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11  structures 373  species 1  interaction 1035  sequences 15  architectures

Family: Peptidase_A4 (PF01828)

Summary: Peptidase A4 family

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Peptidase A4 family Provide feedback

No Pfam abstract.

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000250

The peptidases in family G1 form a subset of what were formerly termed 'pepstatin-insensitive carboxyl proteinases'. After its discovery in about 1970, the pentapeptide pepstatin soon came to be thought of as a very general inhibitor of the endopeptidases that are active at acidic pH. But more recently several acid-acting endopeptidases from bacteria and fungi had been found to be resistant to pepstatin. The unusual active sites of the 'pepstatin-insensitive carboxyl peptidases' proved difficult to characterise, but it has now been established that the enzymes from bacteria are acid-acting serine peptidases in family S53 (clan SB), INTERPRO, whereas the fungal enzymes are in family G1 (formerly A4). The importance of glutamate ('E') and glutamine ('Q') residues in the active sites of the family G1 enzymes led to the family name, Eqolisin [PUBMED:14993599].

This group of glutamate/glutamine peptidases belong to MEROPS peptidase family G1 (eqolisin family, clan GA). An example of this group is scytalidoglutamic peptidase. The proteins are thermostable, pepstatin insensitive and are active at low pH ranges [PUBMED:7674922]. The enzyme has a unique heterodimeric structure, with a 39-residue light chain and a 173-residue heavy chain bound to each other non-covalently [PUBMED:1918060]. The tertiary structure of the active site of scytalidoglutamic peptidase (MEROPS G01.001) with a bound tripeptide product has been interpreted as showing that Glu136 is the primary catalytic residue. The most likely mechanism is suggested to be nucleophilic attack by a water molecule activated by the Glu136 side chain on the si-face of the scissile peptide bond carbon atom to form the tetrahedral intermediate. Electrophilic assistance, and oxyanion stabilisation, are provided by the side-chain amide of Gln53.

Both scytalidoglutamic peptidase (MEROPS G01.001) and aspergilloglutamic peptidase (MEROPS G01.002) cleave the Tyr26 Thr27 bond in the B chain of oxidized insulin; a bond not cleaved by other acid-acting endopeptidases. Scytalidoglutamic peptidase is most active on casein at pH 2 and is inhibited by 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP), a compound that also inhibits pepsin.

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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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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
(136)
Full
(1035)
Representative proteomes UniProt
(1479)
NCBI
(1841)
Meta
(2)
RP15
(193)
RP35
(610)
RP55
(852)
RP75
(1141)
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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
(136)
Full
(1035)
Representative proteomes UniProt
(1479)
NCBI
(1841)
Meta
(2)
RP15
(193)
RP35
(610)
RP55
(852)
RP75
(1141)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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
(136)
Full
(1035)
Representative proteomes UniProt
(1479)
NCBI
(1841)
Meta
(2)
RP15
(193)
RP35
(610)
RP55
(852)
RP75
(1141)
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: MEROPS
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A
Number in seed: 136
Number in full: 1035
Average length of the domain: 195.90 aa
Average identity of full alignment: 31 %
Average coverage of the sequence by the domain: 74.08 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.2 22.2
Trusted cut-off 22.6 22.3
Noise cut-off 22.1 22.0
Model length: 209
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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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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Interactions

There is 1 interaction for this family. More...

Peptidase_A4

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_A4 domain has been found. There are 11 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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