DNAT_DROME
ID DNAT_DROME Reviewed; 275 AA.
AC Q94521; Q8MKK2; Q9TWF1;
DT 16-MAY-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Arylalkylamine N-acetyltransferase 1 {ECO:0000303|PubMed:8901578};
DE EC=2.3.1.87 {ECO:0000269|PubMed:22716280, ECO:0000269|PubMed:25406072, ECO:0000269|PubMed:7498465, ECO:0000269|PubMed:8901578, ECO:0000269|PubMed:9703021};
DE AltName: Full=Dopamine N-acetyltransferase {ECO:0000305};
GN Name=speck {ECO:0000303|PubMed:32709620, ECO:0000312|FlyBase:FBgn0287831};
GN Synonyms=AANAT1 {ECO:0000303|PubMed:8901578},
GN Dat {ECO:0000303|PubMed:9703021}, NAT1 {ECO:0000312|EMBL:CAA69262.1};
GN ORFNames=CG3318 {ECO:0000312|FlyBase:FBgn0287831};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAA69262.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, DEVELOPMENTAL STAGE, AND INDUCTION.
RC STRAIN=Canton-S {ECO:0000312|EMBL:CAA69262.1};
RX PubMed=8901578; DOI=10.1073/pnas.93.22.12315;
RA Hintermann E., Grieder N.C., Amherd R., Brodbeck D., Meyer U.A.;
RT "Cloning of an arylalkylamine N-acetyltransferase (aaNAT1) from Drosophila
RT melanogaster expressed in the nervous system and the gut.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:12315-12320(1996).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), ALTERNATIVE SPLICING, FUNCTION,
RP CATALYTIC ACTIVITY, PATHWAY, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE
RP (ISOFORMS A AND B), AND INDUCTION.
RC STRAIN=Canton-S {ECO:0000269|PubMed:9703021};
RX PubMed=9703021; DOI=10.1089/dna.1998.17.621;
RA Brodbeck D., Amherd R., Callaerts P., Hintermann E., Meyer U.A.,
RA Affolter M.;
RT "Molecular and biochemical characterization of the aaNAT1 (Dat) locus in
RT Drosophila melanogaster: differential expression of two gene products.";
RL DNA Cell Biol. 17:621-633(1998).
RN [3] {ECO:0000312|EMBL:AAF47172.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4] {ECO:0000305, ECO:0000312|EMBL:AAF47172.1}
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAM50640.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley {ECO:0000269|PubMed:12537569};
RC TISSUE=Head {ECO:0000269|PubMed:12537569};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6] {ECO:0000305}
RP PROTEIN SEQUENCE OF 51-70; 76-94 AND 99-102, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=7498465; DOI=10.1016/0014-5793(95)01198-n;
RA Hintermann E., Jeno P., Meyer U.A.;
RT "Isolation and characterization of an arylalkylamine N-acetyltransferase
RT from Drosophila melanogaster.";
RL FEBS Lett. 375:148-150(1995).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE (ISOFORM A).
RX PubMed=10710313; DOI=10.1126/science.287.5459.1834;
RA Shaw P.J., Cirelli C., Greenspan R.J., Tononi G.;
RT "Correlates of sleep and waking in Drosophila melanogaster.";
RL Science 287:1834-1837(2000).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES (ISOFORMS A AND B), PATHWAY, AND MUTAGENESIS OF GLU-82; PRO-83;
RP TYR-99; ASP-177; ARG-188; HIS-213; CYS-216; SER-217; SER-221 AND HIS-255.
RX PubMed=25406072; DOI=10.1021/bi5006078;
RA Dempsey D.R., Jeffries K.A., Bond J.D., Carpenter A.M.,
RA Rodriguez-Ospina S., Breydo L., Caswell K.K., Merkler D.J.;
RT "Mechanistic and structural analysis of Drosophila melanogaster
RT arylalkylamine N-acetyltransferases.";
RL Biochemistry 53:7777-7793(2014).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP DISRUPTION PHENOTYPE, AND DISRUPTION PHENOTYPE (ISOFORM A).
