M20/M25/M40 family metallo-hydrolase [Paucibacter sp. DJ1R-11]
Protein Classification
M28 family metallopeptidase; M4 family metallopeptidase( domain architecture ID 10330171)
M28 family metallopeptidase is a zinc-dependent peptidase that may be an aminopeptidase or a carboxypeptidase with co-catalytic zinc ions| M4 family metallopeptidase is a zinc metallopeptidase that contains a HEXXH motif, where the histidines are zinc ligands and the glutamate is an active site residue, preferably cleaving Xaa+Yaa, in which Xaa is a hydrophobic residue and Yaa is Leu, Phe, Ile, or Val
List of domain hits
| Name | Accession | Description | Interval | E-value | |||||
| Zinc_peptidase_like super family | cl14876 | Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and ... |
155-438 | 3.50e-127 | |||||
Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and signaling pathways throughout all kingdoms of life. This hierarchy contains zinc peptidases that correspond to the MH clan in the MEROPS database, which contains 4 families (M18, M20, M28, M42). The peptidase M20 family includes carboxypeptidases such as the glutamate carboxypeptidase from Pseudomonas, the thermostable carboxypeptidase Ss1 of broad specificity from archaea and yeast Gly-X carboxypeptidase. The dipeptidases include bacterial dipeptidase, peptidase V (PepV), a non-specific eukaryotic dipeptidase, and two Xaa-His dipeptidases (carnosinases). There is also the bacterial aminopeptidase, peptidase T (PepT) that acts only on tripeptide substrates and has therefore been termed a tripeptidase. Peptidase family M28 contains aminopeptidases and carboxypeptidases, and has co-catalytic zinc ions. However, several enzymes in this family utilize other first row transition metal ions such as cobalt and manganese. Each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. The aminopeptidases in this family are also called bacterial leucyl aminopeptidases, but are able to release a variety of N-terminal amino acids. IAP aminopeptidase and aminopeptidase Y preferentially release basic amino acids while glutamate carboxypeptidase II preferentially releases C-terminal glutamates. Glutamate carboxypeptidase II and plasma glutamate carboxypeptidase hydrolyze dipeptides. Peptidase families M18 and M42 contain metallo-aminopeptidases. M18 is widely distributed in bacteria and eukaryotes. However, only yeast aminopeptidase I and mammalian aspartyl aminopeptidase have been characterized in detail. Some M42 (also known as glutamyl aminopeptidase) enzymes exhibit aminopeptidase specificity while others also have acylaminoacyl-peptidase activity (i.e. hydrolysis of acylated N-terminal residues). The actual alignment was detected with superfamily member cd03879: Pssm-ID: 472712 [Multi-domain] Cd Length: 286 Bit Score: 373.50 E-value: 3.50e-127
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| PPC | pfam04151 | Bacterial pre-peptidase C-terminal domain; This domain is normally found at the C-terminus of ... |
469-541 | 3.09e-06 | |||||
Bacterial pre-peptidase C-terminal domain; This domain is normally found at the C-terminus of secreted bacterial peptidases. They are not present in the active peptidase. It is possible that they fulfill a similar role to the PKD (pfam00801) domain, which also are found in this context. Visual analysis suggests that PKD and PPC are distantly related (personal obs:Bateman A, Yeats C). : Pssm-ID: 427748 [Multi-domain] Cd Length: 68 Bit Score: 44.95 E-value: 3.09e-06
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| Name | Accession | Description | Interval | E-value | |||||
| M28_AAP | cd03879 | M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ... |
155-438 | 3.50e-127 | |||||
M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; Aeromonas (Vibrio) proteolytica aminopeptidase (AAP; leucine aminopeptidase from Vibrio proteolyticus; Bacterial leucyl aminopeptidase; E.C. 3.4.11.10) subfamily. AAP is a small (32kDa), heat stable leucine aminopeptidase and is active as a monomer. Similar forms of the enzyme have been isolated from Escherichia coli and Staphylococcus thermophilus. Leucine aminopeptidases, in general, play important roles in many biological processes such as protein catabolism, hormone degradation, regulation of migration and cell proliferation, as well as HIV infection and proliferation. AAP is a broad-specificity enzyme, utilizing two zinc(II) ions in its active site to remove N-terminal amino acids, with preference for large hydrophobic amino acids in the P1 position of the substrate, Leu being the most efficiently cleaved. It can accommodate all residues, except Pro, Asp and Glu in the P1' position. Pssm-ID: 349875 [Multi-domain] Cd Length: 286 Bit Score: 373.50 E-value: 3.50e-127
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| Iap | COG2234 | Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ... |
189-446 | 1.55e-55 | |||||
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein turnover, chaperones, Amino acid transport and metabolism]; Pssm-ID: 441835 [Multi-domain] Cd Length: 257 Bit Score: 187.26 E-value: 1.55e-55
