ZFIN ID: ZDB-PUB-081029-10
Identification of proSAAS homologs in lower vertebrates: conservation of hydrophobic helices and convertase-inhibiting sequences
Kudo, H., Liu, J., Jansen, E.J., Ozawa, A., Panula, P., Martens, G.J., and Lindberg, I.
Date: 2009
Source: Endocrinology   150(3): 1393-1399 (Journal)
Registered Authors: Kudo, Hisaaki, Panula, Pertti
Keywords: prohormone convertase, PC1/3, PC1, proSAAS, peptide hormone, Xenopus, zebrafish
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Conserved Sequence
  • Embryo, Nonmammalian
  • Enzyme Inhibitors/metabolism
  • Hydrophobic and Hydrophilic Interactions
  • Molecular Sequence Data
  • Neuroendocrine Cells/metabolism
  • Neurons/metabolism
  • Neuropeptides/chemistry*
  • Neuropeptides/genetics*
  • Neuropeptides/isolation & purification
  • Neuropeptides/metabolism
  • Phylogeny
  • Proprotein Convertases/antagonists & inhibitors*
  • Protein Structure, Secondary/genetics
  • Sequence Homology, Amino Acid*
  • Vertebrates/genetics*
  • Xenopus laevis/genetics
  • Zebrafish/genetics
PubMed: 18948394 Full text @ Endocrinology
The prohormone convertases PC1/3 and PC2 accomplish the major proteolytic cleavage events in neuroendocrine tissues; each of these convertases has a small associated binding protein which inhibits convertase action in the secretory pathway. The proSAAS protein binds to PC1/3, while the 7B2 protein binds to PC2. However, both convertase-binding proteins are more widely expressed than their cognate enzymes, suggesting that they may carry out other functions as well. All known mammalian proSAASes are over 85% conserved; thus identifying functionally important segments has been impossible. We here report the first identification of non-mammalian proSAAS molecules, from Xenopus and zebrafish (Danio rerio). While these two proteins show an overall amino acid sequence identity of only 29% and 30% with mouse proSAAS, two 14-16 residue hydrophobic segments (predicted to form alpha helices) and two 9-11 residue sequences containing basic convertase cleavage sites are highly conserved; these sequences may therefore be of functional importance. Confidence that these nonmammalian molecules represent authentic proSAAS is supported by the finding that both inhibit mouse PC1/3 with nanomolar inhibition constants; human furin was not inhibited. In vitro, the two proteins were cleaved by PC2 and furin to three or more peptide products. Both zebrafish and Xenopus proSAAS exhibited neural and endocrine distributions, as assessed by in situ and PCR experiments, respectively. In summary, the identification of proSAAS molecules in lower vertebrates provides clues as to functional regions within this widely-expressed neuroendocrine protein.