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Conserved domains on  [gi|403065923|gb|AFR13383|]
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endothelin converting enzyme-like protein 1, partial [Brachymeles gracilis]

Protein Classification

M13 family metallopeptidase N-terminal domain-containing protein( domain architecture ID 10529119)

M13 family metallopeptidase N-terminal domain-containing protein, similar to the N-termini of 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

MEROPS:  M13
PubMed:  7674922|18215274

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Peptidase_M13_N pfam05649
Peptidase family M13; M13 peptidases are well-studied proteases found in a wide range of ...
 83-173 1.25e-31

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: 117.01  E-value: 1.25e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 403065923   83 PCKDFYSFACGGWLRRHAIPEDKLIYGIIAAIGEQNEEKLQQLLMQPVRRPYQASAERKVKEFFRSCLDMAEIDRQGALP 162
Cdd:pfam05649   1 PCDDFYQYACGGWLKNHPIPADKSSWGTFDELRERNEKQLREILEEAAASESDPGAVEKAKDLYKSCMDTDAIEKLGLKP 80

                          90
                  ....*....|.
gi 403065923  163 MLEVIEDCGGW 173
Cdd:pfam05649  81 LKPLLDEIGGP 91
 
Name Accession Description Interval E-value
Peptidase_M13_N pfam05649
Peptidase family M13; M13 peptidases are well-studied proteases found in a wide range of ...
 83-173 1.25e-31

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: 117.01  E-value: 1.25e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 403065923   83 PCKDFYSFACGGWLRRHAIPEDKLIYGIIAAIGEQNEEKLQQLLMQPVRRPYQASAERKVKEFFRSCLDMAEIDRQGALP 162
Cdd:pfam05649   1 PCDDFYQYACGGWLKNHPIPADKSSWGTFDELRERNEKQLREILEEAAASESDPGAVEKAKDLYKSCMDTDAIEKLGLKP 80

                          90
                  ....*....|.
gi 403065923  163 MLEVIEDCGGW 173
Cdd:pfam05649  81 LKPLLDEIGGP 91
M13 cd08662
Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of ...
 81-175 2.72e-30

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: 115.54  E-value: 2.72e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 403065923  81 IDPCKDFYSFACGGWLRRHAIPEDKLIYGIIAAIGEQNEEKLQQLLMQPVRRPYQASAERKVKEFFRSCLDMAEIDRQGA 160
Cdd:cd08662    1 VDPCDDFYQYACGNWLKNHPIPADKSSWGSFSELQDRNEEQLREILEEAASSAADSSAEQKAKDFYKSCMDEEAIEKLGL 80

                         90
                 ....*....|....*
gi 403065923 161 LPMLEVIEDCGGWDM 175
Cdd:cd08662   81 KPLKPLLDKIGGLPS 95
PepO COG3590
Predicted metalloendopeptidase [Posttranslational modification, protein turnover, chaperones];
59-168 1.02e-23

Predicted metalloendopeptidase [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 442809 [Multi-domain]  Cd Length: 674  Bit Score: 96.76  E-value: 1.02e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 403065923  59 GCQERKAFvKASRFIANNIDPTIDPCKDFYSFACGGWLRRHAIPEDKLIYGIIAAIGEQNEEKLQQLLMQPVRRPYQA-S 137
Cdd:COG3590   16 ACAAAAAA-GTSGIDLANMDTSVRPGDDFYRYVNGGWLKTTPIPADRSRWGSFNELRERNEARLRAILEEAAAAPAAAgS 94

                         90       100       110
                 ....*....|....*....|....*....|....
gi 403065923 138 AERKVKEFFRSCLDMAEIDRQGA---LPMLEVIE 168
Cdd:COG3590   95 DEQKIGDLYASFMDEAAIEALGLaplKPDLARID 128
 
Name Accession Description Interval E-value
Peptidase_M13_N pfam05649
Peptidase family M13; M13 peptidases are well-studied proteases found in a wide range of ...
 83-173 1.25e-31

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: 117.01  E-value: 1.25e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 403065923   83 PCKDFYSFACGGWLRRHAIPEDKLIYGIIAAIGEQNEEKLQQLLMQPVRRPYQASAERKVKEFFRSCLDMAEIDRQGALP 162
Cdd:pfam05649   1 PCDDFYQYACGGWLKNHPIPADKSSWGTFDELRERNEKQLREILEEAAASESDPGAVEKAKDLYKSCMDTDAIEKLGLKP 80

                          90
                  ....*....|.
gi 403065923  163 MLEVIEDCGGW 173
Cdd:pfam05649  81 LKPLLDEIGGP 91
M13 cd08662
Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of ...
 81-175 2.72e-30

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: 115.54  E-value: 2.72e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 403065923  81 IDPCKDFYSFACGGWLRRHAIPEDKLIYGIIAAIGEQNEEKLQQLLMQPVRRPYQASAERKVKEFFRSCLDMAEIDRQGA 160
Cdd:cd08662    1 VDPCDDFYQYACGNWLKNHPIPADKSSWGSFSELQDRNEEQLREILEEAASSAADSSAEQKAKDFYKSCMDEEAIEKLGL 80

                         90
                 ....*....|....*
gi 403065923 161 LPMLEVIEDCGGWDM 175
Cdd:cd08662   81 KPLKPLLDKIGGLPS 95
PepO COG3590
Predicted metalloendopeptidase [Posttranslational modification, protein turnover, chaperones];
59-168 1.02e-23

Predicted metalloendopeptidase [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 442809 [Multi-domain]  Cd Length: 674  Bit Score: 96.76  E-value: 1.02e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 403065923  59 GCQERKAFvKASRFIANNIDPTIDPCKDFYSFACGGWLRRHAIPEDKLIYGIIAAIGEQNEEKLQQLLMQPVRRPYQA-S 137
Cdd:COG3590   16 ACAAAAAA-GTSGIDLANMDTSVRPGDDFYRYVNGGWLKTTPIPADRSRWGSFNELRERNEARLRAILEEAAAAPAAAgS 94

                         90       100       110
                 ....*....|....*....|....*....|....
gi 403065923 138 AERKVKEFFRSCLDMAEIDRQGA---LPMLEVIE 168
Cdd:COG3590   95 DEQKIGDLYASFMDEAAIEALGLaplKPDLARID 128
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options: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.
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