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| Peptidase_M28 | pfam04389 | Peptidase family M28; |
229-434 | 3.38e-35 | |||||
Peptidase family M28; Pssm-ID: 461288 [Multi-domain] Cd Length: 192 Bit Score: 130.48 E-value: 3.38e-35
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| PRK08262 | PRK08262 | M20 family peptidase; |
227-331 | 1.75e-06 | |||||
M20 family peptidase; Pssm-ID: 236208 [Multi-domain] Cd Length: 486 Bit Score: 50.71 E-value: 1.75e-06
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| PPC | pfam04151 | Bacterial pre-peptidase C-terminal domain; This domain is normally found at the C-terminus of ... |
469-541 | 3.09e-06 | |||||
Bacterial pre-peptidase C-terminal domain; This domain is normally found at the C-terminus of secreted bacterial peptidases. They are not present in the active peptidase. It is possible that they fulfill a similar role to the PKD (pfam00801) domain, which also are found in this context. Visual analysis suggests that PKD and PPC are distantly related (personal obs:Bateman A, Yeats C). Pssm-ID: 427748 [Multi-domain] Cd Length: 68 Bit Score: 44.95 E-value: 3.09e-06
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| Name | Accession | Description | Interval | E-value | |||||
| M28_AAP | cd03879 | M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ... |
155-438 | 3.50e-127 | |||||
M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; Aeromonas (Vibrio) proteolytica aminopeptidase (AAP; leucine aminopeptidase from Vibrio proteolyticus; Bacterial leucyl aminopeptidase; E.C. 3.4.11.10) subfamily. AAP is a small (32kDa), heat stable leucine aminopeptidase and is active as a monomer. Similar forms of the enzyme have been isolated from Escherichia coli and Staphylococcus thermophilus. Leucine aminopeptidases, in general, play important roles in many biological processes such as protein catabolism, hormone degradation, regulation of migration and cell proliferation, as well as HIV infection and proliferation. AAP is a broad-specificity enzyme, utilizing two zinc(II) ions in its active site to remove N-terminal amino acids, with preference for large hydrophobic amino acids in the P1 position of the substrate, Leu being the most efficiently cleaved. It can accommodate all residues, except Pro, Asp and Glu in the P1' position. Pssm-ID: 349875 [Multi-domain] Cd Length: 286 Bit Score: 373.50 E-value: 3.50e-127
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| Iap | COG2234 | Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ... |
189-446 | 1.55e-55 | |||||
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein turnover, chaperones, Amino acid transport and metabolism]; Pssm-ID: 441835 [Multi-domain] Cd Length: 257 Bit Score: 187.26 E-value: 1.55e-55
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| M28 | cd02690 | M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ... |
226-420 | 2.31e-42 | |||||
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also called aminopeptidase Y family) contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. The aminopeptidases in this family are also called bacterial leucyl aminopeptidases, but are able to release a variety of N-terminal amino acids. IAP aminopeptidase and aminopeptidase Y preferentially release basic amino acids while glutamate carboxypeptidase II preferentially releases C-terminal glutamates. Plasma glutamate carboxypeptidase (PGCP) and glutamate carboxypeptidase II (NAALADase) hydrolyze dipeptides. Several members of the M28 peptidase family have PA domain inserts which may participate in substrate binding and/or in promoting conformational changes, which influence the stability and accessibility of the site to substrate. These include prostate-specific membrane antigen (PSMA), yeast aminopeptidase S (SGAP), human transferrin receptors (TfR1 and TfR2), plasma glutamate carboxypeptidase (PGCP) and several predicted aminopeptidases where relatively little is known about them. Also included in the M28 family are glutaminyl cyclases (QC), which are involved in N-terminal glutamine cyclization of many endocrine peptides. Nicastrin and nicalin belong to this family but lack the amino-acid conservation required for catalytically active aminopeptidases. Pssm-ID: 349868 [Multi-domain] Cd Length: 202 Bit Score: 150.57 E-value: 2.31e-42
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| Peptidase_M28 | pfam04389 | Peptidase family M28; |
229-434 | 3.38e-35 | |||||
Peptidase family M28; Pssm-ID: 461288 [Multi-domain] Cd Length: 192 Bit Score: 130.48 E-value: 3.38e-35
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| M28_like | cd03877 | M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; Peptidase family ... |
229-437 | 2.41e-24 | |||||
