ID AAAD_HUMAN Reviewed; 399 AA. AC P22760; A8K3L3; D3DNJ6; Q8N1A9; DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 5. DT 02-SEP-2026, entry version 205. DE RecName: Full=Deacylase AADAC {ECO:0000305}; DE EC=3.-.-.- {ECO:0000269|PubMed:21856291, ECO:0000269|PubMed:22207054, ECO:0000269|PubMed:22415931, ECO:0000269|PubMed:33446525, ECO:0000269|PubMed:34450168, ECO:0000269|PubMed:37002641}; DE AltName: Full=Acetylesterase AADAC {ECO:0000305}; DE EC=3.1.1.6 {ECO:0000269|PubMed:18034159, ECO:0000269|PubMed:21856291, ECO:0000269|PubMed:22207054, ECO:0000269|PubMed:22415931, ECO:0000269|PubMed:26164127, ECO:0000269|PubMed:33446525, ECO:0000269|PubMed:34450168}; DE AltName: Full=Arylacetamide deacetylase {ECO:0000303|PubMed:8063807}; DE AltName: Full=Arylalkyl acylamidase AADAC {ECO:0000305}; DE EC=3.5.1.76 {ECO:0000269|PubMed:37002641}; DE AltName: Full=Diacylglycerol lipase activity AADAC {ECO:0000250|UniProtKB:Q99PG0}; DE EC=3.1.1.79 {ECO:0000250|UniProtKB:Q99PG0}; GN Name=AADAC {ECO:0000312|HGNC:HGNC:17}; GN Synonyms=DAC {ECO:0000303|PubMed:8063807}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND VARIANT RP ILE-281. RC TISSUE=Liver; RX PubMed=8063807; DOI=10.1016/s0021-9258(17)31855-0; RA Probst M.R., Beer M., Beer D., Jenoe P., Meyer U.A., Gasser R.; RT "Human liver arylacetamide deacetylase. Molecular cloning of a novel RT esterase involved in the metabolic activation of arylamine carcinogens with RT high sequence similarity to hormone-sensitive lipase."; RL J. Biol. Chem. 269:21650-21656(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-281. RC TISSUE=Heart; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ILE-281. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Colon; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PARTIAL PROTEIN SEQUENCE, FUNCTION, AND CATALYTIC ACTIVITY. RC TISSUE=Liver; RX PubMed=2043131; DOI=10.1016/0006-291x(91)92005-5; RA Probst M.R., Jenoe P., Meyer U.A.; RT "Purification and characterization of a human liver arylacetamide RT deacetylase."; RL Biochem. Biophys. Res. Commun. 177:453-459(1991). RN [7] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=18034159; DOI=10.1038/sj.emboj.7601924; RA Tiwari R., Koffel R., Schneiter R.; RT "An acetylation/deacetylation cycle controls the export of sterols and RT steroids from S. cerevisiae."; RL EMBO J. 26:5109-5119(2007). RN [8] RP FUNCTION. RX PubMed=17936933; DOI=10.1002/jbt.20178; RA Ross M.K., Crow J.A.; RT "Human carboxylesterases and their role in xenobiotic and endobiotic RT metabolism."; RL J. Biochem. Mol. Toxicol. 21:187-196(2007). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION. RX PubMed=19339378; DOI=10.1124/dmd.109.026567; RA Watanabe A., Fukami T., Nakajima M., Takamiya M., Aoki Y., Yokoi T.; RT "Human arylacetamide deacetylase is a principal enzyme in flutamide RT hydrolysis."; RL Drug Metab. Dispos. 37:1513-1520(2009). RN [10] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78 AND ASN-282. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [11] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=21856291; DOI=10.1016/j.bcp.2011.08.003; RA Nakajima A., Fukami T., Kobayashi Y., Watanabe A., Nakajima M., Yokoi T.; RT "Human arylacetamide deacetylase is responsible for deacetylation of RT rifamycins: rifampicin, rifabutin, and rifapentine."; RL Biochem. Pharmacol. 