ID ASMT_HUMAN Reviewed; 345 AA. AC P46597; B2RC33; Q16598; Q5JQ72; Q5JQ73; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 27-MAR-2024, entry version 190. DE RecName: Full=Acetylserotonin O-methyltransferase; DE EC=2.1.1.4 {ECO:0000269|PubMed:22775292}; DE AltName: Full=Hydroxyindole O-methyltransferase; DE Short=HIOMT; GN Name=ASMT; 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 [GENOMIC DNA] (ISOFORMS 1; 2 AND 3), AND TISSUE RP SPECIFICITY. RX PubMed=7989373; DOI=10.1016/s0021-9258(18)31790-3; RA Rodriguez I.R., Mazuruk K., Schoen T.J., Chader G.J.; RT "Structural analysis of the human hydroxyindole-O-methyltransferase gene. RT Presence of two distinct promoters."; RL J. Biol. Chem. 269:31969-31977(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RC TISSUE=Pineal gland; RX PubMed=8397829; DOI=10.1089/dna.1993.12.715; RA Donohue S.J., Roseboom P.H., Illnerova H., Weller J.L., Klein D.C.; RT "Human hydroxyindole-O-methyltransferase: presence of LINE-1 fragment in a RT cDNA clone and pineal mRNA."; RL DNA Cell Biol. 12:715-727(1993). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Subthalamic nucleus; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Eye; 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 TISSUE SPECIFICITY. RX PubMed=8574683; DOI=10.1016/0006-8993(95)00651-6; RA Bernard M., Donohue S.J., Klein D.C.; RT "Human hydroxyindole-O-methyltransferase in pineal gland, retina and Y79 RT retinoblastoma cells."; RL Brain Res. 696:37-48(1995). RN [7] RP INDUCTION BY SERUM TREATMENT. RX PubMed=8842389; DOI=10.1016/0006-8993(96)00359-9; RA Bernard M., Voisin P., Klein D.C.; RT "Hydroxyindole-O-methyltransferase in Y-79 cells: regulation by serum."; RL Brain Res. 727:118-124(1996). RN [8] RP INDUCTION BY RETINOIC ACID. RX PubMed=8752109; DOI=10.1046/j.1471-4159.1996.67031032.x; RA Bernard M., Klein D.C.; RT "Retinoic acid increases hydroxyindole-O-methyltransferase activity and RT mRNA in human Y-79 retinoblastoma cells."; RL J. Neurochem. 67:1032-1038(1996). RN [9] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEXES WITH RP S-ADENOSYL-L-METHIONINE; N-ACETYL SEROTONIN AND ZINC IONS, CATALYTIC RP ACTIVITY, FUNCTION, ACTIVE SITE, CHARACTERIZATION OF ISOFORMS 1; 2 AND 3, RP SUBUNIT, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANTS HIS-13; LYS-17; RP GLN-61; GLU-81; MET-171; GLY-210; ARG-219; LEU-243; MET-269; SER-273; RP ALA-278; ASP-288; GLN-291; PHE-298 AND MET-305, AND MUTAGENESIS OF LEU-11; RP ARG-111; TYR-248; THR-296 AND HIS-318. RX PubMed=22775292; DOI=10.1111/j.1600-079x.2012.01020.x; RA Botros H.G., Legrand P., Pagan C., Bondet V., Weber P., Ben-Abdallah M., RA Lemiere N., Huguet G., Bellalou J., Maronde E., Beguin P., Haouz A., RA Shepard W., Bourgeron T.; RT "Crystal structure and functional mapping of human ASMT, the last enzyme of RT the melatonin synthesis pathway."; RL J. Pineal Res. 54:46-57(2013). RN [10] RP VARIANTS ASP-288 AND PHE-298. RX PubMed=17957233; DOI=10.1038/sj.mp.4002069; RA Toma C., Rossi M., Sousa I., Blasi F., Bacchelli E., Alen R., Vanhala R., RA Monaco A.P., Jarvela I., Maestrini