RX PubMed=32955431; DOI=10.7554/elife.53994;
RA Davla S., Artiushin G., Li Y., Chitsaz D., Li S., Sehgal A.,
RA van Meyel D.J.;
RT "AANAT1 functions in astrocytes to regulate sleep homeostasis.";
RL Elife 9:0-0(2020).
RN [10] {ECO:0007744|PDB:3TE4}
RP X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS) OF 56-265 IN COMPLEX WITH
RP ACETYL-COA, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF GLU-82; SER-217; SER-221 AND TYR-241.
RX PubMed=22716280; DOI=10.1042/bj20120520;
RA Cheng K.C., Liao J.N., Lyu P.C.;
RT "Crystal structure of the dopamine N-acetyltransferase-acetyl-CoA complex
RT provides insights into the catalytic mechanism.";
RL Biochem. J. 446:395-404(2012).
RN [11]
RP DISRUPTION PHENOTYPE.
RX PubMed=32709620; DOI=10.1534/g3.120.401470;
RA Spana E.P., Abrams A.B., Ellis K.T., Klein J.C., Ruderman B.T., Shi A.H.,
RA Zhu D., Stewart A., May S.;
RT "speck, First Identified in Drosophila melanogaster in 1910, Is Encoded by
RT the Arylalkalamine N-Acetyltransferase (AANAT1) Gene.";
RL G3 (Bethesda) 10:3387-3398(2020).
CC -!- FUNCTION: Catalyzes N-acetylation of tryptamine, tyramine, dopamine,
CC serotonin and octopamine (PubMed:7498465, PubMed:8901578,
CC PubMed:25406072). In astrocytes, regulates sleep homeostasis by
CC limiting the accumulation of serotonin and dopamine in the brain upon
CC sleep deprivation (PubMed:10710313, PubMed:32955431). Is not essential
CC for sclerotization (PubMed:9703021). {ECO:0000269|PubMed:10710313,
CC ECO:0000269|PubMed:25406072, ECO:0000269|PubMed:32955431,
CC ECO:0000269|PubMed:7498465, ECO:0000269|PubMed:8901578,
CC ECO:0000269|PubMed:9703021}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-arylethylamine + acetyl-CoA = CoA + H(+) + N-acetyl-2-
CC arylethylamine; Xref=Rhea:RHEA:20497, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:55469, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:77827; EC=2.3.1.87;
CC Evidence={ECO:0000269|PubMed:22716280, ECO:0000269|PubMed:25406072,
CC ECO:0000269|PubMed:7498465, ECO:0000269|PubMed:8901578,
CC ECO:0000269|PubMed:9703021};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + serotonin = CoA + H(+) + N-acetylserotonin;
CC Xref=Rhea:RHEA:25217, ChEBI:CHEBI:15378, ChEBI:CHEBI:17697,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:350546;
CC EC=2.3.1.87; Evidence={ECO:0000269|PubMed:25406072,
CC ECO:0000269|PubMed:7498465, ECO:0000269|PubMed:8901578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25218;
CC Evidence={ECO:0000269|PubMed:25406072, ECO:0000269|PubMed:7498465,
CC ECO:0000269|PubMed:8901578};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + dopamine = CoA + H(+) + N-acetyl-dopamine;
CC Xref=Rhea:RHEA:51388, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:59905, ChEBI:CHEBI:125678;
CC Evidence={ECO:0000269|PubMed:7498465, ECO:0000269|PubMed:8901578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51389;
CC Evidence={ECO:0000269|PubMed:7498465, ECO:0000269|PubMed:8901578};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + tyramine = CoA + H(+) + N-acetyltyramine;
CC Xref=Rhea:RHEA:66136, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:125610, ChEBI:CHEBI:327995;
CC Evidence={ECO:0000269|PubMed:22716280, ECO:0000269|PubMed:25406072};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + octopamine = CoA + H(+) + N-acetyloctopamine;
CC Xref=Rhea:RHEA:66140, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:58025, ChEBI:CHEBI:125358;
CC Evidence={ECO:0000269|PubMed:25406072};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-methoxytryptamine + acetyl-CoA = CoA + H(+) + melatonin;
CC Xref=Rhea:RHEA:66144, ChEBI:CHEBI:15378, ChEBI:CHEBI:16796,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:166874;
CC Evidence={ECO:0000269|PubMed:25406072};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-phenylethylamine + acetyl-CoA = CoA + H(+) + N-(2-
CC phenylethyl)acetamide; Xref=Rhea:RHEA:66148, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:18177, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:225237; Evidence={ECO:0000269|PubMed:25406072};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + noradrenaline = CoA + H(+) + N-