82:1747-1756(2011). RN [12] RP BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR RP LOCATION, AND TISSUE SPECIFICITY. RX PubMed=22207054; DOI=10.1124/dmd.111.043067; RA Kobayashi Y., Fukami T., Nakajima A., Watanabe A., Nakajima M., Yokoi T.; RT "Species differences in tissue distribution and enzyme activities of RT arylacetamide deacetylase in human, rat, and mouse."; RL Drug Metab. Dispos. 40:671-679(2012). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP BIOPHYSICOCHEMICAL PROPERTIES, VARIANTS ILE-281 AND GLN-399 EXT, AND RP CHARACTERIZATION OF VARIANTS ILE-281 AND GLN-399 EXT. RX PubMed=22415931; DOI=10.1124/dmd.112.044883; RA Shimizu M., Fukami T., Kobayashi Y., Takamiya M., Aoki Y., Nakajima M., RA Yokoi T.; RT "A novel polymorphic allele of human arylacetamide deacetylase leads to RT decreased enzyme activity."; RL Drug Metab. Dispos. 40:1183-1190(2012). RN [14] RP FUNCTION, AND INDUCTION. RX PubMed=23542347; DOI=10.1016/j.jhep.2013.03.022; RA Nourbakhsh M., Douglas D.N., Pu C.H., Lewis J.T., Kawahara T., Lisboa L.F., RA Wei E., Asthana S., Quiroga A.D., Law L.M., Chen C., Addison W.R., RA Nelson R., Houghton M., Lehner R., Kneteman N.M.; RT "Arylacetamide deacetylase: a novel host factor with important roles in the RT lipolysis of cellular triacylglycerol stores, VLDL assembly and HCV RT production."; RL J. Hepatol. 59:336-343(2013). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, GLYCOSYLATION RP AT ASN-78 AND ASN-282, AND MUTAGENESIS OF ASN-78 AND ASN-282. RX PubMed=24125761; DOI=10.1016/j.bcp.2013.10.001; RA Muta K., Fukami T., Nakajima M., Yokoi T.; RT "N-Glycosylation during translation is essential for human arylacetamide RT deacetylase enzyme activity."; RL Biochem. Pharmacol. 87:352-359(2014). RN [16] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY RP REGULATION. RX PubMed=24464802; DOI=10.1124/dmd.113.056184; RA Shimizu M., Fukami T., Ito Y., Kurokawa T., Kariya M., Nakajima M., RA Yokoi T.; RT "Indiplon is hydrolyzed by arylacetamide deacetylase in human liver."; RL Drug Metab. Dispos. 42:751-758(2014). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=26164127; DOI=10.1016/j.ejps.2015.07.006; RA Fukami T., Kariya M., Kurokawa T., Iida A., Nakajima M.; RT "Comparison of substrate specificity among human arylacetamide deacetylase RT and carboxylesterases."; RL Eur. J. Pharm. Sci. 78:47-53(2015). RN [19] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=27422753; DOI=10.1016/j.bcp.2016.07.007; RA Fukami T., Iida A., Konishi K., Nakajima M.; RT "Human arylacetamide deacetylase hydrolyzes ketoconazole to trigger RT hepatocellular toxicity."; RL Biochem. Pharmacol. 116:153-161(2016). RN [20] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=33446525; DOI=10.1124/dmd.120.000295; RA Hirosawa K., Fukami T., Tashiro K., Sakai Y., Kisui F., Nakano M., RA Nakajima M.; RT "Role of Human Arylacetamide Deacetylase (AADAC) on Hydrolysis of RT Eslicarbazepine Acetate and Effects of AADAC Genetic Polymorphisms on RT Hydrolase Activity."; RL Drug Metab. Dispos. 49:322-329(2021). RN [21] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=34450168; DOI=10.1016/j.lfs.2021.119896; RA Sakai Y., Fukami T., Nagaoka M., Hirosawa K., Ichida H., Sato R., RA Suzuki K., Nakano M., Nakajima M.; RT "Arylacetamide deacetylase as a determinant of the hydrolysis and RT activation of abiraterone acetate in mice and humans."; RL Life Sci. 284:119896-119896(2021). RN [22] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=37002641; DOI=10.1111/jpi.12870; RA Huang Z., Li Y., Konishi K., Sakai Y., Tashiro K., Fukami T., Borjigin J.; RT "In vitro deacetylation of N-acetylserotonin by arylacetamide RT deacetylase."; RL J. Pineal Res. 75:e12870-e12870(2023). RN [23] RP VARIANT ILE-281. RX PubMed=12721789; DOI=10.1007/s10038-003-0021-7; RA Saito S., Iida A., Sekine A., Kawauchi S., Higuchi S., Ogawa C., RA Nakamura Y.; RT "Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine RT esterase genes, and two other genes in the Japanese population."; RL J. Hum. Genet. 