E.; RT "Is ASMT a susceptibility gene for autism spectrum disorders? A replication RT study in European populations."; RL Mol. Psychiatry 12:977-979(2007). RN [11] RP VARIANTS LYS-17; GLU-81; ALA-278 AND PHE-298. RX PubMed=17505466; DOI=10.1038/sj.mp.4002016; RA Melke J., Goubran Botros H., Chaste P., Betancur C., Nygren G., RA Anckarsater H., Rastam M., Stahlberg O., Gillberg I.C., Delorme R., RA Chabane N., Mouren-Simeoni M.C., Fauchereau F., Durand C.M., Chevalier F., RA Drouot X., Collet C., Launay J.M., Leboyer M., Gillberg C., Bourgeron T.; RT "Abnormal melatonin synthesis in autism spectrum disorders."; RL Mol. Psychiatry 13:90-98(2008). RN [12] RP VARIANTS HIS-13; LYS-17; GLN-61; MET-171; GLY-210; ARG-219; LEU-243; RP SER-273; ASP-288; GLN-291 AND PHE-298. RX PubMed=21251267; DOI=10.1186/1471-2350-12-17; RA Pagan C., Botros H.G., Poirier K., Dumaine A., Jamain S., Moreno S., RA de Brouwer A., Van Esch H., Delorme R., Launay J.M., Tzschach A., RA Kalscheuer V., Lacombe D., Briault S., Laumonnier F., Raynaud M., RA van Bon B.W., Willemsen M.H., Leboyer M., Chelly J., Bourgeron T.; RT "Mutation screening of ASMT, the last enzyme of the melatonin pathway, in a RT large sample of patients with intellectual disability."; RL BMC Med. Genet. 12:17-17(2011). RN [13] RP VARIANTS GLY-210 AND PHE-298. RX PubMed=21615493; DOI=10.1111/j.1600-079x.2011.00902.x; RA Chaste P., Clement N., Botros H.G., Guillaume J.L., Konyukh M., Pagan C., RA Scheid I., Nygren G., Anckarsater H., Rastam M., Stahlberg O., RA Gillberg I.C., Melke J., Delorme R., Leblond C., Toro R., Huguet G., RA Fauchereau F., Durand C., Boudarene L., Serrano E., Lemiere N., RA Launay J.M., Leboyer M., Jockers R., Gillberg C., Bourgeron T.; RT "Genetic variations of the melatonin pathway in patients with attention- RT deficit and hyperactivity disorders."; RL J. Pineal Res. 51:394-399(2011). RN [14] RP VARIANTS GLN-61; ARG-219; LEU-243; SER-273; ASP-288; GLN-291; PHE-298 AND RP MET-305. RX PubMed=22694957; DOI=10.1093/hmg/dds227; RA Etain B., Dumaine A., Bellivier F., Pagan C., Francelle L., RA Goubran-Botros H., Moreno S., Deshommes J., Moustafa K., Le Dudal K., RA Mathieu F., Henry C., Kahn J.P., Launay J.M., Muhleisen T.W., Cichon S., RA Bourgeron T., Leboyer M., Jamain S.; RT "Genetic and functional abnormalities of the melatonin biosynthesis pathway RT in patients with bipolar disorder."; RL Hum. Mol. Genet. 21:4030-4037(2012). RN [15] RP VARIANTS LYS-17; TRP-115; SER-151; ILE-166; GLY-179; MET-211; MET-217 AND RP LEU-243. RX PubMed=23349736; DOI=10.1371/journal.pone.0053727; RA Wang L., Li J., Ruan Y., Lu T., Liu C., Jia M., Yue W., Liu J., RA Bourgeron T., Zhang D.; RT "Sequencing ASMT identifies rare mutations in Chinese Han patients with RT autism."; RL PLoS ONE 8:E53727-E53727(2013). CC -!- FUNCTION: [Isoform 1]: Catalyzes the transfer of a methyl group onto N- CC acetylserotonin, producing melatonin (N-acetyl-5-methoxytryptamine). CC {ECO:0000269|PubMed:22775292}. CC -!- FUNCTION: [Isoform 2]: Does not show Acetylserotonin O- CC methyltransferase activity. {ECO:0000269|PubMed:22775292}. CC -!