M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. This subfamily is composed of uncharacterized proteins, many of which contain a protease-associated (PA) domain insert which may participate in substrate binding and/or promote conformational changes, influencing the stability and accessibility of the site to substrate. Some proteins in this subfamily are also associated with the PDZ domain, a widespread protein module that has been recruited to serve multiple functions during the course of evolution. Pssm-ID: 349874 [Multi-domain] Cd Length: 206 Bit Score: 100.78 E-value: 2.41e-24
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| Zinc_peptidase_like | cd03873 | Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and ... |
229-412 | 2.49e-23 | |||||
Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and signaling pathways throughout all kingdoms of life. This hierarchy contains zinc peptidases that correspond to the MH clan in the MEROPS database, which contains 4 families (M18, M20, M28, M42). The peptidase M20 family includes carboxypeptidases such as the glutamate carboxypeptidase from Pseudomonas, the thermostable carboxypeptidase Ss1 of broad specificity from archaea and yeast Gly-X carboxypeptidase. The dipeptidases include bacterial dipeptidase, peptidase V (PepV), a non-specific eukaryotic dipeptidase, and two Xaa-His dipeptidases (carnosinases). There is also the bacterial aminopeptidase, peptidase T (PepT) that acts only on tripeptide substrates and has therefore been termed a tripeptidase. Peptidase family M28 contains aminopeptidases and carboxypeptidases, and has co-catalytic zinc ions. However, several enzymes in this family utilize other first row transition metal ions such as cobalt and manganese. Each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. The aminopeptidases in this family are also called bacterial leucyl aminopeptidases, but are able to release a variety of N-terminal amino acids. IAP aminopeptidase and aminopeptidase Y preferentially release basic amino acids while glutamate carboxypeptidase II preferentially releases C-terminal glutamates. Glutamate carboxypeptidase II and plasma glutamate carboxypeptidase hydrolyze dipeptides. Peptidase families M18 and M42 contain metallo-aminopeptidases. M18 is widely distributed in bacteria and eukaryotes. However, only yeast aminopeptidase I and mammalian aspartyl aminopeptidase have been characterized in detail. Some M42 (also known as glutamyl aminopeptidase) enzymes exhibit aminopeptidase specificity while others also have acylaminoacyl-peptidase activity (i.e. hydrolysis of acylated N-terminal residues). Pssm-ID: 349870 [Multi-domain] Cd Length: 200 Bit Score: 97.88 E-value: 2.49e-23
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| M28_like | cd05642 | M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ... |
164-331 | 2.46e-21 | |||||
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. Pssm-ID: 349894 [Multi-domain] Cd Length: 347 Bit Score: 95.25 E-value: 2.46e-21
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| M28_like_PA | cd05660 | M28 Zn-peptidase containing a protease-associated (PA) domain insert; Peptidase family M28 ... |
229-344 | 4.47e-20 | |||||
M28 Zn-peptidase containing a protease-associated (PA) domain insert; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. This subfamily is composed of uncharacterized proteins containing a protease-associated (PA) domain insert which may participate in substrate binding and/or promote conformational changes, influencing the stability and accessibility of the site to substrate. Pssm-ID: 349910 [Multi-domain] Cd Length: 290 Bit Score: 90.50 E-value: 4.47e-20
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| M28_PSMA_like | cd08022 | M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ... |
165-331 | 2.87e-18 | |||||
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific membrane antigen (PSMA, also called glutamate carboxypeptidase II or GCP-II)-like subfamily. PSMA is a homodimeric type II transmembrane protein containing three distinct domains: protease-like, apical or protease-associated (PA) and helical domains. The protease-like domain is a large extracellular portion (ectodomain). PSMA is over-expressed predominantly in prostate cancer (PCa) as well as in the neovasculature of most solid tumors, but not in the vasculature of the normal tissues. PSMA is considered a biomarker for PCa and possibly for use as an imaging and therapeutic target. The extracellular domain of PSMA possesses two unique enzymatic functions: N-acetylated, alpha-linked acidic dipeptidase (NAALADase) which cleaves terminal glutamate from the neurodipeptide N-acetyl-aspartyl-glutamate (NAAG), and folate hydrolase (FOLH) which cleaves the terminal glutamates from gamma-linked polyglutamates (carboxypeptidase). A mutation in this gene may be associated with impaired intestinal absorption of dietary folates, resulting in low blood folate levels and consequent hyperhomocysteinemia. Expression of this protein in the brain may be involved in a number of pathological conditions associated with glutamate excitotoxicity. Inhibition of GCP-II has been shown to be effective in preclinical models of neurological disorders associated with excessive activation of glutamatergic systems. This gene likely arose from a duplication event of a nearby chromosomal region. Alternative splicing gives rise to multiple transcript variants. Pssm-ID: 349942 [Multi-domain] Cd Length: 287 Bit Score: 85.36 E-value: 2.87e-18