48:249-270(2003). CC -!- FUNCTION: Catalyzes the hydrolysis of ester and amide bonds and is CC largely involved in prodrugs activation, xenobiotic detoxification or CC toxicity, and, in some contexts, lipid and indole metabolism CC (PubMed:17936933, PubMed:18034159, PubMed:19339378, PubMed:2043131, CC PubMed:21856291, PubMed:22207054, PubMed:22415931, PubMed:23542347, CC PubMed:24125761, PubMed:24464802, PubMed:26164127, PubMed:27422753, CC PubMed:33446525, PubMed:34450168, PubMed:37002641, PubMed:8063807). CC Prefers compounds with relatively small acyl groups, especially CC compounds with acetyl group (PubMed:26164127). Participates in the CC hydrolysis of clinical drugs including acetyl esters compounds such as CC eslicarbazepine, abiraterone and rifamycins (rifampicin, rifabutin, and CC rifapentine) and N-acetylarylamine compounds such as flutamide, N- CC monoacetyldapsone, and phenacetin (PubMed:19339378, PubMed:21856291, CC PubMed:22207054, PubMed:22415931, PubMed:24125761, PubMed:24464802, CC PubMed:26164127, PubMed:27422753). Participates in the hydrolysis of CC carcinogen such as 2-acetylaminofluorene (AAF) and propanil CC (PubMed:2043131, PubMed:26164127, PubMed:8063807). In addition, plays a CC role in lipid metabolism by hydrolyzing newly synthesized CC diacylglycerol, so limiting triacylglycerol synthesis for cytoplasmic CC storage droplet formation and for VLDL assembly (PubMed:23542347). Can CC also catalyzes the deacetylation of cholesterol acetate CC (PubMed:18034159). Moreover can play a role in metabolism of pineal CC indoles by catalyzing the deacetylation of N-acetylarylalkylamine CC compounds including N-acetylserotonin (NAS), melatonin and N- CC acetyltryptamine, NAS conversion being the most efficient reaction CC (PubMed:37002641). {ECO:0000269|PubMed:17936933, CC ECO:0000269|PubMed:18034159, ECO:0000269|PubMed:19339378, CC ECO:0000269|PubMed:2043131, ECO:0000269|PubMed:21856291, CC ECO:0000269|PubMed:22207054, ECO:0000269|PubMed:22415931, CC ECO:0000269|PubMed:23542347, ECO:0000269|PubMed:24125761, CC ECO:0000269|PubMed:24464802, ECO:0000269|PubMed:26164127, CC ECO:0000269|PubMed:27422753, ECO:0000269|PubMed:33446525, CC ECO:0000269|PubMed:34450168, ECO:0000269|PubMed:37002641, CC ECO:0000269|PubMed:8063807}. CC -!- CATALYTIC ACTIVITY: CC Reaction=an N-acetylarylalkylamine + H2O = an aralkylamine + acetate; CC Xref=Rhea:RHEA:10352, ChEBI:CHEBI:15377, ChEBI:CHEBI:18096, CC ChEBI:CHEBI:30089, ChEBI:CHEBI:88332; EC=3.5.1.76; CC Evidence={ECO:0000269|PubMed:37002641}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10353; CC Evidence={ECO:0000269|PubMed:37002641}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-acetylserotonin + H2O = serotonin + acetate; CC Xref=Rhea:RHEA:67196, ChEBI:CHEBI:15377, ChEBI:CHEBI:17697, CC ChEBI:CHEBI:30089, ChEBI:CHEBI:350546; CC Evidence={ECO:0000269|PubMed:37002641}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67197; CC Evidence={ECO:0000269|PubMed:37002641}; CC -!