- FUNCTION: [Isoform 3]: Does not show Acetylserotonin O- CC methyltransferase activity. {ECO:0000269|PubMed:22775292}. CC -!- CATALYTIC ACTIVITY: CC Reaction=N-acetylserotonin + S-adenosyl-L-methionine = H(+) + melatonin CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:15573, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16796, ChEBI:CHEBI:17697, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789; EC=2.1.1.4; CC Evidence={ECO:0000269|PubMed:22775292}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15575; CC Evidence={ECO:0000269|PubMed:22775292}; CC -!- PATHWAY: Aromatic compound metabolism; melatonin biosynthesis; CC melatonin from serotonin: step 1/2. {ECO:0000305|PubMed:22775292}. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:22775292}. CC -!- INTERACTION: CC P46597; P46597: ASMT; NbExp=3; IntAct=EBI-6502097, EBI-6502097; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P46597-1; Sequence=Displayed; CC Name=2; CC IsoId=P46597-2; Sequence=VSP_004285; CC Name=3; CC IsoId=P46597-3; Sequence=VSP_004284; CC -!- TISSUE SPECIFICITY: Expressed in the pineal gland (at protein level). CC In the retina, very low expression is found at the mRNA level CC (PubMed:7989373), and not at the protein level (PubMed:8574683). CC {ECO:0000269|PubMed:22775292, ECO:0000269|PubMed:7989373, CC ECO:0000269|PubMed:8574683}. CC -!- INDUCTION: By all-trans-, 9-cis- and 13-cis-retinoic acid and by serum CC treatment, following starvation, in the retinoblastoma cell line Y79. CC {ECO:0000269|PubMed:8752109, ECO:0000269|PubMed:8842389}. CC -!- MISCELLANEOUS: The gene coding for this protein is located in the CC pseudoautosomal region 1 (PAR1) of X and Y chromosomes. CC -!- MISCELLANEOUS: [Isoform 3]: Includes part of a LINE-1 element. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase CC superfamily. Cation-independent O-methyltransferase family. CC {ECO:0000255|PROSITE-ProRule:PRU01020}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=5-hydroxyindole-O-methyltransferase CC entry; CC URL="https://en.wikipedia.org/wiki/5-hydroxyindole-O-methyltransferase"; 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; U11098; AAA75291.1; -; Genomic_DNA. DR EMBL; U11089; AAA75291.1; JOINED; Genomic_DNA. DR EMBL; U11093; AAA75291.1; JOINED; Genomic_DNA. DR EMBL; U11094; AAA75291.1; JOINED; Genomic_DNA. DR EMBL; U11095; AAA75291.1; JOINED; Genomic_DNA. DR EMBL; U11096; AAA75291.1; JOINED; Genomic_DNA. DR EMBL; U11092; AAA75291.1; JOINED; Genomic_DNA. DR EMBL; U11097; AAA75291.1; JOINED; Genomic_DNA. DR EMBL; U11098; AAA75289.1; -; Genomic_DNA. DR EMBL; U11089; AAA75289.1; JOINED; Genomic_DNA. DR EMBL; U11093; AAA75289.1; JOINED; Genomic_DNA. DR EMBL; U11094; AAA75289.1; JOINED; Genomic_DNA. DR EMBL; U11095; AAA75289.1; JOINED; Genomic_DNA. DR EMBL; U11096; AAA75289.1; JOINED; Genomic_DNA. DR EMBL; U11097; AAA75289.1; JOINED; Genomic_DNA. DR EMBL; U11098; AAA75290.1; -; Genomic_DNA. DR EMBL; U11089; AAA75290.1; JOINED; Genomic_DNA. DR EMBL; U11093; AAA75290.1; JOINED; Genomic_DNA. DR EMBL; U11094; AAA75290.1; JOINED; Genomic_DNA. DR