M3 family metallopeptidase contains the HEXXH motif that forms the active site in conjunction with a C-terminally-located Glu residue; similar to mammalian TOP (thimet oligopeptidase) or neurolysin, which hydrolyze oligopeptides such as neurotensin, bradykinin and dynorphin A
Peptidase M3 thimet oligopeptidase (TOP), also includes neurolysin; Peptidase M3 Thimet ...
58-678
0e+00
Peptidase M3 thimet oligopeptidase (TOP), also includes neurolysin; Peptidase M3 Thimet oligopeptidase (TOP; PZ-peptidase; endo-oligopeptidase A; endopeptidase 24.15; soluble metallo-endopeptidase; EC 3.4.24.15) family also includes neurolysin (endopeptidase 24.16, microsomal endopeptidase, mitochondrial oligopeptidase M, neurotensin endopeptidase, soluble angiotensin II-binding protein, thimet oligopeptidase II) which hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A. TOP and neurolysin are neuropeptidases expressed abundantly in the testis, but are also found in the liver, lung and kidney. They are involved in the metabolism of neuropeptides under 20 amino acid residues long and cleave most bioactive peptides at the same sites, but recognize different positions on some naturally occurring and synthetic peptides; they cleave at distinct sites on the 13-residue bioactive peptide neurotensin, which modulates central dopaminergic and cholinergic circuits. TOP has been shown to degrade peptides released by the proteasome, limiting the extent of antigen presentation by major histocompatibility complex class I molecules, and has been associated with amyloid protein precursor processing.
:
Pssm-ID: 341050 [Multi-domain] Cd Length: 642 Bit Score: 862.20 E-value: 0e+00
Peptidase M3 thimet oligopeptidase (TOP), also includes neurolysin; Peptidase M3 Thimet ...
58-678
0e+00
Peptidase M3 thimet oligopeptidase (TOP), also includes neurolysin; Peptidase M3 Thimet oligopeptidase (TOP; PZ-peptidase; endo-oligopeptidase A; endopeptidase 24.15; soluble metallo-endopeptidase; EC 3.4.24.15) family also includes neurolysin (endopeptidase 24.16, microsomal endopeptidase, mitochondrial oligopeptidase M, neurotensin endopeptidase, soluble angiotensin II-binding protein, thimet oligopeptidase II) which hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A. TOP and neurolysin are neuropeptidases expressed abundantly in the testis, but are also found in the liver, lung and kidney. They are involved in the metabolism of neuropeptides under 20 amino acid residues long and cleave most bioactive peptides at the same sites, but recognize different positions on some naturally occurring and synthetic peptides; they cleave at distinct sites on the 13-residue bioactive peptide neurotensin, which modulates central dopaminergic and cholinergic circuits. TOP has been shown to degrade peptides released by the proteasome, limiting the extent of antigen presentation by major histocompatibility complex class I molecules, and has been associated with amyloid protein precursor processing.
Pssm-ID: 341050 [Multi-domain] Cd Length: 642 Bit Score: 862.20 E-value: 0e+00
Peptidase family M3; This is the Thimet oligopeptidase family, large family of mammalian and ...
251-683
1.03e-148
Peptidase family M3; This is the Thimet oligopeptidase family, large family of mammalian and bacterial oligopeptidases that cleave medium sized peptides. The group also contains mitochondrial intermediate peptidase which is encoded by nuclear DNA but functions within the mitochondria to remove the leader sequence.
Pssm-ID: 396149 [Multi-domain] Cd Length: 450 Bit Score: 439.52 E-value: 1.03e-148
Peptidase M3 thimet oligopeptidase (TOP), also includes neurolysin; Peptidase M3 Thimet ...
