Family M12


Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq


Summary Holotypes Alignment Tree Genomes Literature


Summary Holotypes Alignment Tree Genomes Literature

Summary for family M12

NamePeptidase family M12 (astacin/adamalysin family)
Family type peptidaseM12.001 - astacin (Astacus astacus), MEROPS Accession MER0001104 (peptidase unit: 56-243)
Content of familyPeptidase family M12 contains metalloendopeptidases.
History Identifier created: Biochem.J. 290:205-218 (1993)
The study of a crayfish digestive enzyme (astacin, M12.001) led to the discovery of one of the largest families of metallopeptidases, containing the adamalysin ('ADAM') peptidases, the snake venom metallopeptidases (reprolysins) and many other related enzymes (Dumermuth et al., 1991; Seals & Courtneidge, 2003). A book published in 2004 contained 63 chapters on individual peptidases of family M12 (Barrett et al., 2004). Several dedicated websites provide information on aspects of family M12, and links to these are provided on our Community page.
Much of the communication between scientists working on family M12 peptidases is impeded by the unfortunate 'ADAM' terminology that requires the definition of the acronym as 'A Disintegrin and A Metallopeptidase' to be spelled out in almost every publication. In the interests of easier communication, MEROPS recommends wider use of names based on 'adamalysin' (e.g. Gomis-Ruth et al., 1993; Kang et al., 2002; Butler et al., 2004).
Catalytic typeMetallo
Active siteThere is a motif His-Glu-Xaa-Xaa-His-Xaa-Xaa-Gly-Xaa-Xaa-His (see the Alignments) in which the three His residues are ligands of a zinc atom and the Glu has a catalytic role.
Activities and specificitiesMany of the peptidases occur as proenzymes that require activation by limited proteolysis. Activity may be regulated in the proenzymes in subfamily B by a "cysteine switch" mechanism (Grams et al., 1993) similar to that in subfamily A of family M10. The mature enzymes are all endopeptidases, with widely varied specificities. Procollagen C-peptidase (M12.005) has specificity for -XaaAsp- bonds, as does flavastacin (M12.066), the only known member of the family from a bacterium. In general, the peptidases in the family have much broader specificities, however.
InhibitorsMetal chelating agents such as 1,10-phenanthroline inhibit, as is expected for metallopeptidases. Selective synthetic inhibitors have been described, although many of them also affect peptidases in family M10 (Zhang et al., 2004; Delaet et al., 2004; Skotnicki et al., 2003). Physiological inhibitors include alpha2-macroglobulin (as for almost all endopeptidases) and, for some members of the family, timp-3 (Lee et al., 2002).
Molecular structureCrystal structures are available for peptidases from both subfamilies. They show peptidase units with the 'metzincin' fold of subclan M of clan MA in which a conserved methionine C-terminal to the zinc ligands forms what is known as a "Met-turn" (Bode et al., 1993). A variety of non-peptidase domains are present C-terminally to the peptidase domain in various members of the family. These include MAM, MATH, AM and EGF domains in the meprin subunits (Bertenshaw & Bond, 2004), disintegrin-like domains in the adamalysin or 'ADAM' peptidases (Wolfsberg et al., 1995) and thrombospondin domains in the adamalysin-thrombospondin or 'ADAM-TS' proteins (Apte, 2004).
Basis of clan assignmentProtein fold of the peptidase unit for members of this family resembles that of thermolysin, the type example for clan MA.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses -  
Biological functionsThe peptidases are generally secreted proteins, synthesised with signal peptides and propeptides. Biological roles have been investigated for many of them. Astacin (M12.001) is secreted into the digestive system of the crayfish Astacus, meprins A and B (M12.002, M12.004, XM12-001) are embedded in mammalian cell membranes, adamalysin (M12.141) is a component of rattlesnake venom. Other mammalian examples are ADAM17 endopeptidase (M12.217) also known as tumor necrosis factor-alpha converting enzyme, which is responsible for important limited proteolysis events, and the ADAMTS13 endopeptidase (M12.241), also known as von Willebrand factor protease, the activity of which normally prevents von Willebrand disease.
Pharmaceutical and biotech relevanceThrough their membrane-bound and soluble extracellular activities the family M12 peptidases have many functions that can be of importance to human health and disease, and a number of potential drug targets are emerging (Moss & Bartsch, 2004; Duffy et al., 2003).
