Expanding the complexity of the human degradome: polyserases and their tandem serine protease domains.
The large and growing number of protease genes identified in the human genome, more than 560, reflects the complexity and relevance of these enzymes in multiple biological processes. As part of our studies on the human degradome--which is defined as the complete set of human protease genes--we have recently identified and cloned three complex polyserine proteases called polyserases. Polyserase-1 is a member of the type-II transmembrane serine protease (TTSP) family of proteolytic enzymes that undergoes a series of post-translational processing events to generate three distinct and independent serine protease domains called serase-1, -2, and -3. Polyserase-2 is a secreted enzyme that also possesses three serine protease domains, but they remain as an integral part of the initial protein product. Finally, polyserase-3 is also a secreted enzyme that contains two serine protease domains embedded in the same polypeptide chain. Despite all three human polyserases share this complex molecular design characterized by the presence of several catalytic domains in their structure, they also exhibit distinctive features including unique expression patterns and different enzymatic properties. At present, the putative functional advantages derived from the complex structural organization of polyserases remain unknown, but the widespread occurrence of these enzymes in mammalian degradomes provides additional evidence about the complexity of proteolytic systems in these organisms.
Cal
Santiago
S
Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Asturias, Spain. santical@uniovi.es
Moncada-Pazos
Angela
A
Lopez-Otin
Carlos
C
D000818:Animals; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*
D008565:Membrane Proteins; D012697:Serine Endopeptidases