Home  |  Contact
PROSITE documentation PDOC51829 [for PROSITE entry PS51829]

P/Homo B domain profile





Description

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.

-------------------------------------------------------------------------------

Technical section

PROSITE method (with tools and information) covered by this documentation:

P_HOMO_B, PS51829; P/Homo B domain profile  (MATRIX)


References

1AuthorsLipkind G.M. Zhou A. Steiner D.F.
TitleA model for the structure of the P domains in the subtilisin-like prohormone convertases.
SourceProc. Natl. Acad. Sci. U.S.A. 95:7310-7315(1998).
PubMed ID9636145

2AuthorsZhou A. Martin S. Lipkind G. LaMendola J. Steiner D.F.
TitleRegulatory roles of the P domain of the subtilisin-like prohormone convertases.
SourceJ. Biol. Chem. 273:11107-11114(1998).
PubMed ID9556596

3AuthorsHenrich S. Cameron A. Bourenkov G.P. Kiefersauer R. Huber R. Lindberg I. Bode W. Than M.E.
TitleThe crystal structure of the proprotein processing proteinase furin explains its stringent specificity.
SourceNat. Struct. Biol. 10:520-526(2003).
PubMed ID12794637
DOI10.1038/nsb941

4AuthorsKobayashi H. Utsunomiya H. Yamanaka H. Sei Y. Katunuma N. Okamoto K. Tsuge H.
TitleStructural basis for the kexin-like serine protease from Aeromonas sobria as sepsis-causing factor.
SourceJ. Biol. Chem. 284:27655-27663(2009).
PubMed ID19654332
DOI10.1074/jbc.M109.006114



PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)