CC acetylnoradrenaline; Xref=Rhea:RHEA:66152, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:166875,
CC ChEBI:CHEBI:166902; Evidence={ECO:0000269|PubMed:25406072};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=butanoyl-CoA + tyramine = CoA + H(+) + N-butanoyltyramine;
CC Xref=Rhea:RHEA:66156, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57371, ChEBI:CHEBI:166900, ChEBI:CHEBI:327995;
CC Evidence={ECO:0000269|PubMed:25406072};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexanoyl-CoA + tyramine = CoA + H(+) + N-hexanoyltyramine;
CC Xref=Rhea:RHEA:66160, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:62620, ChEBI:CHEBI:166901, ChEBI:CHEBI:327995;
CC Evidence={ECO:0000269|PubMed:25406072};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + tryptamine = CoA + H(+) + N-acetyltryptamine;
CC Xref=Rhea:RHEA:66196, ChEBI:CHEBI:15378, ChEBI:CHEBI:55515,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57887;
CC Evidence={ECO:0000269|PubMed:22716280, ECO:0000269|PubMed:25406072};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dopamine + hexadecanoyl-CoA = CoA + H(+) + N-hexadecanoyl-
CC dopamine; Xref=Rhea:RHEA:51376, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57379, ChEBI:CHEBI:59905, ChEBI:CHEBI:134058;
CC Evidence={ECO:0000269|PubMed:25406072};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51377;
CC Evidence={ECO:0000269|PubMed:25406072};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + dopamine = CoA + H(+) + N-(9Z-
CC octadecanoyl)-dopamine; Xref=Rhea:RHEA:51380, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:31883, ChEBI:CHEBI:57287, ChEBI:CHEBI:57387,
CC ChEBI:CHEBI:59905; Evidence={ECO:0000269|PubMed:25406072};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51381;
CC Evidence={ECO:0000269|PubMed:25406072};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-CoA + serotonin = CoA + H(+) + N-hexadecanoyl-
CC serotonin; Xref=Rhea:RHEA:51384, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:134059,
CC ChEBI:CHEBI:350546; Evidence={ECO:0000269|PubMed:25406072};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51385;
CC Evidence={ECO:0000269|PubMed:25406072};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + serotonin = CoA + H(+) + N-(9Z-
CC octadecenoyl)-serotonin; Xref=Rhea:RHEA:51392, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57387, ChEBI:CHEBI:134064,
CC ChEBI:CHEBI:350546; Evidence={ECO:0000269|PubMed:25406072};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51393;
CC Evidence={ECO:0000269|PubMed:25406072};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=octadecanoyl-CoA + serotonin = CoA + H(+) + N-octadecanoyl-
CC serotonin; Xref=Rhea:RHEA:51400, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57394, ChEBI:CHEBI:134065,
CC ChEBI:CHEBI:350546; Evidence={ECO:0000269|PubMed:25406072};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51401;
CC Evidence={ECO:0000269|PubMed:25406072};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + serotonin = CoA + H(+)
CC + N-[(5Z,8Z,11Z,14Z)-eicosatetraenoyl]-serotonin;
CC Xref=Rhea:RHEA:51396, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57368, ChEBI:CHEBI:132255, ChEBI:CHEBI:350546;
CC Evidence={ECO:0000269|PubMed:25406072};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51397;
CC Evidence={ECO:0000269|PubMed:25406072};
CC -!- ACTIVITY REGULATION: Inhibited by long-chain acyl-CoA thioesters,
CC oleoyl-CoA (an analog of acetyl-CoA) and tyrosol (an analog of
CC tyramine). {ECO:0000269|PubMed:25406072}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.19 mM for tryptamine (in transfected COS-7 cell extracts)
CC {ECO:0000269|PubMed:7498465, ECO:0000269|PubMed:8901578};
CC KM=0.89 mM for tryptamine (using purified enzyme from flies after
CC hydroxylapatite chromatography) {ECO:0000269|PubMed:7498465,
CC ECO:0000269|PubMed:8901578};
CC KM=1.15 mM for dopamine (in transfected COS-7 cell extracts)
CC {ECO:0000269|PubMed:7498465, ECO:0000269|PubMed:8901578};
CC KM=0.97 mM for dopamine (using purified enzyme from flies after
CC hydroxylapatite chromatography) {ECO:0000269|PubMed:7498465,
