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Conserved domains on  [gi|612661350|gb|EZS77597|]
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hypothetical protein W490_01782 [Staphylococcus aureus VET0191R]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
GluZincin super family cl14813
Gluzincin Peptidase family (thermolysin-like proteinases, TLPs) which includes peptidases M1, ...
285-550 3.11e-03

Gluzincin Peptidase family (thermolysin-like proteinases, TLPs) which includes peptidases M1, M2, M3, M4, M13, M32 and M36 (fungalysins); The Gluzincin family (thermolysin-like peptidases or TLPs) includes several zinc-dependent metallopeptidases such as M1, M2, M3, M4, M13, M32, M36 peptidases (MEROPS classification), which contain the HEXXH motif as part of their active site. Peptidases in this family bind a single catalytic zinc ion which is tetrahedrally co-ordinated by three amino acid ligands and a water molecule that forms the nucleophile on activation during catalysis. The M1 family includes aminopeptidase N (APN) and leukotriene A4 hydrolase (LTA4H). APN preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and is present in a variety of human tissues and cell types. LTA4H is a bifunctional enzyme, possessing an aminopeptidase as well as an epoxide hydrolase activity such that the two activities occupy different, but overlapping sites. The M3_like peptidases include the M2_ACE, M3 or neurolysin-like family (subfamilies M3B_PepF and M3A) and M32_Taq peptidases. The M2 peptidase angiotensin converting enzyme (ACE, EC 3.4.15.1) catalyzes the conversion of decapeptide angiotensin I to the potent vasopressor octapeptide angiotensin II. ACE is a key component of the renin-angiotensin system that regulates blood pressure, thus ACE inhibitors are important for the treatment of hypertension. M3A includes thimet oligopeptidase (TOP; endopeptidase 3.4.24.15), neurolysin (3.4.24.16), and the mitochondrial intermediate peptidase; and M3B includes oligopeptidase F. The M32 family includes eukaryotic enzymes from protozoa Trypanosoma cruzi, a causative agent of Chagas' disease, and from Leishmania major, a parasite that causes leishmaniasis, making these enzymes attractive targets for drug development. The M4 family includes secreted protease thermolysin (EC 3.4.24.27), pseudolysin, aureolysin, and neutral protease as well as bacillolysin (EC 3.4.24.28) that degrade extracellular proteins and peptides for bacterial nutrition, especially prior to sporulation. Thermolysin is widely used as a nonspecific protease to obtain fragments for peptide sequencing as well as in production of the artificial sweetener aspartame. The M13 family includes neprilysin (EC 3.4.24.11) and endothelin-converting enzyme I (ECE-1, EC 3.4.24.71), which fulfill a broad range of physiological roles due to the greater variation in the S2' subsite allowing substrate specificity and are prime therapeutic targets for selective inhibition. The peptidase M36 fungalysin family includes endopeptidases from pathogenic fungi. Fungalysin hydrolyzes extracellular matrix proteins such as elastin and keratin. Aspergillus fumigatus causes the pulmonary disease aspergillosis by invading the lungs of immuno-compromised animals and secreting fungalysin that possibly breaks down proteinaceous structural barriers.


The actual alignment was detected with superfamily member cd08662:

Pssm-ID: 472708 [Multi-domain]  Cd Length: 642  Bit Score: 40.43  E-value: 3.11e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612661350 285 IANTQLPKNQKS-DLMSEVN-KTKERIKSqrniILEELARTDDKKYATQRI---------LESIfNKDEADKILKDIRVD 353
Cdd:cd08662   16 LKNHPIPADKSSwGSFSELQdRNEEQLRE----ILEEAASSAADSSAEQKAkdfykscmdEEAI-EKLGLKPLKPLLDKI 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612661350 354 GKTDQQIADQITRHIDQLSLTTSDDLLTSLIDQ-SQDKSLLISQILQTKLGkaeadkLAKDWTNKGLSNRQIVDQLKKHF 432
Cdd:cd08662   91 GGLPSLDDLAAELLLALLRRLGVSLLFGLGVSPdPKNSSRNILYLGQPGLG------LPDRDYYLDEENAEIREAYKKYI 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612661350 433 AstgdtssdDILKAILNNAKDKKQAIETILAtrIERQKAKLLADliTKIETDQNKIFNLVKSALNDKADDLLNLQKRLNQ 512
Cdd:cd08662  165 A--------KLLELLGADEEEAEKLAEDVLA--FETELAKISLS--SEELRDPEKTYNPLTLAELQKLAPSIDWKAYLKA 232
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 612661350 513 TKKDIDYVLSPIVNRPSLLDRLNKNGKTTDLNKLANLM 550
Cdd:cd08662  233 LGPPADDPDKVIVSQPEYLKKLDKLLASTPLRTLKNYL 270
GA super family cl23938
GA module; The GA (protein G-related Albumin-binding) module is composed of three alpha ...
52-106 5.12e-03

GA module; The GA (protein G-related Albumin-binding) module is composed of three alpha helices. This module is found in a range of bacterial cell surface proteins. The GA module from Swiss:Q51911 shows a strong affinity for albumin.


