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236  structures 4540  species 0  interactions 22828  sequences 424  architectures

Family: Peptidase_M14 (PF00246)

Summary: Zinc carboxypeptidase

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Zinc carboxypeptidase". More...

Zinc carboxypeptidase Edit Wikipedia article

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Zinc carboxypeptidase Provide feedback

No Pfam abstract.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000834

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation which is usually zinc, but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophillic role. Many metalloproteases 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 sequences contain a diverse range of gene families, which include metallopeptidases belonging to MEROPS peptidase family M14 (carboxypeptidase A, clan MC), subfamilies M14A and M14B.

The carboxypeptidase A family can be divided into four subfamilies: M14A (carboxypeptidase A or digestive), M14B (carboxypeptidase H or regulatory), M14C (gamma-D-glutamyl-L-diamino acid peptidase I) and M14D (AGTPBP-1/Nna1-like proteins) [ PUBMED:7674922 , PUBMED:17244818 ]. Members of subfamily M14B have longer C-termini than those of subfamily M14A [ PUBMED:1449602 ], and carboxypeptidase M (a member of the H family) is bound to the membrane by a glycosylphosphatidylinositol anchor, unlike the majority of the M14 family, which are soluble [ PUBMED:7674922 ].

ATP/GTP binding protein (AGTPBP-1/Nna1)-like proteins are active metallopeptidases that act on cytosolic proteins such as alpha-tubulin, to remove a C-terminal tyrosine. Mutations in AGTPBP-1/Nna1 cause Purkinje cell degeneration (pcd). AGTPBP-1/Nna1-like proteins from the different phyla are highly diverse, but they all contain a unique N-terminal conserved domain right before the CP domain. It has been suggested that this N-terminal domain might act as a folding domain [ PUBMED:17244817 , PUBMED:11083920 , PUBMED:16952463 , PUBMED:18602413 ].

The zinc ligands have been determined as two histidines and a glutamate, and the catalytic residue has been identified as a C-terminal glutamate, but these do not form the characteristic metalloprotease HEXXH motif [ PUBMED:7674922 , PUBMED:6887246 ]. Members of the carboxypeptidase A family are synthesised as inactive molecules with propeptides that must be cleaved 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 ].

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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Pfam Clan

This family is a member of clan Peptidase_MH (CL0035), which has the following description:

This clan contains peptidases belonging to MEROPS clan MH, MC and MF. We also include Nicastrin that is part of the gamma secretase complex and not known to be a peptidase.

The clan contains the following 17 members:

Amidase_3 AstE_AspA DUF2817 DUF4910 FGase Gamma_PGA_hydro Glycolytic Ncstrn_small Nicastrin Peptidase_M14 Peptidase_M17 Peptidase_M18 Peptidase_M20 Peptidase_M28 Peptidase_M42 Peptidase_M99 SpoIIP

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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

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
(66)
Full
(22828)
Representative proteomes UniProt
(64531)
RP15
(3995)
RP35
(9922)
RP55
(20930)
RP75
(30901)
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PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

Format an alignment

  Seed
(66)
Full
(22828)
Representative proteomes UniProt
(64531)
RP15
(3995)
RP35
(9922)
RP55
(20930)
RP75
(30901)
Alignment:
Format:
Order:
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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
(66)
Full
(22828)
Representative proteomes UniProt
(64531)
RP15
(3995)
RP35
(9922)
RP55
(20930)
RP75
(30901)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

