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.
Internal database links
|SCOOP:||Peptidase_M11 Peptidase_M43 Zincin_1 Peptidase_M54 Peptidase_M66 Peptidase_M57 Reprolysin_2 Reprolysin_3 Reprolysin_4 Reprolysin_5|
|Similarity to PfamA using HHSearch:||Reprolysin_2 Reprolysin_3 Reprolysin_4 Reprolysin_5|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001590
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 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 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.
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)|
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- the UniProt description of the protein sequence
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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 58 members:Aspzincin_M35 Astacin BSP DUF1570 DUF2201_N DUF2268 DUF3152 DUF3267 DUF3633 DUF3810 DUF4157 DUF4344 DUF45 DUF4953 DUF955 HRXXH 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_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_M8 Peptidase_M9 Peptidase_M91 Peptidase_Mx Peptidase_Mx1 Peptidase_U49 Reprolysin Reprolysin_2 Reprolysin_3 Reprolysin_4 Reprolysin_5 SprT-like WLM Zn_peptidase Zn_peptidase_2
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
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Curation and family details
|Number in seed:||19|
|Number in full:||4366|
|Average length of the domain:||187.30 aa|
|Average identity of full alignment:||28 %|
|Average coverage of the sequence by the domain:||23.08 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||15|
|Download:||download the raw HMM for this family|
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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 82 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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