Domain

P domain (IPR002884)

Short name: P_dom

Domain relationships

None.

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 [PMID: 9636145, PMID: 9556596, PMID: 12794637, PMID: 19654332].

The core of the P/Homo B domain consists of a jelly roll-like fold with eight beta-strands. 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 [PMID: 12794637, PMID: 19654332].

Most of the PC family members contained the cognate integrin binding RGD sequence within the middle of the P domain [PMID: 10212221], which may be required for intracellular compartmentalization and maintenance of enzyme stability within the ER. The integrity of the RGD sequence of proprotein convertase PC1 is critical for its zymogen and C-terminal processing and for its cellular trafficking [PMID: 9307023, PMID: 10212221]. The carboxy-terminal tail provides uniqueness to each PC family member being the least conserved region of all convertases [PMID: 10842308].

GO terms

Biological Process

GO:0006508 proteolysis

Molecular Function

GO:0004252 serine-type endopeptidase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
Pfam
PROSITE profiles