- CATALYTIC ACTIVITY: CC Reaction=melatonin + H2O = 5-methoxytryptamine + acetate; CC Xref=Rhea:RHEA:67208, ChEBI:CHEBI:15377, ChEBI:CHEBI:16796, CC ChEBI:CHEBI:30089, ChEBI:CHEBI:166874; CC Evidence={ECO:0000269|PubMed:37002641}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67209; CC Evidence={ECO:0000269|PubMed:37002641}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-acetyltryptamine + H2O = tryptamine + acetate; CC Xref=Rhea:RHEA:67204, ChEBI:CHEBI:15377, ChEBI:CHEBI:30089, CC ChEBI:CHEBI:55515, ChEBI:CHEBI:57887; CC Evidence={ECO:0000269|PubMed:37002641}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67205; CC Evidence={ECO:0000269|PubMed:37002641}; CC -!- CATALYTIC ACTIVITY: CC Reaction=an acetyl ester + H2O = an aliphatic alcohol + acetate + H(+); CC Xref=Rhea:RHEA:12957, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:47622; EC=3.1.1.6; CC Evidence={ECO:0000269|PubMed:21856291, ECO:0000269|PubMed:22207054, CC ECO:0000269|PubMed:22415931, ECO:0000269|PubMed:33446525, CC ECO:0000269|PubMed:34450168}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12958; CC Evidence={ECO:0000269|PubMed:21856291, ECO:0000269|PubMed:22207054, CC ECO:0000269|PubMed:22415931, ECO:0000269|PubMed:33446525, CC ECO:0000269|PubMed:34450168}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a diacylglycerol + H2O = a monoacylglycerol + a fatty acid + CC H(+); Xref=Rhea:RHEA:32731, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17408, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.79; CC Evidence={ECO:0000250|UniProtKB:Q99PG0}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32732; CC Evidence={ECO:0000250|UniProtKB:Q99PG0}; CC -!- ACTIVITY REGULATION: Arylacetamide deacetylase activity is inhibited by CC bis(p-nitrophenyl)phosphate (BPNPP) (non competitive type inhibition), CC diisopropylphosphorofluoride (DFP), eserine and vinblastine CC (PubMed:19339378, PubMed:24464802, PubMed:27422753, PubMed:8063807). CC Arylacetamide deacetylase is moderately inhibited by sodium fluoride, CC phenylmethylsulfonyl fluoride (PMSF), and disulfiram (PubMed:19339378). CC Arylalkyl acylamidase activity is inhibited by eserine in a dose- CC dependent manner (PubMed:37002641). Acetylesterase activity is potently CC inhibited by diisopropylphosphorofluoride (DFP), vinblastine, and CC epigallocatechin gallate (EGCg) and orlistat (PubMed:34450168). CC Acetylesterase activity is moderately inhibited by bis(p- CC nitrophenyl)phosphate (BPNPP) and phenylmethylsulfonyl fluoride (PMSF) CC as well as digitonin and telmisartan (PubMed:34450168). CC {ECO:0000269|PubMed:19339378, ECO:0000269|PubMed:24464802, CC ECO:0000269|PubMed:27422753, ECO:0000269|PubMed:34450168, CC ECO:0000269|PubMed:37002641, ECO:0000269|PubMed:8063807}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=778 uM for flutamide {ECO:0000269|PubMed:19339378}; CC KM=0.6 mM for flutamide {ECO:0000269|PubMed:22207054}; CC KM=0.472 mM for flutamide {ECO:0000269|PubMed:22415931}; CC KM=3.05 mM for phenacetin {ECO:0000269|PubMed:24125761}; CC KM=1.8 nM for phenacetin {ECO:0000269|PubMed:22207054}; CC KM=1.42 mM for phenacetin {ECO:0000269|PubMed:22415931}; CC KM=0.2 mM for rifampicin {ECO:0000269|PubMed:22207054}; CC KM=0.154 mM for rifampicin {ECO:0000269|PubMed:22415931}; CC KM=274 uM for 2-acetylaminofluoren (in liver) CC {ECO:0000269|PubMed:8063807}; CC KM=286 uM for 2-acetylaminofluoren (in colon) CC {ECO:0000269|PubMed:8063807}; CC KM=45.4 uM for indiplon {ECO:0000269|PubMed:24464802}; CC KM=3.7 mM for N-acetylserotonin {ECO:0000269|PubMed:37002641}; CC