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68  structures 230  species 1  interaction 802  sequences 14  architectures

Family: Peptidase_M2 (PF01401)

Summary: Angiotensin-converting enzyme

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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.

Angiotensin-converting enzyme Provide feedback

Members of this family are dipeptidyl carboxydipeptidases (cleave carboxyl dipeptides) and most notably convert angiotensin I to angiotensin II. Many members of this family contain a tandem duplication of the 600 amino acid peptidase domain, both of these are catalytically active. Most members are secreted membrane bound ectoenzymes.

Literature references

  1. Isaac RE, Schoofs L, Williams TA, Corvol P, Veelaert D, Sajid M, Coates D; , Ann N Y Acad Sci 1998;839:288-292.: Toward a role for angiotensin-converting enzyme in insects. PUBMED:9629165 EPMC:9629165

  2. Corvol P, Williams TA, Soubrier F; , Methods Enzymol 1995;248:283-305.: Peptidyl dipeptidase A: angiotensin I-converting enzyme. PUBMED:7674927 EPMC:7674927


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001548

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 group of metallopeptidases belong to the MEROPS peptidase family M2 (clan MA(E)). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA. The catalytic residues and zinc ligands have been identified, the zinc ion being ligated to two His residues within the motif HEXXH, showing that the enzyme belongs to the E sub-group of metalloproteases [PUBMED:7674922].

Pepetidyl-dipeptidase A (angiotensin-converting enzyme) is a mammalian enzyme responsible for cleavage of dipeptides from the C-termini of proteins, notably converting angiotensin I to angiotensin II [PUBMED:7674922]. The enzyme exists in two differentially transcribed forms, the most common of which is from lung endothelium; this contains two homologous domains that have arisen by gene duplication [PUBMED:7674922]. The testis-specific form contains only the C-terminal domain, arising from a duplicated promoter region present in intron 12 of the gene [PUBMED:7674922]. Both enzymatic forms are membrane proteins that are anchored by means of a C-terminal transmembrane domain. Both domains of the endothelial enzyme are active, but have differing kinetic constants [PUBMED:7674922]. PUBMED:1851160]. A number of insect enzymes have been shown to be similar to peptidyl-dipeptidase A, these containing a single catalytic domain.

Gene Ontology

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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
(6)
Full
(802)
Representative proteomes NCBI
(817)
Meta
(299)
RP15
(164)
RP35
(207)
RP55
(346)
RP75
(446)
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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
(6)
Full
(802)
Representative proteomes NCBI
(817)
Meta
(299)
RP15
(164)
RP35
(207)
RP55
(346)
RP75
(446)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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
(6)
Full
(802)
Representative proteomes NCBI
(817)
Meta
(299)
RP15
(164)
RP35
(207)
RP55
(346)
RP75
(446)
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: Swiss-Prot
Previous IDs: none
Type: Family
Author: Bateman A, Coates D
Number in seed: 6
Number in full: 802
Average length of the domain: 468.30 aa
Average identity of full alignment: 35 %
Average coverage of the sequence by the domain: 85.85 %

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 19.4 19.4
Trusted cut-off 19.5 19.5
Noise cut-off 18.7 19.3
Model length: 595
Family (HMM) version: 13
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

Peptidase_M2

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_M2 domain has been found. There are 68 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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