InterPro : IPR009020

Name  Proteinase inhibitor, propeptide Short Name  Prot_inh_propept
Type  Domain Description  Proteinase propeptide inhibitors (sometimes refered to as activation peptides) are responsible for the modulation of folding and activity of the pro-enzyme or zymogen. The pro-segment docks into the enzyme moiety shielding the substrate binding site, thereby promoting inhibition of the enzyme. Several such propeptides share a similar topology [], despite often low sequence identities []. The propeptide region has an open-sandwich antiparallel-alpha/antiparallel-beta fold, with two alpha-helices and four beta-strands with a (beta/alpha/beta)x2 topology.This propeptide inhibitor domain occurs widely across all forms of life, and is found associated with the N-terminal region of a number of MEROPS peptidase families: Metallopeptidase family M14A (carboxypeptidases). These include carboxypeptidase A1, A2 [], A3, A4, A5, A6, U, insect gut carboxypeptidase and B [].Serine peptidase family S8A (subtilisin family). Members of this group belong to MEROPS inhibitor family I9, clan I-.Serine peptidase family S8B (kexin family). The calcium-dependent serine peptidases belonging to MEROPS family S8B include the Kex2/subtilisin-like proprotein convertase (PC) family, which have been identified in all eukaryotes, these include furin, PC1/3, and PC2. The convertases are synthesised as an "inactive" precursor proteins or zymogens. Following the N-terminal signal peptide is the prodomain, consisting of between 80 to 115 residues; it is an integral part ofthe zymogen and acts as a steric chaperone to aid proper folding of the zymogen. An autocatalytic cleavage at the second dibasic site, R-X-K-R, liberates the prodomain, but which remains attached and acts to inhibit any further endopeptidase activity by binding to the catalytic domain. Inhibition is released when the maturing convertase is transported to the trans-Golgi network (TGN) where a decrease in pH causes a second autoproteolytic cleavage to occur at the first dibasic site within the prodomain fragment [].
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Sequence Features

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Proteins

InterPro protein domain ID --> Contigs

 

Other

3 Child Features

Id Name Short Name Type
IPR003146 Proteinase inhibitor, carboxypeptidase propeptide Prot_inh_M14A Domain
IPR015366 Peptidase S53, propeptide Peptidase_S53_propep Domain
IPR010259 Peptidase S8 propeptide/proteinase inhibitor I9 S8pro/Inhibitor_I9 Domain

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0 Found In

0 Parent Features

5 Publications

First Author Title Year Journal Volume Pages
Thacker C A look at the Caenorhabditis elegans Kex2/Subtilisin-like proprotein convertase family. 2000 Bioessays 22 545-53
García-Sáez I The three-dimensional structure of human procarboxypeptidase A2. Deciphering the basis of the inhibition, activation and intrinsic activity of the zymogen. 1997 EMBO J 16 6906-13
Barbosa Pereira PJ Human procarboxypeptidase B: three-dimensional structure and implications for thrombin-activatable fibrinolysis inhibitor (TAFI). 2002 J Mol Biol 321 537-47
Jain SC The crystal structure of an autoprocessed Ser221Cys-subtilisin E-propeptide complex at 2.0 A resolution. 1998 J Mol Biol 284 137-44
Tangrea MA Solution structure of the pro-hormone convertase 1 pro-domain from Mus musculus. 2002 J Mol Biol 320 801-12



To cite PlanMine, please refer to the following publication:

Rozanski, A., Moon, H., Brandl, H., Martín-Durán, J. M., Grohme, M., Hüttner, K., Bartscherer, K., Henry, I., & Rink, J. C.
PlanMine 3.0—improvements to a mineable resource of flatworm biology and biodiversity
Nucleic Acids Research, gky1070. doi:10.1093/nar/gky1070 (2018)