KM=162.9 uM for rifampicin {ECO:0000269|PubMed:21856291}; CC KM=8 uM for rifabutin {ECO:0000269|PubMed:21856291}; CC KM=63.1 uM for rifapentine {ECO:0000269|PubMed:21856291}; CC KM=6.93 uM for ketoconazole {ECO:0000269|PubMed:27422753}; CC KM=162.9 nM for abiraterone acetate {ECO:0000269|PubMed:34450168}; CC KM=0.79 mM for eslicarbazepine acetate {ECO:0000269|PubMed:33446525}; CC KM=3.7 mM for N-acetylserotonin (NAS) {ECO:0000269|PubMed:37002641}; CC Vmax=0.6 nmol/min/mg enzyme toward flutamide CC {ECO:0000269|PubMed:19339378}; CC Vmax=1.1 nmol/min/mg enzyme toward flutamide CC {ECO:0000269|PubMed:22207054}; CC Vmax=0.617 nmol/min/mg enzyme toward flutamide CC {ECO:0000269|PubMed:22415931}; CC Vmax=1.34 nmol/min/mg enzyme toward phenacetin CC {ECO:0000269|PubMed:24125761}; CC Vmax=6.4 nmol/min/mg enzyme toward phenacetin CC {ECO:0000269|PubMed:22207054}; CC Vmax=1.42 nmol/min/mg enzyme toward phenacetin CC {ECO:0000269|PubMed:22415931}; CC Vmax=0.149 nmol/min/mg enzyme toward rifampicin CC {ECO:0000269|PubMed:22207054}; CC Vmax=0.06 nmol/min/mg enzyme toward rifampicin CC {ECO:0000269|PubMed:22415931}; CC Vmax=6.9 nmol/min/mg enzyme toward 2-acetylaminofluoren (in liver) CC {ECO:0000269|PubMed:8063807}; CC Vmax=0.588 nmol/min/mg enzyme toward 2-acetylaminofluoren (in colon) CC {ECO:0000269|PubMed:8063807}; CC Vmax=374 pmol/min/mg enzyme toward indiplon CC {ECO:0000269|PubMed:24464802}; CC Vmax=140.7 pmol/min/mg enzyme toward rifampicin CC {ECO:0000269|PubMed:21856291}; CC Vmax=121.1 pmol/min/mg enzyme toward rifabutin CC {ECO:0000269|PubMed:21856291}; CC Vmax=269.7 pmol/min/mg enzyme toward rifapentine CC {ECO:0000269|PubMed:21856291}; CC Vmax=35.3 pmol/min/mg enzyme toward ketoconazole CC {ECO:0000269|PubMed:27422753}; CC Vmax=128.4 nmol/min/mg enzyme toward abiraterone acetate CC {ECO:0000269|PubMed:34450168}; CC Vmax=157.5 nmol/min/mg enzyme toward eslicarbazepine acetate CC {ECO:0000269|PubMed:33446525}; CC -!- INTERACTION: CC P22760; Q92624: APPBP2; NbExp=3; IntAct=EBI-13217105, EBI-743771; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:19339378}; Single-pass type II membrane protein CC {ECO:0000250|UniProtKB:Q7M370}. Microsome membrane CC {ECO:0000269|PubMed:19339378, ECO:0000269|PubMed:22207054}; Single-pass CC type II membrane protein {ECO:0000250|UniProtKB:Q7M370}. CC -!- TISSUE SPECIFICITY: Detected in liver (at protein level). Mainly CC expressed in liver, small intestine, colon, adrenal gland and bladder. CC {ECO:0000269|PubMed:19339378, ECO:0000269|PubMed:22207054, CC ECO:0000269|PubMed:22415931}. CC -!- INDUCTION: Down-regulated following infection with hepatis C virus CC which results in impaired triacylglycerol lipolysis and impaired CC assembly of very low density lipoproteins. This may represent a CC cellular adaptation to infection that is aimed at limiting viral CC production. {ECO:0000269|PubMed:23542347}. CC -!- PTM: Glycosylation is required for enzyme activity. CC {ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:24125761}. CC -!- POLYMORPHISM: Three alleles are known: AADAC*1, AADAC*2 and AADAC*3. CC The sequence shown is that of AADAC*1 which is found in European CC American, African American, Japanese and Korean populations at allelic CC frequencies of 39.3 to 47.4%. The AADAC*2 allele is found in European CC American, African American, Korean, and Japanese populations at allelic CC frequencies of 52.6 to 63.5% whereas the AADAC*3 allele is found in CC European American (1.3%) and African American (2.0%) samples but not in CC Japanese or Korean samples. {ECO:0000269|PubMed:22415931}. CC -!