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Gene Review

bli-4  -  Protein BLI-4

Caenorhabditis elegans

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Disease relevance of endoprotease


High impact information on endoprotease

  • We have determined the molecular lesions for three bli-4 alleles (h199, h1010, and q508) that result in developmental arrest during late embryogenesis [2].
  • In addition, deletion analysis of conserved sequences outside of coding regions, combined with phenotypic rescue experiments, identified regulatory elements that alter the expression of the bli-4 gene [3].
  • Substrate assays with fluorescent peptides show that O. volvulus blisterase requires a P4 arginine and a basic amino acid at P1 for cleavage [1].
  • We have cloned and expressed blisterase from the parasitic nematode Onchocerca volvulus, a major cause of blindness in Africa. The catalytic domain of the protease exhibits 84% identity with the corresponding domain of its closest homologue, C. elegans blisterase [1].
  • Immunofluorescence studies showed that SNX15 overexpression resulted in mislocalization of furin, the endoprotease responsible for cleavage of insulin and hepatocyte growth factor receptors [4].

Biological context of endoprotease

  • The lesions reside within the first 12 exons that are shared by all of the bli-4/kpc-4 gene products, with the majority of mutations clustered within the protease domain [5].
  • We report the identification of 11 new alleles of bli-4, all early larval lethals, including an allele induced by transposon mutagenesis [6].
  • Lethal mutations in the 0.5 map unit region between dpy-5 and bli-4 on chromosome I in Caenorhabditis elegans were serially rescued using cosmid-containing transgenic strains [7].

Anatomical context of endoprotease

  • PC4, however, may represent a candidate for a precursor-processing endoprotease that is specifically expressed in the testicular germ cells [8].

Associations of endoprotease with chemical compounds


Other interactions of endoprotease


  1. Cloning and biochemical characterization of blisterase, a subtilisin-like convertase from the filarial parasite, Onchocerca volvulus. Poole, C.B., Jin, J., McReynolds, L.A. J. Biol. Chem. (2003) [Pubmed]
  2. The bli-4 locus of Caenorhabditis elegans encodes structurally distinct kex2/subtilisin-like endoproteases essential for early development and adult morphology. Thacker, C., Peters, K., Srayko, M., Rose, A.M. Genes Dev. (1995) [Pubmed]
  3. Functional genomics in Caenorhabditis elegans: An approach involving comparisons of sequences from related nematodes. Thacker, C., Marra, M.A., Jones, A., Baillie, D.L., Rose, A.M. Genome Res. (1999) [Pubmed]
  4. Identification and characterization of SNX15, a novel sorting nexin involved in protein trafficking. Phillips, S.A., Barr, V.A., Haft, D.H., Taylor, S.I., Haft, C.R. J. Biol. Chem. (2001) [Pubmed]
  5. Mutational analysis of bli-4/kpc-4 reveals critical residues required for proprotein convertase function in C. elegans. Thacker, C., Srayko, M., Rose, A.M. Gene (2000) [Pubmed]
  6. Mutations in the bli-4 (I) locus of Caenorhabditis elegans disrupt both adult cuticle and early larval development. Peters, K., McDowall, J., Rose, A.M. Genetics (1991) [Pubmed]
  7. Alignment of the genetic and physical maps in the dpy-5 bli-4 (I) region of C. elegans by the serial cosmid rescue of lethal mutations. McDowall, J.S., Rose, A. Mol. Gen. Genet. (1997) [Pubmed]
  8. Structure and function of eukaryotic proprotein processing enzymes of the subtilisin family of serine proteases. Van de Ven, W.J., Roebroek, A.J., Van Duijnhoven, H.L. Critical reviews in oncogenesis. (1993) [Pubmed]
  9. Isolation of a cDNA encoding a Kex2-like endoprotease with homology to furin from the nematode Caenorhabditis elegans. Gómez-Saladín, E., Luebke, A.E., Wilson, D.L., Dickerson, I.M. DNA Cell Biol. (1997) [Pubmed]
  10. Caenorhabditis elegans dpy-5 is a cuticle procollagen processed by a proprotein convertase. Thacker, C., Sheps, J.A., Rose, A.M. Cell. Mol. Life Sci. (2006) [Pubmed]
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