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Information on EC 3.1.1.77 - acyloxyacyl hydrolase and Organism(s) Mus musculus and UniProt Accession O35298
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3.1.1.77 acyloxyacyl hydrolaseSpecify your search results
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The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
acyloxyacyl hydrolase, neutrophil acyloxyacyl hydrolase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
neutrophil acyloxyacyl hydrolase
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of C-O bond
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-
-
-
CAS REGISTRY NUMBER
COMMENTARY
110277-64-0
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3-(acyloxy)acyl group of bacterial toxin
3-hydroxyacyl group of bacterial toxin + a fatty acid
3-(acyloxy)acyl group of bacterial toxin + H2O
3-hydroxyacyl group of bacterial toxin + a fatty acid
host AOAH selectively removes the secondary fatty acyl chains from bacterial lipopolysaccharides, that are required for lipopolysaccharide recognition by its mammalian signaling receptor, MD-2-TLR4. Possibility that AOAH, by inactivating bacterial lipopolysaccharide within the liver and spleen, is an important endogenous control mechanism. Recombinant AOAH restores hepatic LPS deacylation and prevented LPS-induced hepatomegaly in Aoah-/- mice
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-
?
3-(acyloxy)acyl group of bacterial toxin
3-hydroxyacyl group of bacterial toxin + a fatty acid
3-(acyloxy)acyl group of bacterial toxin + H2O
3-hydroxyacyl group of bacterial toxin + a fatty acid
additional information
?
-
-
the enzyme inactivates lipopolysaccharides deacylating secondary fatty acyl chains on the lipid A moiety of lipopolysaccharide
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-
?
3-(acyloxy)acyl group of bacterial toxin
3-hydroxyacyl group of bacterial toxin + a fatty acid
deacylation greatly reduces the ability of lipopolysaccharide to stimulate cells via CD14-MD-2-Toll-like receptor 4. Cortical tubule cells may produce and secrete the enzyme to limit inflammatory responses to gram-negative bacteria throughout the urinary tract
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-
?
3-(acyloxy)acyl group of bacterial toxin
3-hydroxyacyl group of bacterial toxin + a fatty acid
Salmonella enterica serovar typhimurium lipopolysaccharide is used as substrate
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-
?
3-(acyloxy)acyl group of bacterial toxin
3-hydroxyacyl group of bacterial toxin + a fatty acid
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detoxification of LPS
-
?
3-(acyloxy)acyl group of bacterial toxin
3-hydroxyacyl group of bacterial toxin + a fatty acid
-
detoxification of LPS
-
?
3-(acyloxy)acyl group of bacterial toxin
3-hydroxyacyl group of bacterial toxin + a fatty acid
-
the major mammalian enzyme that deacylates the lipopolysaccharides contained in phygocytosed bacteria. The enzymatic deacylation of lipopolysaccharides is an intrinsic, regulated mechanism by which dendritic cells may modulate host response to this potent bacterial agonist
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-
?
3-(acyloxy)acyl group of bacterial toxin + H2O
3-hydroxyacyl group of bacterial toxin + a fatty acid
-
-
-
?
3-(acyloxy)acyl group of bacterial toxin + H2O
3-hydroxyacyl group of bacterial toxin + a fatty acid
-
-
-
?
3-(acyloxy)acyl group of bacterial toxin + H2O
3-hydroxyacyl group of bacterial toxin + a fatty acid
-
detoxification of lipopolysaccharide
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3-(acyloxy)acyl group of bacterial toxin
3-hydroxyacyl group of bacterial toxin + a fatty acid
deacylation greatly reduces the ability of lipopolysaccharide to stimulate cells via CD14-MD-2-Toll-like receptor 4. Cortical tubule cells may produce and secrete the enzyme to limit inflammatory responses to gram-negative bacteria throughout the urinary tract
-
-
?
3-(acyloxy)acyl group of bacterial toxin + H2O
3-hydroxyacyl group of bacterial toxin + a fatty acid
host AOAH selectively removes the secondary fatty acyl chains from bacterial lipopolysaccharides, that are required for lipopolysaccharide recognition by its mammalian signaling receptor, MD-2-TLR4. Possibility that AOAH, by inactivating bacterial lipopolysaccharide within the liver and spleen, is an important endogenous control mechanism. Recombinant AOAH restores hepatic LPS deacylation and prevented LPS-induced hepatomegaly in Aoah-/- mice
-
-
?
3-(acyloxy)acyl group of bacterial toxin
3-hydroxyacyl group of bacterial toxin + a fatty acid
additional information
?
-
-
the enzyme inactivates lipopolysaccharides deacylating secondary fatty acyl chains on the lipid A moiety of lipopolysaccharide
-
-
?
3-(acyloxy)acyl group of bacterial toxin
3-hydroxyacyl group of bacterial toxin + a fatty acid
-
detoxification of LPS
-
?
3-(acyloxy)acyl group of bacterial toxin
3-hydroxyacyl group of bacterial toxin + a fatty acid
-
detoxification of LPS
-
?