58-678
0e+00
Peptidase M3 thimet oligopeptidase (TOP), also includes neurolysin; Peptidase M3 Thimet oligopeptidase (TOP; PZ-peptidase; endo-oligopeptidase A; endopeptidase 24.15; soluble metallo-endopeptidase; EC 3.4.24.15) family also includes neurolysin (endopeptidase 24.16, microsomal endopeptidase, mitochondrial oligopeptidase M, neurotensin endopeptidase, soluble angiotensin II-binding protein, thimet oligopeptidase II) which hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A. TOP and neurolysin are neuropeptidases expressed abundantly in the testis, but are also found in the liver, lung and kidney. They are involved in the metabolism of neuropeptides under 20 amino acid residues long and cleave most bioactive peptides at the same sites, but recognize different positions on some naturally occurring and synthetic peptides; they cleave at distinct sites on the 13-residue bioactive peptide neurotensin, which modulates central dopaminergic and cholinergic circuits. TOP has been shown to degrade peptides released by the proteasome, limiting the extent of antigen presentation by major histocompatibility complex class I molecules, and has been associated with amyloid protein precursor processing.
Pssm-ID: 341050 [Multi-domain] Cd Length: 642 Bit Score: 862.20 E-value: 0e+00
Peptidase M3A family includes thimet oligopeptidase, dipeptidyl carboxypeptidase and ...
58-681
0e+00
Peptidase M3A family includes thimet oligopeptidase, dipeptidyl carboxypeptidase and mitochondrial intermediate peptidase; The M3-like family also called neurolysin-like family, is part of the "zincins" metallopeptidases, and includes M3, M2 and M32 families of metallopeptidases. The M3 family is subdivided into two subfamilies: the widespread M3A, represented by this CD, which comprises a number of high-molecular mass endo- and exopeptidases from bacteria, archaea, protozoa, fungi, plants and animals, and the small M3B, whose members are enzymes primarily from bacteria. Well-known mammalian/eukaryotic M3A endopeptidases are the thimet oligopeptidase (TOP; endopeptidase 3.4.24.15), neurolysin (alias endopeptidase 3.4.24.16), and the mitochondrial intermediate peptidase. The first two are intracellular oligopeptidases, which act only on relatively short substrates of less than 20 amino acid residues, while the latter cleaves N-terminal octapeptides from proteins during their import into the mitochondria. The M3A subfamily also contains several bacterial endopeptidases, called oligopeptidases A, as well as a large number of bacterial carboxypeptidases, called dipeptidyl peptidases (Dcp; Dcp II; peptidyl dipeptidase; EC 3.4.15.5). The peptidases in the M3 family contain the HEXXH motif that forms part of the active site in conjunction with a C-terminally-located Glutamic acid (Glu) residue. A single zinc ion is ligated by the side-chains of the two Histidine (His) residues, and the more C-terminal Glu. Most of the peptidases are synthesized without signal peptides or propeptides, and function intracellularly.
Pssm-ID: 341068 [Multi-domain] Cd Length: 587 Bit Score: 839.51 E-value: 0e+00
Peptidase family M3, dipeptidyl carboxypeptidase (DCP); Peptidase family M3 dipeptidyl ...
81-683
7.11e-157
Peptidase family M3, dipeptidyl carboxypeptidase (DCP); Peptidase family M3 dipeptidyl carboxypeptidase (DCP; Dcp II; peptidyl dipeptidase; EC 3.4.15.5). This metal-binding M3A family also includes oligopeptidase A (OpdA; EC 3.4.24.70). DCP cleaves dipeptides off the C-termini of various peptides and proteins, the smallest substrate being N-blocked tripeptides and unblocked tetrapeptides. DCP from Escherichia coli is inhibited by the anti-hypertensive drug captopril, an inhibitor of the mammalian angiotensin converting enzyme (ACE, also called peptidyl dipeptidase A). OpdA may play a specific role in the degradation of signal peptides after they are released from precursor forms of secreted proteins. It can also cleave N-acetyl-L-Ala. This family also includes Arabidopsis thaliana organellar oligopeptidase OOP (At5g65620), which plays a role in targeting peptide degradation in mitochondria and chloroplasts; it degrades peptide substrates that are between 8 to 23 amino acid residues, and shows a weak preference for hydrophobic residues (F/L) at the P1 position.
Pssm-ID: 341051 [Multi-domain] Cd Length: 653 Bit Score: 467.70 E-value: 7.11e-157
Peptidase family M3; This is the Thimet oligopeptidase family, large family of mammalian and ...
251-683
1.03e-148
Peptidase family M3; This is the Thimet oligopeptidase family, large family of mammalian and bacterial oligopeptidases that cleave medium sized peptides. The group also contains mitochondrial intermediate peptidase which is encoded by nuclear DNA but functions within the mitochondria to remove the leader sequence.
