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15  structures 324  species 0  interactions 2457  sequences 25  architectures

Family: A1_Propeptide (PF07966)

Summary: A1 Propeptide

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 "Aspartic protease". More...

Aspartic protease Edit Wikipedia article

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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.

A1 Propeptide Provide feedback

Most eukaryotic endopeptidases (Merops Family A1) are synthesised with signal and propeptides. The animal pepsin-like endopeptidase propeptides form a distinct family of propeptides, which contain a conserved motif approximately 30 residues long. In pepsinogen A, the first 11 residues of the mature pepsin sequence are displaced by residues of the propeptide. The propeptide contains two helices that block the active site cleft, in particular the conserved Asp11 residue, in pepsin, hydrogen bonds to a conserved Arg residues in the propeptide. This hydrogen bond stabilises the propeptide conformation and is probably responsible for triggering the conversion of pepsinogen to pepsin under acidic conditions [1,2].

Literature references

  1. Hartsuck JA, Koelsch G, Remington SJ; , Proteins 1992;13:1-25.: The high-resolution crystal structure of porcine pepsinogen. PUBMED:1594574 EPMC:1594574

  2. Sielecki AR, Fujinaga M, Read RJ, James MN; , J Mol Biol 1991;219:671-692.: Refined structure of porcine pepsinogen at 1.8 A resolution. PUBMED:2056534 EPMC:2056534


This tab holds annotation information from the InterPro database.

InterPro entry IPR012848

This entry represents the N-terminal domain of the aspartic peptidases.

Aspartic peptidase, also known as aspartyl proteases ([intenz:3.4.23.-]) are a widely distributed family of proteolytic enzymes [ PUBMED:6795036 , PUBMED:2194475 , PUBMED:1851433 ] known to exist in vertebrates, fungi, plants, retroviruses and some plant viruses. Aspartate proteases of eukaryotes are monomeric enzymes which consist of two domains. Each domain contains an active site centred on a catalytic aspartyl residue. The two domains most probably evolved from the duplication of an ancestral gene encoding a primordial domain. Currently known eukaryotic aspartyl proteases are:

  • Vertebrate gastric pepsins A and C (also known as gastricsin). Vertebrate chymosin (rennin), involved in digestion and used for making cheese.
  • Vertebrate lysosomal cathepsins D (EC 3.4.23.5) and E (EC 3.4.23.34).
  • Mammalian renin (EC 3.4.23.15) whose function is to generate angiotensin I from angiotensinogen in the plasma.
  • Fungal proteases such as aspergillopepsin A (EC 3.4.23.18), candidapepsin (EC 3.4.23.24), mucoropepsin (EC 3.4.23.23) (mucor rennin), endothiapepsin (EC 3.4.23.22), polyporopepsin (EC 3.4.23.29), and rhizopuspepsin (EC 3.4.23.21).
  • Yeast saccharopepsin (EC 3.4.23.25) (proteinase A) (gene PEP4). PEP4 is implicated in posttranslational regulation of vacuolar hydrolases.
  • Yeast barrierpepsin (EC 3.4.23.35) (gene BAR1); a protease that cleaves alpha-factor and thus acts as an antagonist of the mating pheromone.
  • Fission yeast sxa1 which is involved in degrading or processing the mating pheromones.

Most retroviruses and some plant viruses, such as badnaviruses, encode for an aspartyl protease which is an homodimer of a chain of about 95 to 125 amino acids. In most retroviruses, the protease is encoded as a segment of a polyprotein which is cleaved during the maturation process of the virus. It is generally part of the pol polyprotein and, more rarely, of the gag polyprotein.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

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
(121)
Full
(2457)
Representative proteomes UniProt
(4389)
RP15
(125)
RP35
(500)
RP55
(1769)
RP75
(2466)
Jalview View  View  View  View  View  View  View 
HTML View  View           
PP/heatmap 1 View           

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

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

Format an alignment

  Seed
(121)
Full
(2457)
Representative proteomes UniProt
(4389)
RP15
(125)
RP35
(500)
RP55
(1769)
RP75
(2466)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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
(121)
Full
(2457)
Representative proteomes UniProt
(4389)
RP15
(125)
RP35
(500)
RP55
(1769)
RP75
(2466)
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_386 (release 15.0)
Previous IDs: none
Type: Motif
Sequence Ontology: SO:0001067
Author: Rawlings ND , Finn RD
Number in seed: 121
Number in full: 2457
Average length of the domain: 26 aa
Average identity of full alignment: 38 %
Average coverage of the sequence by the domain: 6.8 %

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 20.5 20.5
Trusted cut-off 20.5 20.5
Noise cut-off 20.4 20.4
Model length: 27
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 A1_Propeptide domain has been found. There are 15 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
A0A0R4INF8 View 3D Structure Click here
A0A5S6PWH1 View 3D Structure Click here
B7ZWD6 View 3D Structure Click here
F1QDA2 View 3D Structure Click here
G3V8C5 View 3D Structure Click here
G4VEV6 View 3D Structure Click here
P00791 View 3D Structure Click here
P00792 View 3D Structure Click here
P00793 View 3D Structure Click here
P00794 View 3D Structure Click here
P00796 View 3D Structure Click here
P00797 View 3D Structure Click here
P04073 View 3D Structure Click here
P06281 View 3D Structure Click here
P07339 View 3D Structure Click here
P0DJD7 View 3D Structure Click here
P0DJD8 View 3D Structure Click here
P0DJD9 View 3D Structure Click here
P11489 View 3D Structure Click here
P14091 View 3D Structure Click here
P16228 View 3D Structure Click here
P16476 View 3D Structure Click here
P18242 View 3D Structure Click here
P18276 View 3D Structure Click here
P20142 View 3D Structure Click here
P24268 View 3D Structure Click here
P25796 View 3D Structure Click here
P27821 View 3D Structure Click here
P27822 View 3D Structure Click here
P27823 View 3D Structure Click here
P28712 View 3D Structure Click here
P28713 View 3D Structure Click here
P30879 View 3D Structure Click here
P43159 View 3D Structure Click here
P52115 View 3D Structure Click here
P60016 View 3D Structure Click here
P70269 View 3D Structure Click here
P83493 View 3D Structure Click here
P83495 View 3D Structure Click here
Q10735 View 3D Structure Click here