EMBL; U11095; AAA75290.1; JOINED; Genomic_DNA. DR EMBL; U11096; AAA75290.1; JOINED; Genomic_DNA. DR EMBL; U11092; AAA75290.1; JOINED; Genomic_DNA. DR EMBL; U11097; AAA75290.1; JOINED; Genomic_DNA. DR EMBL; U11090; AAA58582.1; -; mRNA. DR EMBL; U11091; AAA58583.1; -; mRNA. DR EMBL; M83779; AAA17020.1; -; mRNA. DR EMBL; AK314922; BAG37430.1; -; mRNA. DR EMBL; AL683807; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC001620; AAH01620.1; -; mRNA. DR CCDS; CCDS14117.1; -. [P46597-3] DR CCDS; CCDS55364.1; -. [P46597-2] DR PIR; I37463; I37463. DR RefSeq; NP_001164509.1; NM_001171038.1. [P46597-3] DR RefSeq; NP_001164510.1; NM_001171039.1. [P46597-2] DR RefSeq; NP_004034.2; NM_004043.2. DR PDB; 4A6D; X-ray; 2.40 A; A=1-345. DR PDB; 4A6E; X-ray; 2.70 A; A=1-345. DR PDBsum; 4A6D; -. DR PDBsum; 4A6E; -. DR AlphaFoldDB; P46597; -. DR SMR; P46597; -. DR BioGRID; 106930; 1. DR STRING; 9606.ENSP00000370639; -. DR DrugBank; DB01065; Melatonin. DR BioMuta; ASMT; -. DR DMDM; 1170276; -. DR MassIVE; P46597; -. DR MaxQB; P46597; -. DR PaxDb; 9606-ENSP00000370639; -. DR PeptideAtlas; P46597; -. DR ProteomicsDB; 55743; -. [P46597-1] DR ProteomicsDB; 55744; -. [P46597-2] DR ProteomicsDB; 55745; -. [P46597-3] DR Antibodypedia; 35250; 193 antibodies from 24 providers. DR DNASU; 438; -. DR Ensembl; ENST00000381229.9; ENSP00000370627.4; ENSG00000196433.13. [P46597-1] DR Ensembl; ENST00000381233.8; ENSP00000370631.3; ENSG00000196433.13. [P46597-2] DR Ensembl; ENST00000381241.9; ENSP00000370639.3; ENSG00000196433.13. [P46597-3] DR Ensembl; ENST00000711208.1; ENSP00000518606.1; ENSG00000292336.1. [P46597-2] DR Ensembl; ENST00000711209.1; ENSP00000518607.1; ENSG00000292336.1. [P46597-1] DR Ensembl; ENST00000711210.1; ENSP00000518608.1; ENSG00000292336.1. [P46597-3] DR GeneID; 438; -. DR KEGG; hsa:438; -. DR MANE-Select; ENST00000381241.9; ENSP00000370639.3; NM_001171038.2; NP_001164509.1. [P46597-3] DR UCSC; uc010ncy.4; human. [P46597-1] DR AGR; HGNC:750; -. DR CTD; 438; -. DR DisGeNET; 438; -. DR GeneCards; ASMT; -. DR HGNC; HGNC:750; ASMT. DR HPA; ENSG00000196433; Tissue enriched (choroid). DR MIM; 300015; gene. DR MIM; 402500; gene. DR neXtProt; NX_P46597; -. DR OpenTargets; ENSG00000196433; -. DR PharmGKB; PA25049; -. DR VEuPathDB; HostDB:ENSG00000196433; -. DR eggNOG; KOG3178; Eukaryota. DR GeneTree; ENSGT00940000161561; -. DR HOGENOM; CLU_005533_4_2_1; -. DR InParanoid; P46597; -. DR OMA; FWPYVFG; -. DR OrthoDB; 5230501at2759; -. DR PhylomeDB; P46597; -. DR TreeFam; TF314574; -. DR BioCyc; MetaCyc:HS09884-MONOMER; -. DR BRENDA; 2.1.1.4; 2681. DR PathwayCommons; P46597; -. DR Reactome; R-HSA-209931; Serotonin and melatonin biosynthesis. DR SIGNOR; P46597; -. DR UniPathway; UPA00837; UER00815. DR BioGRID-ORCS; 438; 8 hits in 611 CRISPR screens. DR ChiTaRS; ASMT; human. DR GeneWiki; Acetylserotonin_O-methyltransferase; -. DR GenomeRNAi; 438; -. DR Pharos; P46597; Tbio. DR PRO; PR:P46597; -. DR Proteomes; UP000005640; Chromosome X. DR Proteomes; UP000005640; Chromosome Y. DR RNAct; P46597; Protein. DR Bgee; ENSG00000196433; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 97 other cell types or tissues. DR ExpressionAtlas; P46597; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0017096; F:acetylserotonin O-methyltransferase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0008171; F:O-methyltransferase activity; TAS:ProtInc. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0008172; F:S-methyltransferase activity; TAS:Reactome. DR GO; GO:0046219; P:indolalkylamine biosynthetic process; TAS:Reactome. DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW. DR GO; GO:0030187; P:melatonin biosynthetic process; IDA:UniProtKB. DR GO; GO:0032259; P:methylation; IBA:GO_Central. DR GO; GO:0006412; P:translation; TAS:ProtInc. DR CDD; cd02440; AdoMet_MTases; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. DR InterPro; IPR031725; ASMT_dimerisation. DR InterPro; IPR016461; COMT-like. DR InterPro; IPR001077; O_MeTrfase_dom. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. DR PANTHER; PTHR11746:SF327; ACETYLSEROTONIN O-METHYLTRANSFERASE; 1. DR PANTHER; PTHR11746; O-METHYLTRANSFERASE; 1. DR Pfam; PF16864; Dimerisation2; 1. DR Pfam; PF00891; Methyltransf_2; 1. DR PIRSF; PIRSF005739; O-mtase; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR PROSITE; PS51683; SAM_OMT_II; 1. DR Genevisible; P46597; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Lipid metabolism; KW Melatonin biosynthesis; Methyltransferase; Reference proteome; KW S-adenosyl-L-methionine; Transferase. FT CHAIN 1..345 FT /note="Acetylserotonin O-methyltransferase" FT /id="PRO_0000083982" FT ACT_SITE 255 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000305|PubMed:22775292" FT BINDING 147 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT BINDING 164 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT BINDING 210 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT BINDING 235..237 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT BINDING 252 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT BINDING 256 FT /ligand="substrate" FT BINDING 302 FT /ligand="substrate" FT BINDING 306 FT /ligand="substrate" FT VAR_SEQ 188 FT /note="G -> GTWIKLETIILSKLSQGQKTKHRVFSLIG (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:8397829" FT /id="VSP_004284" FT VAR_SEQ 189..235 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_004285" FT VARIANT 13 FT /note="N -> H (no effect on enzyme activity; FT dbSNP:rs121918819)" FT /evidence="ECO:0000269|PubMed:21251267, FT ECO:0000269|PubMed:22775292" FT /id="VAR_069111" FT VARIANT 17 FT /note="N -> K (nearly abolishes enzyme activity; FT dbSNP:rs17149149)" FT /evidence="ECO:0000269|PubMed:17505466, FT ECO:0000269|PubMed:21251267, ECO:0000269|PubMed:22775292, FT ECO:0000269|PubMed:23349736" FT /id="VAR_045991" FT VARIANT 61 FT /note="E -> Q (reduced enzyme activity; dbSNP:rs121918823)" FT /evidence="ECO:0000269|PubMed:21251267, FT ECO:0000269|PubMed:22694957, ECO:0000269|PubMed:22775292" FT /id="VAR_069112" FT VARIANT 81 FT /note="K -> E (no effect on enzyme activity; FT dbSNP:rs117343570)" FT /evidence="ECO:0000269|PubMed:17505466, FT ECO:0000269|PubMed:22775292" FT /id="VAR_069114" FT VARIANT 115 