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94  structures 437  species 0  interactions 13086  sequences 616  architectures

Family: Reprolysin (PF01421)

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

  1. Rawlings ND, Barrett AJ; , Meth Enzymol 1995;248:183-228.: Evolutionary families of metallopeptidases. PUBMED:7674922 EPMC:7674922

  2. 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

External database links

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.

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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB 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
(17)
Full
(13086)
Representative proteomes UniProt
(22749)
RP15
(1541)
RP35
(4260)
RP55
(10972)
RP75
(14954)
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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
(17)
Full
(13086)
Representative proteomes UniProt
(22749)
RP15
(1541)
RP35
(4260)
RP55
(10972)
RP75
(14954)
Alignment:
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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
(17)
Full
(13086)
Representative proteomes UniProt
(22749)
RP15
(1541)
RP35
(4260)
RP55
(10972)
RP75
(14954)
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: Swissprot
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 17
Number in full: 13086
Average length of the domain: 189.30 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 20.50 %

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 20.8 20.8
Trusted cut-off 20.8 20.8
Noise cut-off 20.7 20.7
Model length: 200
Family (HMM) version: 21
Download: download the raw HMM for this family

Species distribution

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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 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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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
A0A0G2JX23 View 3D Structure Click here
A0A0G2K0E8 View 3D Structure Click here
A0A0G2K229 View 3D Structure Click here
A0A0G2K693 View 3D Structure Click here
A0A0G2KI55 View 3D Structure Click here
A0A0G2KPG1 View 3D Structure Click here
A0A0R4IES1 View 3D Structure Click here
A0A0R4IHE4 View 3D Structure Click here
A0A0R4INJ8 View 3D Structure Click here
A0A0R4ISF7 View 3D Structure Click here
A0A1W2Q6C2 View 3D Structure Click here
A0A286Y999 View 3D Structure Click here
A0A2R8Q0T5 View 3D Structure Click here
A0A2R8Q4Q9 View 3D Structure Click here
A0A2R8Q748 View 3D Structure Click here
A0A2R8Q7V2 View 3D Structure Click here
A0A2R8Q9M6 View 3D Structure Click here
A0A2R8QAQ1 View 3D Structure Click here
A0A2R8QND5 View 3D Structure Click here
A0A2R8RLE2 View 3D Structure Click here
A0A5A4YQ91 View 3D Structure Click here
A2RSG8 View 3D Structure Click here
B0S6F1 View 3D Structure Click here
B2RSY5 View 3D Structure Click here
B2RUD9 View 3D Structure Click here
D3Z1A5 View 3D Structure Click here
D3Z8G4 View 3D Structure Click here
D3ZB52 View 3D Structure Click here
D3ZEP8 View 3D Structure Click here
D3ZIP6 View 3D Structure Click here
D3ZLL7 View 3D Structure Click here
D3ZMB0 View 3D Structure Click here
D3ZN23 View 3D Structure Click here
D3ZPM7 View 3D Structure Click here
D3ZT36 View 3D Structure Click here
D3ZTE7 View 3D Structure Click here
D3ZTJ3 View 3D Structure Click here
D3ZW34 View 3D Structure Click here
D3ZXM1 View 3D Structure Click here
D4A065 View 3D Structure Click here
D4A0T9 View 3D Structure Click here
D4A2E7 View 3D Structure Click here
D4AAT1 View 3D Structure Click here
D4ABB3 View 3D Structure Click here
D4AD55 View 3D Structure Click here
E7F494 View 3D Structure Click here
E7F698 View 3D Structure Click here
E7F6J8 View 3D Structure Click here
E7FCQ4 View 3D Structure Click here
E7FEJ5 View 3D Structure Click here
E7FEN5 View 3D Structure Click here
E7FFX0 View 3D Structure Click here
E7FGJ0 View 3D Structure Click here
E7FGU7 View 3D Structure Click here
E9PTA4 View 3D Structure Click here
E9PTQ3 View 3D Structure Click here
E9PUN6 View 3D Structure Click here
E9PX39 View 3D Structure Click here
E9Q287 View 3D Structure Click here
E9Q4D1 View 3D Structure Click here
F1LW54 View 3D Structure Click here
F1LWE4 View 3D Structure Click here
F1LXB5 View 3D Structure Click here
