Summary: Peptidase A4 family
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Peptidase A4 family Provide feedback
No Pfam abstract.
External database links
MEROPS: | A4 |
SCOP: | 1s2b |
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.
Molecular function | aspartic-type endopeptidase activity (GO:0004190) |
Biological process | proteolysis (GO:0006508) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan Concanavalin (CL0004), which has the following description:
This superfamily includes a diverse range of carbohydrate binding domains and glycosyl hydrolase enzymes that share a common structure.
The clan contains the following 49 members:
Alginate_lyase2 ArabFuran-catal Arabino_trans_N Bac_rhamnosid Bact_lectin bCoV_S1_N Calreticulin Cleaved_Adhesin DUF1080 DUF1349 DUF1583 DUF1961 DUF2401 DUF3472 DUF4975 Exotox-A_bind Gal-bind_lectin GalBD_like GH131_N GH43_C2 Glyco_hydro_11 Glyco_hydro_12 Glyco_hydro_16 Glyco_hydro_32C Glyco_hydro_7 HA1 Laminin_G_1 Laminin_G_2 Laminin_G_3 Lectin_leg-like Lectin_legB MAM Methyltransf_FA Neuralized Pentaxin Peptidase_A4 Polysacc_lyase PRY Reoviridae_Vp9 Sial-lect-inser Sialidase SKN1 SPRY TgMIC1 Toxin_R_bind_N TSP_C VP4_haemagglut XET_C YrpDAlignments
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 (133) |
Full (1296) |
Representative proteomes | UniProt (2151) |
NCBI (2859) |
Meta (2) |
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RP15 (73) |
RP35 (518) |
RP55 (873) |
RP75 (1355) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
not generated,
— not available.
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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 (133) |
Full (1296) |
Representative proteomes | UniProt (2151) |
NCBI (2859) |
Meta (2) |
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---|---|---|---|---|---|---|---|---|---|
RP15 (73) |
RP35 (518) |
RP55 (873) |
RP75 (1355) |
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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: | MEROPS |
Previous IDs: | none |
Type: | Family |
Sequence Ontology: | SO:0100021 |
Author: |
Bateman A |
Number in seed: | 133 |
Number in full: | 1296 |
Average length of the domain: | 195.30 aa |
Average identity of full alignment: | 32 % |
Average coverage of the sequence by the domain: | 74.02 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 209 | ||||||||||||
Family (HMM) version: | 18 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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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_A4Structures
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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