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Protease propeptides/inhibitors superfamily

SCOP classification
Root:   SCOP hierarchy in SUPERFAMILY [ 0] (11)
Class:   Alpha and beta proteins (a+b) [ 53931] (376)
Fold:   Ferredoxin-like [ 54861] (59)
Superfamily:   Protease propeptides/inhibitors [ 54897] (3)
Families:   Pancreatic carboxypeptidase, activation domain [ 54898] (2)
  Subtilase propeptides/inhibitors [ 54905] (3)
  Prohormone convertase 1 pro-domain [ 75431]

Superfamily statistics
Genomes (835) Uniprot 2018_03 genome PDB chains (SCOP 1.75)
Domains 5,713 22,481 16
Proteins 5,672 22,308 16

Functional annotation
General category Processes_IC
Detailed category Proteases

Function annotation of SCOP domain superfamilies

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEO levelAnnotation (direct or inherited)
Enzyme Commission (EC)Acting on peptide bonds (peptide hydrolases)0Least InformativeDirect
Enzyme Commission (EC)Serine endopeptidases0.0001429Moderately InformativeDirect
Enzyme Commission (EC)Dipeptidyl-peptidases and tripeptidyl-peptidases0.00002239InformativeDirect
Enzyme Commission (EC)Metallocarboxypeptidases0Highly InformativeDirect
Enzyme Commission (EC)Furin0.0000000000001568Highly InformativeDirect
Enzyme Commission (EC)Proprotein convertase 20.00000000008229Highly InformativeDirect
Enzyme Commission (EC)Proprotein convertase 10.000000001803Highly InformativeDirect

Document: EC annotation of SCOP domains

Worm Phenotype (WP)

(show details)
WP termFDR (all)SDWP levelAnnotation (direct or inherited)
Worm Phenotype (WP)larval lethal0Least InformativeDirect
Worm Phenotype (WP)larval development variant0Least InformativeDirect
Worm Phenotype (WP)larval growth variant0Least InformativeDirect
Worm Phenotype (WP)pericellular component development variant0.000000000009504Moderately InformativeDirect
Worm Phenotype (WP)organism segment morphology variant0.05959Moderately InformativeInherited
Worm Phenotype (WP)body region morphology variant0.06024Moderately InformativeInherited
Worm Phenotype (WP)basement membrane remodeling variant0.000000000001058InformativeDirect
Worm Phenotype (WP)dumpy0.00091Highly InformativeDirect

Document: WP annotation of SCOP domains

Yeast Phenotype (YP)

(show details) Document: YP annotation of SCOP domains

Fly Anatomy (FA)

(show details) Document: FA annotation of SCOP domains

Zebrafish Anatomy (ZA)

(show details)
ZA termFDR (all)SDZA levelAnnotation (direct or inherited)
Zebrafish Anatomy (ZA)nervous system0.2619Least InformativeInherited
Zebrafish Anatomy (ZA)multi-tissue structure0.6912Least InformativeInherited
Zebrafish Anatomy (ZA)compound organ0.8945Least InformativeInherited
Zebrafish Anatomy (ZA)central nervous system0.2507Moderately InformativeInherited
Zebrafish Anatomy (ZA)optic tectum0.0009038InformativeDirect

Document: ZA annotation of SCOP domains

Xenopus Anatomy (XA)

(show details)
XA termFDR (all)SDXA levelAnnotation (direct or inherited)
Xenopus ANatomical entity (XAN)cavitated compound organ0Least InformativeDirect
Xenopus DEvelopment stage (XDE)post-embryonic stage0.5931Least InformativeInherited

Document: XA annotation of SCOP domains

Arabidopsis Plant Ontology (AP)

(show details)
AP termFDR (all)SDAP levelAnnotation (direct or inherited)
Plant ANatomical entity (PAN)flower0Least InformativeDirect
Plant ANatomical entity (PAN)collective phyllome structure0Least InformativeDirect
Plant ANatomical entity (PAN)root system0Least InformativeDirect

Document: AP annotation of SCOP domains

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEC levelAnnotation (direct or inherited)
Enzyme Commission (EC)Hydrolases0Least InformativeDirect
Enzyme Commission (EC)Acting on peptide bonds (peptidases)0Moderately InformativeDirect
Enzyme Commission (EC)Serine endopeptidases0.001555InformativeInherited
Enzyme Commission (EC)Dipeptidyl-peptidases and tripeptidyl-peptidases0Highly InformativeDirect
Enzyme Commission (EC)Metallocarboxypeptidases0Highly InformativeDirect

Document: EC annotation of SCOP domains

InterPro annotation
Cross references IPR009020 SSF54897 Protein matches

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 [PubMed12095256], despite often low sequence identities [PubMed9811547]. 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 [PubMed9384570], A3, A4, A5, A6, U, insect gut carboxypeptidase and B [PubMed12162965].

  • 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 of the 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 [PubMed10842308].

InterPro database

PDBeMotif information about ligands, sequence and structure motifs
Cross references PDB entries
Ligand binding statistics
Nucleic-acid binding statistics
Occurrence of secondary structure elements
Occurrence of small 3D structural motifs

PDBeMotif resource

Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Enzyme Commission (EC) · Worm Phenotype (WP) · Yeast Phenotype (YP) · Fly Anatomy (FA) · Zebrafish Anatomy (ZA) · Xenopus Anatomy (XA) · Arabidopsis Plant Ontology (AP) · Enzyme Commission (EC) ]

Internal database links

Browse genome assignments for this superfamily. The SUPERFAMILY hidden Markov model library has been used to carry out SCOP domain assignments to all genomes at the superfamily level.

Alignments of sequences to 14 models in this superfamily are available by clicking on the 'Alignments' icon above. PDB sequences less than 40% identical are shown by default, but any other sequence(s) may be aligned. Select PDB sequences, genome sequences, or paste in or upload your own sequences.

Browse and view proteins in genomes which have different domain combinations including a Protease propeptides/inhibitors domain.

Examine the distribution of domain superfamilies, or families, across the major taxonomic kingdoms or genomes within a kingdom. This gives an immediate impression of how superfamilies, or families, are restricted to certain kingdoms of life.

Explore domain occurrence network where nodes represent genomes and edges are domain architectures (shared between genomes) containing the superfamily of interest.

There are 14 hidden Markov models representing the Protease propeptides/inhibitors superfamily. Information on how the models are built, and plots showing hydrophobicity, match emmission probabilities and insertion/deletion probabilities can be inspected.

Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Enzyme Commission (EC) · Worm Phenotype (WP) · Yeast Phenotype (YP) · Fly Anatomy (FA) · Zebrafish Anatomy (ZA) · Xenopus Anatomy (XA) · Arabidopsis Plant Ontology (AP) · Enzyme Commission (EC) · Internal database links ]