PROSITE documentation PDOC51829 [for PROSITE entry PS51829]P/Homo B domain profile
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.
Last update:February 2017 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Lipkind G.M. Zhou A. Steiner D.F. |
| Title | A model for the structure of the P domains in the subtilisin-like prohormone convertases. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 95:7310-7315(1998). | |
| PubMed ID | 9636145 |
| 2 | Authors | Zhou A. Martin S. Lipkind G. LaMendola J. Steiner D.F. |
| Title | Regulatory roles of the P domain of the subtilisin-like prohormone convertases. | |
| Source | J. Biol. Chem. 273:11107-11114(1998). | |
| PubMed ID | 9556596 |
| 3 | Authors | Henrich S. Cameron A. Bourenkov G.P. Kiefersauer R. Huber R. Lindberg I. Bode W. Than M.E. |
| Title | The crystal structure of the proprotein processing proteinase furin explains its stringent specificity. | |
| Source | Nat. Struct. Biol. 10:520-526(2003). | |
| PubMed ID | 12794637 | |
| DOI | 10.1038/nsb941 |
| 4 | Authors | Kobayashi H. Utsunomiya H. Yamanaka H. Sei Y. Katunuma N. Okamoto K. Tsuge H. |
| Title | Structural basis for the kexin-like serine protease from Aeromonas sobria as sepsis-causing factor. | |
| Source | J. Biol. Chem. 284:27655-27663(2009). | |
| PubMed ID | 19654332 | |
| DOI | 10.1074/jbc.M109.006114 |
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