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| M28_like | cd05640 | M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase ... |
212-412 | 3.59e-18 | |||||
M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. Pssm-ID: 349893 [Multi-domain] Cd Length: 281 Bit Score: 84.81 E-value: 3.59e-18
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| M28_like_PA_PDZ_associated | cd05663 | M28 Zn-peptidase containing a protease-associated (PA) domain insert and associated with a PDZ ... |
190-412 | 4.28e-17 | |||||
M28 Zn-peptidase containing a protease-associated (PA) domain insert and associated with a PDZ domain; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. This subfamily is composed of uncharacterized proteins, many of which contain a protease-associated (PA) domain insert which may participate in substrate binding and/or promote conformational changes, influencing the stability and accessibility of the site to substrate. Proteins in this subfamily are also associated with the PDZ domain, a widespread protein module that has been recruited to serve multiple functions during the course of evolution. Pssm-ID: 349913 [Multi-domain] Cd Length: 266 Bit Score: 81.35 E-value: 4.28e-17
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| M28_like_PA | cd05661 | M28 Zn-peptidase containing a PA domain insert; Peptidase family M28 (also called ... |
213-415 | 4.57e-16 | |||||
M28 Zn-peptidase containing a PA domain insert; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. This subfamily is composed of uncharacterized proteins containing a protease-associated (PA) domain insert which may participate in substrate binding and/or promote conformational changes, influencing the stability and accessibility of the site to substrate. Pssm-ID: 349911 [Multi-domain] Cd Length: 262 Bit Score: 78.38 E-value: 4.57e-16
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| M28_Pgcp_like | cd03883 | M28 Zn-Peptidase Plasma glutamate carboxypeptidase; Peptidase M28 family; Plasma glutamate ... |
229-412 | 4.59e-14 | |||||
M28 Zn-Peptidase Plasma glutamate carboxypeptidase; Peptidase M28 family; Plasma glutamate carboxypeptidase (PGCP; blood plasma glutamate carboxypeptidase; EC 3.4.17.21) subfamily. PGCP is a 56kDa glutamate carboxypeptidase that is mainly produced in mammalian placenta and kidney, the majority of which is thought to be secreted into the bloodstream. Similar proteins are also found in other species, including bacteria. These proteins contain protease-associated (PA) domain inserts between the first and second strands of the central beta sheet in the protease-like domain. The PA domains may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate. The exact physiological substrates of PGCP are unknown, although this enzyme may play an important role in the hydrolysis of circulating peptides. Its closest homolog encodes an important brain glutamate carboxypeptidase II (NAALADase) identical to the prostate-specific membrane antigen (PSMA), which serves as a marker for prostatic cancer metastasis. Hypermethylation of PGCP gene has been associated with human bronchial epithelial (HBE) cell immortalization and lung cancer. PGCP also provides an attractive target for serological analysis in hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) patients. Pssm-ID: 349879 [Multi-domain] Cd Length: 425 Bit Score: 74.27 E-value: 4.59e-14
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| M28_SGAP_like | cd03876 | M28 Zn-peptidase Streptomyces griseus aminopeptidase and similar proteins; Peptidase family ... |
185-342 | 7.31e-14 | |||||
M28 Zn-peptidase Streptomyces griseus aminopeptidase and similar proteins; Peptidase family M28; Streptomyces griseus Aminopeptidase (SGAP, Leucine aminopeptidase (LAP), aminopeptidase S, Mername-AA022 peptidase) subfamily. SGAP is a di-zinc exopeptidase with high preference towards large hydrophobic amino-terminal residues, with Leu being the most efficiently cleaved. It can accommodate all except Pro and Glu residues in the P1' position. It is a monomeric (30 kDa), calcium-activated and calcium-stabilized enzyme; its activation by calcium correlates with substrate specificity and it has thermal stability only in the presence of calcium. Although SGAP contains a calcium binding site, it is not conserved in many members of this subfamily. SGAP is present in the extracellular fluid of S. griseus cultures. Pssm-ID: 349873 [Multi-domain] Cd Length: 289 Bit Score: 72.33 E-value: 7.31e-14
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| M28_like | cd08015 | M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ... |
228-413 | 7.95e-14 | |||||
