SUPERFAMILY 1.75 HMM library and genome assignments server


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 (826) Uniprot 2014_06 PDB chains (SCOP 1.75)
Domains 5,601 8,367 16
Proteins 5,568 8,342 16


Functional annotation
General category Processes_IC
Detailed category Proteases

Document:
Function annotation of SCOP domain superfamilies

Gene Ontology (high-quality)

(show details) Document: GO annotation of SCOP domains

Gene Ontology (high-coverage)

(show details)
GO term FDR (all) SDFO level Annotation (direct or inherited)
Biological Process (BP) protein metabolic process 0 Least Informative Direct
Biological Process (BP) developmental process 0.0002407 Least Informative Direct
Biological Process (BP) multicellular organismal process 0.002601 Least Informative Inherited
Biological Process (BP) cellular macromolecule metabolic process 1 Least Informative Inherited
Biological Process (BP) nitrogen compound metabolic process 1 Least Informative Inherited
Biological Process (BP) biosynthetic process 1 Least Informative Inherited
Biological Process (BP) regulation of cellular process 1 Least Informative Inherited
Biological Process (BP) single-organism cellular process 1 Least Informative Inherited
Biological Process (BP) cellular component organization or biogenesis 1 Least Informative Inherited
Biological Process (BP) cellular catabolic process 8.557e-10 Moderately Informative Direct
Biological Process (BP) regulation of biological quality 4.92e-06 Moderately Informative Direct
Biological Process (BP) organic substance catabolic process 9.956e-06 Moderately Informative Direct
Biological Process (BP) cellular nitrogen compound biosynthetic process 0.6796 Moderately Informative Inherited
Biological Process (BP) organonitrogen compound biosynthetic process 0.4222 Moderately Informative Inherited
Biological Process (BP) gene expression 0.06204 Moderately Informative Inherited
Biological Process (BP) organelle organization 0.9587 Moderately Informative Inherited
Biological Process (BP) proteolysis 4.057e-10 Informative Direct
Biological Process (BP) peptide metabolic process 7.347e-15 Informative Direct
Biological Process (BP) regulation of hormone levels 5.386e-13 Informative Direct
Biological Process (BP) protein catabolic process 6.675e-07 Informative Direct
Biological Process (BP) amide biosynthetic process 0.0009874 Informative Direct
Biological Process (BP) cellular macromolecule catabolic process 4.779e-12 Informative Direct
Biological Process (BP) organonitrogen compound catabolic process 0.5789 Informative Inherited
Biological Process (BP) protein processing 0 Highly Informative Direct
Biological Process (BP) peptide biosynthetic process 3.96e-05 Highly Informative Direct
Biological Process (BP) regulation of neuron apoptotic process 0 Highly Informative Direct
Biological Process (BP) pattern specification process 0.3431 Highly Informative Inherited
Molecular Function (MF) hydrolase activity 0 Least Informative Direct
Molecular Function (MF) binding 1 Least Informative Inherited
Molecular Function (MF) peptidase activity 0 Informative Direct
Molecular Function (MF) amide binding 4.591e-05 Informative Direct
Molecular Function (MF) exopeptidase activity 9.953e-06 Highly Informative Direct
Molecular Function (MF) serine hydrolase activity 0 Highly Informative Direct
Molecular Function (MF) peptide binding 3.14e-05 Highly Informative Direct
Cellular Component (CC) intracellular organelle part 1 Least Informative Inherited
Cellular Component (CC) intracellular membrane-bounded organelle 0.1128 Least Informative Inherited
Cellular Component (CC) membrane 1 Least Informative Inherited
Cellular Component (CC) cytoplasmic part 0.00451 Least Informative Inherited
Cellular Component (CC) endoplasmic reticulum 1.592e-11 Moderately Informative Direct
Cellular Component (CC) endomembrane system 0.0003431 Moderately Informative Direct
Cellular Component (CC) vesicle 1.982e-06 Moderately Informative Direct
Cellular Component (CC) extracellular region part 8.115e-06 Moderately Informative Direct
Cellular Component (CC) organelle membrane 0.2211 Moderately Informative Inherited
Cellular Component (CC) intracellular organelle lumen 0.5176 Moderately Informative Inherited
Cellular Component (CC) lytic vacuole 0 Informative Direct
Cellular Component (CC) extracellular space 2.442e-05 Informative Direct
Cellular Component (CC) endosome 5.097e-12 Informative Direct
Cellular Component (CC) Golgi apparatus 0 Informative Direct
Cellular Component (CC) cell surface 9.965e-11 Informative Direct
Cellular Component (CC) secretory granule 7.754e-06 Informative Direct
Cellular Component (CC) late endosome 1.094e-08 Highly Informative Direct

