Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
2  structures 2048  species 2  interactions 2841  sequences 10  architectures

Family: Peptidase_A24 (PF01478)

Summary: Type IV leader peptidase family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

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.

Type IV leader peptidase family Provide feedback

Peptidase A24, or the prepilin peptidase as it is also known, processes the N-terminus of the prepilins [1]. The processing is essential for the correct formation of the pseudopili of type IV bacterial protein secretion. The enzyme is found across eubacteria and archaea [2].

Literature references

  1. LaPointe CF, Taylor RK; , J Biol Chem 2000;275:1502-1510.: The type 4 prepilin peptidases comprise a novel family of aspartic acid proteases. PUBMED:10625704 EPMC:10625704

  2. Albers SV, Szabo Z, Driessen AJ; , J Bacteriol 2003;185:3918-3925.: Archaeal homolog of bacterial type IV prepilin signal peptidases with broad substrate specificity. PUBMED:12813086 EPMC:12813086


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000045

This group of aspartic endopeptidases belong to MEROPS peptidase family A24 (type IV prepilin peptidase family). The family is divided into two subfamilies: subfamily A24A includes the type IV prepilin peptidase from bacteria and subfamily A24B includes the preflagellin peptidase from archaea. Peptidases in the family are also known as "GXGD membrane proteases" because of the common motif that includes one of the two active site residues [PUBMED:21765428].

Bacteria produce a number of protein precursors that undergo post-translational methylation and proteolysis prior to secretion as active proteins. Type IV prepilin leader peptidases are enzymes that mediate this type of post-translational modification. Type IV pilin is a protein found on the surface of Pseudomonas aeruginosa, Neisseria gonorrhoeae and other Gram-negative pathogens. Pilin subunits attach the infecting organism to the surface of host epithelial cells. They are synthesised as prepilin subunits, which differ from mature pilin by virtue of containing a 6-8 residue leader peptide consisting of charged amino acids. Mature type IV pilins also contain a methylated N-terminal phenylalanine residue.

The bifunctional enzyme prepilin peptidase (PilD) from Pseudomonas aeruginosa is a key determinant in both type-IV pilus biogenesis and extracellular protein secretion, in its roles as a leader peptidase and methyl transferase (MTase). It is responsible for endopeptidic cleavage of the unique leader peptides that characterise type-IV pilin precursors, as well as proteins with homologous leader sequences that are essential components of the general secretion pathway found in a variety of Gram-negative pathogens. Following removal of the leader peptides, the same enzyme is responsible for the second post-translational modification that characterises the type-IV pilins and their homologues, namely N-methylation of the newly exposed N-terminal amino acid residue [PUBMED:9224881].

In type IV prepilin peptidase, the two active-site Asp residues occur in the motifs Xaa-Xaa-Asp-Xaa-Xbb-Xcc-Xcc-Xcc-Xaa-Pro and Xaa-Gly-Xcc-Gly-Asp-Xaa-Lys-Xaa-Xaa-Xaa (where Xaa is hydrophobic, Xbb is charged and Xcc is any amino acid).

Some archaea possess a flagellum that contains a flagellin protein. Flagellin is synthesized as a precursor with a positively charged leader peptide. This leader peptide is removed by prepilin peptidase before flagellin is incorporated into the filament [PUBMED:14622420]. The tertiary structure of the preflagellin peptidase from Methanococcus maripaludis has been solved, and shows a bundle of six helices. The active site residues are far apart on transmembrane helices 1 and 4, which implies that a conformational change is required to activate the peptidase [PUBMED:21765428].

This entry represents the peptidase domain from the prepilin type IV endopeptidases [PUBMED:10625704]. It can be found on its own, or in the case of the bifunctional enzymes, next to a methylation domain.

Aspartic peptidases, also known as aspartyl proteases (EC), are widely distributed proteolytic enzymes [PUBMED:6795036, PUBMED:2194475, PUBMED:1851433] known to exist in vertebrates, fungi, plants, protozoa, bacteria, archaea, retroviruses and some plant viruses. All known aspartic peptidases are endopeptidases. A water molecule, activated by two aspartic acid residues, acts as the nucleophile in catalysis. Aspartic peptidases can be grouped into five clans, each of which shows a unique structural fold [PUBMED:8439290].

