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386  structures 5978  species 0  interactions 11306  sequences 91  architectures

Family: Peptidase_M17 (PF00883)

Summary: Cytosol aminopeptidase family, catalytic domain

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Cytosol aminopeptidase family, catalytic domain Provide feedback

The two associated zinc ions and the active site are entirely enclosed within the C-terminal catalytic domain in leucine aminopeptidase.

Literature references

  1. Burley SK, David PR, Taylor A, Lipscomb WN; , Proc Natl Acad Sci U S A 1990;87:6878-6882.: Molecular structure of leucine aminopeptidase at 2.7-A resolution. PUBMED:2395881 EPMC:2395881


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000819

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation which is usually zinc, but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophillic role. Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site [ PUBMED:7674922 ]. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases [ PUBMED:7674922 ].

This group of metallopeptidases belong to the MEROPS peptidase family M17 (leucyl aminopeptidase family, clan MF), the type example being leucyl aminopeptidase from Bos taurus (Bovine).

Aminopeptidases are exopeptidases involved in the processing and regular turnover of intracellular proteins, although their precise role in cellular metabolism is unclear [ PUBMED:1555602 , PUBMED:2395881 ]. Leucine aminopeptidases cleave leucine residues from the N-terminal of polypeptide chains, but substantial rates are evident for all amino acids [ PUBMED:2395881 ].

The enzymes exist as homo-hexamers, comprising 2 trimers stacked on top of one another [ PUBMED:2395881 ]. Each monomer binds 2 zinc ions and folds into 2 alpha/beta-type quasi-spherical globular domains, producing a comma-like shape [ PUBMED:2395881 ]. The N-terminal 150 residues form a 5-stranded beta-sheet with 4 parallel and 1 anti-parallel strand sandwiched between 4 alpha-helices [ PUBMED:2395881 ]. An alpha-helix extends into the C-terminal domain, which comprises a central 8-stranded saddle-shaped beta-sheet sandwiched between groups of helices, forming the monomer hydrophobic core [ PUBMED:2395881 ]. A 3-stranded beta-sheet resides on the surface of the monomer, where it interacts with other members of the hexamer [ PUBMED:2395881 ]. The 2 zinc ions and the active site are entirely located in the C-terminal catalytic domain [ PUBMED:2395881 ].

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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Pfam Clan

This family is a member of clan Peptidase_MH (CL0035), which has the following description:

This clan contains peptidases belonging to MEROPS clan MH, MC and MF. We also include Nicastrin that is part of the gamma secretase complex and not known to be a peptidase.

The clan contains the following 17 members:

Amidase_3 AstE_AspA DUF2817 DUF4910 FGase Gamma_PGA_hydro Glycolytic Ncstrn_small Nicastrin Peptidase_M14 Peptidase_M17 Peptidase_M18 Peptidase_M20 Peptidase_M28 Peptidase_M42 Peptidase_M99 SpoIIP

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
(655)
Full
(11306)
Representative proteomes UniProt
(48062)
RP15
(1898)
RP35
(5501)
RP55
(11158)
RP75
(18034)
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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
(655)
Full
(11306)
Representative proteomes UniProt
(48062)
RP15
(1898)
RP35
(5501)
RP55
(11158)
RP75
(18034)
Alignment:
Format:
Order:
Sequence:
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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
(655)
Full
(11306)
Representative proteomes UniProt
(48062)
RP15
(1898)
RP35
(5501)
RP55
(11158)
RP75
(18034)
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_990 (release 3.0)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Griffiths-Jones SR
Number in seed: 655
Number in full: 11306
Average length of the domain: 296.20 aa
Average identity of full alignment: 38 %
Average coverage of the sequence by the domain: 61.75 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 25.1 25.0
Noise cut-off 24.3 24.9
Model length: 311
Family (HMM) version: 23
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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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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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_M17 domain has been found. There are 386 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
A0A0C4FEI8 View 3D Structure Click here
A0A1D6EKT0 View 3D Structure Click here
A0A1D6GRR2 View 3D Structure Click here
A0A1D6H8U7 View 3D Structure Click here
A0A1D6HN63 View 3D Structure Click here
A0A1D6KCG4 View 3D Structure Click here
A0A1D6KD06 View 3D Structure Click here
A0A1D6KID2 View 3D Structure Click here
A1Z9G3 View 3D Structure Click here
A2BIC6 View 3D Structure Click here
A4HUX2 View 3D Structure Click here
A4HUX3 View 3D Structure Click here
A4I0E4 View 3D Structure Click here
A4I996 View 3D Structure Click here
D4A3E2 View 3D Structure Click here
F1Q6S1 View 3D Structure Click here
F1QPJ6 View 3D Structure Click here
I1JGP8 View 3D Structure Click here
I1MT23 View 3D Structure Click here
I1N7G4 View 3D Structure Click here
K7MGH8 View 3D Structure Click here
P28838 View 3D Structure Click here
P30184 View 3D Structure Click here
P34629 View 3D Structure Click here
P37095 View 3D Structure Click here
P68767 View 3D Structure Click here
P9WHT3 View 3D Structure Click here
Q09735 View 3D Structure Click here
Q27245 View 3D Structure Click here
Q2FZV6 View 3D Structure Click here
Q2QSB9 View 3D Structure Click here
Q4D4Y0 View 3D Structure Click here
Q4DEX4 View 3D Structure Click here
Q4DZJ3 View 3D Structure Click here
Q4E2R9 View 3D Structure Click here
Q500X4 View 3D Structure Click here
Q5V9F0 View 3D Structure Click here
Q68FS4 View 3D Structure Click here
Q6K669 View 3D Structure Click here
Q6NSR8 View 3D Structure Click here
Q7K2S9 View 3D Structure Click here
Q7K5K9 View 3D Structure Click here
Q8IL11 View 3D Structure Click here
Q8NDH3 View 3D Structure Click here
Q8RX72 View 3D Structure Click here
Q944P7 View 3D Structure Click here
Q95R35 View 3D Structure Click here
Q961W5 View 3D Structure Click here
Q9CPY7 View 3D Structure Click here
Q9VFQ9 View 3D Structure Click here
Q9VSM6 View 3D Structure Click here
Q9VSM7 View 3D Structure Click here