CC ECO:0000269|PubMed:8901578};
CC KM=1.62 mM for serotonin (in transfected COS-7 cell extracts)
CC {ECO:0000269|PubMed:7498465, ECO:0000269|PubMed:8901578};
CC KM=0.91 mM for serotonin (using purified enzyme from flies after
CC hydroxylapatite chromatography) {ECO:0000269|PubMed:7498465,
CC ECO:0000269|PubMed:8901578};
CC KM=0.47 mM for tryptamine (at pH 7.2 and with acetyl-CoA as
CC cosubstrate) {ECO:0000269|PubMed:22716280};
CC KM=0.43 mM for acetyl-CoA (at pH 7.2 and with tryptamine as
CC cosubstrate) {ECO:0000269|PubMed:22716280};
CC Vmax=11.5 nmol/h/mg enzyme toward tryptamine (in transfected COS-7
CC cells) {ECO:0000269|PubMed:7498465, ECO:0000269|PubMed:8901578};
CC Vmax=1010 umol/h/mg enzyme toward tryptamine (using purified enzyme
CC from flies after hydroxylapatite chromatography)
CC {ECO:0000269|PubMed:7498465, ECO:0000269|PubMed:8901578};
CC Note=kcat is 21.9 sec(-1) with tryptamine and acetyl-CoA as substrate
CC (at pH 7.2). {ECO:0000269|PubMed:22716280};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius. Retains 84% of activity
CC when incubated at 4 degrees Celsius for 3 days.
CC {ECO:0000269|PubMed:7498465, ECO:0000269|PubMed:8901578};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform A]:
CC Kinetic parameters:
CC KM=80 uM for benzoyl-CoA (at pH 8 and with tyramine as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC KM=64 uM for acetyl-CoA (at pH 8 and with tyramine as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC KM=19 uM for butyryl-CoA (at pH 8 and with tyramine as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC KM=23 uM for hexanoyl-CoA (at pH 8 and with tyramine as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform B]:
CC Kinetic parameters:
CC KM=39 uM for acetyl-CoA (at pH 8 and with tyramine as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC KM=65 uM for benzoyl-CoA (at pH 8 and with tyramine as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC KM=36 uM for butanoyl-CoA (at pH 8 and with tyramine as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC KM=23 uM for hexanoyl-CoA (at pH 8 and with tyramine as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC KM=18 uM for octanoyl-CoA (at pH 8 and with tyramine as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC KM=23 uM for decanoyl-CoA (at pH 8 and with tyramine as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC KM=12 uM for tyramine (at pH 8 and with acetyl-CoA as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC KM=10 uM for octapamine (at pH 8 and with acetyl-CoA as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC KM=25 uM for dopamine (at pH 8 and with acetyl-CoA as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC KM=33 uM for tryptamine (at pH 8 and with acetyl-CoA as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC KM=54 uM for 5-methoxytryptamine (at pH 8 and with acetyl-CoA as
CC cosubstrate) {ECO:0000269|PubMed:25406072};
CC KM=32 uM for noradrenaline (at pH 8 and with acetyl-CoA as
CC cosubstrate) {ECO:0000269|PubMed:25406072};
CC KM=56 uM for 2-phenylethylamine (at pH 8 and with acetyl-CoA as
CC cosubstrate) {ECO:0000269|PubMed:25406072};
CC KM=110 uM for serotonin (at pH 8 and with acetyl-CoA as cosubstrate)
CC {ECO:0000269|PubMed:25406072};
CC Note=kcat is 19 sec(-1) for tyramine (at pH 8 and with acetyl-CoA as
CC cosubstrate) (PubMed:25406072). kcat is 13 sec(-1) for octapamine (at
CC pH 8 and with acetyl-CoA as cosubstrate) (PubMed:25406072). kcat is
CC 17.6 sec(-1) for dopamine (at pH 8 and with acetyl-CoA as
CC cosubstrate) (PubMed:25406072). kcat is 22 sec(-1) for tryptamine (at
CC pH 8 and with acetyl-CoA as cosubstrate) (PubMed:25406072). kcat is
CC 35 sec(-1) for 5-methoxytryptamine (at pH 8 and with acetyl-CoA as
CC cosubstrate) (PubMed:25406072). kcat is 20 sec(-1) for noradrenaline
CC (at pH 8 and with acetyl-CoA as cosubstrate) (PubMed:25406072). kcat
CC is 30 sec(-1) for 2-phenylethylamine (at pH 8 and with acetyl-CoA as
CC cosubstrate). kcat is 29.7 sec(-1) for serotonine (at pH 8 and with
CC acetyl-CoA as cosubstrate) (PubMed:25406072).
