ASMT_RAT
ID ASMT_RAT Reviewed; 432 AA.
AC B3GSH5; O09179;
DT 25-JAN-2012, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Acetylserotonin O-methyltransferase;
DE EC=2.1.1.4 {ECO:0000269|PubMed:8930356};
DE AltName: Full=Hydroxyindole O-methyltransferase;
GN Name=Asmt; Synonyms=Hiomt;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP INDUCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Pineal gland;
RX PubMed=8930356; DOI=10.1016/0006-8993(96)00632-4;
RA Gauer F., Craft C.M.;
RT "Circadian regulation of hydroxyindole-O-methyltransferase mRNA levels in
RT rat pineal and retina.";
RL Brain Res. 737:99-109(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Amaral F.G., Coon S.L., Klein D.C.;
RT "Significant sequence revision of rat acetylserotonin O-methyltransferase
RT mRNA increases length of predicted protein.";
RL Submitted (MAY-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
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).
CC -!- FUNCTION: Catalyzes the transfer of a methyl group onto N-
CC acetylserotonin, producing melatonin (N-acetyl-5-methoxytryptamine).
CC {ECO:0000269|PubMed:8930356}.
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; Evidence={ECO:0000269|PubMed:8930356};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15574;
CC Evidence={ECO:0000305|PubMed:8930356};
CC -!- PATHWAY: Aromatic compound metabolism; melatonin biosynthesis;
CC melatonin from serotonin: step 1/2. {ECO:0000305|PubMed:8930356}.
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:8574683, ECO:0000269|PubMed:8930356}.
CC -!- INDUCTION: Exhibits very slight night/day variation, if any.
CC {ECO:0000269|PubMed:8930356}.
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 -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01020}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB61243.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; L78306; AAB61243.1; ALT_FRAME; mRNA.
DR EMBL; EU741665; ACD87748.1; -; mRNA.
DR EMBL; CH474012; EDL89812.1; -; Genomic_DNA.
DR RefSeq; NP_653360.2; NM_144759.2.
DR AlphaFoldDB; B3GSH5; -.
DR SMR; B3GSH5; -.
DR STRING; 10116.ENSRNOP00000001791; -.
DR PaxDb; B3GSH5; -.
DR PRIDE; B3GSH5; -.
DR Ensembl; ENSRNOT00000001791; ENSRNOP00000001791; ENSRNOG00000001324.
DR GeneID; 246281; -.
DR KEGG; rno:246281; -.
DR UCSC; RGD:708472; rat.
DR CTD; 438; -.
DR RGD; 708472; Asmt.
DR eggNOG; KOG3178; Eukaryota.
DR GeneTree; ENSGT00940000161561; -.
DR HOGENOM; CLU_005533_4_2_1; -.
DR InParanoid; B3GSH5; -.
DR OMA; NTNHGEL; -.
DR OrthoDB; 817726at2759; -.
DR BRENDA; 2.1.1.4; 5301.
DR Reactome; R-RNO-209931; Serotonin and melatonin biosynthesis.
DR UniPathway; UPA00837; UER00815.
DR PRO; PR:B3GSH5; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Proteomes; UP000234681; Chromosome 12.
DR Bgee; ENSRNOG00000001324; Expressed in cerebellum and 5 other tissues.
DR Genevisible; B3GSH5; RN.
DR GO; GO:0017096; F:acetylserotonin O-methyltransferase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0008171; F:O-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; IDA:RGD.
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:0030187; P:melatonin biosynthetic process; IDA:RGD.
DR GO; GO:0032259; P:methylation; IBA:GO_Central.
DR GO; GO:2000019; P:negative regulation of male gonad development; ISO:RGD.
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 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..432
FT /note="Acetylserotonin O-methyltransferase"
FT /id="PRO_0000414796"
FT REGION 373..432
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 382..407
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 255
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 146
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 163
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 209
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 235..237
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 252
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 256
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 302
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 306
FT /ligand="substrate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 432 AA; 45588 MW; 0F782CD0AB6293F5 CRC64;
MAPGREGELD RDFRVLMSLA HGFMVSQVLF AALDLGIFDL AAQGPVAAEA VAQTGGWSPR
GTQLLMDACT RLGLLRGAGD GSYTNSALSS TFLVSGSPQS QRCMLLYLAG TTYGCWAHLA
AGVREGRNQY SRAVGISAED PFSAIYRSEP ERLLFMRGLQ ETWSLCGGRV LTAFDLSRFR
VICDLGGGSG ALAQEAARLY PGSSVCVFDL PDVIAAARTH FLSPGARPSV RFVAGDFFRS
RLPRADLFIL ARVLHDWADG ACVELLGRLH RACRPGGALL LVEAVLAKGG AGPLRSLLLS
LNMMLQAEGW ERQASDYRNL ATRAGFPRLQ LRRPGGPYHA MLARRGPRPG IITGVGSNTT
GTGSFVTGIR RDVPGARSDA AGTGSGTGNT GSGIMLQGET LESEVSAPQA GSDVGGAGNE
PRSGTLKQGD WK
