M13 family metallopeptidase similar to neutral endopeptidase (neprilysin), which degrades and inactivates bioactive peptides, and to endothelin-converting enzyme, which catalyzes the hydrolysis of the bond between Trp-21 and Val-22 in big endothelin to form endothelin 1
Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of ...
97-730
6.03e-166
Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of metallopeptidases includes neprilysin (neutral endopeptidase, NEP, enkephalinase, CD10, CALLA, EC 3.4.24.11), endothelin-converting enzyme I (ECE-1, EC 3.4.24.71), erythrocyte surface antigen KELL (ECE-3), phosphate-regulating gene on the X chromosome (PHEX), soluble secreted endopeptidase (SEP), and damage-induced neuronal endopeptidase (DINE)/X-converting enzyme (XCE). Proteins in this family fulfill a broad range of physiological roles due to the greater variation in the active site's S2' subsite allowing substrate specificity. NEP is expressed in a variety of tissues including kidney and brain, and is involved in many physiological and pathological processes, including blood pressure and inflammatory response. It degrades a wide array of substrates such as substance P, enkephalins, cholecystokinin, neurotensin and somatostatin. It is an important enzyme in the regulation of amyloid-beta (Abeta) protein that forms amyloid plaques that are associated with Alzeimers disease (AD). ECE-1 catalyzes the final rate-limiting step in the biosynthesis of endothelins via post-translational conversion of the biologically inactive big endothelins. Like NEP, it also hydrolyzes bradykinin, substance P, neurotensin, and Abeta. Endothelin-1 overproduction has been implicated in various diseases including stroke, asthma, hypertension, and cardiac and renal failure. Kell is a homolog of NEP and constitutes a major antigen on human erythrocytes; it preferentially cleaves big endothelin-3 to produce bioactive endothelin-3, but is also known to cleave substance P and neurokinin A. PHEX forms a complex interaction with fibroblast growth factor 23 (FGF23) and matrix extracellular phosphoglycoprotein, causing bone mineralization. A loss-of-function mutation in PHEX disrupts this interaction leading to hypophosphatemic rickets; X-linked hypophosphatemic (XLH) rickets is the most common form of metabolic rickets. ECEL1 is a brain metalloprotease which plays a critical role in the nervous regulation of the respiratory system, while DINE is abundantly expressed in the hypothalamus and its expression responds to nerve injury. A majority of these M13 proteases are prime therapeutic targets for selective inhibition.
:
Pssm-ID: 341056 [Multi-domain] Cd Length: 642 Bit Score: 492.27 E-value: 6.03e-166
Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of ...
97-730
6.03e-166
Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of metallopeptidases includes neprilysin (neutral endopeptidase, NEP, enkephalinase, CD10, CALLA, EC 3.4.24.11), endothelin-converting enzyme I (ECE-1, EC 3.4.24.71), erythrocyte surface antigen KELL (ECE-3), phosphate-regulating gene on the X chromosome (PHEX), soluble secreted endopeptidase (SEP), and damage-induced neuronal endopeptidase (DINE)/X-converting enzyme (XCE). Proteins in this family fulfill a broad range of physiological roles due to the greater variation in the active site's S2' subsite allowing substrate specificity. NEP is expressed in a variety of tissues including kidney and brain, and is involved in many physiological and pathological processes, including blood pressure and inflammatory response. It degrades a wide array of substrates such as substance P, enkephalins, cholecystokinin, neurotensin and somatostatin. It is an important enzyme in the regulation of amyloid-beta (Abeta) protein that forms amyloid plaques that are associated with Alzeimers disease (AD). ECE-1 catalyzes the final rate-limiting step in the biosynthesis of endothelins via post-translational conversion of the biologically inactive big endothelins. Like NEP, it also hydrolyzes bradykinin, substance P, neurotensin, and Abeta. Endothelin-1 overproduction has been implicated in various diseases including stroke, asthma, hypertension, and cardiac and renal failure. Kell is a homolog of NEP and constitutes a major antigen on human erythrocytes; it preferentially cleaves big endothelin-3 to produce bioactive endothelin-3, but is also known to cleave substance P and neurokinin A. PHEX forms a complex interaction with fibroblast growth factor 23 (FGF23) and matrix extracellular phosphoglycoprotein, causing bone mineralization. A loss-of-function mutation in PHEX disrupts this interaction leading to hypophosphatemic rickets; X-linked hypophosphatemic (XLH) rickets is the most common form of metabolic rickets. ECEL1 is a brain metalloprotease which plays a critical role in the nervous regulation of the respiratory system, while DINE is abundantly expressed in the hypothalamus and its expression responds to nerve injury. A majority of these M13 proteases are prime therapeutic targets for selective inhibition.
Pssm-ID: 341056 [Multi-domain] Cd Length: 642 Bit Score: 492.27 E-value: 6.03e-166
Peptidase family M13; M13 peptidases are well-studied proteases found in a wide range of ...
