In eukaryotes, many essential secreted proteins and peptide hormones are excised from larger precursors by members of a class of calcium-dependent endoproteinases, the prohormone-proprotein convertases (PCs).The P (known as such because it is essential for proteolytic activity), or Homo B, domain of ~150 residues is a distinctive characteristic of members of the proprotein convertase family. The P/Homo B domain appears to be necessary to both fold and maintain the subtilisin-like active catalytic module and to regulate its specialized features of calcium and more acidic pH dependence [1,2,3,4].

The core of the P/Homo B domain consists of a jelly roll-like fold with eight β-strands (see <PDB:3HJR>). Nonbonded interactions between the catalytic and P/Homo B domains provide additional structural stabilization of the catalytic domains, which alone appear to be thermodynamically unstable [3,4].

Some proteins known to contain a P/Homo B domain are listed below:

• Fungal kexin-like protein, a component of the subtilase family involved in the processing of proproteins to their active forms.
• Mammalian furin (also called SPC1/PACE; EC 3.4.21.75), likely to represent the ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RX(K/R)R consensus motif.
• Mammalian neuroendocrine convertase 1 and 2 (NEC1 and NEC2), involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues.
• Mammalina PACE4, likely to represent an endoprotease activity within the constitutive secretory pathway, with unique restricted distribution in both neuroendocrine and non-neuroendocrine tissues and capable of cleavage at the RX(K/R)R consensus motif.
• Mammalian PC4, proprotein convertase involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues.
• Mammalian PC5/PC6, plays an essential role in pregnancy establishment by proteolytic activation of a number of important factors such as BMP2, CALD1 and α-integrins.
• Mammalian PC7/PC8/LPC/SPC7, likely to represent a ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RXXX[KR]R consensus motif.
• Aeromonas salmonicida microbial serine proteinase (EC:3.4.21.-) (AspA).

The profile we developed covers the entire P/Homo B domain.