Statistics for family M12Sequences:17637
Identifiers with PDB entries:33
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily M12A
Name Peptidase subfamily M12A
Subfamily type peptidase M12.001 - astacin (Astacus astacus), MEROPS Accession MER0001104 (peptidase unit: 56-243)
Active site residues H141 E142 H145 H151 
Statistics Sequences: 8889
Identifiers: 72
Identifiers with PDB entries: 5
Other databases CATH 3.40.390.10
HSSP 1ast
PFAM PF01400
SCOP 55516
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
meprin alpha subunitM12.002Yes
procollagen C-peptidaseM12.005Yes
choriolysin LM12.006-
choriolysin HM12.007Yes
blastula protease 10 (Paracentrotus)M12.012-
SpAN g.p. (Strongylocentrotus purpuratus)M12.013-
hatching enzyme (Xenopus-type)M12.014-
vertebrate tolloid-like 1 proteinM12.016Yes
HMP1-type peptidaseM12.017-
mammalian-type tolloid-like 2 proteinM12.018-
LAST peptidase (Limulus-type)M12.032-
LAST_MAM peptidase (Limulus-type)M12.033-
metallopeptidase MTP-1M12.310-
NAS-37 peptidaseM12.318-
NAS-36 peptidaseM12.319-
TOH-2 peptidaseM12.321-
avian-type hatching enzymeM12.324-
seminal metalloprotease-1 (Drosophila melanogaster) and similarM12.330-
LALP peptidase (Loxosceles intermedia)M12.333-
CG6974 protein (Drosophila melanogaster)M12.A01-
CG10280 protein (Drosophila melanogaster)M12.A02-
CG5715 protein (Drosophila melanogaster)M12.A06-
CG6763 protein (Drosophila melanogaster)M12.A07-
CG6696 protein (Drosophila melanogaster)M12.A08-
CG15254 protein (Drosophila melanogaster)M12.A09-
CG15253 protein (Drosophila melanogaster)M12.A10-
CG11865 protein (Drosophila melanogaster)M12.A11-
BG:BACR44L22.6 protein (Drosophila melanogaster)M12.A12-
BG:BACR44L22.1 protein (Drosophila melanogaster)M12.A13-
NAS-1 peptidase (Caenorhabditis elegans)M12.A14-
NAS-2 peptidase (Caenorhabditis elegans)M12.A15-
NAS-3 peptidase (Caenorhabditis elegans)M12.A16-
TOH-1 peptidase (Caenorhabditis elegans)M12.A17-
nas-7 g.p. (Caenorhabditis elegans)M12.A18-
nas-4 g.p. (Caenorhabditis elegans)M12.A19-
nas-12 g.p. (Caenorhabditis elegans)M12.A20-
nas-8 g.p. (Caenorhabditis elegans)M12.A21-
nas-9 g.p. (Caenorhabditis elegans)M12.A22-
nas-14 g.p. (Caenorhabditis elegans)M12.A23-
nas-39 g.p. (Caenorhabditis elegans)M12.A24-
hch-1 g.p. (Caenorhabditis elegans)M12.A25-
nas-28 g.p. (Caenorhabditis elegans)M12.A26-
nas-25 g.p. (Caenorhabditis elegans)M12.A27-
nas-38 g.p. (Caenorhabditis elegans)M12.A28-
nas-29 g.p. (Caenorhabditis elegans)M12.A29-
K03D8.1 g.p. (Caenorhabditis elegans)M12.A30-
K03D8.2 g.p. (Caenorhabditis elegans)M12.A31-
K03D8.3 g.p. (Caenorhabditis elegans)M12.A32-
K03D8.5 g.p. (Caenorhabditis elegans)M12.A33-
nas-33 g.p. (Caenorhabditis elegans)M12.A34-
nas-10 g.p. (Caenorhabditis elegans)M12.A35-
nas-11 g.p. (Caenorhabditis elegans)M12.A36-
nas-23 g.p. (Caenorhabditis elegans)M12.A37-
nas-13 g.p. (Caenorhabditis elegans)M12.A38-
nas-24 g.p. (Caenorhabditis elegans)M12.A39-
nas-32 g.p. (Caenorhabditis elegans)M12.A40-
nas-15 g.p. (Caenorhabditis elegans)M12.A41-
nas-20 g.p. (Caenorhabditis elegans)M12.A42-
nas-22 g.p. (Caenorhabditis elegans)M12.A43-
nas-27 g.p. (Caenorhabditis elegans)M12.A44-
nas-5 g.p. (Caenorhabditis elegans)M12.A45-
nas-30 g.p. (Caenorhabditis elegans)M12.A46-
subfamily M12A non-peptidase homologuesnon-peptidase homologue-
subfamily M12B non-peptidase homologuesnon-peptidase homologue-