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. Pssm-ID: 349937 [Multi-domain] Cd Length: 218 Bit Score: 70.70 E-value: 7.95e-14
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| M20_18_42 | cd18669 | M20, M18 and M42 Zn-peptidases include aminopeptidases and carboxypeptidases; This family ... |
229-350 | 5.81e-12 | |||||
M20, M18 and M42 Zn-peptidases include aminopeptidases and carboxypeptidases; This family corresponds to the MEROPS MH clan families M18, M20, and M42. The peptidase M20 family contains exopeptidases, including carboxypeptidases such as the glutamate carboxypeptidase from Pseudomonas, the thermostable carboxypeptidase Ss1 of broad specificity from archaea and yeast Gly-X carboxypeptidase, dipeptidases such as bacterial dipeptidase, peptidase V (PepV), a eukaryotic, non-specific dipeptidase, and two Xaa-His dipeptidases (carnosinases). This family also includes the bacterial aminopeptidase peptidase T (PepT) that acts only on tripeptide substrates and has therefore been termed a tripeptidase. These peptidases generally hydrolyze the late products of protein degradation so as to complete the conversion of proteins to free amino acids. Glutamate carboxypeptidase hydrolyzes folate analogs such as methotrexate, and therefore can be used to treat methotrexate toxicity. Peptidase families M18 and M42 contain metallo-aminopeptidases. M18 (aspartyl aminopeptidase, DAP) family cleaves only unblocked N-terminal acidic amino-acid residues and is highly selective for hydrolyzing aspartate or glutamate residues. Some M42 (also known as glutamyl aminopeptidase) enzymes exhibit aminopeptidase specificity while others also have acylaminoacyl-peptidase activity (i.e. hydrolysis of acylated N-terminal residues). Pssm-ID: 349948 [Multi-domain] Cd Length: 198 Bit Score: 64.76 E-value: 5.81e-12
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| M28_like | cd05662 | M28 Zn-Peptidases; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized ... |
229-415 | 1.83e-11 | |||||
M28 Zn-Peptidases; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. This subfamily is composed of uncharacterized proteins that do not contain a protease-associated (PA) domain. Pssm-ID: 349912 [Multi-domain] Cd Length: 268 Bit Score: 64.80 E-value: 1.83e-11
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| M28_Fxna_like | cd03875 | M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic ... |
153-309 | 4.10e-11 | |||||
M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic reticulum metallopeptidase 1 (ERMP1; Felix-ina, FXNA or Fxna peptidase; KIAA1815) subfamily. ERMP1 is a multi-pass membrane protein located in the endoplasmic reticulum membrane. In humans, Fxna may play a crucial role in processing proteins required for the organization of somatic cells and oocytes into discrete follicular structures, although which proteins are hydrolyzed has not yet been determined. Another member of this subfamily is the 24-kDa vacuolar protein (VP24) which is probably involved in the formation of intravacuolar pigmented globules (cyanoplasts) in highly anthocyanin-containing vacuoles; however, the biological function of the C-terminal region which includes the putative transmembrane metallopeptidase domain is unknown. Pssm-ID: 349872 [Multi-domain] Cd Length: 307 Bit Score: 64.15 E-value: 4.10e-11
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| M28_PMSA_TfR_like | cd03874 | M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ... |
190-330 | 1.55e-09 | |||||
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor (TfR) and prostate-specific membrane antigen (PSMA, also called glutamate carboxypeptidase or GCP-II) subfamily. TfR and PSMA are homodimeric type II transmembrane proteins containing three distinct domains: protease-like, apical or protease-associated (PA) and helical domains. The protease-like domain is a large extracellular portion (ectodomain). In TfR, it contains a binding site for the transferrin molecule and has 28% identity to membrane glutamate carboxypeptidase II (mGCP-II or PSMA). The PA domain is inserted between the first and second strands of the central beta sheet in the protease-like domain. TfR1 is widely expressed, and is a key player in the uptake of iron-loaded transferrin (Tf) into cells. The TfR1 homodimer binds two molecules of Tf and the complex is then internalized. TfR1 may also participate in cell growth and proliferation. TfR2 binds Tf but with a significantly lower affinity than TfR1. It is expressed chiefly in hepatocytes, hematopoietic cells, and duodenal crypt cells; its expression overlaps with that of hereditary hemochromatosis protein (HFE). TfR2 is involved in iron homeostasis; in humans, mutations in TfR2 are associated with a form of hemochromatosis (HFE3). PSMA is over-expressed predominantly in prostate cancer (PCa) as well as in the neovasculature of most solid tumors, but not in the vasculature of normal tissues. PSMA is considered a biomarker for PCa and possibly for use as an imaging