99-480
1.04e-104
Peptidase family M13; M13 peptidases are well-studied proteases found in a wide range of organizms including mammals and bacteria. In mammals they participate in processes such as cardiovascular development, blood-pressure regulation, nervous control of respiration, and regulation of the function of neuropeptides in the central nervous system. In bacteria they may be used for digestion of milk.
Pssm-ID: 461703 Cd Length: 382 Bit Score: 325.02 E-value: 1.04e-104
Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of ...
97-730
6.03e-166
Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of metallopeptidases includes neprilysin (neutral endopeptidase, NEP, enkephalinase, CD10, CALLA, EC 3.4.24.11), endothelin-converting enzyme I (ECE-1, EC 3.4.24.71), erythrocyte surface antigen KELL (ECE-3), phosphate-regulating gene on the X chromosome (PHEX), soluble secreted endopeptidase (SEP), and damage-induced neuronal endopeptidase (DINE)/X-converting enzyme (XCE). Proteins in this family fulfill a broad range of physiological roles due to the greater variation in the active site's S2' subsite allowing substrate specificity. NEP is expressed in a variety of tissues including kidney and brain, and is involved in many physiological and pathological processes, including blood pressure and inflammatory response. It degrades a wide array of substrates such as substance P, enkephalins, cholecystokinin, neurotensin and somatostatin. It is an important enzyme in the regulation of amyloid-beta (Abeta) protein that forms amyloid plaques that are associated with Alzeimers disease (AD). ECE-1 catalyzes the final rate-limiting step in the biosynthesis of endothelins via post-translational conversion of the biologically inactive big endothelins. Like NEP, it also hydrolyzes bradykinin, substance P, neurotensin, and Abeta. Endothelin-1 overproduction has been implicated in various diseases including stroke, asthma, hypertension, and cardiac and renal failure. Kell is a homolog of NEP and constitutes a major antigen on human erythrocytes; it preferentially cleaves big endothelin-3 to produce bioactive endothelin-3, but is also known to cleave substance P and neurokinin A. PHEX forms a complex interaction with fibroblast growth factor 23 (FGF23) and matrix extracellular phosphoglycoprotein, causing bone mineralization. A loss-of-function mutation in PHEX disrupts this interaction leading to hypophosphatemic rickets; X-linked hypophosphatemic (XLH) rickets is the most common form of metabolic rickets. ECEL1 is a brain metalloprotease which plays a critical role in the nervous regulation of the respiratory system, while DINE is abundantly expressed in the hypothalamus and its expression responds to nerve injury. A majority of these M13 proteases are prime therapeutic targets for selective inhibition.
Pssm-ID: 341056 [Multi-domain] Cd Length: 642 Bit Score: 492.27 E-value: 6.03e-166
Peptidase family M13; M13 peptidases are well-studied proteases found in a wide range of ...
99-480
1.04e-104
Peptidase family M13; M13 peptidases are well-studied proteases found in a wide range of organizms including mammals and bacteria. In mammals they participate in processes such as cardiovascular development, blood-pressure regulation, nervous control of respiration, and regulation of the function of neuropeptides in the central nervous system. In bacteria they may be used for digestion of milk.
Pssm-ID: 461703 Cd Length: 382 Bit Score: 325.02 E-value: 1.04e-104
Peptidase family M13; Mammalian enzymes are typically type-II membrane anchored enzymes which ...
540-731
2.28e-88
Peptidase family M13; Mammalian enzymes are typically type-II membrane anchored enzymes which are known, or believed to activate or inactivate oligopeptide (pro)-hormones such as opioid peptides. The family also contains a bacterial member believed to be involved with milk protein cleavage.
Pssm-ID: 279739 [Multi-domain] Cd Length: 205 Bit Score: 275.83 E-value: 2.28e-88
The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexins; BAR domains are dimerization, lipid ...
343-499
5.64e-04
The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.
Pssm-ID: 153280 [Multi-domain] Cd Length: 218 Bit Score: 41.96 E-value: 5.64e-04
Ras-associating (RA) domain found in Ras-association domain-containing protein 3 (RASSF3); ...
129-176
9.05e-03
Ras-associating (RA) domain found in Ras-association domain-containing protein 3 (RASSF3); RASSF3 is a member of a family of six related classical RASSF1-6 proteins (the classical RASSF proteins). RASSF3 has three transcripts (A-C) due to alternative splicing of the exons. The RASSF3B and 3C isoforms are shorter than RASSF3A, and unlike RASSF3A do not contain the RA or SARAH domains. The RA domain of the classical RASSF proteins has a beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. The RA domain mediates interactions with Ras and other small GTPases, and the SARAH domain mediates protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. RASSF3A regulates apoptosis and cell cycle via p53 stabilization and possibly is involved in DNA repair.
Pssm-ID: 340739 Cd Length: 141 Bit Score: 37.16 E-value: 9.05e-03
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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Functional characterization of the conserved domain architecture found on the query.
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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.
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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.
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