CC {ECO:0000269|PubMed:25406072};
CC -!- PATHWAY: Aromatic compound metabolism; melatonin biosynthesis;
CC melatonin from serotonin: step 1/2. {ECO:0000269|PubMed:25406072,
CC ECO:0000269|PubMed:7498465, ECO:0000269|PubMed:8901578,
CC ECO:0000269|PubMed:9703021}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:32955431}. Nucleus
CC {ECO:0000269|PubMed:32955431}. Note=In astrocytes, is primarily
CC cytoplasmic, but in neurons is also nuclear.
CC {ECO:0000269|PubMed:32955431}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B {ECO:0000269|PubMed:8901578, ECO:0000269|PubMed:9703021};
CC Synonyms=aaNAT1a {ECO:0000269|PubMed:9703021}, AANATA
CC {ECO:0000269|PubMed:25406072};
CC IsoId=Q94521-1; Sequence=Displayed;
CC Name=A {ECO:0000269|PubMed:9703021}; Synonyms=aaNAT1b
CC {ECO:0000269|PubMed:9703021}, AANATB {ECO:0000269|PubMed:25406072};
CC IsoId=Q94521-2; Sequence=VSP_043741;
CC -!- TISSUE SPECIFICITY: In the adult, expressed in the midgut portion of
CC the thoracic segments and the frontal half of the abdomen (at protein
CC level) (PubMed:9703021). Expressed in the epithelial cell layer facing
CC the lumen of the gut (at protein level) (PubMed:9703021). In the brain,
CC expressed in a sub-populations of neurons and astrocytes, and in a set
CC of distinct stripes in the optic lobes (at protein level)
CC (PubMed:9703021, PubMed:32955431). Expressed mainly in serotonergic
CC neurons but also in subsets of glutamatergic, GABAergic and cholinergic
CC neurons (at protein level) (PubMed:32955431).
CC {ECO:0000269|PubMed:32955431, ECO:0000269|PubMed:9703021}.
CC -!- DEVELOPMENTAL STAGE: [Isoform B]: Detected in late pupal stages and in
CC adult (at protein level). {ECO:0000269|PubMed:8901578,
CC ECO:0000269|PubMed:9703021}.
CC -!- DEVELOPMENTAL STAGE: [Isoform A]: Detected from 8h up to the adult
CC stage at relatively constant levels (at protein level)
CC (PubMed:9703021). From 16 hours embryo, detected in cells of the brain,
CC the ventral nerve cord, and the midgut (PubMed:9703021).
CC {ECO:0000269|PubMed:9703021}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the embryonic central nervous system
CC (at protein level) (PubMed:32955431). First detected in stage 14
CC embryos in cells of the future proventriculus (PubMed:8901578). From
CC stage 15 onwards, strongly expressed in the proventriculus as well as
CC in endodermal cells of the anterior and posterior midgut, whereas the
CC remainder of the midgut shows only very weak expression
CC (PubMed:8901578). No expression is observed in the cells of the
CC developing gastric caeca (PubMed:8901578). Expression in the ventral
CC cord and the brain is nonsegmental (PubMed:8901578).