3-(acyloxy)acyl group of bacterial toxin
3-hydroxyacyl group of bacterial toxin + a fatty acid
-
the major mammalian enzyme that deacylates the lipopolysaccharides contained in phygocytosed bacteria. The enzymatic deacylation of lipopolysaccharides is an intrinsic, regulated mechanism by which dendritic cells may modulate host response to this potent bacterial agonist
-
-
?
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
renal corticular tubule cells produce AOAH and secrete it into urine, where it can deacylate lipopolysaccharides
renal corticular tubule cells produce AOAH and secrete it into urine, where it can deacylate lipopolysaccharides
renal corticular tubule cells produce AOAH and secrete it into urine, where it can deacylate lipopolysaccharides
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XS52, an immature dendritic cell line derived from newborn BALB/c mouse epidermis and a bone marrow derived cell line
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
malfunction
physiological function
physiological function
alveolar macrophages increase Aoah expression upon exposure to lipopolysaccharide and Aoah+/+ mice recover more rapidly than Aoah-/- mice from acute lung injury induced by nasally instilled lipopolysaccharide or Klebsiella pneumoniae. Aoah-/- mouse lungs have more prolonged leukocyte infiltration, greater pro- and anti-inflammatory cytokine expression, and longer lasting alveolar barrier damage. The persistently bioactive lipopolysaccharide in Aoah-/- alveoli can stimulate alveolar macrophages directly and epithelial cells indirectly to produce chemoattractants that recruit neutrophils to the lung and may prevent their clearance. Alveolar macrophages that lack AOAH maintain or increase their responses to bioactive lipopolysaccharides and sustained inflammation
physiological function
in a murine neurogenic cystitis model, the gene encoding acyloxyacyl hydrolase is induced in the sacral spinal cord of pseudorabies virus-infected mice. Aoah-deficient mice exhibit increased vesicomotor reflex in response to bladder distension, consistent with spontaneous bladder hypersensitivity, and increased pelvic allodynia in neurogenic cystitis and postbacterial chronic pain models. Aoah deficiency results in greater bladder pathology and tumor necrosis factor production in pseudorabies virus neurogenic cystitis. Aoah-deficient mice have significantly higher levels of bladder vascular endothelial growth factor
malfunction
-
transgenic mice overexpressing AOAH in dendritic cells and macrophages deacylate lipopolysaccharide more rapidly than wildtype controls. Transgenic mice are also protected from lipopolysaccharide-induced hepatosplenomegaly, recover more quickly from lipopolysaccharide-induced weight loss, and are more likely to survive when challenged with live Escherichia coli
malfunction
-
Aoah-/- mice with low doses of bacterial lipopolysaccharide, from from Escherichia coli strain O14, or Gram-negative bacteria have livers remaining enlarged, as much as 80% above normal, many weeks longer than do the livers of Aoah+/+ animals. When compared with livers from bacterial lipopolysaccharide-primed Aoah+/+ mice, bacterial lipopolysaccharide-primed Aoah-/- livers have more numerous and larger Kupffer cells, intrasinusoidal leukocyte aggregates and activated sinusoidal endothelial cells, and sustained production of interleukin-10 and mRNAs for tumor necrosis factor, interleukin-10, and IRAKM, phenotype, overview
malfunction
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acyloxyacyl hydrolase deficiency in colonic dendritic cells impairs mucosal Th17 polarization and immunity due to altered inactivation of commensal lipopolysaccharides. Lipopolysaccharide-containing Gram-negative microbiota augment the differentiation of antigen-specific Th17 cells
physiological function
-
bacterial lipopolysaccharide, from Escherichia coli strain O14, induce hepatomegaly in mice, a recovery requires the murine enzyme, acyloxyacyl hydrolase, that inactivates bacterial lipopolysaccharide, overview
physiological function
-
acyloxyacyl hydrolase is a mammalian enzyme expressed by antigen-presenting cells that deacylates and thereby inactivates lipopolysaccharide in host tissues. Deacylated lipopolysaccharide does not activate TLR4 and competitively inhibits signaling by biologically active lipopolysaccharide. The enzyme shows ability to modulate microbial signals that influence mucosal T cell immunity. Colonic dendritic cell subset (CD103+CD11beta+ALDH-) display a unique capacity to both express the enzyme and polarize interleukin 17-secreting CD4+ helper T cells, Th17 cells
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). AOAH_MOUSE
574
0
65155
Swiss-Prot
Secretory Pathway (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proximal tubule cells secrete the pro-enzyme, which can be taken up by bladder cells and processed to the heterodimeric, more enzymatically active, mature enzyme form
glycoprotein
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
AOAH-deficient (Aoah-/-) mice, recovery from the tolerant state induced by Gram-negative bacteria is greatly delayed in mice that lack acyloxyacyl hydrolase (AOAH). Wild-type mice regain normal responsiveness within 14 days after they receive an intraperitoneal injection of LPS or Gram-negative bacteria, AOAH-deficient mice have greatly reduced proinflammatory responses to a second LPS injection for at least 3 weeks
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
constitutive overexpression of AOAH in vivo hasten recovery from lipopolysaccharide exposure without interfering with the normal acute inflammatory response
medicine
alveolar macrophages increase AOAH expression upon exposure to lipopolysaccharide and Aoah+/+ mice recover more rapidly than Aoah-/- mice from acute lung injury induced by nasally instilled lipopolysaccharide or Klebsiella pneumoniae. Aoah-/- mouse lungs have more prolonged leukocyte infiltration, greater pro- and anti-inflammatory cytokine expression, and longer lasting alveolar barrier damage. The persistently bioactive lipopolysaccharide in Aoah-/- alveoli can stimulate alveolar macrophages directly and epithelial cells indirectly to produce chemoattractants that recruit neutrophils to the lung and may prevent their clearance. Alveolar macrophages that lack AOAH maintain or increase their responses to bioactive lipopolysaccharides and sustained inflammation
medicine
in a murine neurogenic cystitis model, the gene encoding acyloxyacyl hydrolase is induced in the sacral spinal cord of pseudorabies virus-infected mice. Aoah-deficient mice exhibit increased vesicomotor reflex in response to bladder distension, consistent with spontaneous bladder hypersensitivity, and increased pelvic allodynia in neurogenic cystitis and postbacterial chronic pain models. Aoah deficiency results in greater bladder pathology and tumor necrosis factor production in pseudorabies virus neurogenic cystitis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Cody, M.J.; Salkowski, C.A.; Henricson, B.E.; Detore, G.R.; Munford, R.S.; Vogel, S.N.
