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41  structures 803  species 0  interactions 13016  sequences 218  architectures

Family: Inhibitor_I29 (PF08246)

Summary: Cathepsin propeptide inhibitor domain (I29)

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.

Cathepsin propeptide inhibitor domain (I29) Provide feedback

This domain is found at the N-terminus of some C1 peptidases such as Cathepsin L where it acts as a propeptide. There are also a number of proteins that are composed solely of multiple copies of this domain such as the peptidase inhibitor salarin Q70SU8. This family is classified as I29 by MEROPS.

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR013201

This entry represents a peptidase inhibitor domain, which belongs to MEROPS peptidase inhibitor family I29. The domain is also found at the N terminus of a variety of peptidase precursors that belong to MEROPS peptidase subfamily C1A; these include cathepsin L, papain, and procaricain ( SWISSPROT ) [ PUBMED:8939744 ]. It forms an alpha-helical domain that runs through the substrate-binding site, preventing access. Removal of this region by proteolytic cleavage results in activation of the enzyme. This domain is also found, in one or more copies, in a variety of cysteine peptidase inhibitors such as salarin [ PUBMED:14505823 ].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

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
(56)
Full
(13016)
Representative proteomes UniProt
(22418)
RP15
(2920)
RP35
(6763)
RP55
(11003)
RP75
(13866)
Jalview View  View  View  View  View  View  View 
HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(56)
Full
(13016)
Representative proteomes UniProt
(22418)
RP15
(2920)
RP35
(6763)
RP55
(11003)
RP75
(13866)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

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
(56)
Full
(13016)
Representative proteomes UniProt
(22418)
RP15
(2920)
RP35
(6763)
RP55
(11003)
RP75
(13866)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

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 View help on the curation process

Seed source: Pfam-B_14 (release 17.0)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 56
Number in full: 13016
Average length of the domain: 58.2 aa
Average identity of full alignment: 32 %
Average coverage of the sequence by the domain: 16.12 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.4 24.4
Trusted cut-off 24.4 24.4
Noise cut-off 24.3 24.3
Model length: 58
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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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...

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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_I29 domain has been found. There are 41 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.

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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.

Protein Predicted structure External Information
A0A044RM09 View 3D Structure Click here
A0A044RVL0 View 3D Structure Click here
A0A044S545 View 3D Structure Click here
A0A044SU60 View 3D Structure Click here
A0A044SUF8 View 3D Structure Click here
A0A044TYP6 View 3D Structure Click here
A0A072UTP9 View 3D Structure Click here
A0A077YZI7 View 3D Structure Click here
A0A077Z0Q9 View 3D Structure Click here
A0A0G2JX50 View 3D Structure Click here
A0A0H5S901 View 3D Structure Click here
A0A0J9XKB3 View 3D Structure Click here
A0A0J9Y464 View 3D Structure Click here
A0A0J9Y553 View 3D Structure Click here
A0A0K0DTI1 View 3D Structure Click here
A0A0K0DYH0 View 3D Structure Click here
A0A0K0E0S6 View 3D Structure Click here
A0A0K0E2U4 View 3D Structure Click here
A0A0K0EHC3 View 3D Structure Click here
A0A0N4U4Q3 View 3D Structure Click here
A0A0N4U7C7 View 3D Structure Click here
A0A0N4UAM5 View 3D Structure Click here
A0A0N4UAM6 View 3D Structure Click here
A0A0N4UAP0 View 3D Structure Click here
A0A0N4UL75 View 3D Structure Click here
A0A0N7KCX2 View 3D Structure Click here
A0A0N7KMT7 View 3D Structure Click here
A0A0N7KRA0 View 3D Structure Click here
A0A0P0VBV2 View 3D Structure Click here
A0A0P0W3U6 View 3D Structure Click here
A0A0P0WNU3 View 3D Structure Click here
A0A0P0XQB7 View 3D Structure Click here
A0A0P0XQH0 View 3D Structure Click here
A0A0P0XQX8 View 3D Structure Click here
A0A0P0XR37 View 3D Structure Click here
A0A0P0XRA0 View 3D Structure Click here
A0A0R0EQB4 View 3D Structure Click here
A0A0R0F6I9 View 3D Structure Click here
A0A0R0F8Z1 View 3D Structure Click here
A0A0R0FYJ1 View 3D Structure Click here