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 (827) Uniprot 2014_06 PDB chains (SCOP 1.75)
Domains 5,602 8,367 16
Proteins 5,569 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)
GO termFDR (singleton)FDR (all)SDFO levelAnnotation (direct or inherited)
Biological Process (BP)regulation of metabolic process0.090241Least InformativeInherited
Biological Process (BP)negative regulation of metabolic process0.0010070.9961Moderately InformativeInherited
Biological Process (BP)regulation of gene expression0.0038151Moderately InformativeInherited
Biological Process (BP)regulation of protein metabolic process0.0010460.2564Moderately InformativeInherited
Biological Process (BP)negative regulation of protein processing0.0000090640.0005611InformativeDirect

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 0.0002524 Least Informative Direct
Biological Process (BP) nitrogen compound metabolic process 0.5987 Least Informative Inherited
Biological Process (BP) multicellular organismal process 0.001167 Least Informative Inherited
Biological Process (BP) cellular macromolecule metabolic process 1 Least Informative Inherited
Biological Process (BP) regulation of metabolic 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 0.00000000339 Moderately Informative Direct
Biological Process (BP) regulation of biological quality 0.0000005017 Moderately Informative Direct
Biological Process (BP) organic substance catabolic process 0.00001867 Moderately Informative Direct
Biological Process (BP) negative regulation of metabolic process 0.9961 Moderately Informative Inherited
Biological Process (BP) regulation of gene expression 1 Moderately Informative Inherited
Biological Process (BP) regulation of protein metabolic process 0.2564 Moderately Informative Inherited
Biological Process (BP) gene expression 0.04514 Moderately Informative Inherited
Biological Process (BP) proteolysis 0.0000000011 Informative Direct
Biological Process (BP) peptide metabolic process 0 Informative Direct
Biological Process (BP) regulation of hormone levels 0.00000000000001752 Informative Direct
Biological Process (BP) negative regulation of protein processing 0.0005611 Informative Direct
Biological Process (BP) protein catabolic process 0.00000128 Informative Direct
Biological Process (BP) regulation of apoptotic process 0.000008126 Informative Direct
Biological Process (BP) cellular macromolecule catabolic process 0.000000000005677 Informative Direct
Biological Process (BP) multicellular organismal homeostasis 0.000000221 Informative Direct
Biological Process (BP) protein maturation 0 Informative Direct
Biological Process (BP) anatomical structure homeostasis 0.001121 Informative Inherited
Biological Process (BP) organonitrogen compound catabolic process 1 Informative Inherited
Biological Process (BP) cell recognition 0.0002325 Highly Informative Direct
Biological Process (BP) regulation of neuron apoptotic process 0 Highly Informative Direct
Biological Process (BP) pattern specification process 0.3896 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 0.00004678 Informative Direct
Molecular Function (MF) exopeptidase activity 0.00002652 Highly Informative Direct
Molecular Function (MF) serine hydrolase activity 0 Highly Informative Direct
Molecular Function (MF) peptide binding 0.00003204 Highly Informative Direct
Cellular Component (CC) intracellular organelle part 0.9787 Least Informative Inherited
Cellular Component (CC) intracellular membrane-bounded organelle 0.07381 Least Informative Inherited
Cellular Component (CC) cytoplasmic part 0.004729 Least Informative Inherited
Cellular Component (CC) endoplasmic reticulum 0.00000000001599 Moderately Informative Direct
Cellular Component (CC) vesicle 0.00000227 Moderately Informative Direct
Cellular Component (CC) extracellular region part 0.000008298 Moderately Informative Direct
Cellular Component (CC) intracellular organelle lumen 0.3726 Moderately Informative Inherited
Cellular Component (CC) lytic vacuole 0 Informative Direct
Cellular Component (CC) extracellular space 0.00002352 Informative Direct
Cellular Component (CC) endosome 0.000000000005237 Informative Direct
Cellular Component (CC) Golgi apparatus 0 Informative Direct
Cellular Component (CC) cell surface 0.0000000003256 Informative Direct
Cellular Component (CC) secretory granule 0.000001636 Informative Direct
Cellular Component (CC) late endosome 0.00000001169 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-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)growth variant0Least InformativeDirect
Worm Phenotype (WP)larval development variant0Least InformativeDirect
Worm Phenotype (WP)larval lethal0Moderately InformativeDirect
Worm Phenotype (WP)pericellular component development variant0.0000000001005Moderately InformativeDirect
Worm Phenotype (WP)organism segment morphology variant0.02094Moderately InformativeInherited
Worm Phenotype (WP)basement membrane remodeling variant0.00000000002271InformativeDirect
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 endopeptidases0.0000119InformativeDirect
Enzyme Commission (EC)Metallocarboxypeptidases0Highly InformativeDirect
Enzyme Commission (EC)Dipeptidyl-peptidases and tripeptidyl-peptidases0.00001214Highly InformativeDirect

Document: EC annotation of SCOP domains

DrugBank ATC (DB)

(show details)
DB termFDR (all)SDDB levelAnnotation (direct or inherited)
Drugbank ATC_code (DB)alimentary tract and metabolism0Least InformativeDirect

Document: DB annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processApoptosis0.00000000000006456Moderately InformativeDirect
Biological processLipid metabolism0.0004076Moderately InformativeDirect
Biological processSteroid metabolism0InformativeDirect
Biological processVirulence0InformativeDirect
Biological processSporulation0.000000000007218InformativeDirect
Biological processHemostasis0.00000004238InformativeDirect
Biological processCholesterol metabolism0Highly InformativeDirect
Biological processBlood coagulation0.00000004048Highly InformativeDirect
Cellular componentSecreted0Moderately InformativeDirect
Cellular componentGolgi apparatus6.436e-16Moderately InformativeDirect
Cellular componentEndosome0.000000000003175Moderately InformativeDirect
Cellular componentCytoplasmic vesicle0.00000000142Moderately InformativeDirect
Cellular componentEndoplasmic reticulum0.0000007438Moderately InformativeDirect
Cellular componentLysosome0InformativeDirect
Cellular componentVacuole0.0000000187InformativeDirect
DomainSignal0Least InformativeDirect
Molecular functionZinc0.000000005166Least InformativeDirect
Molecular functionMetal-binding0.0000001166Least 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) · DrugBank ATC (DB) · 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) · DrugBank ATC (DB) · UniProtKB KeyWords (KW) · Internal database links ]