CC {ECO:0000269|PubMed:32955431, ECO:0000269|PubMed:8901578}.
CC -!- INDUCTION: Expression at the transcriptional or the translational level
CC is not regulated in a circadian fashion. {ECO:0000269|PubMed:8901578,
CC ECO:0000269|PubMed:9703021}.
CC -!- DISRUPTION PHENOTYPE: Has a darker body color (PubMed:32709620). Shows
CC ectopic pigmentation in the wing hinge, the posterior pupal case, leg
CC joints and cuticular sutures (PubMed:32709620). RNAi-mediated knockdown
CC in astrocytes, does not affect numbers of astrocytes present in the
CC brain (PubMed:32955431). Shows normal baseline patterns and amounts of
CC daytime and nighttime sleep, but while awake are less active
CC (PubMed:32955431). Upon overnight mechanical sleep deprivation, results
CC in increased recovery sleep next day (PubMed:32955431). RNAi-mediated
CC knockdown in neurons results in normal patterns of baseline sleep
CC (PubMed:32955431). Shows lower levels of activity while awake during
CC daytime (PubMed:32955431). During the night, increases duration of
CC sleep bouts and decrease their numbers, suggesting improved sleep
CC consolidation at night (PubMed:32955431). Do not display enhanced
CC recovery sleep the next day following overnight mechanical sleep
CC deprivation (PubMed:32955431). {ECO:0000269|PubMed:32709620,
CC ECO:0000269|PubMed:32955431}.
CC -!- DISRUPTION PHENOTYPE: [Isoform A]: Does not affect the percentage or
CC circadian distribution of rest and waking (PubMed:10710313,
CC PubMed:32955431). Shows normal amounts and pattern of activity
CC (PubMed:10710313, PubMed:32955431). Increases homeostatic sleep
CC following deprivation (PubMed:10710313, PubMed:32955431). Reduces
CC catabolism of serotonin and dopamine in the brains in response to sleep
CC deprivation, leading to inappropriate accumulation of these monoamines
CC (PubMed:32955431). {ECO:0000269|PubMed:10710313,
CC ECO:0000269|PubMed:32955431}.
CC -!- SIMILARITY: Belongs to the acetyltransferase family. AANAT subfamily.
CC {ECO:0000305}.
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DR EMBL; Y07964; CAA69262.1; -; mRNA.
DR EMBL; AE013599; AAF47172.1; -; Genomic_DNA.
DR EMBL; AE013599; AAM68307.1; -; Genomic_DNA.
DR EMBL; AY118780; AAM50640.1; -; mRNA.
DR RefSeq; NP_523839.2; NM_079115.3. [Q94521-2]
DR RefSeq; NP_995934.1; NM_206212.2. [Q94521-1]
DR PDB; 3TE4; X-ray; 1.46 A; A=56-265.
DR PDB; 3V8I; X-ray; 1.80 A; A/B=56-265.
DR PDB; 5GI5; X-ray; 1.45 A; A=56-265.
DR PDB; 5GI6; X-ray; 1.65 A; A=56-265.
DR PDB; 5GI7; X-ray; 1.20 A; A=56-265.
DR PDB; 5GI8; X-ray; 1.30 A; A=56-265.
DR PDB; 5GI9; X-ray; 1.40 A; A=56-265.
DR PDB; 5GIF; X-ray; 1.30 A; A=56-265.
DR PDB; 5GIG; X-ray; 1.30 A; A=56-265.
DR PDB; 5GIH; X-ray; 1.39 A; A=56-265.
DR PDB; 5GII; X-ray; 1.29 A; A=56-265.
DR PDB; 6K80; X-ray; 1.28 A; A=56-265.
DR PDBsum; 3TE4; -.
DR PDBsum; 3V8I; -.
DR PDBsum; 5GI5; -.
DR PDBsum; 5GI6; -.
DR PDBsum; 5GI7; -.
DR PDBsum; 5GI8; -.
DR PDBsum; 5GI9; -.
DR PDBsum; 5GIF; -.