and therapeutic target. The extracellular domain of PSMA possesses two unique enzymatic functions: N-acetylated, alpha-linked acidic dipeptidase (NAALADase) which cleaves terminal glutamate from the neurodipeptide N-acetyl-aspartyl-glutamate (NAAG), and folate hydrolase (FOLH) which cleaves the terminal glutamates from gamma-linked polyglutamates (carboxypeptidase). A mutation in this gene may be associated with impaired intestinal absorption of dietary folates, resulting in low blood folate levels and consequent hyperhomocysteinemia. Expression of this protein in the brain may be involved in a number of pathological conditions associated with glutamate excitotoxicity. This gene likely arose from a duplication event of a nearby chromosomal region. Alternative splicing gives rise to multiple transcript variants. While related in sequence to peptidase M28 GCP-II, TfR lacks the metal ion coordination centers and protease activity. Pssm-ID: 349871 [Multi-domain] Cd Length: 278 Bit Score: 58.85 E-value: 1.55e-09
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| Peptidase_M20 | pfam01546 | Peptidase family M20/M25/M40; This family includes a range of zinc metallopeptidases belonging ... |
244-327 | 1.07e-06 | |||||
Peptidase family M20/M25/M40; This family includes a range of zinc metallopeptidases belonging to several families in the peptidase classification. Family M20 are Glutamate carboxypeptidases. Peptidase family M25 contains X-His dipeptidases. Pssm-ID: 460247 [Multi-domain] Cd Length: 315 Bit Score: 50.81 E-value: 1.07e-06
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| PRK08262 | PRK08262 | M20 family peptidase; |
227-331 | 1.75e-06 | |||||
M20 family peptidase; Pssm-ID: 236208 [Multi-domain] Cd Length: 486 Bit Score: 50.71 E-value: 1.75e-06
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| PPC | pfam04151 | Bacterial pre-peptidase C-terminal domain; This domain is normally found at the C-terminus of ... |
469-541 | 3.09e-06 | |||||
Bacterial pre-peptidase C-terminal domain; This domain is normally found at the C-terminus of secreted bacterial peptidases. They are not present in the active peptidase. It is possible that they fulfill a similar role to the PKD (pfam00801) domain, which also are found in this context. Visual analysis suggests that PKD and PPC are distantly related (personal obs:Bateman A, Yeats C). Pssm-ID: 427748 [Multi-domain] Cd Length: 68 Bit Score: 44.95 E-value: 3.09e-06
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| ArgE | COG0624 | Acetylornithine deacetylase/Succinyl-diaminopimelate desuccinylase or related deacylase [Amino ... |
228-318 | 5.48e-06 | |||||
Acetylornithine deacetylase/Succinyl-diaminopimelate desuccinylase or related deacylase [Amino acid transport and metabolism]; Acetylornithine deacetylase/Succinyl-diaminopimelate desuccinylase or related deacylase is part of the Pathway/BioSystem: Arginine biosynthesis Pssm-ID: 440389 [Multi-domain] Cd Length: 388 Bit Score: 48.73 E-value: 5.48e-06
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| FrvX | COG1363 | Putative aminopeptidase FrvX [Amino acid transport and metabolism, Carbohydrate transport and ... |
268-346 | 5.56e-06 | |||||
Putative aminopeptidase FrvX [Amino acid transport and metabolism, Carbohydrate transport and metabolism]; Pssm-ID: 440974 [Multi-domain] Cd Length: 353 Bit Score: 48.58 E-value: 5.56e-06
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| M20_yscS_like | cd05675 | M20 Peptidase, carboxypeptidase yscS-like; Peptidase M20 family, yscS (GlyX-carboxypeptidase, ... |
184-305 | 1.99e-05 | |||||
M20 Peptidase, carboxypeptidase yscS-like; Peptidase M20 family, yscS (GlyX-carboxypeptidase, CPS1, carboxypeptidase S, carboxypeptidase a, carboxypeptidase yscS, glycine carboxypeptidase)-like subfamily. This group contains proteins that have been uncharacterized to date with similarity to vacuolar proteins involved in nitrogen metabolism which are essential for use of certain peptides that are sole nitrogen sources. YscS releases a C-terminal amino acid from a peptide that has glycine as the penultimate residue. It is synthesized as one polypeptide chain precursor which yields two active precursor molecules after carbohydrate modification in the secretory pathway. The proteolytically unprocessed forms are associated with the membrane, whereas the mature forms of the enzyme are soluble. Enzymes in this subfamily may also cleave intracellularly generated peptides in order to recycle amino acids for protein synthesis. Pssm-ID: 349924 [Multi-domain] Cd Length: 431 Bit Score: 46.97 E-value: 1.99e-05
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| M20_bAS | cd03884 | M20 Peptidase beta-alanine synthase, an amidohydrolase; Peptidase M20 family, beta-alanine ... |
229-313 | 4.84e-05 | |||||
