M28 Zn-peptidase glutaminyl cyclase; Peptidase M28 family, glutaminyl cyclase (QC; EC 2.3.2.5) subfamily. QC is involved in N-terminal glutamine cyclization of many endocrine peptides and is typically abundant in brain tissue. N-terminal glutamine residue cyclization is an important post-translational event in the processing of numerous bioactive proteins, including neuropeptides, hormones, and cytokines during their maturation in the secretory pathway. The N-terminal pGlu protects them from exopeptidase degradation and/or enables them to have proper conformation for binding to their receptors. QCs are highly conserved from yeast to human. In humans, several genetic diseases, such as osteoporosis, appear to result from mutations of the QC gene. N-terminal glutamate cyclization into pyroglutamate (pGlu) is a reaction that may be related to the formation of several plaque-forming peptides, such as amyloid-(A) peptides and collagen-like Alzheimer amyloid plaque component, which play a pivotal role in Alzheimer's disease.
:
Pssm-ID: 349876 [Multi-domain] Cd Length: 305 Bit Score: 457.86 E-value: 1.33e-162
M28 Zn-peptidase glutaminyl cyclase; Peptidase M28 family, glutaminyl cyclase (QC; EC 2.3.2.5) subfamily. QC is involved in N-terminal glutamine cyclization of many endocrine peptides and is typically abundant in brain tissue. N-terminal glutamine residue cyclization is an important post-translational event in the processing of numerous bioactive proteins, including neuropeptides, hormones, and cytokines during their maturation in the secretory pathway. The N-terminal pGlu protects them from exopeptidase degradation and/or enables them to have proper conformation for binding to their receptors. QCs are highly conserved from yeast to human. In humans, several genetic diseases, such as osteoporosis, appear to result from mutations of the QC gene. N-terminal glutamate cyclization into pyroglutamate (pGlu) is a reaction that may be related to the formation of several plaque-forming peptides, such as amyloid-(A) peptides and collagen-like Alzheimer amyloid plaque component, which play a pivotal role in Alzheimer's disease.
Pssm-ID: 349876 [Multi-domain] Cd Length: 305 Bit Score: 457.86 E-value: 1.33e-162
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
107-380
8.78e-20
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: 87.88 E-value: 8.78e-20
M28 Zn-peptidase glutaminyl cyclase; Peptidase M28 family, glutaminyl cyclase (QC; EC 2.3.2.5) subfamily. QC is involved in N-terminal glutamine cyclization of many endocrine peptides and is typically abundant in brain tissue. N-terminal glutamine residue cyclization is an important post-translational event in the processing of numerous bioactive proteins, including neuropeptides, hormones, and cytokines during their maturation in the secretory pathway. The N-terminal pGlu protects them from exopeptidase degradation and/or enables them to have proper conformation for binding to their receptors. QCs are highly conserved from yeast to human. In humans, several genetic diseases, such as osteoporosis, appear to result from mutations of the QC gene. N-terminal glutamate cyclization into pyroglutamate (pGlu) is a reaction that may be related to the formation of several plaque-forming peptides, such as amyloid-(A) peptides and collagen-like Alzheimer amyloid plaque component, which play a pivotal role in Alzheimer's disease.
Pssm-ID: 349876 [Multi-domain] Cd Length: 305 Bit Score: 457.86 E-value: 1.33e-162
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
151-377
1.76e-32
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: 120.91 E-value: 1.76e-32
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
107-380
8.78e-20
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: 87.88 E-value: 8.78e-20
M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase ...
106-361
1.21e-15
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: 349943 [Multi-domain] Cd Length: 287 Bit Score: 76.41 E-value: 1.21e-15
M28 Zn-Peptidases; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized ...
106-373
2.00e-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: 63.64 E-value: 2.00e-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: 55.67 E-value: 1.55e-08
M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; Peptidase family ...
151-362
1.61e-08
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: 54.17 E-value: 1.61e-08
M28 Zn-peptidase containing a protease-associated (PA) domain insert and associated with a PDZ ...
100-373
3.82e-08
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: 54.00 E-value: 3.82e-08
M28 Zn-peptidase containing a PA domain insert; Peptidase family M28 (also called ...
105-363
6.13e-07
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: 50.26 E-value: 6.13e-07
M28 Zn-peptidase containing a protease-associated (PA) domain insert; Peptidase family M28 ...
106-340
6.75e-07
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: 50.44 E-value: 6.75e-07
Peptidase M20 acetylornithine deacetylase/succinyl-diaminopimelate desuccinylase (ArgE/DapE)-like; Peptidase M20 acetylornithine deacetylase/succinyl-diaminopimelate desuccinylase (ArgE/DapE) like family of enzymes catalyze analogous reactions and share a common activator, the metal ion (usually Co2+ or Zn2+). ArgE catalyzes a broad range of substrates, including N-acetylornithine, alpha-N-acetylmethionine and alpha-N-formylmethionine, while DapE catalyzes the hydrolysis of N-succinyl-L,L-diaminopimelate (L,L-SDAP) to L,L-diaminopimelate and succinate. Proteins in this family are mostly bacterial and have been inferred by homology as being related to both ArgE and DapE. This family also includes N-acetyl-L-citrulline deacetylase (ACDase; acetylcitrulline deacetylase), a unique, novel enzyme found in Xanthomonas campestris, a plant pathogen, in which N-acetyl-L-ornithine is the substrate for transcarbamoylation reaction, and the product is N-acetyl-L-citrulline. Thus, in the arginine biosynthesis pathway, ACDase subsequently catalyzes the hydrolysis of N-acetyl-L-citrulline to acetate and L-citrulline.
Pssm-ID: 349944 [Multi-domain] Cd Length: 361 Bit Score: 40.75 E-value: 9.76e-04
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