  • Peptidases in clan AA are either bilobed (family A1 or the pepsin family) or are a homodimer (all other families in the clan, including retropepsin from HIV-1/AIDS) [PUBMED:2682266]. Each lobe consists of a single domain with a closed beta-barrel and each lobe contributes one Asp to form the active site. Most peptidases in the clan are inhibited by the naturally occurring small-molecule inhibitor pepstatin [PUBMED:4912600].
  • Clan AC contains the single family A8: the signal peptidase 2 family. Members of the family are found in all bacteria. Signal peptidase 2 processes the premurein precursor, removing the signal peptide. The peptidase has four transmembrane domains and the active site is on the periplasmic side of the cell membrane. Cleavage occurs on the amino side of a cysteine where the thiol group has been substituted by a diacylglyceryl group. Site-directed mutagenesis has identified two essential aspartic acid residues which occur in the motifs GNXXDRX and FNXAD (where X is a hydrophobic residue) [PUBMED:10497172]. No tertiary structures have been solved for any member of the family, but because of the intramembrane location, the structure is assumed not to be pepsin-like.
  • Clan AD contains two families of transmembrane endopeptidases: A22 and A24. These are also known as "GXGD peptidases" because of a common GXGD motif which includes one of the pair of catalytic aspartic acid residues. Structures are known for members of both families and show a unique, common fold with up to nine transmembrane regions [PUBMED:21765428]. The active site aspartic acids are located within a large cavity in the membrane amnd into which water can gain access [PUBMED:23254940].
  • Clan AE contains two families, A25 and A31. Tertiary structures have been solved for members of both families and show a common fold consisting of an alpha-beta-alpha sandwich, in which the beta sheet is five stranded [PUBMED:10331925, PUBMED:10864493].
  • Clan AF contains the single family A26. Members of the clan are membrane-proteins with a unique fold. Homologues are known only from bacteria. The structure of omptin (also known as OmpT) shows a cylindrical barrel containing ten beta strands inserted in the membrane with the active site residues on the outer surface [PUBMED:11566868].
  • There are two families of aspartic peptidases for which neither structure nor active site residues are known and these are not assigned to clans. Family A5 includes thermopsin, an endopeptidase found only in thermophilic archaea. Family A36 contains sporulation factor SpoIIGA, which is known to process and activate sigma factor E, one of the transcription factors that controls sporulation in bacteria [PUBMED:21751400].

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...

Loading domain graphics...

Pfam Clan

This family is a member of clan Peptidase_AD (CL0130), which has the following description:

Members of this clan are peptidases that are integral membrane proteins. The catalytic aspartate is in the conserved GXGD motif.

The clan contains the following 4 members:

Peptidase_A22B Peptidase_A24 Presenilin SPP

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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics 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
(79)
Full
(2841)
Representative proteomes UniProt
(11963)
NCBI
(19076)
Meta
(938)
RP15
(860)
RP35
(2305)
RP55
(3881)
RP75
(6162)
Jalview View  View  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
(79)
Full
(2841)
Representative proteomes UniProt
(11963)
NCBI
(19076)
Meta
(938)
RP15
(860)
RP35
(2305)
RP55
(3881)
RP75
(6162)
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
(79)
Full
(2841)
Representative proteomes UniProt
(11963)
NCBI
(19076)
Meta
(938)
RP15
(860)
RP35
(2305)
RP55
(3881)
RP75
(6162)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   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: Yeats C
Previous IDs: Peptidase_C20;
Type: Family
Author: Bateman A, Yeats C
Number in seed: 79
Number in full: 2841
Average length of the domain: 111.50 aa
Average identity of full alignment: 23 %
Average coverage of the sequence by the domain: 48.95 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.0 23.0
Trusted cut-off 23.0 23.0
Noise cut-off 22.9 22.9
Model length: 107
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

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

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...

Loading sunburst data...

Tree controls

Hide

The 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.

Interactions

There are 2 interactions for this family. More...

Peptidase_A24 Arc_PepC_II

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 Peptidase_A24 domain has been found. There are 2 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 seqence.

Loading structure mapping...