- SIMILARITY: Belongs to the 'GDXG' lipolytic enzyme family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA35551.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L32179; AAA35551.1; ALT_FRAME; mRNA. DR EMBL; AK290628; BAF83317.1; -; mRNA. DR EMBL; AC068647; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471052; EAW78791.1; -; Genomic_DNA. DR EMBL; CH471052; EAW78792.1; -; Genomic_DNA. DR EMBL; BC032309; AAH32309.1; -; mRNA. DR CCDS; CCDS33877.1; -. DR PIR; A53856; A53856. DR RefSeq; NP_001077.2; NM_001086.3. DR AlphaFoldDB; P22760; -. DR SMR; P22760; -. DR BioGRID; 106531; 2. DR FunCoup; P22760; 34. DR IntAct; P22760; 1. DR STRING; 9606.ENSP00000232892; -. DR BindingDB; P22760; -. DR ChEMBL; CHEMBL3509584; -. DR DrugBank; DB16349; Vicagrel. DR ESTHER; human-AADAC; Arylacetamide_deacetylase. DR MEROPS; S09.991; -. DR GlyCosmos; P22760; 2 sites, No reported glycans. DR GlyGen; P22760; 2 sites. DR iPTMnet; P22760; -. DR PhosphoSitePlus; P22760; -. DR BioMuta; AADAC; -. DR DMDM; 317373587; -. DR jPOST; P22760; -. DR MassIVE; P22760; -. DR PaxDb; 9606-ENSP00000232892; -. DR PeptideAtlas; P22760; -. DR ProteomicsDB; 54037; -. DR Antibodypedia; 1182; 198 antibodies from 28 providers. DR DNASU; 13; -. DR Ensembl; ENST00000232892.12; ENSP00000232892.6; ENSG00000114771.15. DR Ensembl; ENST00000854454.1; ENSP00000524513.1; ENSG00000114771.15. DR Ensembl; ENST00000854455.1; ENSP00000524514.1; ENSG00000114771.15. DR GeneID; 13; -. DR KEGG; hsa:13; -. DR MANE-Select; ENST00000232892.12; ENSP00000232892.6; NM_001086.3; NP_001077.2. DR UCSC; uc003eze.4; human. DR AGR; HGNC:17; -. DR ClinPGx; PA24363; -. DR CTD; 13; -. DR DisGeNET; 13; -. DR GeneCards; AADAC; -. DR HGNC; HGNC:17; AADAC. DR HPA; ENSG00000114771; Group enriched (adrenal gland, intestine, liver). DR MIM; 600338; gene. DR OpenTargets; ENSG00000114771; -. DR VEuPathDB; HostDB:ENSG00000114771; -. DR eggNOG; KOG1515; Eukaryota. DR GeneTree; ENSGT00940000155975; -. DR HOGENOM; CLU_012494_12_0_1; -. DR InParanoid; P22760; -. DR OMA; PKHMARW; -. DR OrthoDB; 408631at2759; -. DR PAN-GO; P22760; 4 GO annotations based on evolutionary models. DR PhylomeDB; P22760; -. DR PathwayCommons; P22760; -. DR Reactome; R-HSA-211945; Phase I - Functionalization of compounds. DR SABIO-RK; P22760; -. DR SignaLink; P22760; -. DR Agora; ENSG00000114771; -. DR BioGRID-ORCS; 13; 6 hits in 1160 CRISPR screens. DR GeneWiki; AADAC; -. DR GenomeRNAi; 13; -. DR Pharos; P22760; Tchem. DR PRO; PR:P22760; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P22760; protein. DR Bgee; ENSG00000114771; Expressed in jejunal mucosa and 121 other cell types or tissues. DR ExpressionAtlas; P22760; baseline and differential. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0008126; F:acetylesterase activity; IDA:UniProtKB. DR GO; GO:0047416; F:arylalkyl acylamidase activity; IDA:UniProtKB. DR GO; GO:0003824; F:catalytic activity; TAS:ProtInc. DR GO; GO:0019213; F:deacetylase activity; IDA:UniProtKB. DR GO; GO:0120516; F:diacylglycerol lipase activity; ISS:UniProtKB. DR GO; GO:0016810; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds; IDA:UniProtKB. DR GO; GO:0016298; F:lipase activity; TAS:UniProtKB. DR GO; GO:0017171; F:serine hydrolase activity; IDA:UniProtKB. DR GO; GO:0004806; F:triacylglycerol lipase activity; IBA:GO_Central. DR GO; GO:0098754; P:detoxification; IDA:UniProtKB. DR