Summary: Peptidase inhibitor I9
Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.
This is the Wikipedia entry entitled "Protease inhibitor (biology)". More...
Protease inhibitor (biology) Edit Wikipedia article
- For the drugs used in AIDS, please refer to protease inhibitor (pharmacology)
In biology and biochemistry, protease inhibitors are molecules (usually enzymes) that inhibit the function of peptidases (old name: protease, hence the term protease inhibitor).
In medicine, protease inhibitor is often used interchangably with alpha 1-antitrypsin (A1AT, which is abbreviated Pi for this reason). A1AT is indeed the protease inhibitor that most often causes disease, namely in alpha 1-antitrypsin deficiency.
Classes of protease inhibitors are:
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Peptidase inhibitor I9 Provide feedback
This family includes the proteinase B inhibitor from Saccharomyces cerevisiae and the activation peptides from peptidases of the subtilisin family. The subtilisin propeptides are known to function as molecular chaperones, assisting in the folding of the mature peptidase [1] but have also been shown to act as 'temporary inhibitors' [2].
Literature references
-
Li Y, Hu Z, Jordan F, Inouye M; , J Biol Chem. 1995;270:25127-25132.: Functional analysis of the propeptide of subtilisin E as an intramolecular chaperone for protein folding. Refolding and inhibitory abilities of propeptide mutants. PUBMED:7559646 EPMC:7559646
-
Kojima S, Minagawa T, Miura K; , FEBS Lett. 1997;411:128-132.: The propeptide of subtilisin BPN' as a temporary inhibitor and effect of an amino acid replacement on its inhibitory activity. PUBMED:9247157 EPMC:9247157
Internal database links
SCOOP: | Peptidase_S8 |
External database links
MEROPS: | I9 |
SCOP: | 1gns |
This tab holds annotation information from the InterPro database.
InterPro entry IPR010259
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 [ PUBMED:12095256 ], despite often low sequence identities [ PUBMED:9811547 ]. 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 entry represents the propeptide domain at the N terminus of peptidases belonging to MEROPS family S8A, subtilisins. The subtilisin propeptides are known to function as molecular chaperones, assisting in the folding of the mature peptidase [ PUBMED:7559646 ]. The propeptide is removed by proteolytic cleavage; removal activating the enzyme. This domain is also found in members of MEROPS proteinase inhibitor family I9.
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
Loading domain graphics...
Pfam Clan
This family is a member of clan PPP-I (CL0570), which has the following description:
This superfamily is characterised by families of short N-terminal domains such as the pancreatic carboxypeptidase activation domain, the subtilase propeptides/inhibitors, the prohormone convertase 1 pro-domain, and the peptidase- S8 pro-domain. All families exbhibit an alpha+beta sandwich with antiparallel beta-sheets in a (beta-alpha-beta)x2 conformation.
The clan contains the following 7 members:
Inhibitor_I9 ORF_2_N Pro-kuma_activ Pro_sub2 Propep_M14 S8_pro-domain Tk-SP_N-proAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
View options
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
Seed (71) |
Full (16698) |
Representative proteomes | UniProt (32669) |
||||
---|---|---|---|---|---|---|---|
RP15 (2203) |
RP35 (8145) |
RP55 (14358) |
RP75 (20350) |
||||
Jalview | |||||||
HTML | |||||||
PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
not generated,
— not available.
Format an alignment
Download options
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
Seed (71) |
Full (16698) |
Representative proteomes | UniProt (32669) |
||||
---|---|---|---|---|---|---|---|
RP15 (2203) |
RP35 (8145) |
RP55 (14358) |
RP75 (20350) |
||||
Raw Stockholm | |||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
Seed source: | Pfam-B_52 (release 8.0) |
Previous IDs: | Subtilisin_N; |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Yeats C |
Number in seed: | 71 |
Number in full: | 16698 |
Average length of the domain: | 81.3 aa |
Average identity of full alignment: | 21 % |
Average coverage of the sequence by the domain: | 12.68 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|
||||||||||||
Model details: |
|
||||||||||||
Model length: | 82 | ||||||||||||
Family (HMM) version: | 19 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
Sunburst controls
HideWeight segments by...
Change the size of the sunburst
Colour assignments
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
Selections
Align selected sequences to HMM
Generate a FASTA-format file
Clear selection
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...
Tree controls
HideThe tree shows the occurrence of this domain across different species. More...
Loading...
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Inhibitor_I9 domain has been found. There are 52 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
Loading structure mapping...
AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.