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Pcsk4  -  proprotein convertase subtilisin/kexin type 4

Mus musculus

Synonyms: AI647044, KEX2-like endoprotease 3, L21221, NEC 3, NEC3, ...
 
 
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Disease relevance of Pcsk4

  • They also expressed tetanus toxin receptors, PC4, M1 and Thy-1 antigens [1].
  • PC4 and PC13 (20 mg kg-1, i.p.) partly reversed hypothermia induced by low dose apomorphine (5 mg kg-1, s.c.) but were less effective for higher doses of apomorphine (16 mg kg-1, s.c.). At 200 mg kg-1, intraperitoneal PC13 enhanced the toxic effects of yohimbine (30 mg kg-1, s.c.), while PC4 was inactive [2].
 

Psychiatry related information on Pcsk4

  • Only at intraperitoneal doses of 100 mg kg-1 did PC4 or PC13 significantly decrease locomotor activity [2].
 

High impact information on Pcsk4

  • In vitro, the fertilizing ability of Pcsk4 null spermatozoa was also found to be significantly reduced [3].
  • In an effort to elucidate this function, we have disrupted its locus (Pcsk4) by homologous recombination in embryonic stem cells and have produced mice carrying the mutation [3].
  • Impaired fertility in mice deficient for the testicular germ-cell protease PC4 [3].
  • PC4 is a member of the proprotein convertase family of serine proteases implicated in the processing of a variety of polypeptides including prohormones, proneuropeptides, and cell surface proteins [3].
  • These results suggest that PC4 in the male may be important for achieving fertilization and for supporting early embryonic development in mice [3].
 

Biological context of Pcsk4

  • These data suggest that PC4 represents a prime candidate for a precursor-processing endoprotease in the testicular germ cells and that its gene expression is regulated during spermatogenesis [4].
  • The multiple forms of PC4 mRNA can all be explained by alternate splicing of primary transcripts of a single gene [5].
  • The genes for three subtilisin/kexin-like proprotein convertases, PC4, PC5, and PACE4, were mapped in the mouse by RFLP analysis of a DNA panel from a (C57BL/6JEi x SPRET/Ei)F1 x SPRET/Ei backcross [6].
  • These observations suggest that, within testis, PC4 is involved in processing of peptide precursors such as proenkephalin and may play a role in regulation of sperm maturation, while furin may serve as a more general processing endoprotease [7].
  • Recent studies using PC4-transgenic mice revealed that male PC4-null mice exhibited severely impaired fertility, although spermatogenesis appeared to be normal [8].
 

Anatomical context of Pcsk4

  • Northern blot analysis indicated that the PC4 mRNA was detectable only in the testes after the 20th day of postnatal development [4].
  • Furin transcript was detected in both germ and somatic cells, while PC4 transcript was found only in round spermatids [7].
  • In rodents, PC4 transcripts have been detected in spermatocytes and round spermatids exclusively, suggesting a reproductive function for this enzyme [3].
  • However, whether PC4 is the sole endoprotease for the PACAP precursor in the gonads remains unknown [8].
  • In the adult retina, only PC4 antigen is detectably expressed and is localized in the inner segments of photoreceptor cells [9].
 

Associations of Pcsk4 with chemical compounds

  • Proprotein convertase 4 (PC4) is a mammalian secretory serine endoproteinase similar to the yeast KEX2 gene product and specifically expressed in testicular germs cells [5].
  • The study concludes that the most probable sequence motif for recognition by PC4 is KXKXXR or KXXR, where X is any amino acid other than cysteine and that it prefers proline at P3, P5 and/or P2' positions [10].
  • The potential antidepressant effects of two pyridazine derivatives, 5-benzyl 6-methyl 2-[4-(3-trifluoro-methyl phenyl) piperazin-1-yl] methylpyridazin-3-one (PC4) and 5-benzyl 6-methyl 2-[4-(3-chlorophenyl) piperazin-1-yl] methylpyridazin-3-one (PC13), were evaluated using classical psychopharmacological tests in mice [2].
 

Other interactions of Pcsk4

  • PC4 is expressed only in the testis and ovary, where neither PC1 nor PC2 is expressed [8].
  • PC4 antigen is normally detectable in the inner segments of photoreceptor cells, even when these have started to degenerate in the case of Purkinje cell degeneration [9].
 

Analytical, diagnostic and therapeutic context of Pcsk4

References

  1. Maintenance of immunocytologically identified Purkinje cells from mouse cerebellum in monolayer culture. Weber, A., Schachner, M. Brain Res. (1984) [Pubmed]
  2. Behavioural profile of two potential antidepressant pyridazine derivatives including arylpiperazinyl moieties in their structure, in mice. Rubat, C., Coudert, P., Bastide, P., Tronche, P. J. Pharm. Pharmacol. (1995) [Pubmed]
  3. Impaired fertility in mice deficient for the testicular germ-cell protease PC4. Mbikay, M., Tadros, H., Ishida, N., Lerner, C.P., De Lamirande, E., Chen, A., El-Alfy, M., Clermont, Y., Seidah, N.G., Chrétien, M., Gagnon, C., Simpson, E.M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  4. Identification of the fourth member of the mammalian endoprotease family homologous to the yeast Kex2 protease. Its testis-specific expression. Nakayama, K., Kim, W.S., Torii, S., Hosaka, M., Nakagawa, T., Ikemizu, J., Baba, T., Murakami, K. J. Biol. Chem. (1992) [Pubmed]
  5. Structure of the gene for the testis-specific proprotein convertase 4 and of its alternate messenger RNA isoforms. Mbikay, M., Raffin-Sanson, M.L., Tadros, H., Sirois, F., Seidah, N.G., Chretien, M. Genomics (1994) [Pubmed]
  6. Chromosomal assignment of the genes for proprotein convertases PC4, PC5, and PACE 4 in mouse and human. Mbikay, M., Seidah, N.G., Chrétien, M., Simpson, E.M. Genomics (1995) [Pubmed]
  7. Localization of Kex2-like processing endoproteases, furin and PC4, within mouse testis by in situ hybridization. Torii, S., Yamagishi, T., Murakami, K., Nakayama, K. FEBS Lett. (1993) [Pubmed]
  8. Pituitary adenylate cyclase-activating polypeptide precursor is processed solely by prohormone convertase 4 in the gonads. Li, M., Mbikay, M., Arimura, A. Endocrinology (2000) [Pubmed]
  9. Development and expression of cytoplasmic antigens in Purkinje cells recognized by monoclonal antibodies. Studies in neurologically mutant mice. Weber, A., Schachner, M. Cell Tissue Res. (1982) [Pubmed]
  10. In vitro elucidation of substrate specificity and bioassay of proprotein convertase 4 using intramolecularly quenched fluorogenic peptides. Basak, S., Chrétien, M., Mbikay, M., Basak, A. Biochem. J. (2004) [Pubmed]
 
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