M20 Peptidase beta-alanine synthase, an amidohydrolase; Peptidase M20 family, beta-alanine synthase (bAS; N-carbamoyl-beta-alanine amidohydrolase and beta-ureidopropionase; EC 3.5.1.6) subfamily. bAS is an amidohydrolase and is the final enzyme in the pyrimidine catabolic pathway, which is involved in the regulation of the cellular pyrimidine pool. bAS catalyzes the irreversible hydrolysis of the N-carbamylated beta-amino acids to beta-alanine or aminoisobutyrate with the release of carbon dioxide and ammonia. Also included in this subfamily is allantoate amidohydrolase (allantoate deiminase), which catalyzes the conversion of allantoate to (S)-ureidoglycolate, one of the crucial alternate steps in purine metabolism. It is possible that these two enzymes arose from the same ancestral peptidase that evolved into two structurally related enzymes with distinct catalytic properties and biochemical roles within the cell. Downstream enzyme (S)-ureidoglycolate amidohydrolase (UAH) is homologous in structure and sequence with AAH and catalyzes the conversion of (S)-ureidoglycolate into glyoxylate, releasing two molecules of ammonia as by-products. Yeast requires beta-alanine as a precursor of pantothenate and coenzyme A biosynthesis, but generates it mostly via degradation of spermine. Disorders in pyrimidine degradation and beta-alanine metabolism caused by beta-ureidopropionase deficiency (UPB1 gene) in humans are normally associated with neurological disorders. Pssm-ID: 349880 [Multi-domain] Cd Length: 398 Bit Score: 45.98 E-value: 4.84e-05
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| PRK09290 | PRK09290 | allantoate amidohydrolase; Reviewed |
232-303 | 1.05e-04 | |||||
allantoate amidohydrolase; Reviewed Pssm-ID: 236456 [Multi-domain] Cd Length: 413 Bit Score: 44.76 E-value: 1.05e-04
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| PRK06133 | PRK06133 | glutamate carboxypeptidase; Reviewed |
215-318 | 1.67e-04 | |||||
glutamate carboxypeptidase; Reviewed Pssm-ID: 235710 [Multi-domain] Cd Length: 410 Bit Score: 44.24 E-value: 1.67e-04
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| M20_yscS | cd05674 | M20 Peptidase, carboxypeptidase yscS; Peptidase M20 family, yscS (GlyX-carboxypeptidase, CPS1, ... |
227-314 | 3.51e-04 | |||||
M20 Peptidase, carboxypeptidase yscS; Peptidase M20 family, yscS (GlyX-carboxypeptidase, CPS1, carboxypeptidase S, carboxypeptidase a, carboxypeptidase yscS, glycine carboxypeptidase)-like subfamily. This group mostly contains proteins that have been uncharacterized to date, but also includes vacuolar proteins involved in nitrogen metabolism which are essential for use of certain peptides that are sole nitrogen sources. YscS releases a C-terminal amino acid from a peptide that has glycine as the penultimate residue. It is synthesized as one polypeptide chain precursor which yields two active precursor molecules after carbohydrate modification in the secretory pathway. The proteolytically unprocessed forms are associated with the membrane, whereas the mature forms of the enzyme are soluble. Enzymes in this subfamily may also cleave intracellularly generated peptides in order to recycle amino acids for protein synthesis. Also included in this subfamily is peptidase M20 domain containing 1 (PM20D1), that is enriched in uncoupling protein 1, UCP1(+) versus UCP1(-) adipocytes is a bidirectional enzyme in vitro, catalyzing both the condensation of fatty acids and amino acids to generate N-acyl amino acids and also the reverse hydrolytic reaction; N-acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. Mice studies show increased circulating PM20D1 augments respiration and increases N-acyl amino acids in blood, and administration of N-acyl amino acids improves glucose homeostasis and increases energy expenditure. Pssm-ID: 349923 [Multi-domain] Cd Length: 471 Bit Score: 43.01 E-value: 3.51e-04
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| PepD2 | COG2195 | Di- or tripeptidase [Amino acid transport and metabolism]; |
229-309 | 3.93e-04 | |||||
Di- or tripeptidase [Amino acid transport and metabolism]; Pssm-ID: 441798 [Multi-domain] Cd Length: 364 Bit Score: 42.73 E-value: 3.93e-04
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| M28_TfR | cd09848 | M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) ... |
234-311 | 4.15e-04 | |||||
M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) subfamily. TfRs are homodimeric type II transmembrane proteins containing three distinct domains: protease-like, apical or protease-associated (PA), and helical domains. The protease-like domain is a large extracellular portion (ectodomain). In TfR, it contains a binding site for the transferrin molecule and has 28% identity to membrane glutamate carboxypeptidase II (mGCP-II or PSMA). The PA domain is inserted between the first and second strands of the central beta sheet in the protease-like domain. TfR1 is widely expressed, and is a key player in the uptake of iron-loaded transferrin (Tf) into cells. The TfR1 homodimer binds two molecules of Tf and the complex is then internalized. TfR1 may also participate in cell growth and proliferation. TfR2 binds Tf but with a significantly lower affinity than TfR1. It is expressed chiefly in hepatocytes, hematopoietic cells, and duodenal crypt cells; its expression overlaps with that of hereditary hemochromatosis protein (HFE). TfR2 is involved in iron homeostasis; in humans, mutations in TfR2 are associated with a form of hemochromatosis (HFE3). While related in sequence to peptidase M28 glutamate carboxypeptidase II (also called prostate-specific membrane antigen or PSMA), TfR lacks the metal ion coordination centers and protease activity of that group. Pssm-ID: 349946 [Multi-domain] Cd Length: 285 Bit Score: 42.36 E-value: 4.15e-04
