. (1996) used fluorescence in situ hybridization (FISH) to localize the PRSS9 gene to human chromosome 19q13.3 and noted that the kallikreins and PSA are also localized to that region. Little et al. (1997) determined the same localization using cell hybrid panels and FISH. They pointed out that this region shows genetic linkage with late onset familial Alzheimer's disease (AD2; 104310).
By genomic sequence analysis, Gan et al. (2000) localized the KLK6 gene within the KLK gene cluster on chromosome 19q13. This cluster includes 13 KLK genes and 5 pseudogenes.
Anisowicz, A., Sotiropoulou, G., Stenman, G., Mok, S. C., Sager, R. A novel protease homolog differentially expressed in breast and ovarian cancer. Molec. Med. 2: 624-636, 1996. [PubMed: 8898378]
Elliott, M. B., Irwin, D. M., Diamandis, E. P. In silico identification and Bayesian phylogenetic analysis of multiple new mammalian kallikrein gene families. Genomics 88: 591-599, 2006. [PubMed: 16829021] [Full Text: https://doi.org/10.1016/j.ygeno.2006.06.001]
Gan, L., Lee, I., Smith, R., Argonza-Barrett, R., Lei, H., McCuaig, J., Moss, P., Paeper, B., Wang, K. Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region. Gene 257: 119-130, 2000. [PubMed: 11054574] [Full Text: https://doi.org/10.1016/s0378-1119(00)00382-6]
Iwata, A., Maruyama, M., Akagi, T., Hashikawa, T., Kanazawa, I., Tsuji, S., Nukina, N. Alpha-synuclein degradation by serine protease neurosin: implication for pathogenesis of synucleinopathies. Hum. Molec. Genet. 12: 2625-2635, 2003. [PubMed: 12928483] [Full Text: https://doi.org/10.1093/hmg/ddg283]
Little, S. P., Dixon, E. P., Norris, F., Buckley, W., Becker, G. W., Johnson, M., Dobbins, J. R., Wyrick, T., Miller, J. R., MacKellar, W., Hepburn, D., Corvalan, J., McClure, D., Liu, X., Stephenson, D., Clemens, J., Johnstone, E. M. Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from Alzheimer's disease brain. J. Biol. Chem. 272: 25135-25142, 1997. [PubMed: 9312124] [Full Text: https://doi.org/10.1074/jbc.272.40.25135]
Yamashiro, K., Tsuruoka, N., Kodama, S., Tsujimoto, M., Yamamura, Y., Tanaka, T., Nakazato, H., Yamaguchi, N. Molecular cloning of a novel trypsin-like serine protease (neurosin) preferentially expressed in brain. Biochim. Biophys. Acta 1350: 11-14, 1997. [PubMed: 9003450] [Full Text: https://doi.org/10.1016/s0167-4781(96)00187-x]