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24  structures 167  species 2  interactions 1016  sequences 15  architectures

Family: Propep_M14 (PF02244)

Summary: Carboxypeptidase activation peptide

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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.

Carboxypeptidase activation peptide Provide feedback

Carboxypeptidases are found in abundance in pancreatic secretions. The pro-segment moiety (activation peptide) accounts for up to a quarter of the total length of the peptidase, and is responsible for modulation of folding and activity of the pro-enzyme.

Literature references

  1. Aloy P, Catasus L, Villegas V, Reverter D, Vendrell J, Aviles FX; , Biol Chem 1998;379:149-155.: Comparative analysis of the sequences and three-dimensional models of human procarboxypeptidases A1, A2 and B. PUBMED:9524066 EPMC:9524066


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003146

Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors, respectively. In many cases they are synthesised as part of a larger precursor protein, either as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. This domain prevents access of the substrate to the active site. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen. Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism; while yet others use a conformational change-based trapping mechanism that depends on their structural and thermodynamic properties.

The peptidases are synthesised as inactive molecules, zymogens, with propeptides that must be removed by proteolytic cleavage to activate the enzyme. Structural studies of carboxypeptidases A and B reveal the propeptide to exist as a globular domain, followed by an extended alpha-helix; this shields the catalytic site, without specifically binding to it, while the substrate-binding site is blocked by making specific contacts [PUBMED:7674922, PUBMED:1548696].

Members of this propeptide family are found in the metallocarboxypeptidases: A1, A2 [PUBMED:9384570], A3, A4, A5, A6, U, insect gut carboxypeptidase and B [PUBMED:12162965], and and are associated with peptidases belonging to MEROPS peptidase family M14A.

Carboxypeptidases are found in abundance in pancreatic secretions. The pro-segment moiety (activation peptide) accounts for up to a quarter of the total length of the peptidase.

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
(103)
Full
(1016)
Representative proteomes NCBI
(999)
Meta
(1)
RP15
(141)
RP35
(201)
RP55
(408)
RP75
(581)
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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
(103)
Full
(1016)
Representative proteomes NCBI
(999)
Meta
(1)
RP15
(141)
RP35
(201)
RP55
(408)
RP75
(581)
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
(103)
Full
(1016)
Representative proteomes NCBI
(999)
Meta
(1)
RP15
(141)
RP35
(201)
RP55
(408)
RP75
(581)
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.

Pfam alignments:

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_2335 (release 5.2)
Previous IDs: none
Type: Domain
Author: Bateman A, Mian N
Number in seed: 103
Number in full: 1016
Average length of the domain: 73.10 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 16.68 %

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 22.1 22.1
Trusted cut-off 22.1 22.2
Noise cut-off 22.0 22.0
Model length: 74
Family (HMM) version: 11
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

Trypsin Peptidase_M14

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 Propep_M14 domain has been found. There are 24 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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