KIAA1363-A Multifunctional Enzyme in Xenobiotic Detoxification and Lipid Ester Hydrolysis.
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AADACL3 is one of three AADAC-family members with no established function, a statement made explicitly by the family's own review literature rather than inferred from an absence of search hits.
"Except for AADACL1, more commonly known as KIAA1363, all other members of the AADACL protein family, AADACL2, AADACL3, and AADACL4, have so far been only poorly investigated and no functional roles can be concluded."
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The family prototype is a type II membrane glycoprotein with its catalytic face in the endoplasmic reticulum lumen, which is the topology the membrane IBA transfers to AADACL3.
"The arylacetamide deacetylase (AADAC) protein family name giving protein AADAC is a type II membrane glycoprotein, facing with its active side to the lumen of the endoplasmic reticulum (ER) [1]."
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The characterised chemistry of the family spans endogenous neutral lipids and xenobiotic drugs, which is why the ester-hydrolase annotation on AADACL3 is best left substrate-agnostic.
"AADAC substrates include neutral lipids such as diglycerides, but also several xenobiotics, including a number of clinical drugs, such as the antiandrogen drug flutamide, the analgesic antipyretic drug phenacetin, and the antituberculosis drug rifamycin [1,4,5,6,7]."
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Substrate preference is not conserved even between the two best-characterised members, so a substrate cannot be inferred for AADACL3 from family membership.
"This hypothesis has been tested in yeast, where KIAA1363 (AADACL1) was unable to rescue the cholesterol acetate accumulation phenotype of the AADAC yeast ortholog Say1Δ-mutant [6], suggesting that the two enzymes have different substrate specificity, with the latter lacking sterol acetate hydrolase activity."