F1M8J6 View 3D Structure Click here
F1M9Z9 View 3D Structure Click here
F1Q4N9 View 3D Structure Click here
F1QDC4 View 3D Structure Click here
F1QF43 View 3D Structure Click here
F1QFD2 View 3D Structure Click here
F1QU24 View 3D Structure Click here
F1R6Q4 View 3D Structure Click here
F1R8A1 View 3D Structure Click here
F1RDA9 View 3D Structure Click here
F8VQ03 View 3D Structure Click here
F8W3T1 View 3D Structure Click here
G3V673 View 3D Structure Click here
G5ECS8 View 3D Structure Click here
G5EDW5 View 3D Structure Click here
G5EFD5 View 3D Structure Click here
M0R5P8 View 3D Structure Click here
O15072 View 3D Structure Click here
O15204 View 3D Structure Click here
O35227 View 3D Structure Click here
O35674 View 3D Structure Click here
O43184 View 3D Structure Click here
O43506 View 3D Structure Click here
O75077 View 3D Structure Click here
O75078 View 3D Structure Click here
O75173 View 3D Structure Click here
O88839 View 3D Structure Click here
O95450 View 3D Structure Click here
P57110 View 3D Structure Click here
P58397 View 3D Structure Click here
P58459 View 3D Structure Click here
P59384 View 3D Structure Click here
P59509 View 3D Structure Click here
P59510 View 3D Structure Click here
P59511 View 3D Structure Click here
P70505 View 3D Structure Click here
P78325 View 3D Structure Click here
P97776 View 3D Structure Click here
P97857 View 3D Structure Click here
Q05910 View 3D Structure Click here
Q13443 View 3D Structure Click here
Q13444 View 3D Structure Click here
Q19204 View 3D Structure Click here
Q19791 View 3D Structure Click here
Q19844 View 3D Structure Click here
Q1EHB3 View 3D Structure Click here
Q20930 View 3D Structure Click here
Q3B7V9 View 3D Structure Click here
Q3TTE0 View 3D Structure Click here
Q4VC17 View 3D Structure Click here
Q5BK84 View 3D Structure Click here
Q60718 View 3D Structure Click here
Q60813 View 3D Structure Click here
Q61072 View 3D Structure Click here
Q61824 View 3D Structure Click here
Q63180 View 3D Structure Click here
Q63202 View 3D Structure Click here
Q68SA9 View 3D Structure Click here
Q69Z28 View 3D Structure Click here
Q6IMH6 View 3D Structure Click here
Q6IMH7 View 3D Structure Click here
Q6QU65 View 3D Structure Click here
Q769J6 View 3D Structure Click here
Q76LX8 View 3D Structure Click here
Q7M762 View 3D Structure Click here
Q7M763 View 3D Structure Click here
Q7M766 View 3D Structure Click here
Q7ZYZ9 View 3D Structure Click here
Q811B3 View 3D Structure Click here
Q811Q3 View 3D Structure Click here
Q811Q4 View 3D Structure Click here
Q8BNJ2 View 3D Structure Click here
Q8C9W3 View 3D Structure Click here
Q8CGQ2 View 3D Structure Click here
Q8K410 View 3D Structure Click here
Q8R534 View 3D Structure Click here
Q8TC27 View 3D Structure Click here
Q8TE56 View 3D Structure Click here
Q8TE57 View 3D Structure Click here
Q8TE58 View 3D Structure Click here
Q8TE59 View 3D Structure Click here
Q8TE60 View 3D Structure Click here
Q8WXS8 View 3D Structure Click here
Q923W9 View 3D Structure Click here
Q99965 View 3D Structure Click here
Q9BZ11 View 3D Structure Click here
Q9ESP7 View 3D Structure Click here
Q9H013 View 3D Structure Click here
Q9H2U9 View 3D Structure Click here
Q9H324 View 3D Structure Click here
Q9JI76 View 3D Structure Click here
Q9JLN6 View 3D Structure Click here
Q9N5X7 View 3D Structure Click here
Q9P0K1 View 3D Structure Click here
Q9P2N4 View 3D Structure Click here
Q9QYV0 View 3D Structure Click here
Q9R001 View 3D Structure Click here
Q9R0X2 View 3D Structure Click here
Q9R157 View 3D Structure Click here
Q9R158 View 3D Structure Click here
Q9R159 View 3D Structure Click here
Q9R160 View 3D Structure Click here
Q9R1V4 View 3D Structure Click here
Q9R1V6 View 3D Structure Click here
Q9R1V7 View 3D Structure Click here
Q9UHI8 View 3D Structure Click here
Q9UKF2 View 3D Structure Click here
Q9UKF5 View 3D Structure Click here
Q9UKJ8 View 3D Structure Click here
Q9UKP4 View 3D Structure Click here
Q9UKP5 View 3D Structure Click here
Q9UKQ2 View 3D Structure Click here
Q9UNA0 View 3D Structure Click here
Q9UP79 View 3D Structure Click here
Q9W1Z6 View 3D Structure Click here
Q9W493 View 3D Structure Click here
Q9WUQ1 View 3D Structure Click here
Q9Y3Q7 View 3D Structure Click here
X2JE21 View 3D Structure Click here