Document: GO annotation of SCOP domains

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-peptidases2.239e-05InformativeDirect
Enzyme Commission (EC)Metallocarboxypeptidases0Highly InformativeDirect
Enzyme Commission (EC)Furin1.568e-13Highly InformativeDirect
Enzyme Commission (EC)Proprotein convertase 28.229e-11Highly InformativeDirect
Enzyme Commission (EC)Proprotein convertase 11.803e-09Highly InformativeDirect

Document: EC annotation of SCOP domains

Worm Phenotype (WP)

(show details)
WP termFDR (all)SDWP levelAnnotation (direct or inherited)
Worm Phenotype (WP)growth variant0Least InformativeDirect
Worm Phenotype (WP)larval development variant0Least InformativeDirect
Worm Phenotype (WP)larval lethal0Moderately InformativeDirect
Worm Phenotype (WP)pericellular component development variant1.005e-10Moderately InformativeDirect
Worm Phenotype (WP)organism segment morphology variant0.02094Moderately InformativeInherited
Worm Phenotype (WP)basement membrane remodeling variant2.271e-11InformativeDirect
Worm Phenotype (WP)body length variant0.005116InformativeInherited
Worm Phenotype (WP)body width variant0.00613InformativeInherited

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

Xenopus Anatomy (XA)

(show details) 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 (peptide hydrolases)0Moderately InformativeDirect
Enzyme Commission (EC)Serine endopeptidases1.19e-05InformativeDirect
Enzyme Commission (EC)Metallocarboxypeptidases0Highly InformativeDirect
Enzyme Commission (EC)Dipeptidyl-peptidases and tripeptidyl-peptidases1.214e-05Highly InformativeDirect

Document: EC annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processApoptosis6.456e-14Moderately InformativeDirect
Biological processLipid metabolism0.0004076Moderately InformativeDirect
Biological processSteroid metabolism0InformativeDirect
Biological processVirulence0InformativeDirect
Biological processSporulation7.218e-12InformativeDirect
Biological processHemostasis4.238e-08InformativeDirect
Biological processCholesterol metabolism0Highly InformativeDirect
Biological processBlood coagulation4.048e-08Highly InformativeDirect
Cellular componentSecreted0Moderately InformativeDirect
Cellular componentGolgi apparatus6.436e-16Moderately InformativeDirect
Cellular componentEndosome3.175e-12Moderately InformativeDirect
Cellular componentCytoplasmic vesicle1.42e-09Moderately InformativeDirect
Cellular componentEndoplasmic reticulum7.438e-07Moderately InformativeDirect
Cellular componentLysosome0InformativeDirect
Cellular componentVacuole1.87e-08InformativeDirect
DomainSignal0Least InformativeDirect
Molecular functionZinc5.166e-09Least InformativeDirect
Molecular functionMetal-binding1.166e-07Least InformativeDirect
Molecular functionCalcium0Moderately InformativeDirect
Post-translational modificationHydrolase0Least InformativeDirect
Post-translational modificationProtease0Moderately InformativeDirect
Post-translational modificationSerine protease0InformativeDirect
Post-translational modificationCarboxypeptidase0Highly InformativeDirect
Post-translational modificationGlycoprotein0Least InformativeDirect
Post-translational modificationCleavage on pair of basic residues0Moderately InformativeDirect
Post-translational modificationSulfation0InformativeDirect
Post-translational modificationZymogen0InformativeDirect
Post-translational modificationAutocatalytic cleavage9.055e-16InformativeDirect

Document: KW annotation of SCOP domains

InterPro annotation
Cross references IPR009020 SSF54897 Protein matches
Abstract

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 · Gene Ontology (high-quality) · Gene Ontology (high-coverage) · Enzyme Commission (EC) · Worm Phenotype (WP) · Yeast Phenotype (YP) · Fly Anatomy (FA) · Xenopus Anatomy (XA) · Arabidopsis Plant Ontology (AP) · Enzyme Commission (EC) · UniProtKB KeyWords (KW) ]

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 13 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 13 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 · Gene Ontology (high-quality) · Gene Ontology (high-coverage) · Enzyme Commission (EC) · Worm Phenotype (WP) · Yeast Phenotype (YP) · Fly Anatomy (FA) · Xenopus Anatomy (XA) · Arabidopsis Plant Ontology (AP) · Enzyme Commission (EC) · UniProtKB KeyWords (KW) · Internal database links ]