GO; GO:0046340; P:diacylglycerol catabolic process; ISS:UniProtKB. DR GO; GO:0010898; P:positive regulation of triglyceride catabolic process; IBA:GO_Central. DR GO; GO:0016125; P:sterol metabolic process; IDA:UniProtKB. DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:UniProtKB. DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1. DR InterPro; IPR013094; AB_hydrolase_3. DR InterPro; IPR029058; AB_hydrolase_fold. DR InterPro; IPR017157; Arylacetamide_deacetylase. DR InterPro; IPR050300; GDXG_lipolytic_enzyme. DR InterPro; IPR033140; Lipase_GDXG_put_SER_AS. DR PANTHER; PTHR48081; AB HYDROLASE SUPERFAMILY PROTEIN C4A8.06C; 1. DR PANTHER; PTHR48081:SF28; ALPHA_BETA HYDROLASE FOLD-3 DOMAIN-CONTAINING PROTEIN; 1. DR Pfam; PF07859; Abhydrolase_3; 2. DR PIRSF; PIRSF037251; Arylacetamide_deacetylase; 1. DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1. DR PROSITE; PS01174; LIPASE_GDXG_SER; 1. PE 1: Evidence at protein level; KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; KW Glycoprotein; Hydrolase; Lipid metabolism; Membrane; Microsome; KW Proteomics identification; Reference proteome; Signal-anchor; KW Transmembrane; Transmembrane helix. FT CHAIN 1..399 FT /note="Deacylase AADAC" FT /id="PRO_0000071542" FT TOPO_DOM 1..5 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 6..23 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 24..399 FT /note="Lumenal" FT /evidence="ECO:0000255" FT MOTIF 111..113 FT /note="Involved in the stabilization of the negatively FT charged intermediate by the formation of the oxyanion hole" FT /evidence="ECO:0000250|UniProtKB:Q5NUF3" FT ACT_SITE 189 FT /evidence="ECO:0000250|UniProtKB:Q8BLF1, FT ECO:0000255|PROSITE-ProRule:PRU10038" FT ACT_SITE 343 FT /evidence="ECO:0000250|UniProtKB:Q8BLF1" FT ACT_SITE 373 FT /evidence="ECO:0000250|UniProtKB:Q8BLF1" FT CARBOHYD 78 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:24125761" FT CARBOHYD 282 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:24125761" FT DISULFID 116..340 FT /evidence="ECO:0000250" FT VARIANT 281 FT /note="V -> I (in alleles AADAC*2 and AADAC*3; mildly FT decreased enzyme activity; dbSNP:rs1803155)" FT /evidence="ECO:0000269|PubMed:12721789, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:22415931, FT ECO:0000269|PubMed:8063807, ECO:0000269|Ref.4" FT /id="VAR_014798" FT VARIANT 399 FT /note="L -> LQ (in allele AADAC*3; decreased enzyme FT activity)" FT /evidence="ECO:0000269|PubMed:22415931" FT /id="VAR_070543" FT MUTAGEN 78 FT /note="N->Q: Abolishes glycosylation at this site and FT causes moderate decrease in activity." FT /evidence="ECO:0000269|PubMed:24125761" FT MUTAGEN 282 FT /note="N->Q: Abolishes glycosylation at this site and FT causes substantial decrease in activity and reduced FT substrate affinity." FT /evidence="ECO:0000269|PubMed:24125761" FT CONFLICT 3 FT /note="R -> M (in Ref. 6; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 55..57 FT /note="LHH -> VHI (in Ref. 1; AAA35551)" FT /evidence="ECO:0000305" SQ SEQUENCE 399 AA; 45734 MW; 34F9CB717DD7417A CRC64; MGRKSLYLLI VGILIAYYIY TPLPDNVEEP WRMMWINAHL KTIQNLATFV ELLGLHHFMD SFKVVGSFDE VPPTSDENVT VTETKFNNIL VRVYVPKRKS EALRRGLFYI HGGGWCVGSA ALSGYDLLSR WTADRLDAVV VSTNYRLAPK YHFPIQFEDV YNALRWFLRK KVLAKYGVNP ERIGISGDSA GGNLAAAVTQ QLLDDPDVKI KLKIQSLIYP ALQPLDVDLP SYQENSNFLF LSKSLMVRFW SEYFTTDRSL EKAMLSRQHV PVESSHLFKF VNWSSLLPER FIKGHVYNNP NYGSSELAKK YPGFLDVRAA PLLADDNKLR GLPLTYVITC QYDLLRDDGL MYVTRLRNTG VQVTHNHVED GFHGAFSFLG LKISHRLINQ YIEWLKENL //