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 ...
54-708
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: 866.06 E-value: 0e+00
Peptidase M3 thimet oligopeptidase (TOP), also includes neurolysin; Peptidase M3 Thimet ...
54-708
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: 866.06 E-value: 0e+00
Peptidase family M3; This is the Thimet oligopeptidase family, large family of mammalian and ...
250-710
2.39e-172
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: 501.15 E-value: 2.39e-172
Peptidase M3 thimet oligopeptidase (TOP), also includes neurolysin; Peptidase M3 Thimet ...
54-708
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: 866.06 E-value: 0e+00
Peptidase family M3; This is the Thimet oligopeptidase family, large family of mammalian and ...
250-710
2.39e-172
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: 501.15 E-value: 2.39e-172
Peptidase family M3, dipeptidyl carboxypeptidase (DCP); Peptidase family M3 dipeptidyl ...
72-710
1.43e-163
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: 485.81 E-value: 1.43e-163
Peptidase M3A family includes thimet oligopeptidase, dipeptidyl carboxypeptidase and ...
72-705
9.67e-141
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: 425.03 E-value: 9.67e-141
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: 338.76 E-value: 3.03e-107
M3-like Peptidases, zincin metallopeptidases, include M2_ACE, M3A, M3B_PepF, and M32 families; ...
256-705
1.41e-34
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: 137.56 E-value: 1.41e-34
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.
Click on the triangle to view details about the feature, including a multiple sequence alignment
of your query sequence and the protein sequences used to curate the domain model,
where hash marks (#) above the aligned sequences show the location of the conserved feature residues.
The thumbnail image, if present, provides an approximate view of the feature's location in 3 dimensions.
Click on the triangle for interactive 3D structure viewing options.
Functional characterization of the conserved domain architecture found on the query.
Click here to see more details.
This image shows a graphical summary of conserved domains identified on the query sequence.
The Show Concise/Full Display button at the top of the page can be used to select the desired level of detail: only top scoring hits
(labeled illustration) or all hits
(labeled illustration).
Domains are color coded according to superfamilies
to which they have been assigned. Hits with scores that pass a domain-specific threshold
(specific hits) are drawn in bright colors.
Others (non-specific hits) and
superfamily placeholders are drawn in pastel colors.
if a domain or superfamily has been annotated with functional sites (conserved features),
they are mapped to the query sequence and indicated through sets of triangles
with the same color and shade of the domain or superfamily that provides the annotation. Mouse over the colored bars or triangles to see descriptions of the domains and features.
click on the bars or triangles to view your query sequence embedded in a multiple sequence alignment of the proteins used to develop the corresponding domain model.
The table lists conserved domains identified on the query sequence. Click on the plus sign (+) on the left to display full descriptions, alignments, and scores.
Click on the domain model's accession number to view the multiple sequence alignment of the proteins used to develop the corresponding domain model.
To view your query sequence embedded in that multiple sequence alignment, click on the colored bars in the Graphical Summary portion of the search results page,
or click on the triangles, if present, that represent functional sites (conserved features)
mapped to the query sequence.
Concise Display shows only the best scoring domain model, in each hit category listed below except non-specific hits, for each region on the query sequence.
(labeled illustration) Standard Display shows only the best scoring domain model from each source, in each hit category listed below for each region on the query sequence.
(labeled illustration) Full Display shows all domain models, in each hit category below, that meet or exceed the RPS-BLAST threshold for statistical significance.
(labeled illustration) Four types of hits can be shown, as available,
for each region on the query sequence:
specific hits meet or exceed a domain-specific e-value threshold
(illustrated example)
and represent a very high confidence that the query sequence belongs to the same protein family as the sequences use to create the domain model
non-specific hits
meet or exceed the RPS-BLAST threshold for statistical significance (default E-value cutoff of 0.01, or an E-value selected by user via the
advanced search options)
the domain superfamily to which the specific and non-specific hits belong
multi-domain models that were computationally detected and are likely to contain multiple single domains
Retrieve proteins that contain one or more of the domains present in the query sequence, using the Conserved Domain Architecture Retrieval Tool
(CDART).
Modify your query to search against a different database and/or use advanced search options