subfamily M12A unassigned peptidasesunassigned-
Subfamily M12B
Name Peptidase subfamily M12B
Subfamily type peptidase M12.141 - adamalysin (Crotalus adamanteus), MEROPS Accession MER0001125 (peptidase unit: 1-203)
Active site residues H143 E144 H147 H153 
Statistics Sequences: 8743
Identifiers: 160
Identifiers with PDB entries: 28
Other databases CATH 3.40.390.10
HSSP 1iag
PFAM PF01421
PFAM PF13574
PFAM PF13582
PFAM PF13583
PFAM PF13688
SCOP 55519
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
MIG-17 peptidaseM12.019-
ADAM28 peptidase (mouse-type)M12.020-
ADAMTS9 peptidaseM12.021-
brevilysin H6M12.022-
ADAMTS14 peptidaseM12.024-
ADAMTS15 peptidaseM12.025-
ADAMTS16 peptidaseM12.026-
ADAMTS17 peptidaseM12.027-
ADAMTS18 peptidaseM12.028-
ADAMTS19 peptidaseM12.029-
Mername-AA298 peptidaseM12.030-
peptidase similar to ADAMTS-9 peptidaseM12.031-
acutolysin AM12.131Yes
bilitoxin (Agkistrodon bilineatus)M12.132-
halylysin aM12.134-
gon-1 peptidaseM12.135-
BHRa hemorrhagin (Bitis arietans)M12.137-
atrolysin AM12.142-
atrolysin BM12.143-
atrolysin CM12.144Yes
atrolysin EM12.145-
atrolysin FM12.146-
fibrinolytic peptidase (Philodryas olfersii)M12.153-
trimerelysin IM12.154-
trimerelysin IIM12.155Yes
trimerelysin IIAM12.156-
venom metallopeptidase PREHM12.160-
kistomin (Calloselasma rhodostoma)M12.161Yes
mutalysin IIM12.162-
graminelysin (Trimeresurus gramineus)M12.163-
hemorrhagin VRH-1 (Daboia russellii)M12.165-
BaH1 peptidase (Bothrops asper)M12.166-
alpha peptidase (Crotalus atrox)M12.168-
metallopeptidase B (Bothrops moojeni)M12.169-
jararafibrase II (Bothrops jararaca)M12.170-
HT-1 peptidase (Crotalus viridis)M12.171-
hemorrhagic toxin I (Crotalus ruber)M12.175-
fibrinolytic peptidase M5 (Crotalus molossus)M12.176-
brevilysin L6M12.178-
bilitoxin 2 (Agkistrodon bilineatus)M12.179-
hemorrhagic factor a (Trimeresurus mucrosqamatus)M12.181-
hemorrhagic metallopeptidase a (Trimeresurus mucrosquamatus)M12.182-
hemorrhagic metallopeptidase b (Trimeresurus mucrosquamatus)M12.183-
mutalysin IM12.184-
vascular apoptosis-inducing protein 1M12.186Yes
ADAMTS20 peptidase (mouse-type)M12.188-
Mername-AA254 peptidaseM12.189-
ADAM1 peptidaseM12.201-
ADAM1A peptidaseM12.202-
Adam1B g.p. (Mus musculus)M12.203-
ADAM8 peptidaseM12.208Yes
ADAM9 peptidaseM12.209Yes
ADAM10 peptidaseM12.210Yes
Kuzbanian peptidase (non-mammalian)M12.211-
ADAM12 peptidaseM12.212-
ADAM13 peptidaseM12.213-
ADAM19 peptidaseM12.214-
ADAM15 peptidaseM12.215-
jerdohagin (Trimeresurus jerdonii)M12.216-
ADAM17 peptidaseM12.217Yes
ADAM20 peptidaseM12.218-
ADAMDEC1 peptidaseM12.219-
ADAMTS3 peptidaseM12.220-
ADAMTS4 peptidaseM12.221Yes
ADAMTS1 peptidaseM12.222Yes
ADAM28 peptidase (Homo sapiens-type)M12.224-
ADAMTS5 peptidaseM12.225Yes
ADAMTS8 peptidaseM12.226-
ADAM24 peptidaseM12.227-
ADAM25 peptidaseM12.228-
ADAM26 peptidaseM12.229-
ADAMTS6 peptidaseM12.230-
ADAMTS7 peptidaseM12.231-
ADAM30 peptidaseM12.232-
ADAM31 peptidase (rodent)M12.233-
ADAM21 peptidase (Homo sapiens-type)M12.234-
ADAMTS10 peptidaseM12.235-
ADAMTS12 peptidaseM12.237-
membrane-anchored metallopeptidase (Xenopus laevis)M12.238-
Mername-AA107 peptidaseM12.240-
ADAMTS13 peptidaseM12.241Yes
TM-3 peptidase (Trimeresurus mucrosquamatus)M12.242Yes
testase 4M12.243-
ADAM33 peptidaseM12.244Yes
ADAMTS20 peptidase (Homo sapiens-type)M12.246-