FT /note="R -> W (in dbSNP:rs201053197)" FT /evidence="ECO:0000269|PubMed:23349736" FT /id="VAR_069115" FT VARIANT 151 FT /note="G -> S (in dbSNP:rs192710293)" FT /evidence="ECO:0000269|PubMed:23349736" FT /id="VAR_069116" FT VARIANT 166 FT /note="V -> I (in dbSNP:rs373339042)" FT /evidence="ECO:0000269|PubMed:23349736" FT /id="VAR_069117" FT VARIANT 171 FT /note="V -> M (nearly abolishes enzyme activity; FT dbSNP:rs121918820)" FT /evidence="ECO:0000269|PubMed:21251267, FT ECO:0000269|PubMed:22775292" FT /id="VAR_069118" FT VARIANT 179 FT /note="V -> G (in dbSNP:rs1215166326)" FT /evidence="ECO:0000269|PubMed:23349736" FT /id="VAR_069119" FT VARIANT 210 FT /note="D -> G (nearly abolishes enzyme activity; FT dbSNP:rs121918824)" FT /evidence="ECO:0000269|PubMed:21251267, FT ECO:0000269|PubMed:21615493, ECO:0000269|PubMed:22775292" FT /id="VAR_069120" FT VARIANT 211 FT /note="I -> M (in dbSNP:rs201316181)" FT /evidence="ECO:0000269|PubMed:23349736" FT /id="VAR_069121" FT VARIANT 217 FT /note="T -> M (in dbSNP:rs148036160)" FT /evidence="ECO:0000269|PubMed:23349736" FT /id="VAR_069122" FT VARIANT 219 FT /note="K -> R (no effect on enzyme activity; FT dbSNP:rs121918825)" FT /evidence="ECO:0000269|PubMed:21251267, FT ECO:0000269|PubMed:22694957, ECO:0000269|PubMed:22775292" FT /id="VAR_069123" FT VARIANT 243 FT /note="P -> L (reduced enzyme activity; dbSNP:rs121918826)" FT /evidence="ECO:0000269|PubMed:21251267, FT ECO:0000269|PubMed:22694957, ECO:0000269|PubMed:22775292, FT ECO:0000269|PubMed:23349736" FT /id="VAR_069125" FT VARIANT 269 FT /note="I -> M (reduced enzyme activity; dbSNP:rs146121655)" FT /evidence="ECO:0000269|PubMed:22775292" FT /id="VAR_069126" FT VARIANT 273 FT /note="C -> S (reduced enzyme activity; dbSNP:rs121918827)" FT /evidence="ECO:0000269|PubMed:21251267, FT ECO:0000269|PubMed:22694957, ECO:0000269|PubMed:22775292" FT /id="VAR_069127" FT VARIANT 278 FT /note="G -> A (reduced enzyme activity; FT dbSNP:rs1188440875)" FT /evidence="ECO:0000269|PubMed:17505466, FT ECO:0000269|PubMed:22775292" FT /id="VAR_069128" FT VARIANT 288 FT /note="E -> D (no effect on enzyme activity; FT dbSNP:rs121918821)" FT /evidence="ECO:0000269|PubMed:17957233, FT ECO:0000269|PubMed:21251267, ECO:0000269|PubMed:22694957, FT ECO:0000269|PubMed:22775292" FT /id="VAR_069129" FT VARIANT 291 FT /note="R -> Q (nearly abolishes enzyme activity; FT dbSNP:rs121918828)" FT /evidence="ECO:0000269|PubMed:21251267, FT ECO:0000269|PubMed:22694957, ECO:0000269|PubMed:22775292" FT /id="VAR_069130" FT VARIANT 298 FT /note="L -> F (found in patients with neuropsychiatric FT disorders; uncertain significance; nearly abolishes enzyme FT activity; dbSNP:rs121918822)" FT /evidence="ECO:0000269|PubMed:17505466, FT ECO:0000269|PubMed:17957233, ECO:0000269|PubMed:21251267, FT ECO:0000269|PubMed:21615493, ECO:0000269|PubMed:22694957, FT ECO:0000269|PubMed:22775292" FT /id="VAR_069131" FT VARIANT 305 FT /note="V -> M (found in a patient with bipolar disorder; FT uncertain significance; reduced enzyme activity)" FT /evidence="ECO:0000269|PubMed:22694957, FT ECO:0000269|PubMed:22775292" FT /id="VAR_069132" FT MUTAGEN 11 FT /note="L->F: Reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:22775292" FT MUTAGEN 31 FT /note="L->H: No effect on enzyme activity." FT MUTAGEN 111 FT /note="R->K: No effect on enzyme activity." FT /evidence="ECO:0000269|PubMed:22775292" FT MUTAGEN 248 FT /note="Y->H: Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:22775292" FT MUTAGEN 296 FT /note="T->M: Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:22775292" FT MUTAGEN 318 FT /note="H->D: Reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:22775292" FT CONFLICT 302 FT /note="N -> S (in Ref. 3; BAG37430)" FT /evidence="ECO:0000305" FT HELIX 7..31 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 33..39 FT /evidence="ECO:0007829|PDB:4A6D" FT STRAND 40..42 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 46..53 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 57..69 FT /evidence="ECO:0007829|PDB:4A6D" FT STRAND 72..78 FT /evidence="ECO:0007829|PDB:4A6D" FT STRAND 81..86 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 88..94 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 103..111 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 113..117 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 120..126 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 131..135 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 142..146 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 150..161 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 164..173 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 177..179 FT /evidence="ECO:0007829|PDB:4A6D" FT STRAND 181..186 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 192..200 FT /evidence="ECO:0007829|PDB:4A6D" FT STRAND 205..210 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 212..221 FT /evidence="ECO:0007829|PDB:4A6D" FT STRAND 229..235 FT /evidence="ECO:0007829|PDB:4A6D" FT TURN 237..239 FT /evidence="ECO:0007829|PDB:4A6D" FT STRAND 246..253 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 254..256 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 259..272 FT /evidence="ECO:0007829|PDB:4A6D" FT STRAND 278..283 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 294..305 FT /evidence="ECO:0007829|PDB:4A6D" FT STRAND 306..308 FT /evidence="ECO:0007829|PDB:4A6D" FT HELIX 314..324 FT /evidence="ECO:0007829|PDB:4A6D" FT STRAND 327..332 FT /evidence="ECO:0007829|PDB:4A6D" FT STRAND 335..337 FT /evidence="ECO:0007829|PDB:4A6D" FT STRAND 339..344 FT /evidence="ECO:0007829|PDB:4A6D" FT CONFLICT P46597-3:190 FT /note="W -> R (in Ref. 1; AAA58582/AAA58583/AAA75290, 2; FT AAA17020 and 3; BAG37430)" FT /evidence="ECO:0000305" SQ SEQUENCE 345 AA; 38453 MW; 187A375E1E2940B7 CRC64; MGSSEDQAYR LLNDYANGFM VSQVLFAACE LGVFDLLAEA PGPLDVAAVA AGVRASAHGT ELLLDICVSL KLLKVETRGG KAFYRNTELS SDYLTTVSPT SQCSMLKYMG RTSYRCWGHL ADAVREGRNQ YLETFGVPAE ELFTAIYRSE GERLQFMQAL QEVWSVNGRS VLTAFDLSVF PLMCDLGGGA GALAKECMSL YPGCKITVFD IPEVVWTAKQ HFSFQEEEQI DFQEGDFFKD PLPEADLYIL ARVLHDWADG KCSHLLERIY HTCKPGGGIL VIESLLDEDR RGPLLTQLYS LNMLVQTEGQ ERTPTHYHML LSSAGFRDFQ FKKTGAIYDA ILARK //