Family M28

Family

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

M28A

Summary Holotypes Alignment Tree Genomes Literature

M28B

Summary Holotypes Alignment Tree Genomes Literature

M28C

Summary Holotypes Alignment Tree Genomes Literature

M28D

Summary Holotypes Alignment Tree Genomes Literature

M28E

Summary Holotypes Alignment Tree Genomes Literature

M28F

Summary Holotypes Genomes Literature

Summary for family M28

NamePeptidase family M28 (aminopeptidase Y family)
Family type peptidaseM28.003 - aminopeptidase S (Streptomyces-type) (Streptomyces griseus), MEROPS Accession MER0002161 (peptidase unit: 46-329)
Content of familyFamily M28 contains aminopeptidases and carboxypeptidases.
History Identifier created: Methods Enzymol. 248:183-228 (1995)
Peptidases in family M28 have co-catalytic zinc ions. It is unusual for both aminopeptidases and carboxypeptidases to be members of the same family, but not unprecedented: see for example family S12.
Catalytic typeMetallo
Active siteEach zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. The zinc ligands (with the metal ion that is bound indicated by Roman numerals) occur in the sequence in the order His (II), Asp (I and II), Glu (I), Asp or Glu (II) and His (I). In addition, two other residues, an Asp and a Glu, are believed to be important for catalysis (Chevrier et al., 1996). Four of these residues occur in the motifs His-Xaa-Asp and Glu-Glu. Mutations in Tyr246 resulted in about 100-fold reduction of activity, suggesting that this residue is involved in the stabilization of the transition state intermediate (Fundoiano-Hershcovitz et al., 2004).
Activities and specificitiesThe aminopeptidases in the family have been described as 'bacterial leucyl aminopeptidases', but are able to release a variety of N-terminal amino acids. IAP aminopeptidase (M28.005) and aminopeptidase Y (M28.001) preferably release basic amino acids. Glutamate carboxypeptidase II (M28.010) preferentially releases C-terminal glutamates. Glutamate carbxypeptidase II and plasma glutamate carboxypeptidase (M28.014) efficiently hydrolyse dipeptides and each had previously been considered to be a dipeptidase only (Luthi-Carter et al., 1998,Dolenc & Mihelic, 2003).
InhibitorsGeneral inhibitors include the metal chelators EDTA and 1,10-phenanthroline; the aminopeptidases are inhibited by bestatin and amastatin. Glutamate carboxypeptidase II is inhibited by substituted phosphonylglutamates (Jackson et al., 1996).
Molecular structureThe tertiary structures have been determined for aminopeptidase S (M28.003), glutamate carboxypeptidase II (M28.010) and aminopeptidase Ap1 (M20.001), and each shows a six-stranded beta-sheet surrounded by helices. Aminopeptidase Ap1 is the type structure for clan MH. The structures are similar to those for peptidases in clans MC and ML, but because the positions and number of the metal ligands are not conserved, we do not consider that the ancestral protein was a peptidase, hence the peptidases are assigned to different clans.
ClanMH
Basis of clan assignmentType family of clan MH.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses -  
Biological functionsGlutamate carboxypeptidase II (M28.010) degrades the neuropeptide Ac-AspGlu in the brain and also converts folylpoly-gamma-glutamate to pteroylglutamate in the intestine. IAP aminopeptidase is thought to convert one form of bacterial alkaline phosphatase to another by successively releasing N-terminal arginines (Ishino et al., 1987). There are many non-peptidase homologues in the family, including the transferrin receptor (M28.972).
Pharmaceutical and biotech relevanceGlutamate carboxypeptidase II (M28.010) is a known marker in prostate cancer, and an intracellular form may be responsible for tumour cell resistance to methotrexate (Heston, 1997; Rawlings & Barrett, %1997). There is much interest in inhibitors of glutamate carboxypeptidase II as drugs (e.g. Ghadge et al., 2003; Yamamoto et al., 2004; Kozikowski et al., 2004).
Statistics for family M28Sequences:6947
Identifiers:46
Identifiers with PDB entries:13
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily M28A
Name Peptidase subfamily M28A
Subfamily type peptidase M28.003 - aminopeptidase S ({Streptomyces}-type) (Streptomyces griseus), MEROPS Accession MER0002161 (peptidase unit: 46-329)
Active site residues H130 D132 D142 E176 E177 D,E205 H292 
Statistics Sequences: 962
Identifiers: 5
Identifiers with PDB entries: 3
Other databases CATH 3.40.630.10
HOMSTRAD apbact
HSSP 1amp
INTERPRO IPR007484
PANTHER PTHR12147
PFAM PF04389
PFAM PF09940
SCOP 53204
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
aminopeptidase YM28.001-
aminopeptidase S (Streptomyces-type)M28.003Yes
secreted aminopeptidase (Pseudomonas-type)M28.008-
aminopeptidase SSAP (Streptomyces septatus)M28.019-
