ASMT_HUMAN
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 03-AUG-2022, entry version 181.
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";
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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. [P46597-3]
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 MaxQB; P46597; -.
DR PeptideAtlas; P46597; -.
DR PRIDE; P46597; -.
DR ProteomicsDB; 55743; -. [P46597-1]
DR ProteomicsDB; 55744; -. [P46597-2]
DR ProteomicsDB; 55745; -. [P46597-3]
DR Antibodypedia; 35250; 174 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 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 CTD; 438; -.
DR DisGeNET; 438; -.
DR GeneCards; ASMT; -.
DR HGNC; HGNC:750; ASMT.
DR HPA; ENSG00000196433; Tissue enhanced (brain).
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; EYMEGFL; -.
DR PhylomeDB; P46597; -.
DR TreeFam; TF314574; -.
DR BioCyc; MetaCyc:HS09884-MON; -.
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; 6 hits in 566 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 RNAct; P46597; protein.
DR Bgee; ENSG00000196433; Expressed in adenohypophysis and 95 other tissues.
DR ExpressionAtlas; P46597; baseline and differential.
DR Genevisible; P46597; HS.
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; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; IBA:GO_Central.
DR GO; GO:0008172; F:S-methyltransferase activity; TAS:Reactome.
DR GO; GO:0019438; P:aromatic compound biosynthetic process; IBA:GO_Central.
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 Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.150; -; 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; PTHR11746; 1.
DR Pfam; PF16864; Dimerisation2; 1.
DR Pfam; PF00891; Methyltransf_2; 1.
DR PIRSF; PIRSF005739; O-mtase; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
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; unknown pathological significance; nearly
FT abolishes enzyme 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 unknown pathological significance; reduced enzyme
FT 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
