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201  structures 5099  species 3  interactions 20523  sequences 77  architectures

Family: Peptidase_M24 (PF00557)

Summary: Metallopeptidase family M24

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.

Metallopeptidase family M24 Provide feedback

This family contains metallopeptidases. It also contains non-peptidase homologues such as the N terminal domain of Spt16 which is a histone H3-H4 binding module [3].

Literature references

  1. Roderick SL, Matthews BW , Biochemistry 1993;32:3907-3912.: Structure of the cobalt-dependent methionine aminopeptidase from Escherichia coli: a new type of proteolytic enzyme. PUBMED:8471602 EPMC:8471602

  2. Rawlings ND, Barrett AJ; , Meth Enzymol 1995;248:183-228.: Evolutionary families of metallopeptidases. PUBMED:7674922 EPMC:7674922

  3. Stuwe T, Hothorn M, Lejeune E, Rybin V, Bortfeld M, Scheffzek K, Ladurner AG; , Proc Natl Acad Sci U S A. 2008;105:8884-8889.: The FACT Spt16 "peptidase" domain is a histone H3-H4 binding module. PUBMED:18579787 EPMC:18579787


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000994

In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:

  • Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, N-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.
  • Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; N, asparagine; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule. In the case of the asparagine endopeptidases, the nucleophile is asparagine and all are self-processing endopeptidases.

In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding.

Metalloproteases are the most diverse of the four main types of protease, with more than 50 families identified to date. In these enzymes, a divalent cation, usually zinc, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. The known metal ligands are His, Glu, Asp or Lys and at least one other residue is required for catalysis, which may play an electrophillic role. Of the known metalloproteases, around half 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 entry contains proteins that belong to MEROPS peptidase family M24 (clan MG), which share a common structural-fold, the "pita-bread" fold. The fold contains both alpha helices and an anti-parallel beta sheet within two structurally similar domains that are thought to be derived from an ancient gene duplication. The active site, where conserved, is located between the two domains. The fold is common to methionine aminopeptidase (EC), aminopeptidase P (EC), prolidase (EC), agropine synthase and creatinase (EC). Though many of these peptidases require a divalent cation, creatinase is not a metal-dependent enzyme [PUBMED:8146141, PUBMED:12136144, PUBMED:8471602].

The entry also contains proteins that have lost catalytic activity, for example Spt16, which is a component of the FACT complex. The crystal structure of the N-terminal domain of Spt16, determined to 2.1A, reveals an aminopeptidase P fold whose enzymatic activity has been lost. This fold binds directly to histones H3-H4 through a interaction with their globular core domains, as well as with their N-terminal tails [PUBMED:18579787].

The FACT complex is a stable heterodimer in Saccharomyces cerevisiae (Baker's yeast) comprising Spt16p (SWISSPROT, INTERPRO) and Pob3p (SWISSPROT, INTERPRO). The complex plays a role in transcription initiation and promotes binding of TATA-binding protein (TBP) to a TATA box in chromatin [PUBMED:15987999]; it also facilitates RNA Polymerase II transcription elongation through nucleosomes by destabilising and then reassembling nucleosome structure [PUBMED:12524332, PUBMED:12934006, PUBMED:18579787].

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, 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
(656)
Full
(20523)
Representative proteomes NCBI
(15852)
Meta
(9743)
RP15
(2007)
RP35
(3696)
RP55
(5023)
RP75
(5995)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

Format an alignment

  Seed
(656)
Full
(20523)
Representative proteomes NCBI
(15852)
Meta
(9743)
RP15
(2007)
RP35
(3696)
RP55
(5023)
RP75
(5995)
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
(656)
Full
(20523)
Representative proteomes NCBI
(15852)
Meta
(9743)
RP15
(2007)
RP35
(3696)
RP55
(5023)
RP75
(5995)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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: SCOP
Previous IDs: pep_M24;
Type: Domain
Author: Bateman A
Number in seed: 656
Number in full: 20523
Average length of the domain: 218.60 aa
Average identity of full alignment: 23 %
Average coverage of the sequence by the domain: 58.35 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.7 20.7
Trusted cut-off 20.7 20.7
Noise cut-off 20.6 20.5
Model length: 207
Family (HMM) version: 19
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 3 interactions for this family. More...

Peptidase_M24 AMP_N Creatinase_N

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_M24 domain has been found. There are 201 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.

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