{PDOC51829}
{PS51829; P_HOMO_B}
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* P/Homo B domain profile *
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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
beta-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 alpha-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: February 2017 / First entry.

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

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