Family M1

Family

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

Summary for family M1

Family type peptidaseM01.001 - aminopeptidase N (Homo sapiens), MEROPS Accession MER0000997 (peptidase unit: 301-517)
Content of familyPeptidase family M1 contains mainly aminopeptidases.
History Identifier created: Biochem.J. 290:205-218 (1993)
Catalytic typeMetallo
Active site residuesH388 E389 H392 E411 Y477 
Active siteA catalytic zinc ion bound is by two histidines and a glutamate. The histidines are within an "HEXXH" motif on one long helix with the glutamate on another antiparallel helix. The catalytic mechanism is believed to involve activation of a water molecule by the zinc ion. The glutamate of the HEXXH motif is known to be important for catalysis and a tyrosine may also be involved.
Activities and specificitiesThe peptidases of family M1 are dependent on a single zinc ion for activity, and all members of the family act on the N-terminus of polypeptides, many of them being aminopeptidases. The family also contains pyroglutamyl-peptidase II (M01.008), an omega peptidase that releases pyroglutamate from thyrotropin-releasing hormone. Cleavage of dipeptides also occurs and aminopeptidase N was formerly known as Cys-Gly dipeptidase. Although the aminopeptidases show a preference for some amino acids, each is capable of releasing a variety of residues, so names like 'alanyl aminopeptidase' can be misleading. We are not aware of any member of family M1 that hydrolyses Xaa-Pro-bonds, and some that are normally aminopeptidases release the Xaa-Pro dipeptide. Leukotriene A4 hydrolase (M01.004) has an additional catalytic activity as an epoxide hydrolase converting leukotriene A4 to the inflammatory mediator leukotriene B4, which is dependent on a second active site (Mueller et al., 1996).
InhibitorsBestatin and amastatin are effective inhibitors, as are metal chelators such as EDTA and 1,10-phenanthroline, but these agents inhibit other metallo-aminopeptidases and indeed other metallopeptidases also. There are no known protein inhibitors. Cytosolic alanyl aminopeptidase (M01.010) is inhibited by puromycin.
Molecular structureThe structure of leukotriene A4 hydrolase (Thunnissen et al., 2001) shows a three-domain protein in which the catalytic domain is the middle one. The catalytic domain contains an antiparallel beta sheet and alpha helices, similar to that of thermolysin (M04.001), so family M1 is included in clan MA.
ClanMA
SubclanMA(E)
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 functionsAminopeptidase N is important for the inactivation in the kidney of blood-borne polypeptidases such as enkephalins, substance P and interleukin 8, and contributes to proteolysis in the small intestine. The insect aminopeptidase A (M01.013) is the receptor for the insecticidal CrylAc toxin of Bacillus thuringiensis (Knight et al., 1995). Like many members of the family, leukotriene A4 hydrolase is cytosolic, and in archaea, two of the components of the tricorn complex (XP01-001) are members of family M1. Pyroglutamyl-peptidase II and aminopeptidase N are membrane-bound with N-terminal cytoplasmic and transmembrane domains. The insect aminopeptidase N (M01.013) is membrane-bound by a glycosylphosphatidinylinositide anchor. Membrane-bound members of the family, with the bulk of the protein outside the cell, are also known as surface antigens, e.g. aminopeptidase N as the myeloid leukaemia marker CD13.
Statistics for family M1Sequences:14653
Identifiers:64
Identifiers with PDB entries:12
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
aminopeptidase NM01.001Yes
lysyl aminopeptidase (bacteria)M01.002-
aminopeptidase AM01.003Yes
leukotriene A4 hydrolaseM01.004Yes
alanyl aminopeptidase (bacterial-type)M01.005Yes
Ape2 aminopeptidaseM01.006-
Aap1’ aminopeptidaseM01.007-
pyroglutamyl-peptidase IIM01.008-
aminopeptidase N (actinomycete-type)M01.009-
cytosol alanyl aminopeptidaseM01.010-
cystinyl aminopeptidaseM01.011Yes
aminopeptidase GM01.012-
aminopeptidase N (insect)M01.013-
aminopeptidase BM01.014-
aminopeptidase H11 (nematode)M01.015-
aminopeptidase EyM01.016-
TMA108 protein (Saccharomyces cerevisiae)M01.017-
endoplasmic reticulum aminopeptidase 1M01.018Yes
tricorn interacting factor F2M01.020-
tricorn interacting factor F3M01.021Yes
arginyl aminopeptidase-like 1M01.022-
ERAP2 aminopeptidaseM01.024Yes
aminopeptidase-1 (Caenorhabditis-type)M01.025-
aminopeptidase QM01.026-
aminopeptidase OM01.028-
M1 aminopeptidase (Plasmodium spp.)M01.029Yes
aminopeptidase N2 (insect)M01.030-
cold-active aminopeptidase (Colwellia psychrerythraea)-type peptidaseM01.031Yes
lysyl aminopeptidase 1 (Streptomyces sp.)M01.032-
lysyl endopeptidase (Streptomyces albulus)M01.033-
leukotriene A4 hydrolase (Saccharomyces cerevisiae)M01.034Yes
Tata binding protein associated factorM01.972-
similar to RIKEN cDNA 4833403I15 (Rattus norvegicus)M01.973-
slamdance (Drosophila melanogaster)M01.A02-
BG:DS00365.1 protein (Drosophila melanogaster)M01.A03-
CG5845 protein (Drosophila melanogaster)M01.A05-
CG5849 protein (Drosophila melanogaster)M01.A06-
CG3502 protein (Drosophila melanogaster)M01.A07-
CG11951 protein (Drosophila melanogaster)M01.A08-
CG11956 protein (Drosophila melanogaster)M01.A09-
Dgri protein (Drosophila melanogaster)M01.A10-
CG8774 protein (Drosophila melanogaster)M01.A11-
CG8773 protein (Drosophila melanogaster)M01.A12-
CG31343 protein (Drosophila melanogaster)M01.A13-
CG5839 protein (Drosophila melanogaster)M01.A14-
Y105E8A.a g.p. (obs.) (Caenorhabditis elegans)M01.A15-
Y67D8C.9 g.p. (Caenorhabditis elegans)M01.A16-
T16G12.1 g.p. (Caenorhabditis elegans)M01.A17-
ZC416.6 g.p. (Caenorhabditis elegans)M01.A18-
R03G8.4 g.p. (Caenorhabditis elegans)M01.A19-
T12E12.6 g.p. (Caenorhabditis elegans)M01.A20-
T16G12.1 g.p. (Caenorhabditis elegans)M01.A21-
Y42A5A.1 g.p. (Caenorhabditis elegans)M01.A22-
R03G8.6 g.p. (Caenorhabditis elegans)M01.A23-
CG1009 g.p. (Drosophila melanogaster)M01.A24-
AT4g33090 g.p. (Arabidopsis thaliana)M01.A25-
At5g13520 g.p. (Arabidopsis thaliana)M01.A26-
CG10602 g.p. (Drosophila melanogaster)M01.A27-
pam-1 g.p. (Caenorhabditis elegans)M01.A28-
ape1 g.p. (Schizosaccharomyces pombe)M01.A29-
DDB_G0273539 g.p. (Dictyostelium discoideum)M01.A30-
PsaA g.p. (Dictyostelium discoideum)M01.A31-
lkhA g.p. (Dictyostelium discoideum)M01.A32-
PF2063 g.p. (Pyrococcus furiosus)M01.A33-
family M1 non-peptidase homologuesnon-peptidase homologue-
family M1 unassigned peptidasesunassignedYes