AOAH
AOAH | |||
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Identifiers | |||
Gene ontology | |||
Molecular function | |||
Cellular component | |||
Biological process | |||
Sources:Amigo / QuickGO |
Ensembl | |||||||||
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UniProt | |||||||||
RefSeq (mRNA) | |||||||||
RefSeq (protein) | |||||||||
Location (UCSC) | Chr 7: 36.51 – 36.72 Mb | Chr 13: 20.98 – 21.22 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Acyloxyacyl hydrolase, also known as AOAH, is a eukaryotic protein encoded by the AOAH gene.[5] AOAH is produced by macrophages (including Kupffer cells and microglia), dendritic cells (especially in the colon), NK cells, ILC1 cells, neutrophils and renal proximal tubule cells.[6]
Species distribution
The AOAH gene has been found in many invertebrates and in all vertebrates studied to date except fish. Although mice have other well-established mechanisms for preventing LPS signaling, none of these has prevented long-term persistence of stimulatory LPS in animals that lack AOAH.[7][8]
Structure
The enzyme's 2 disulfide-linked subunits are encoded by a single mRNA. The smaller subunit is a member of the saposin-like (SAPLIP) protein family and the larger subunit, which contains the active site serine, is a GDSL lipase. The enzyme's 3D structure and catalytic mechanism were reported by Gorelik et al.[9]
Function
Acyloxyacyl hydrolase (AOAH) is a lipase that selectively releases the secondary (acyloxyacyl-linked) fatty acyl chains from the hexaacyl lipid A moiety found in many bacterial lipopolysaccharides (LPSs, also called endotoxins).[5][6] The resulting tetraacyl LPS is non-stimulatory and can be a potent inhibitor of LPS sensing via the MD-2--Toll-like Receptor 4 (TLR4). The enzyme's other known substrates include bacterial lipopeptides and several host glycerolipids, including lyso-and oxidized phospholipids.[6][10]
Animal studies
Absence of the enzyme in genetically engineered mice has been associated with distinctive phenotypes. AOAH-deficient animals are unable to inactivate even small amounts of LPS in most tissues; the LPS remains bioactive and may pass from cell to cell in vivo for many weeks. The LPS-injected mice develop strikingly high titers of polyclonal antibodies, prolonged hepatomegaly, and innate immune "tolerance" that results in slow and inadequate responses to a bacterial challenge. Absence of the enzyme renders mice more likely to develop severe lung injury and die if they are challenged with intratracheal LPS, Gram-negative bacteria, or acid (AOAH may also inactivate oxidized phospholipids).[10][11] Other studies have found that AOAH reduces the stimulatory potency of LPS that translocates from the gastrointestinal tract to the liver and other organs.[12] AOAH may also prevent LPS-induced arterial foam cell formation in vivo.[13]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000136250 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021322 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ PMID 6356132.
- ^ PMID 33454018.
- PMID 18779055.
- PMID 23675296.
- PMID 29343645.
- ^ PMID 34783310.
- PMID 28622363.
- PMID 30021797.
- PMID 34522852.
External links
- Human AOAH genome location and AOAH gene details page in the UCSC Genome Browser.