glutaminyl-peptide cyclotransferase-like non-peptidase homologueM28.979Yes
subfamily M28A non-peptidase homologuesnon-peptidase homologueYes
subfamily M28A unassigned peptidasesunassigned-
Subfamily M28B
Name Peptidase subfamily M28B
Subfamily type peptidase M28.010 - glutamate carboxypeptidase II (Homo sapiens), MEROPS Accession MER0002104 (peptidase unit: 291-576)
Active site residues H377 D379 D387 E424 E425 D,E453 H553 
Statistics Sequences: 1256
Identifiers: 11
Identifiers with PDB entries: 4
Other databases CATH 3.40.630.10
HOMSTRAD apbact
HSSP 1xjo
INTERPRO IPR007484
PFAM PF04389
SCOP 53204
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
ALTERED MERISTEM PROGRAM1-like peptidaseM28.007-
glutamate carboxypeptidase IIM28.010Yes
NAALADASE L peptidaseM28.011Yes
glutamate carboxypeptidase IIIM28.012Yes
transferrin receptor proteinM28.972Yes
transferrin receptor 2 proteinM28.973-
glutamate carboxypeptidase II (Homo sapiens)-type non-peptidase homologueM28.975-
protein similar to glutamate carboxypeptidase II (rodent)M28.976-
At5g19740 (Arabidopsis thaliana)-type peptidaseM28.A02-
C35C5.2 g.p. (Caenorhabditis elegans)M28.A18-
R57.1 g.p. (Caenorhabditis elegans)M28.A19-
subfamily M28B unassigned peptidasesunassigned-
Subfamily M28C
Name Peptidase subfamily M28C
Subfamily type peptidase M28.005 - IAP aminopeptidase (Escherichia coli), MEROPS Accession MER0001290 (peptidase unit: 1-345)
Active site residues H117 D119 D143 E175 E176 D,E204 H305 
Statistics Sequences: 169
Identifiers: 2
Identifiers with PDB entries: 0
Other databases INTERPRO IPR007484
PANTHER PTHR12147
PFAM PF04389
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
IAP aminopeptidaseM28.005-
AaaA aminopeptidaseM28.021-
subfamily M28C non-peptidase homologuesnon-peptidase homologue-
subfamily M28C unassigned peptidasesunassigned-
Subfamily M28D
Name Peptidase subfamily M28D
Subfamily type peptidase M28.015 - aminopeptidase ES-62 ({Acanthocheilonema viteae}) (Acanthocheilonema viteae), MEROPS Accession MER0005241 (peptidase unit: 253-492)
Active site residues H277 D279 D289 E328 E329 D357 H434 
Statistics Sequences: 626
Identifiers: 2
Identifiers with PDB entries: 1
Other databases PFAM PF04389
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
carboxypeptidase QM28.014-
aminopeptidase ES-62 (Acanthocheilonema viteae)M28.015-
subfamily M28D non-peptidase homologuesnon-peptidase homologue-
subfamily M28D unassigned peptidasesunassignedYes
Subfamily M28E
Name Peptidase subfamily M28E
Subfamily type peptidase M28.002 - aminopeptidase Ap1 (Vibrio proteolyticus), MEROPS Accession MER0001284 (peptidase unit: 148-401)
Active site residues H203 D205 D223 E257 E258 D,E285 H362 
Statistics Sequences: 656
Identifiers: 4
Identifiers with PDB entries: 1
Other databases CATH 3.40.630.10
HOMSTRAD apbact
HSSP 1lok
INTERPRO IPR007484
PANTHER PTHR12147
PFAM PF04389
SCOP 53204
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
aminopeptidase Ap1M28.002Yes
aminopeptidase ACM28.004-
Mername-AA063 peptidaseM28.006-
leucine aminopeptidase-1 (Aspergillus fumigatus)M28.022-
subfamily M28E non-peptidase homologuesnon-peptidase homologue-
subfamily M28E unassigned peptidasesunassigned-
Subfamily M28F
Name Peptidase subfamily M28F
Subfamily type peptidase M28.009 - YwaD peptidase (Bacillus subtilis), MEROPS Accession MER0001289 (peptidase unit: 168-438)
Active site residues H250 D252 D262 E294 E295 D,E323 H401 
Statistics Sequences: 1019
Identifiers: 3
Identifiers with PDB entries: 1
Other databases INTERPRO IPR007484
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
YwaD peptidaseM28.009-
AM-1 aminopeptidaseM28.020Yes
BSNT_05883 g.p. (Bacillus subtilis)M28.A01-
subfamily M28F unassigned peptidasesunassigned-
Peptidases not assigned to subfamily
Peptidases and Homologues MEROPS ID Structure
Mername-AA103 peptidaseM28.016Yes
Fxna peptidaseM28.018-
glutaminyl cyclaseM28.974Yes
nicalinM28.978-
At5g20660 (Arabidopsis thaliana)M28.A03-
At1g67420 (Arabidopsis thaliana)M28.A04-
hypothetical 47 kDa protein (Saccharomyces cerevisiae)M28.A05-
Cg33012 protein (Drosophila melanogaster)M28.A07-
Cg33013-pb protein (Drosophila melanogaster)M28.A08-
Lp07082 (Drosophila melanogaster)M28.A09-
Cg30047 protein (Drosophila melanogaster)M28.A10-
Re28322p (Drosophila melanogaster)M28.A11-
CG13160 protein (Drosophila melanogaster)M28.A12-
CG11961 protein (Drosophila melanogaster)M28.A13-
CG10051 protein (Drosophila melanogaster)M28.A14-
CG10062 protein (Drosophila melanogaster)M28.A15-
Cg10081 protein (Drosophila melanogaster)M28.A16-
CG10073 protein (Drosophila melanogaster)M28.A17-
B0495.7 g.p. (Caenorhabditis elegans)M28.A20-
subfamily M28B non-peptidase homologuesnon-peptidase homologue-
family M28 non-peptidase homologuesnon-peptidase homologue-
family M28 unassigned peptidasesunassignedYes