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 ...
48-682
5.59e-85
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: 280.41 E-value: 5.59e-85
Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of ...
48-682
5.59e-85
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: 280.41 E-value: 5.59e-85
Peptidase family M13; Mammalian enzymes are typically type-II membrane anchored enzymes which ...
491-683
2.78e-32
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: 124.06 E-value: 2.78e-32
Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of ...
48-682
5.59e-85
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: 280.41 E-value: 5.59e-85
Peptidase family M13; Mammalian enzymes are typically type-II membrane anchored enzymes which ...
491-683
2.78e-32
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: 124.06 E-value: 2.78e-32
Peptidase family M13; M13 peptidases are well-studied proteases found in a wide range of ...
50-418
3.88e-27
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: 113.93 E-value: 3.88e-27
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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This image shows a graphical summary of conserved domains identified on the query sequence.
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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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(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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