The actual alignment was detected with superfamily member pfam01468:

Pssm-ID: 420104 [Multi-domain]  Cd Length: 55  Bit Score: 35.59  E-value: 5.12e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 612661350   52 KQDLLDKVDKANRQIEQLKQLSASSKAHYKAQLNEAKTASQIDEIIKRANELDSK 106
Cdd:pfam01468   1 DQKLAQAKQDAKQEINGLTGLNDAQKQALKDQINQATTRTEVNQILQKAKALNNA 55
 
Name Accession Description Interval E-value
M13 cd08662
Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of ...
285-550 3.11e-03

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: 40.43  E-value: 3.11e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612661350 285 IANTQLPKNQKS-DLMSEVN-KTKERIKSqrniILEELARTDDKKYATQRI---------LESIfNKDEADKILKDIRVD 353
Cdd:cd08662   16 LKNHPIPADKSSwGSFSELQdRNEEQLRE----ILEEAASSAADSSAEQKAkdfykscmdEEAI-EKLGLKPLKPLLDKI 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612661350 354 GKTDQQIADQITRHIDQLSLTTSDDLLTSLIDQ-SQDKSLLISQILQTKLGkaeadkLAKDWTNKGLSNRQIVDQLKKHF 432
Cdd:cd08662   91 GGLPSLDDLAAELLLALLRRLGVSLLFGLGVSPdPKNSSRNILYLGQPGLG------LPDRDYYLDEENAEIREAYKKYI 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612661350 433 AstgdtssdDILKAILNNAKDKKQAIETILAtrIERQKAKLLADliTKIETDQNKIFNLVKSALNDKADDLLNLQKRLNQ 512
Cdd:cd08662  165 A--------KLLELLGADEEEAEKLAEDVLA--FETELAKISLS--SEELRDPEKTYNPLTLAELQKLAPSIDWKAYLKA 232
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 612661350 513 TKKDIDYVLSPIVNRPSLLDRLNKNGKTTDLNKLANLM 550
Cdd:cd08662  233 LGPPADDPDKVIVSQPEYLKKLDKLLASTPLRTLKNYL 270
GA pfam01468
GA module; The GA (protein G-related Albumin-binding) module is composed of three alpha ...
52-106 5.12e-03

GA module; The GA (protein G-related Albumin-binding) module is composed of three alpha helices. This module is found in a range of bacterial cell surface proteins. The GA module from Swiss:Q51911 shows a strong affinity for albumin.


Pssm-ID: 396173 [Multi-domain]  Cd Length: 55  Bit Score: 35.59  E-value: 5.12e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 612661350   52 KQDLLDKVDKANRQIEQLKQLSASSKAHYKAQLNEAKTASQIDEIIKRANELDSK 106
Cdd:pfam01468   1 DQKLAQAKQDAKQEINGLTGLNDAQKQALKDQINQATTRTEVNQILQKAKALNNA 55
 
Name Accession Description Interval E-value
M13 cd08662
Peptidase family M13 includes neprilysin and endothelin-converting enzyme I; The M13 family of ...
285-550 3.11e-03

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: 40.43  E-value: 3.11e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612661350 285 IANTQLPKNQKS-DLMSEVN-KTKERIKSqrniILEELARTDDKKYATQRI---------LESIfNKDEADKILKDIRVD 353
Cdd:cd08662   16 LKNHPIPADKSSwGSFSELQdRNEEQLRE----ILEEAASSAADSSAEQKAkdfykscmdEEAI-EKLGLKPLKPLLDKI 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612661350 354 GKTDQQIADQITRHIDQLSLTTSDDLLTSLIDQ-SQDKSLLISQILQTKLGkaeadkLAKDWTNKGLSNRQIVDQLKKHF 432
Cdd:cd08662   91 GGLPSLDDLAAELLLALLRRLGVSLLFGLGVSPdPKNSSRNILYLGQPGLG------LPDRDYYLDEENAEIREAYKKYI 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612661350 433 AstgdtssdDILKAILNNAKDKKQAIETILAtrIERQKAKLLADliTKIETDQNKIFNLVKSALNDKADDLLNLQKRLNQ 512
Cdd:cd08662  165 A--------KLLELLGADEEEAEKLAEDVLA--FETELAKISLS--SEELRDPEKTYNPLTLAELQKLAPSIDWKAYLKA 232
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 612661350 513 TKKDIDYVLSPIVNRPSLLDRLNKNGKTTDLNKLANLM 550
Cdd:cd08662  233 LGPPADDPDKVIVSQPEYLKKLDKLLASTPLRTLKNYL 270
GA pfam01468
GA module; The GA (protein G-related Albumin-binding) module is composed of three alpha ...
52-106 5.12e-03

GA module; The GA (protein G-related Albumin-binding) module is composed of three alpha helices. This module is found in a range of bacterial cell surface proteins. The GA module from Swiss:Q51911 shows a strong affinity for albumin.


Pssm-ID: 396173 [Multi-domain]  Cd Length: 55  Bit Score: 35.59  E-value: 5.12e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 612661350   52 KQDLLDKVDKANRQIEQLKQLSASSKAHYKAQLNEAKTASQIDEIIKRANELDSK 106
Cdd:pfam01468   1 DQKLAQAKQDAKQEINGLTGLNDAQKQALKDQINQATTRTEVNQILQKAKALNNA 55
 
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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