Summary: Reprolysin (M12B) family zinc metalloprotease
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Reprolysin (M12B) family zinc metalloprotease Provide feedback
The members of this family are enzymes that cleave peptides. These proteases require zinc for catalysis. Members of this family are also known as adamalysins. Most members of this family are snake venom endopeptidases, but there are also some mammalian proteins such as P78325 and fertilin Q28472. Fertilin and closely related proteins appear to not have some active site residues and may not be active enzymes.
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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Seals DF, Courtneidge SA; , Genes Dev 2003;17:7-30.: The ADAMs family of metalloproteases: multidomain proteins with multiple functions. PUBMED:12514095 EPMC:12514095
Internal database links
SCOOP: | Disintegrin Peptidase_M10 Reprolysin_2 Reprolysin_3 Reprolysin_4 Reprolysin_5 |
Similarity to PfamA using HHSearch: | Reprolysin_2 Reprolysin_3 Reprolysin_4 Reprolysin_5 |
External database links
HOMSTRAD: | svmp |
MEROPS: | M12 |
PROSITE: | PDOC00129 |
SCOP: | 1ast |
This tab holds annotation information from the InterPro database.
InterPro entry IPR001590
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 metallopeptidases belong to the MEROPS peptidase family M12, subfamily M12B (adamalysin family, clan (MA(M)). 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].
The M12B proteinases are also referred to as adamalysins or reprolysins [PUBMED:27196928, PUBMED:15922769]. The adamalysins are zinc dependent endopeptidases found in snake venom. There are some mammalian proteins such as SWISSPROT, and fertilin SWISSPROT. Fertilin and closely related proteins appear to not have some active site residues and may not be active enzymes.
CD156 (also called ADAM8 (EC) or MS2 human) has been implicated in extravasation of leukocytes.
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
Molecular function | metalloendopeptidase activity (GO:0004222) |
Biological process | proteolysis (GO:0006508) |
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_MA (CL0126), which has the following description:
Clan MA is one of two zinc-dependent metallopeptidases that contain the HEXXH motif. The two histidines are zinc ligands. The structures of this clan show the active site is between its two sub-domains.
The clan contains the following 74 members:
Aminopep Aspzincin_M35 Astacin ATLF BSP DA1-like DUF1570 DUF2201_N DUF2268 DUF3152 DUF3267 DUF3810 DUF3920 DUF4157 DUF4344 DUF45 DUF4953 DUF5700 DUF885 HRXXH Metallopep MPTase-PolyVal Peptidase_M1 Peptidase_M10 Peptidase_M11 Peptidase_M13 Peptidase_M2 Peptidase_M27 Peptidase_M3 Peptidase_M30 Peptidase_M32 Peptidase_M35 Peptidase_M36 Peptidase_M4 Peptidase_M41 Peptidase_M43 Peptidase_M48 Peptidase_M49 Peptidase_M4_C Peptidase_M50 Peptidase_M50B Peptidase_M54 Peptidase_M56 Peptidase_M57 Peptidase_M6 Peptidase_M60 Peptidase_M61 Peptidase_M64 Peptidase_M66 Peptidase_M7 Peptidase_M76 Peptidase_M78 Peptidase_M8 Peptidase_M85 Peptidase_M9 Peptidase_M90 Peptidase_M91 Peptidase_MA_2 Peptidase_Mx Peptidase_Mx1 Peptidase_U49 PhageMetallopep Reprolysin Reprolysin_2 Reprolysin_3 Reprolysin_4 Reprolysin_5 SprT-like UPF0054 WLM Zincin_1 Zincin_2 Zn_peptidase Zn_peptidase_2Alignments
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, the UniProtKB sequence database, 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 (18) |
Full (9446) |
Representative proteomes | UniProt (16164) |
NCBI (33357) |
Meta (29) |
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RP15 (1121) |
RP35 (2710) |
RP55 (6192) |
RP75 (9751) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
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not generated,
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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 (18) |
Full (9446) |
Representative proteomes | UniProt (16164) |
NCBI (33357) |
Meta (29) |
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RP15 (1121) |
RP35 (2710) |
RP55 (6192) |
RP75 (9751) |
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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: | Swissprot |
Previous IDs: | none |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Bateman A |
Number in seed: | 18 |
Number in full: | 9446 |
Average length of the domain: | 189.70 aa |
Average identity of full alignment: | 28 % |
Average coverage of the sequence by the domain: | 20.67 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 200 | ||||||||||||
Family (HMM) version: | 20 | ||||||||||||
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 Reprolysin domain has been found. There are 94 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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