Pssm-ID: 396149 [Multi-domain] Cd Length: 450 Bit Score: 439.52 E-value: 1.03e-148
M3-like Peptidases, zincin metallopeptidases, include M2_ACE, M3A, M3B_PepF, and M32 families; ...
92-681
1.16e-94
M3-like Peptidases, zincin metallopeptidases, include M2_ACE, M3A, M3B_PepF, and M32 families; The peptidase M3-like family, also called neurolysin-like family, is part of the "zincin" metallopeptidases, and includes the M2, M3 and M32 families of metallopeptidases. The M2 angiotensin converting enzyme (ACE, EC 3.4.15.1) is a membrane-bound, zinc-dependent dipeptidase that catalyzes the conversion of the decapeptide angiotensin I to the potent vasopressor octapeptide angiotensin II. The M3 family is subdivided into two subfamilies: the widespread M3A, which comprises a number of high-molecular mass endo- and exopeptidases from bacteria, archaea, protozoa, fungi, plants and animals, and the small M3B, whose members are enzymes primarily from bacteria. Well-known mammalian/eukaryotic M3A endopeptidases are the thimet oligopeptidase (TOP; endopeptidase 3.4.24.15), neurolysin (alias endopeptidase 3.4.24.16), and the mitochondrial intermediate peptidase. The first two are intracellular oligopeptidases, which act only on relatively short substrates of less than 20 amino acid residues, while the latter cleaves N-terminal octapeptides from proteins during their import into the mitochondria. The M3A subfamily also contains several bacterial endopeptidases, called oligopeptidases A, as well as a large number of bacterial carboxypeptidases, called dipeptidyl peptidases (Dcp; Dcp II; peptidyl dipeptidase; EC 3.4.15.5). M3B subfamily consists of oligopeptidase F (PepF) which hydrolyzes peptides containing 7-17 amino acid residues with fairly broad specificity. Peptidases in the M3 family contain the HEXXH motif that forms part of the active site in conjunction with a C-terminally-located Glutamic acid (Glu) residue. A single zinc ion is ligated by the side-chains of the two Histidine (His) residues, and the more C-terminal Glu. Most of the peptidases are synthesized without signal peptides or propeptides, and function intracellularly. There are similarities to the thermostable carboxypeptidases from Pyrococcus furiosus carboxypeptidase (PfuCP), and Thermus aquaticus (TaqCP), belonging to peptidase family M32. Little is known about function of this family, including carboxypeptidases Taq and Pfu.
Pssm-ID: 341049 [Multi-domain] Cd Length: 473 Bit Score: 300.88 E-value: 1.16e-94
Peptidase M3 mitochondrial intermediate peptidase (MIP); Peptidase M3 mitochondrial intermediate peptidase (MIP; EC 3.4.24.59) belongs to the widespread subfamily M3A, that shows similarity to Thimet oligopeptidase (TOP). It is one of three peptidases responsible for the proteolytic processing of both nuclear and mitochondrial encoded precursor polypeptides targeted to various subcompartments of the mitochondria. It cleaves intermediate-size proteins initially processed by mitochondrial processing peptidase (MPP) to yield a processing intermediate with a typical N-terminal octapeptide that is sequentially cleaved by MIP to mature-size protein. MIP cleaves precursor proteins of respiratory components, including subunits of the electron transport chain and tri-carboxylic acid cycle enzymes, and components of the mitochondrial genetic machinery, including ribosomal proteins, translation factors, and proteins required for mitochondrial DNA metabolism. It has been suggested that the human MIP (HMIP polypeptide (gene symbol MIPEP) may be one of the loci predicted to influence the clinical manifestations of Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative disease caused by the lack of human frataxin. These proteins are enriched in cysteine residues, two of which are highly conserved, suggesting their importance to stability as well as in formation of metal binding sites, thus playing a role in MIP activity.
Pssm-ID: 341052 [Multi-domain] Cd Length: 613 Bit Score: 292.54 E-value: 6.46e-90
Database: CDSEARCH/cdd Low complexity filter: no Composition Based Adjustment: yes E-value threshold: 0.01
References:
Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
of the residues that compose this conserved feature have been mapped to the query sequence.
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