SUPERFAMILY 1.75 HMM library and genome assignments server

Superfamily is undergoing a server migration - you are now browsing on the new server. Please contact us if you experience any problems.


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 2017_06 genome PDB chains (SCOP 1.75)
Domains 5,713 18,980 16
Proteins 5,672 18,812 16


Functional annotation
General category Processes_IC
Detailed category Proteases

Document:
Function annotation of SCOP domain superfamilies

Gene Ontology (high-coverage)

(show details)
GO term FDR (all) SDFO level Annotation (direct or inherited)
Biological Process (BP) multicellular organismal process 0.0000005908 Least Informative Direct
Biological Process (BP) macromolecule metabolic process 0 Least Informative Direct
Biological Process (BP) primary metabolic process 0.0000000000001156 Least Informative Direct
Biological Process (BP) organonitrogen compound metabolic process 0 Least Informative Direct
Biological Process (BP) biological regulation 0.01567 Least Informative Inherited
Biological Process (BP) cellular nitrogen compound metabolic process 0.5799 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) peptide metabolic process 0.00000000004134 Moderately Informative Direct
Biological Process (BP) cellular catabolic process 0.000000000054 Moderately Informative Direct
Biological Process (BP) regulation of biological quality 0.000000002482 Moderately Informative Direct
Biological Process (BP) organic substance catabolic process 0.000005686 Moderately Informative Direct
Biological Process (BP) tissue development 1 Moderately Informative Inherited
Biological Process (BP) animal organ development 1 Moderately Informative Inherited
Biological Process (BP) gene expression 0.00756 Moderately Informative Inherited
Biological Process (BP) organelle organization 1 Moderately Informative Inherited
Biological Process (BP) proteolysis 0 Informative Direct
Biological Process (BP) regulation of hormone levels 0.00000000002049 Informative Direct
Biological Process (BP) regulation of apoptotic process 0.000001133 Informative Direct
Biological Process (BP) cellular macromolecule catabolic process 0.00000000000424 Informative Direct
Biological Process (BP) regulation of neuron apoptotic process 0 Highly Informative Direct
Biological Process (BP) cellular protein catabolic process 0.0000000000003956 Highly Informative Direct
Biological Process (BP) multicellular organismal homeostasis 0.000007065 Highly Informative Direct
Biological Process (BP) protein maturation 0 Highly Informative Direct
Biological Process (BP) anatomical structure homeostasis 0.0008432 Highly Informative Direct
Molecular Function (MF) hydrolase activity 0 Least Informative Direct
Molecular Function (MF) binding 1 Least Informative Inherited
Molecular Function (MF) amide binding 0.0001165 Informative Direct
Molecular Function (MF) macromolecular complex binding 0.00000000000006452 Informative Direct
Molecular Function (MF) peptidase activity, acting on L-amino acid peptides 0.5714 Informative Inherited
Molecular Function (MF) exopeptidase activity 0.00009557 Highly Informative Direct
Molecular Function (MF) serine hydrolase activity 0 Highly Informative Direct
Molecular Function (MF) peptide binding 0.00005165 Highly Informative Direct
Cellular Component (CC) intracellular organelle part 0.8533 Least Informative Inherited
Cellular Component (CC) intracellular membrane-bounded organelle 0.3428 Least Informative Inherited
Cellular Component (CC) cytoplasmic part 0.00783 Least Informative Inherited
Cellular Component (CC) vacuole 0 Moderately Informative Direct
Cellular Component (CC) endomembrane system 0.00000000000003647 Moderately Informative Direct
Cellular Component (CC) vesicle 0.0000000000000228 Moderately Informative Direct
Cellular Component (CC) extracellular region part 0.0000001556 Moderately Informative Direct
Cellular Component (CC) intracellular organelle lumen 0.1766 Moderately Informative Inherited
Cellular Component (CC) lytic vacuole 0 Informative Direct
Cellular Component (CC) endosome 0.0006514 Informative Direct
Cellular Component (CC) Golgi apparatus 0 Informative Direct
Cellular Component (CC) cell surface 0.00000000001836 Informative Direct
Cellular Component (CC) secretory granule 0.0002768 Informative Direct
Cellular Component (CC) cytoplasmic vesicle part 0.000172 Informative Direct
Cellular Component (CC) late endosome 0.0000000002902 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

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processVirulence0Moderately InformativeDirect
Biological processApoptosis0.000000000000158Moderately InformativeDirect
Biological processLipid metabolism0.0007712Moderately InformativeDirect
Biological processSteroid metabolism0InformativeDirect
Biological processSporulation0.00000000002805InformativeDirect
Biological processHemostasis0.00000005013InformativeDirect
Biological processCholesterol metabolism0Highly InformativeDirect
Biological processBlood coagulation0.00000004783Highly InformativeDirect
Cellular componentSecreted0Moderately InformativeDirect
Cellular componentEndosome3.314e-16Moderately InformativeDirect
Cellular componentGolgi apparatus6.573e-16Moderately InformativeDirect
Cellular componentCytoplasmic vesicle0.000000000000624Moderately InformativeDirect
Cellular componentEndoplasmic reticulum0.00000414Moderately InformativeDirect
Cellular componentLysosome0InformativeDirect
Cellular componentVacuole0.00000007176InformativeDirect
DomainSignal0Least InformativeDirect
Molecular functionZinc0.00000001614Least InformativeDirect
Molecular functionMetal-binding0.0000006307Least InformativeDirect
Molecular functionCalcium0Moderately InformativeDirect
Post-translational modificationHydrolase0Least InformativeDirect
Post-translational modificationProtease0Moderately InformativeDirect
Post-translational modificationSerine protease0InformativeDirect
Post-translational modificationCarboxypeptidase0.000000000000003055Highly InformativeDirect
Post-translational modificationGlycoprotein0Least InformativeDirect
Post-translational modificationCleavage on pair of basic residues0Moderately InformativeDirect
Post-translational modificationSulfation0InformativeDirect
Post-translational modificationAutocatalytic cleavage0InformativeDirect
Post-translational modificationZymogen0InformativeDirect

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-coverage) · 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-coverage) · Enzyme Commission (EC) · UniProtKB KeyWords (KW) · Internal database links ]