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: Prosite & Pfam-B_4832 (Release 7.5)
Previous IDs: Zn_carbOpept;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD , Bateman A
Number in seed: 66
Number in full: 22828
Average length of the domain: 247.30 aa
Average identity of full alignment: 18 %
Average coverage of the sequence by the domain: 45.15 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.6 21.6
Trusted cut-off 21.6 21.6
Noise cut-off 21.5 21.5
Model length: 287
Family (HMM) version: 26
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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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_M14 domain has been found. There are 236 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
A0A0H2UKN9 View 3D Structure Click here
A0A0P0WSN8 View 3D Structure Click here
A0A0R0I4R5 View 3D Structure Click here
A0A0R4I9C2 View 3D Structure Click here
A0A0R4IUK4 View 3D Structure Click here
A0A1B0GWW4 View 3D Structure Click here
A0A1D6HCX2 View 3D Structure Click here
A0A1D6KJA5 View 3D Structure Click here
A0A1D6QUJ6 View 3D Structure Click here
A0A1D8PJK3 View 3D Structure Click here
A0A1X7YGD9 View 3D Structure Click here
A0A2R8Q372 View 3D Structure Click here
A0A2R8QDT6 View 3D Structure Click here
A0A2R8QHK9 View 3D Structure Click here
A0A2R8RVA1 View 3D Structure Click here
A0A2R8S0L7 View 3D Structure Click here
A2RUV9 View 3D Structure Click here
A4I8N7 View 3D Structure Click here
A4IA60 View 3D Structure Click here
A4ICZ2 View 3D Structure Click here
A6H8T7 View 3D Structure Click here
A8WGN2 View 3D Structure Click here
B2GV17 View 3D Structure Click here
B2RS76 View 3D Structure Click here
B7Z0Z5 View 3D Structure Click here
B8JLQ9 View 3D Structure Click here
D3ZHS5 View 3D Structure Click here
D3ZNU5 View 3D Structure Click here
D3ZW78 View 3D Structure Click here
D4A3W7 View 3D Structure Click here
D4A536 View 3D Structure Click here
D4A9Q5 View 3D Structure Click here
E7F254 View 3D Structure Click here
E7F254 View 3D Structure Click here
E7F254 View 3D Structure Click here
E7F2H8 View 3D Structure Click here
E7F829 View 3D Structure Click here
E7F897 View 3D Structure Click here
E7FFQ7 View 3D Structure Click here
E7FFQ7 View 3D Structure Click here
E7FFQ7 View 3D Structure Click here
F1LYK5 View 3D Structure Click here
F1M4P0 View 3D Structure Click here
F1QJN9 View 3D Structure Click here
F1QL16 View 3D Structure Click here
F1QRY2 View 3D Structure Click here
F1QVD7 View 3D Structure Click here
F1RAC0 View 3D Structure Click here
G3MU29 View 3D Structure Click here
G3V8G1 View 3D Structure Click here
G5EC13 View 3D Structure Click here
G5EC96 View 3D Structure Click here
H2L0D7 View 3D Structure Click here
H2L0K5 View 3D Structure Click here
I1NH52 View 3D Structure Click here
K7KHN2 View 3D Structure Click here
K7KSJ5 View 3D Structure Click here
M9PEV1 View 3D Structure Click here
O17754 View 3D Structure Click here
O54858 View 3D Structure Click here
O74818 View 3D Structure Click here
O75976 View 3D Structure Click here
O75976 View 3D Structure Click here
O75976 View 3D Structure Click here
O76373 View 3D Structure Click here
O89001 View 3D Structure Click here
O89001 View 3D Structure Click here
O89001 View 3D Structure Click here
P00731 View 3D Structure Click here
P0ACV6 View 3D Structure Click here
P14384 View 3D Structure Click here
P15085 View 3D Structure Click here
P15086 View 3D Structure Click here
P15087 View 3D Structure Click here
P15088 View 3D Structure Click here
P15089 View 3D Structure Click here
P15169 View 3D Structure Click here
P16870 View 3D Structure Click here
P19222 View 3D Structure Click here
P19223 View 3D Structure Click here
P21961 View 3D Structure Click here
P38836 View 3D Structure Click here
P42787 View 3D Structure Click here
P42787 View 3D Structure Click here
P48052 View 3D Structure Click here
P91359 View 3D Structure Click here
Q00493 View 3D Structure Click here
Q09296 View 3D Structure Click here
Q09LZ8 View 3D Structure Click here
Q09M02 View 3D Structure Click here
Q09M05 View 3D Structure Click here
Q0E9F9 View 3D Structure Click here
Q22825 View 3D Structure Click here
Q4CSH9 View 3D Structure Click here
Q4D6P1 View 3D Structure Click here
Q4D725 View 3D Structure Click here
Q4DJX9 View 3D Structure Click here
Q4DXS8 View 3D Structure Click here
Q4U2V3 View 3D Structure Click here
Q504N0 View 3D Structure Click here
Q54I77 View 3D Structure Click here
Q5U2W3 View 3D Structure Click here
Q5U5Z8 View 3D Structure Click here
Q5U901 View 3D Structure Click here
Q5VU57 View 3D Structure Click here
Q640N1 View 3D Structure Click here
Q641K1 View 3D Structure Click here
Q66K79 View 3D Structure Click here
Q68EI3 View 3D Structure Click here
Q6A577 View 3D Structure Click here
Q6NSM5 View 3D Structure Click here
Q6P8K8 View 3D Structure Click here
Q6PHV5 View 3D Structure Click here
Q6YUT3 View 3D Structure Click here
Q7JYV3 View 3D Structure Click here
Q7TPZ8 View 3D Structure Click here
Q80V42 View 3D Structure Click here
Q8CDK2 View 3D Structure Click here
Q8CDP0 View 3D Structure Click here
Q8IMH9 View 3D Structure Click here
Q8IUX7 View 3D Structure Click here
Q8IVL8 View 3D Structure Click here
Q8N436 View 3D Structure Click here
Q8N4T0 View 3D Structure Click here
Q8NDL9 View 3D Structure Click here
Q8NEM8 View 3D Structure Click here
Q8R4H4 View 3D Structure Click here
Q8R4V4 View 3D Structure Click here
Q8WXQ8 View 3D Structure Click here
Q961J8 View 3D Structure Click here
Q96IY4 View 3D Structure Click here
Q96MI9 View 3D Structure Click here
Q96SM3 View 3D Structure Click here
Q9BL88 View 3D Structure Click here
Q9D2L5 View 3D Structure Click here
Q9EQV8 View 3D Structure Click here
Q9EQV9 View 3D Structure Click here
Q9JHH6 View 3D Structure Click here
Q9JHW1 View 3D Structure Click here
Q9JHW1 View 3D Structure Click here
Q9JHW1 View 3D Structure Click here
Q9JJN5 View 3D Structure Click here
Q9M9H7 View 3D Structure Click here
Q9TZC6 View 3D Structure Click here
Q9UI42 View 3D Structure Click here
Q9UPW5 View 3D Structure Click here
Q9VCM8 View 3D Structure Click here
Q9VL86 View 3D Structure Click here
Q9VL87 View 3D Structure Click here
Q9VLZ1 View 3D Structure Click here
Q9VLZ2 View 3D Structure Click here
Q9VRZ3 View 3D Structure Click here
Q9VS64 View 3D Structure Click here
Q9VS65 View 3D Structure Click here
Q9VS66 View 3D Structure Click here
Q9VS67 View 3D Structure Click here
Q9VS80 View 3D Structure Click here
Q9VX86 View 3D Structure Click here
Q9VY99 View 3D Structure Click here
Q9W475 View 3D Structure Click here
Q9W477 View 3D Structure Click here
Q9W478 View 3D Structure Click here
Q9XU75 View 3D Structure Click here
Q9Z100 View 3D Structure Click here