peptidase similar to ADAM 21 peptidase (Mus musculus)M12.247-
peptidase similar to ADAMTS-6 peptidase (Mus musculus-type)M12.248-
procollagen I N-peptidaseM12.301-
ADAMTS adt-1 (Caenorhabditis elegans)-type peptidaseM12.302-
acutolysin CM12.303-
jararafibrase III (Bothrops jararaca)M12.304-
jararafibrase IV (Bothrops jararaca)M12.305-
BHRb haemorrhagin (Bitis arietans)M12.306-
halylysin bM12.307-
halylysin cM12.308-
hemorrhagic toxin I (Gloydius halys blomhoffii)M12.309-
BaP1 peptidase (Bothrops asper)M12.311Yes
neuwiedase (Bothrops neuwiedi)M12.312-
EBR1 peptidaseM12.314-
triflamp (Trimeresurus flavoviridis)M12.316-
acutolysin DM12.317-
hemorrhagic factor 3 (Bothrops jararaca)-like peptidaseM12.320-
Kuzbanian-like peptidaseM12.322-
insularinase AM12.325-
brevilysin L4M12.326Yes
SUP-17 peptidase (Caenorhabditis elegans) and similarM12.328-
ADM-4 peptidase (Caenorhabditis elegans)M12.329-
fibrinogenase-2 (Deinagkistrodon acutus)M12.334-
baltergin (Bothrops alternatus)M12.335-
PCADAM-type peptidaseM12.336-
acutolysin FM12.337Yes
BmooMPalpha-I (Bothrops sp.)M12.338Yes
BmHF-1 (Bothrops marajoensis)M12.339-
BJ-PI peptidaseM12.340-
bothrojaractivase (Bothrops jararaca)M12.341-
ADAM41 peptidase (Xenopus tropicalis)M12.343-
protease A (Bitis arietans)M12.344-
moojeni peptidase AM12.345-
ADAM2 proteinM12.950-
ADAM3 protein (rodent-type)M12.951-
ADAM4 proteinM12.952-
ADAM5 proteinM12.953-
ADAM6 proteinM12.954-
ADAM7 proteinM12.956-
ADAM18 proteinM12.957-
ADAM27 protein (Mus musculus)M12.958-
tMDC V protein (Rattus)M12.959-
ADAM32 proteinM12.960-
non-peptidase homologue (Homo sapiens chromosome 4)M12.962-
family M12 non-peptidase homologue (Homo sapiens chromosome 16)M12.963-
family M12 non-peptidase homologue (Homo sapiens chromosome 15)M12.964-
ADAM3B protein (Homo sapiens-type)M12.975-
ADAM11 proteinM12.976-
ADAM22 proteinM12.978Yes
ADAM23 proteinM12.979-
ADAM29 proteinM12.981-
Mername-AA112 homologueM12.982-
Mername-AA113 homologueM12.983-
protein similar to ADAM29 peptidase isoform 1 peptidaseM12.984-
protein similar to ADAM26 peptidase (Mus musculus-type)M12.985-
protein similar to ADAM21 peptidase (Mus musculus)M12.986-
protein similar to ADAM21 peptidase preproprotein (Homo sapiens)M12.987-
protein similar to ADAM25 peptidase (Rattus norvegicus)M12.988-
ADAM6 peptidase (mouse-type)M12.989-
Mername-AA225 peptidase homologue (Homo sapiens)M12.990-
Adam6B g.p. (Mus musculus)M12.992-
Mername-AA235 peptidase homologue (Mus musculus)M12.993-
ADAM34 (Mus musculus)-type proteinM12.994-
ADAMTS-A (Drosophila melanogaster)M12.A03-
CG7649 protein (Drosophila melanogaster)M12.A04-
CG4096 protein (Drosophila melanogaster)M12.A05-
adt-2 g.p. (Caenorhabditis elegans)M12.A47-
T19D2.1 g.p. (Caenorhabditis elegans)M12.A48-
adm-2 g.p. (Caenorhabditis elegans)M12.A49-
tag-275 g.p. (Caenorhabditis elegans)M12.A50-
Lp02257p/Cg9850-pa (Drosophila melanogaster)M12.A51-
stall peptidase (Drosophila melanogaster)M12.A52-
ADAM3A g.p. (Homo sapiens)M12.P02-
ADAM1 g.p. (Homo sapiens)M12.P03-
subfamily M12B unassigned peptidasesunassignedYes
Peptidases not assigned to subfamily
Peptidases and Homologues MEROPS ID Structure
Mde10 metallopeptidase (Schizosaccharomyces)M12.180-
putative ADAM pseudogene (chromosome 4, Homo sapiens)M12.P01-
family M12 non-peptidase homologuesnon-peptidase homologue-
family M12 unassigned peptidasesunassigned-