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34  structures 3469  species 0  interactions 12200  sequences 157  architectures

Family: Peptidase_M13 (PF01431)

Summary: Peptidase family M13

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Peptidase family M13 Provide feedback

Mammalian enzymes are typically type-II membrane anchored enzymes which are known, or believed to activate or inactivate oligopeptide (pro)-hormones such as opioid peptides. The family also contains a bacterial member believed to be involved with milk protein cleavage.

Literature references

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

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR018497

This group of metallopeptidases belong to the MEROPS peptidase family M13 (neprilysin family, clan MA(E)). The M13 family includes neprilysin (neutral endopeptidase, NEP, enkephalinase, CD10, CALLA, EC ), endothelin-converting enzyme I (ECE-1, EC ), erythrocyte surface antigen KELL (ECE-3), phosphate-regulating gene on the X chromosome (PHEX), soluble secreted endopeptidase (SEP), and damage-induced neuronal endopeptidase (DINE)/X-converting enzyme (XCE). These proteins consist of a short N-terminal cytoplasmic domain, a single transmembrane helix, and a larger C-terminal extracellular domain containing the active site. The cytoplasmic domain contains a conformationally-restrained octapeptide, which is thought to act as a stop transfer sequence that prevents proteolysis and secretion [ PUBMED:7674922 , PUBMED:3555489 ]. Proteins in this family fulfill a broad range of physiological roles due to the greater variation in the S2' subsite allowing substrate specificity [ PUBMED:7674922 , PUBMED:10849750 ]. The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA and the predicted active site residues for members of this family and thermolysin occur in the motif HEXXH [ PUBMED:7674922 ].

M13 peptidases are well-studied proteases found in a wide range of organisms including mammals and bacteria. In mammals they participate in processes such as cardiovascular development, blood-pressure regulation, nervous control of respiration, and regulation of the function of neuropeptides in the central nervous system. In bacteria they may be used for digestion of milk [ PUBMED:11223883 , PUBMED:7674922 ]. The family includes eukaryotic and prokaryotic oligopeptidases, as well as some of the proteins responsible for the molecular basis of the blood group antigens e.g. Kell [ PUBMED:7674922 ].

Neprilysin (NEP), is expressed in a variety of tissues including kidney and brain, and is involved in many physiological and pathological processes, including blood pressure and inflammatory response. It is a plasma membrane-bound mammalian enzyme that is able to digest biologically-active peptides, including enkephalins [ PUBMED:7674922 ], substance P, cholecystokinin, neurotensin and somatostatin. It is an important enzyme in the regulation of amyloid-beta (Abeta) protein that forms amyloid plaques that are associated with Alzeimers disease (AD). The zinc ligands of neprilysin are known and are analogous to those in thermolysin, a related peptidase [ PUBMED:7674922 , PUBMED:8099556 ]. Neprilysins, like thermolysin, are inhibited by phosphoramidon, which appears to selectively inhibit this family in mammals. The enzymes are all oligopeptidases, digesting oligo- and polypeptides, but not proteins [ PUBMED:7674922 ].

This entry represents the C-terminal domain of M13 peptidases.

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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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...

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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.

Representative proteomes UniProt
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Representative proteomes UniProt

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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...


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: Swiss-Prot
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A , Dudgeon T
Number in seed: 9
Number in full: 12200
Average length of the domain: 188.40 aa
Average identity of full alignment: 37 %
Average coverage of the sequence by the domain: 28.71 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.5 24.5
Trusted cut-off 24.5 24.5
Noise cut-off 24.4 24.4
Model length: 205
Family (HMM) version: 24
Download: download the raw HMM for this family

Species distribution

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Colour assignments

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


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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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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_M13 domain has been found. There are 34 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
A0A024B5K5 View 3D Structure Click here
A0A0B4K692 View 3D Structure Click here
A0A131MCS3 View 3D Structure Click here
A0A140LH71 View 3D Structure Click here
A0A5S9MNU9 View 3D Structure Click here
A1Z910 View 3D Structure Click here
D4A4U1 View 3D Structure Click here
E7FE30 View 3D Structure Click here
F1M761 View 3D Structure Click here
F1QE95 View 3D Structure Click here
F1R6K1 View 3D Structure Click here
F8W3A9 View 3D Structure Click here
G3V723 View 3D Structure Click here
G4SHR1 View 3D Structure Click here
G5ED52 View 3D Structure Click here
I6X8R2 View 3D Structure Click here
O16607 View 3D Structure Click here
O16636 View 3D Structure Click here
O16652 View 3D Structure Click here
O16789 View 3D Structure Click here
O16790 View 3D Structure Click here
O16795 View 3D Structure Click here
O16796 View 3D Structure Click here
O44857 View 3D Structure Click here
O45311 View 3D Structure Click here
O45569 View 3D Structure Click here
O95672 View 3D Structure Click here
P07861 View 3D Structure Click here
P08473 View 3D Structure Click here
P0C1T0 View 3D Structure Click here
P0DPD6 View 3D Structure Click here
P0DPD8 View 3D Structure Click here
P0DPD9 View 3D Structure Click here
P23276 View 3D Structure Click here
P42892 View 3D Structure Click here
P42893 View 3D Structure Click here
P70669 View 3D Structure Click here
P78562 View 3D Structure Click here
Q09946 View 3D Structure Click here
Q18673 View 3D Structure Click here