phosphate-regulating neutral endopeptidase PHEX isoform X4 [Homo sapiens]
Protein Classification
M13 family metallopeptidase( domain architecture ID 10171382)
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
List of domain hits
| Name | Accession | Description | Interval | E-value | ||||||
| M13 | cd08662 | Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of ... |
1-371 | 7.13e-170 | ||||||
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: 488.80 E-value: 7.13e-170
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| Name | Accession | Description | Interval | E-value | ||||||
| M13 | cd08662 | Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of ... |
1-371 | 7.13e-170 | ||||||
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: 488.80 E-value: 7.13e-170
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| PepO | COG3590 | Predicted metalloendopeptidase [Posttranslational modification, protein turnover, chaperones]; |
1-380 | 1.14e-123 | ||||||
Predicted metalloendopeptidase [Posttranslational modification, protein turnover, chaperones]; Pssm-ID: 442809 [Multi-domain] Cd Length: 674 Bit Score: 371.41 E-value: 1.14e-123
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| Peptidase_M13 | pfam01431 | Peptidase family M13; Mammalian enzymes are typically type-II membrane anchored enzymes which ... |
169-379 | 2.24e-79 | ||||||
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: 242.32 E-value: 2.24e-79
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| Name | Accession | Description | Interval | E-value | ||||||
| M13 | cd08662 | Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of ... |
1-371 | 7.13e-170 | ||||||
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: 488.80 E-value: 7.13e-170
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| PepO | COG3590 | Predicted metalloendopeptidase [Posttranslational modification, protein turnover, chaperones]; |
1-380 | 1.14e-123 | ||||||
Predicted metalloendopeptidase [Posttranslational modification, protein turnover, chaperones]; Pssm-ID: 442809 [Multi-domain] Cd Length: 674 Bit Score: 371.41 E-value: 1.14e-123
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| Peptidase_M13 | pfam01431 | Peptidase family M13; Mammalian enzymes are typically type-II membrane anchored enzymes which ... |
169-379 | 2.24e-79 | ||||||
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: 242.32 E-value: 2.24e-79
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| Peptidase_M13_N | pfam05649 | Peptidase family M13; M13 peptidases are well-studied proteases found in a wide range of ... |
1-110 | 5.91e-35 | ||||||
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: 132.04 E-value: 5.91e-35
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