Effect of inflammatory and anti-inflammatory stimuli on acyloxyacyl hydrolase activity in murine macrophages
J. Endotoxin Res.
4
371-379
1997
Mus musculus
-
Staab, J.F.; Fosmire, S.; Zhang, M.; Varley, A.W.; Munford, R.S.
Distinctive structural features are shared by human, lapine, and murine acloxyacyl hydrolases
J. Endotoxin Res.
5
205-208
1999
Oryctolagus cuniculus, Homo sapiens, Mus musculus
-
feulner, J.A.; Lu, M.; Shelton, J.M.; Zhang, M.; Richardson, J.A.; Munford, R.S.
Identification of acyloxyacyl hydrolase, a lipopolysaccharide-detoxifying enzyme, in the murine urinary tract
Infect. Immun.
72
3171-3178
2004
Mus musculus (O35298), Mus musculus
Lu, M.; Zhang, M.; Kitchens, R.L.; Fosmire, S.; Takashima, A.; Munford, R.S.
Stimulus-dependent deacylation of bacterial lipopolysaccharide by dendritic cells
J. EXp. Med.
197
1745-1754
2003
Mus musculus
Shao, B.; Lu, M.; Katz, S.C.; Varley, A.W.; Hardwick, J.; Rogers, T.E.; Ojogun, N.; Rockey, D.C.; Dematteo, R.P.; Munford, R.S.
A host lipase detoxifies bacterial lipopolysaccharides in the liver and spleen
J. Biol. Chem.
282
13726-13735
2007
Mus musculus (O35298)
Lu, M.; Varley, A.W.; Ohta, S.; Hardwick, J.; Munford, R.S.
Host inactivation of bacterial lipopolysaccharide prevents prolonged tolerance following gram-negative bacterial infection
Cell host microbe
4
293-302
2008
Mus musculus (O35298)
Ojogun, N.; Kuang, T.Y.; Shao, B.; Greaves, D.R.; Munford, R.S.; Varley, A.W.
Overproduction of acyloxyacyl hydrolase by macrophages and dendritic cells prevents prolonged reactions to bacterial lipopolysaccharide in vivo
J. Infect. Dis.
200
1685-1693
2009
Mus musculus
Shao, B.; Kitchens, R.; Munford, R.; Rogers, T.; Rockey, D.; Varley, A.
Prolonged hepatomegaly in mice that cannot inactivate bacterial endotoxin
Hepatology
54
1051-1062
2011
Mus musculus
Janelsins, B.M.; Lu, M.; Datta, S.K.
Altered inactivation of commensal LPS due to acyloxyacyl hydrolase deficiency in colonic dendritic cells impairs mucosal Th17 immunity
Proc. Natl. Acad. Sci. USA
111
373-378
2014
Mus musculus
Yang, W.; Yaggie, R.E.; Jiang, M.C.; Rudick, C.N.; Done, J.; Heckman, C.J.; Rosen, J.M.; Schaeffer, A.J.; Klumpp, D.J.
Acyloxyacyl hydrolase modulates pelvic pain severity
Am. J. Physiol. Regul. Integr. Comp. Physiol.
314
R353-R365
2018
Mus musculus (O35298), Mus musculus
Zou, B.; Jiang, W.; Han, H.; Li, J.; Mao, W.; Tang, Z.; Yang, Q.; Qian, G.; Qian, J.; Zeng, W.; Gu, J.; Chu, T.; Zhu, N.; Zhang, W.; Yan, D.; He, R.; Chu, Y.; Lu, M.
Acyloxyacyl hydrolase promotes the resolution of lipopolysaccharide-induced acute lung injury
PLoS Pathog.
13
e1006436
2017
Mus musculus (O35298), Mus musculus
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