Alternative titles; symbols
HGNC Approved Gene Symbol: PRSS8
Cytogenetic location: 16p11.2 Genomic coordinates (GRCh38): 16:31,131,433-31,135,727 (from NCBI)
Human seminal fluid contains a variety of proteolytic enzymes, including prostate-specific antigen (176820) and acrosin (102480). These enzymes are involved in the postejaculatory hydrolysis of proteins and in semen coagulation and liquefaction. Yu et al. (1995) obtained partial amino acid sequence of a 40-kD protein isolated from seminal fluid originally by Yu et al. (1994). Yu et al. (1995) designed degenerate primers based on the amino acid sequence and used to screen a human prostate cDNA library by PCR. The 3-prime end of the cDNA was obtained by the RACE (rapid amplification of cDNA ends) method. A 1.8-kb cDNA sequence was assembled encoding a predicted protein of 343 amino acids which contains a 32-amino acid signal peptide. The protein, designated serine protease-8 (PRSS8), was called prostasin by the authors. The precursor, proprostasin, is cleaved between residues 12 and 13 to produce a 12-amino acid light chain and a 299-amino acid heavy chain which are associated through a disulfide bond. The predicted amino acid sequence is between 34 and 42% identical to human acrosin, plasma kallikrein (229000), and hepsin (142440). The deduced protein has a hydrophobic domain at the C terminus, indicating to the authors that it may be membrane anchored. The authors showed that the hydrophobic region is cleaved between residues 290 and 291 during secretion. Expression levels of the prostasin mRNA were assayed by Southern blots of RT-PCR products. Expression was noted in a wide variety of tissues. In the prostate gland, expression was localized to the epithelial cells.
Donaldson et al. (2002) found evidence for the regulation of the epithelial sodium channel (ENaC; see 600228) by prostasin. They cloned prostasin in their search for a human homolog of a channel-activating protease (xCAP1) of Xenopus kidney epithelial cells. They determined that prostasin shares 41% sequence identity with the Xenopus protease and 76% identity with the mouse homolog.
Donaldson et al. (2002) found that coexpression of prostasin with either Xenopus or rat ENaC in Xenopus oocytes resulted in a 60 to 80% increase in amiloride-sensitive sodium currents, and that the addition of aprotinin, a serine protease inhibitor, completely prevented this activation. By in situ hybridization, they determined that both prostasin and TMPRSS2 (602060) show a tissue distribution in human airway epithelia consistent with a role in ENaC regulation. Both had strong expression in superficial epithelial cells lining the nose, trachea, and distal airways, and both were expressed at the alveolar level, most notably at alveolar junctions in a distribution characteristic of type II pneumocytes. Expression was also pronounced in submucosal glands associated with nasal, tracheal, and bronchial tissues. Donaldson et al. (2002) suggested that prostasin is likely to be the more physiologically relevant protease.
Yu et al. (1996) isolated and characterized the full-length PRSS8 gene. They found that it consists of 6 exons and 5 introns. The authors characterized the 5-prime flanking region of the gene and found a number of potential regulatory elements, including an AP2 site, 2 erythroid-specific promoter elements, and a sterol regulatory element, although no TATA box was found. In addition, there were a variant GC box and a variant AP1 site in the promoter region. Yu et al. (1996) found that PRSS8 is a single-copy gene.
By fluorescence in situ hybridization, Yu et al. (1996) mapped the PRSS8 gene to chromosome 16p11.2.
Donaldson, S. H., Hirsh, A., Li, D. C., Holloway, G., Chao, J., Boucher, R. C., Gabriel, S. E. Regulation of the epithelial sodium channel by serine proteases in human airways. J. Biol. Chem. 277: 8338-8345, 2002. [PubMed: 11756432] [Full Text: https://doi.org/10.1074/jbc.M105044200]
Yu, J. X., Chao, L., Chao, J. Prostasin is a novel human serine proteinase from seminal fluid: purification, tissue distribution, and localization in prostate gland. J. Biol. Chem. 269: 18843-18848, 1994. [PubMed: 8034638]
Yu, J. X., Chao, L., Chao, J. Molecular cloning, tissue-specific expression, and cellular localization of human prostasin mRNA. J. Biol. Chem. 270: 13483-13489, 1995. [PubMed: 7768952] [Full Text: https://doi.org/10.1074/jbc.270.22.13483]
Yu, J. X., Chao, L., Ward, D. C., Chao, J. Structure and chromosomal localization of the human prostasin (PRSS8) gene. Genomics 32: 334-340, 1996. [PubMed: 8838796] [Full Text: https://doi.org/10.1006/geno.1996.0127]