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| M28_like | cd05643 | M28 Zn-peptidase-like; Peptidase family M28 (also called aminopeptidase Y family), ... |
264-412 | 4.34e-04 | |||||
M28 Zn-peptidase-like; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They typically have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. This protein subfamily conserves some of the metal-coordinating residues of the typically co-catalytic M28 family which might suggest binding of a single metal ion. Pssm-ID: 349895 [Multi-domain] Cd Length: 290 Bit Score: 42.39 E-value: 4.34e-04
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| PRK12893 | PRK12893 | Zn-dependent hydrolase; |
229-307 | 6.62e-04 | |||||
Zn-dependent hydrolase; Pssm-ID: 237250 [Multi-domain] Cd Length: 412 Bit Score: 42.18 E-value: 6.62e-04
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| PRK12890 | PRK12890 | allantoate amidohydrolase; Reviewed |
229-320 | 1.11e-03 | |||||
allantoate amidohydrolase; Reviewed Pssm-ID: 237248 [Multi-domain] Cd Length: 414 Bit Score: 41.43 E-value: 1.11e-03
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| PRK10199 | PRK10199 | alkaline phosphatase isozyme conversion aminopeptidase; Provisional |
228-330 | 1.27e-03 | |||||
alkaline phosphatase isozyme conversion aminopeptidase; Provisional Pssm-ID: 182299 [Multi-domain] Cd Length: 346 Bit Score: 41.26 E-value: 1.27e-03
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| M20_peptT_like | cd05683 | M20 Peptidase T like enzymes specifically cleave tripeptides; Peptidase M20 family, PeptT ... |
229-315 | 1.35e-03 | |||||
M20 Peptidase T like enzymes specifically cleave tripeptides; Peptidase M20 family, PeptT (tripeptide aminopeptidase; tripeptidase)-like subfamily. This group includes bacterial tripeptidases as well as predicted tripeptidases. Peptidase T acts only on tripeptide substrates, and is thus called a tripeptidase. It catalyzes the release of N-terminal amino acids with hydrophobic side chains from tripeptides with high specificity; dipeptides, tetrapeptides or tripeptides with the N-terminus blocked are not cleaved. Tripeptidases are known to function at the final stage of proteolysis in lactococcal bacteria and release amino acids from tripeptides produced during the digestion of milk proteins such as casein. Pssm-ID: 349932 [Multi-domain] Cd Length: 368 Bit Score: 41.28 E-value: 1.35e-03
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| Peptidase_M42 | pfam05343 | M42 glutamyl aminopeptidase; These peptidases are found in Archaea and Bacteria. The example ... |
268-340 | 4.27e-03 | |||||
M42 glutamyl aminopeptidase; These peptidases are found in Archaea and Bacteria. The example in Lactococcus lactis, PepA, aids growth on milk. Pyrococcus horikoshii contain a thermostable de-blocking aminopeptidase member of this family used commercially for N-terminal protein sequencing. Pssm-ID: 428431 [Multi-domain] Cd Length: 292 Bit Score: 39.48 E-value: 4.27e-03
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| M20_CPDG2 | cd03885 | M20 Peptidase Glutamate carboxypeptidase, a periplasmic enzyme; Peptidase M20 family, ... |
228-319 | 8.95e-03 | |||||
M20 Peptidase Glutamate carboxypeptidase, a periplasmic enzyme; Peptidase M20 family, Glutamate carboxypeptidase (carboxypeptidase G; carboxypeptidase G1; carboxypeptidase G2; CPDG2; CPG2; Folate hydrolase G2; Pteroylmonoglutamic acid hydrolase G2; Glucarpidase; E.C. 3.4.17.11) subfamily. CPDG2 is a periplasmic enzyme that is synthesized with a signal peptide. It is a dimeric zinc-dependent exopeptidase, with two domains, a catalytic domain, which provides the ligands for the two zinc ions in the active site, and a dimerization domain. CPDG2 cleaves the C-terminal glutamate moiety from a wide range of N-acyl groups, including peptidyl, aminoacyl, benzoyl, benzyloxycarbonyl, folyl, and pteroyl groups to release benzoic acid, phenol, and aniline mustards. It is used clinically to treat methotrexate toxicity by hydrolyzing it to inactive and non-toxic metabolites. It is also proposed for use in antibody-directed enzyme prodrug therapy; for example, glutamate can be cleaved from glutamated benzoyl nitrogen mustards, producing nitrogen mustards with effective cytotoxicity against tumor cells. Pssm-ID: 349881 [Multi-domain] Cd Length: 362 Bit Score: 38.34 E-value: 8.95e-03
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