ASMT_MOUSE
ID ASMT_MOUSE Reviewed; 387 AA.
AC D3KU66; D3KU65;
DT 25-JAN-2012, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Acetylserotonin O-methyltransferase;
DE EC=2.1.1.4 {ECO:0000269|PubMed:20308563};
DE AltName: Full=Hydroxyindole O-methyltransferase;
GN Name=Asmt; Synonyms=Hiomt {ECO:0000303|PubMed:20308563};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], CATALYTIC ACTIVITY, VARIANTS
RP GLY-78 AND CYS-242, IDENTIFICATION OF STRAIN-SPECIFIC VARIANTS, INDUCTION,
RP AND TISSUE SPECIFICITY.
RC STRAIN=C3H/He, and C57BL/6J; TISSUE=Pineal gland;
RX PubMed=20308563; DOI=10.1073/pnas.0914399107;
RA Kasahara T., Abe K., Mekada K., Yoshiki A., Kato T.;
RT "Genetic variation of melatonin productivity in laboratory mice under
RT domestication.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:6412-6417(2010).
CC -!- FUNCTION: Catalyzes the transfer of a methyl group onto N-
CC acetylserotonin, producing melatonin (N-acetyl-5-methoxytryptamine).
CC {ECO:0000269|PubMed:20308563}.
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:20308563};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15574;
CC Evidence={ECO:0000305|PubMed:20308563};
CC -!- PATHWAY: Aromatic compound metabolism; melatonin biosynthesis;
CC melatonin from serotonin: step 1/2. {ECO:0000269|PubMed:20308563}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in the pineal gland (at
CC protein level). Very low expression, if any, in the retina.
CC {ECO:0000269|PubMed:20308563}.
CC -!- INDUCTION: Exhibits very subtle night/day variation, if any.
CC {ECO:0000269|PubMed:20308563}.
CC -!- MISCELLANEOUS: Pineal melatonin synthesis is severely compromised in
CC most inbred strains. In many inbred strains, genetic defects in ASMT
CC have been identified. Melatonin production may have an impact on
CC gonadal development, testis development being significantly promoted in
CC melatonin-deficient C57BL/6J x Mus musculus molossinus animals
CC (PubMed:20308563). {ECO:0000305|PubMed:20308563}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01020}.
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DR EMBL; AB512670; BAI82191.1; -; mRNA.
DR EMBL; AB512671; BAI82192.1; -; mRNA.
DR EMBL; AB512673; BAI82194.1; -; Genomic_DNA.
DR EMBL; AB512674; BAI82195.1; -; Genomic_DNA.
DR RefSeq; NP_001186141.1; NM_001199212.1.
DR RefSeq; NP_001295417.1; NM_001308488.1.
DR AlphaFoldDB; D3KU66; -.
DR SMR; D3KU66; -.
DR STRING; 10090.ENSMUSP00000137135; -.
DR PaxDb; D3KU66; -.
DR PRIDE; D3KU66; -.
DR GeneID; 107626; -.
DR KEGG; mmu:107626; -.
DR UCSC; uc029xop.1; mouse.
DR CTD; 438; -.
DR MGI; MGI:96090; Asmt.
DR eggNOG; KOG3178; Eukaryota.
DR InParanoid; D3KU66; -.
DR OrthoDB; 817726at2759; -.
DR TreeFam; TF314574; -.
DR BRENDA; 2.1.1.4; 3474.
DR Reactome; R-MMU-209931; Serotonin and melatonin biosynthesis.
DR UniPathway; UPA00837; UER00815.
DR BioGRID-ORCS; 107626; 1 hit in 51 CRISPR screens.
DR PRO; PR:D3KU66; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; D3KU66; protein.
DR GO; GO:0017096; F:acetylserotonin O-methyltransferase activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008171; F:O-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; ISO:MGI.
DR GO; GO:0019438; P:aromatic compound biosynthetic process; IBA:GO_Central.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0008584; P:male gonad development; IMP:MGI.
DR GO; GO:0030187; P:melatonin biosynthetic process; IDA:MGI.
DR GO; GO:0032259; P:methylation; IBA:GO_Central.
DR GO; GO:2000019; P:negative regulation of male gonad development; IMP:MGI.
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 Lipid metabolism; Melatonin biosynthesis; Methyltransferase;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..387
FT /note="Acetylserotonin O-methyltransferase"
FT /id="PRO_0000414794"
FT REGION 354..387
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..387
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 266
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 153
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 170
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 216
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 246..248
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 263
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 267
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 317
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT VARIANT 78
FT /note="R -> G (in strain: C57BL/6J, 129/Sv, BALB/c, FVB/N
FT and more; reduces protein expression)"
FT /evidence="ECO:0000269|PubMed:20308563"
FT VARIANT 242
FT /note="R -> C (in strain: C57BL/6J, 129/Sv, BALB/c, FVB/N
FT and more; reduces protein expression)"
FT /evidence="ECO:0000269|PubMed:20308563"
SQ SEQUENCE 387 AA; 40925 MW; DFCC2B0CDDB12680 CRC64;
MHRGRSASAR QERDFRALMD LAHGFMASQV LFAGCALRVF DAAALGPVDA AALARSSGLS
PRGTRLLLDA CAGLGLLRRR RGAGPRGPAY TNSPLASTFL VAGSPLSQRS LLLYLAGTTY
LCWGHLADGV REGRSQYARA VGVDADDPFT AIYRSEAERL LFMRGLQETW SLCGGRVLTA
FDLSPFRVIC DLGGGSGALA RMAARLYPGS EVTVFETPDV VAAARAHFPP PADEDGAEPR
VRFLSGDFFR SPLPPADLYV LARVLHDWAD AACVELLRRV RGALRPGGAV LLVESVLSPG
GAGPTRTLLL SLTMLLQARG RERTEAEYRA LTARAGFSRL RLRRPRGPYH AMMAARGGGA
GARSDGGGGD ATSQTGSGTG SEVGAQD