DR PDBsum; 5GIG; -.
DR PDBsum; 5GIH; -.
DR PDBsum; 5GII; -.
DR PDBsum; 6K80; -.
DR AlphaFoldDB; Q94521; -.
DR SMR; Q94521; -.
DR BioGRID; 63445; 3.
DR STRING; 7227.FBpp0089101; -.
DR PaxDb; Q94521; -.
DR PRIDE; Q94521; -.
DR DNASU; 37867; -.
DR EnsemblMetazoa; FBtr0072254; FBpp0072163; FBgn0019643. [Q94521-2]
DR EnsemblMetazoa; FBtr0072255; FBpp0089101; FBgn0019643. [Q94521-1]
DR GeneID; 37867; -.
DR KEGG; dme:Dmel_CG3318; -.
DR UCSC; CG3318-RA; d. melanogaster.
DR UCSC; CG3318-RB; d. melanogaster. [Q94521-1]
DR CTD; 393677; -.
DR FlyBase; FBgn0287831; speck.
DR VEuPathDB; VectorBase:FBgn0019643; -.
DR eggNOG; ENOG502S2IU; Eukaryota.
DR GeneTree; ENSGT00940000164149; -.
DR InParanoid; Q94521; -.
DR OMA; IMALMDH; -.
DR PhylomeDB; Q94521; -.
DR UniPathway; UPA00837; UER00815.
DR GenomeRNAi; 37867; -.
DR PRO; PR:Q94521; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0019643; Expressed in adult midgut (Drosophila) and 21 other tissues.
DR Genevisible; Q94521; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004059; F:aralkylamine N-acetyltransferase activity; IDA:FlyBase.
DR GO; GO:0004060; F:arylamine N-acetyltransferase activity; IDA:FlyBase.
DR GO; GO:0008080; F:N-acetyltransferase activity; IDA:FlyBase.
DR GO; GO:0006584; P:catecholamine metabolic process; IDA:FlyBase.
DR GO; GO:0007593; P:chitin-based cuticle sclerotization; IMP:FlyBase.
DR GO; GO:0042420; P:dopamine catabolic process; NAS:FlyBase.
DR GO; GO:0030187; P:melatonin biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0046334; P:octopamine catabolic process; NAS:FlyBase.
DR GO; GO:0045187; P:regulation of circadian sleep/wake cycle, sleep; TAS:FlyBase.
DR GO; GO:0042429; P:serotonin catabolic process; NAS:FlyBase.
DR GO; GO:0030431; P:sleep; TAS:FlyBase.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR000182; GNAT_dom.
DR Pfam; PF00583; Acetyltransf_1; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR PROSITE; PS51186; GNAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Melatonin biosynthesis; Nucleus;
KW Reference proteome; Transferase.
FT CHAIN 1..275
FT /note="Arylalkylamine N-acetyltransferase 1"
FT /id="PRO_0000417450"
FT DOMAIN 181..254
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT BINDING 181..183
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:22716280,
FT ECO:0007744|PDB:3TE4"
FT BINDING 189..193
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:22716280,
FT ECO:0007744|PDB:3TE4"
FT SITE 82
FT /note="Has a role in the catalytic activity"
FT /evidence="ECO:0000269|PubMed:25406072"
FT SITE 99
FT /note="Might be involved in substrate binding"
FT /evidence="ECO:0000269|PubMed:25406072"
FT SITE 188
FT /note="Regulates binding affinity for coenzyme A (CoASH)"
FT /evidence="ECO:0000269|PubMed:25406072"
FT SITE 217
FT /note="Has a role in the catalytic activity"
FT /evidence="ECO:0000269|PubMed:25406072"
FT SITE 221
FT /note="Has a role in the catalytic activity"
FT /evidence="ECO:0000269|PubMed:25406072"
FT SITE 227
FT /note="Acetyl-CoA"
FT /evidence="ECO:0000269|PubMed:22716280,
FT ECO:0007744|PDB:3TE4"
FT VAR_SEQ 1..35
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000303|PubMed:12537569,
FT ECO:0000303|PubMed:9703021"
FT /id="VSP_043741"
FT MUTAGEN 82
FT /note="E->A: Reduces catalytic activity towards
FT tryptamine."
