Summary: Peptidase family M13
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Peptidase family M13 Provide feedback
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.
Literature references
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Rawlings ND, Barrett AJ; , Meth Enzymol 1995;248:183-228.: Evolutionary families of metallopeptidases. PUBMED:7674922 EPMC:7674922
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Turner AJ, Isaac RE, Coates D; , Bioessays 2001;23:261-269.: The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function. PUBMED:11223883 EPMC:11223883
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Bianchetti L, Oudet C, Poch O; , Proteins 2002;47:481-488.: M13 endopeptidases: New conserved motifs correlated with structure, and simultaneous phylogenetic occurrence of PHEX and the bony fish. PUBMED:12001226 EPMC:12001226
External database links
MEROPS: | M13 |
SCOP: | 1dmt |
This tab holds annotation information from the InterPro database.
InterPro entry IPR008753
This entry represents the N-terminal domain of M13 peptidases.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].
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
Biological process | proteolysis (GO:0006508) |
Domain organisation
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Alignments
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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 (868) |
Full (8576) |
Representative proteomes | UniProt (18321) |
NCBI (27117) |
Meta (333) |
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RP15 (2305) |
RP35 (4882) |
RP55 (7434) |
RP75 (9768) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
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Seed (868) |
Full (8576) |
Representative proteomes | UniProt (18321) |
NCBI (27117) |
Meta (333) |
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RP15 (2305) |
RP35 (4882) |
RP55 (7434) |
RP75 (9768) |
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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: | Swiss-Prot |
Previous IDs: | none |
Type: | Family |
Sequence Ontology: | SO:0100021 |
Author: |
Studholme DJ |
Number in seed: | 868 |
Number in full: | 8576 |
Average length of the domain: | 344.50 aa |
Average identity of full alignment: | 21 % |
Average coverage of the sequence by the domain: | 53.06 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 382 | ||||||||||||
Family (HMM) version: | 13 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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Interactions
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_M13_N domain has been found. There are 19 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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