FT /evidence="ECO:0000269|PubMed:22716280,
FT ECO:0000269|PubMed:25406072"
FT MUTAGEN 83
FT /note="P->A: Reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:25406072"
FT MUTAGEN 99
FT /note="Y->A: Reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:25406072"
FT MUTAGEN 177
FT /note="D->A: Does not affect catalytic activity."
FT /evidence="ECO:0000269|PubMed:25406072"
FT MUTAGEN 188
FT /note="R->A: Reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:25406072"
FT MUTAGEN 213
FT /note="H->A: Does not affect catalytic activity."
FT /evidence="ECO:0000269|PubMed:25406072"
FT MUTAGEN 216
FT /note="C->A: Does not affect catalytic activity."
FT /evidence="ECO:0000269|PubMed:25406072"
FT MUTAGEN 217
FT /note="S->A: Reduces catalytic activity towards
FT tryptamine."
FT /evidence="ECO:0000269|PubMed:22716280,
FT ECO:0000269|PubMed:25406072"
FT MUTAGEN 221
FT /note="S->A: Reduces catalytic activity towards
FT tryptamine."
FT /evidence="ECO:0000269|PubMed:22716280,
FT ECO:0000269|PubMed:25406072"
FT MUTAGEN 241
FT /note="Y->A: No effect on the catalytic activity towards
FT tryptamine."
FT /evidence="ECO:0000269|PubMed:22716280"
FT MUTAGEN 241
FT /note="Y->F: No effect on the catalytic activity towards
FT tryptamine."
FT /evidence="ECO:0000269|PubMed:22716280"
FT MUTAGEN 255
FT /note="H->A: Reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:25406072"
FT STRAND 57..61
FT /evidence="ECO:0007829|PDB:5GI7"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:5GI7"
FT HELIX 67..76
FT /evidence="ECO:0007829|PDB:5GI7"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:5GI7"
FT HELIX 83..88
FT /evidence="ECO:0007829|PDB:5GI7"
FT HELIX 94..101
FT /evidence="ECO:0007829|PDB:5GI7"
FT HELIX 104..106
FT /evidence="ECO:0007829|PDB:5GI7"
FT STRAND 110..114
FT /evidence="ECO:0007829|PDB:5GI7"
FT STRAND 119..129
FT /evidence="ECO:0007829|PDB:5GI7"
FT HELIX 140..143
FT /evidence="ECO:0007829|PDB:5GI7"
FT HELIX 147..162
FT /evidence="ECO:0007829|PDB:5GI7"
FT HELIX 165..168
FT /evidence="ECO:0007829|PDB:5GI7"
FT STRAND 173..183
FT /evidence="ECO:0007829|PDB:5GI7"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:5GI7"
FT HELIX 192..207
FT /evidence="ECO:0007829|PDB:5GI7"
FT STRAND 211..218
FT /evidence="ECO:0007829|PDB:5GI7"
FT HELIX 219..227
FT /evidence="ECO:0007829|PDB:5GI7"
FT STRAND 231..237
FT /evidence="ECO:0007829|PDB:5GI7"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:5GI7"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:5GI5"
FT HELIX 253..255
FT /evidence="ECO:0007829|PDB:5GI7"
FT STRAND 257..264
FT /evidence="ECO:0007829|PDB:5GI7"
SQ SEQUENCE 275 AA; 30976 MW; 40E5CD99F72DF604 CRC64;
MEVQKLPDQS LISSMMLDSR CGLNDLYPIA RLTQKMEDAL TVSGKPAACP VDQDCPYTIE
LIQPEDGEAV IAMLKTFFFK DEPLNTFLDL GECKELEKYS LKPLPDNCSY KAVNKKGEII
GVFLNGLMRR PSPDDVPEKA ADSCEHPKFK KILSLMDHVE EQFNIFDVYP DEELILDGKI
LSVDTNYRGL GIAGRLTERA YEYMRENGIN VYHVLCSSHY SARVMEKLGF HEVFRMQFAD
YKPQGEVVFK PAAPHVGIQV MAKEVGPAKA AQTKL
