SNAT_MOUSE
ID SNAT_MOUSE Reviewed; 205 AA.
AC O88816;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Serotonin N-acetyltransferase;
DE Short=Serotonin acetylase;
DE EC=2.3.1.87 {ECO:0000250|UniProtKB:Q29495};
DE AltName: Full=Aralkylamine N-acetyltransferase;
DE Short=AA-NAT;
GN Name=Aanat; Synonyms=Snat;
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 [MRNA], AND INDUCTION.
RC STRAIN=BALB/cJ; TISSUE=Retina;
RX PubMed=9708862; DOI=10.1016/s0304-3940(98)00462-5;
RA Sakamoto K., Ishida N.;
RT "Molecular cloning of serotonin N-acetyltransferase gene from the mouse and
RT its daily expression in the retina.";
RL Neurosci. Lett. 250:181-184(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, INDUCTION,
RP AND IDENTIFICATION OF A TRUNCATED FORM IN C57BL/6.
RC STRAIN=129/Sv, and C3H/He; TISSUE=Pineal gland;
RX PubMed=9838107; DOI=10.1016/s0169-328x(98)00273-3;
RA Roseboom P.H., Namboodiri M.A.A., Zimonjic D.B., Popescu N.C.,
RA Rodriguez I.R., Gastel J.A., Klein D.C.;
RT "Natural melatonin 'knockdown' in C57BL/6J mice: rare mechanism truncates
RT serotonin N-acetyltransferase.";
RL Brain Res. Mol. Brain Res. 63:189-197(1998).
RN [3]
RP INDUCTION.
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: Controls the night/day rhythm of melatonin production in the
CC pineal gland. Catalyzes the N-acetylation of serotonin into N-
CC acetylserotonin, the penultimate step in the synthesis of melatonin.
CC {ECO:0000250|UniProtKB:Q29495}.
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:0000250|UniProtKB:Q29495};
CC -!- PATHWAY: Aromatic compound metabolism; melatonin biosynthesis;
CC melatonin from serotonin: step 1/2.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with several 14-3-3
CC proteins, including YWHAB, YWHAE, YWHAG and YWHAZ, preferentially when
CC phosphorylated at Thr-29 (By similarity). Phosphorylation on Ser-203
CC also allows binding to YWHAZ, but with lower affinity (By similarity).
CC The interaction with YWHAZ considerably increases affinity for
CC arylalkylamines and acetyl-CoA and protects the enzyme from
CC dephosphorylation and proteasomal degradation. It may also prevent
CC thiol-dependent inactivation (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q16613}.
CC -!- TISSUE SPECIFICITY: Highly expressed in pineal gland at night.
CC Expression in the retina has not been confirmed. Extrapineal expression
CC could be strain-specific. {ECO:0000269|PubMed:9838107}.
CC -!- INDUCTION: Exhibits night/day variations with a drastically increased
CC expression at night in the pineal gland. {ECO:0000269|PubMed:20308563,
CC ECO:0000269|PubMed:9708862, ECO:0000269|PubMed:9838107}.
CC -!- PTM: cAMP-dependent phosphorylation on both N-terminal Thr-29 and C-
CC terminal Ser-203 regulates AANAT activity by promoting interaction with
CC 14-3-3 proteins. {ECO:0000250}.
CC -!- MISCELLANEOUS: Pineal melatonin synthesis is severely compromised in
CC most inbred strains of mice. In C57BL/6, a polymorphism activates a
CC cryptic splice site causing the production of an alternative form
CC containing a premature stop codon. The predicted resulting protein
CC would lack the putative catalytic and acetyl-CoA binding domains and
CC therefore would be inactive.
CC -!- SIMILARITY: Belongs to the acetyltransferase family. AANAT subfamily.
CC {ECO:0000305}.
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DR EMBL; AB013358; BAA31526.1; -; mRNA.
DR EMBL; AF004108; AAD09408.1; -; mRNA.
DR EMBL; U83462; AAD08637.1; -; Genomic_DNA.
DR CCDS; CCDS25671.1; -.
DR RefSeq; NP_033721.1; NM_009591.3.
DR AlphaFoldDB; O88816; -.
DR SMR; O88816; -.
DR STRING; 10090.ENSMUSP00000122895; -.
DR iPTMnet; O88816; -.
DR PhosphoSitePlus; O88816; -.
DR PaxDb; O88816; -.
DR PRIDE; O88816; -.
DR Antibodypedia; 32420; 299 antibodies from 30 providers.
DR DNASU; 11298; -.
DR Ensembl; ENSMUST00000153476; ENSMUSP00000122895; ENSMUSG00000020804.
DR GeneID; 11298; -.
DR KEGG; mmu:11298; -.
DR UCSC; uc007mlo.2; mouse.
DR CTD; 15; -.
DR MGI; MGI:1328365; Aanat.
DR VEuPathDB; HostDB:ENSMUSG00000020804; -.
DR eggNOG; KOG4144; Eukaryota.
DR GeneTree; ENSGT00390000015579; -.
DR HOGENOM; CLU_061829_3_1_1; -.
DR InParanoid; O88816; -.
DR OMA; HFLNLCP; -.
DR OrthoDB; 1528352at2759; -.
DR PhylomeDB; O88816; -.
DR TreeFam; TF331622; -.
DR Reactome; R-MMU-209931; Serotonin and melatonin biosynthesis.
DR UniPathway; UPA00837; UER00815.
DR BioGRID-ORCS; 11298; 4 hits in 76 CRISPR screens.
DR PRO; PR:O88816; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O88816; protein.
DR Bgee; ENSMUSG00000020804; Expressed in visual cortex and 34 other tissues.
DR ExpressionAtlas; O88816; baseline and differential.
DR Genevisible; O88816; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; ISO:MGI.
DR GO; GO:0004059; F:aralkylamine N-acetyltransferase activity; ISS:UniProtKB.
DR GO; GO:0004060; F:arylamine N-acetyltransferase activity; IDA:MGI.
DR GO; GO:0071320; P:cellular response to cAMP; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR GO; GO:0030187; P:melatonin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006474; P:N-terminal protein amino acid acetylation; ISS:UniProtKB.
DR GO; GO:0009648; P:photoperiodism; ISO:MGI.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0046688; P:response to copper ion; ISO:MGI.
DR GO; GO:0051412; P:response to corticosterone; IEA:Ensembl.
DR GO; GO:0034097; P:response to cytokine; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin; ISO:MGI.
DR GO; GO:0009416; P:response to light stimulus; IBA:GO_Central.
DR GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI.
DR GO; GO:0034695; P:response to prostaglandin E; ISO:MGI.
DR GO; GO:0010043; P:response to zinc ion; ISO:MGI.
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 2: Evidence at transcript level;
KW Acyltransferase; Biological rhythms; Cytoplasm; Melatonin biosynthesis;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..205
FT /note="Serotonin N-acetyltransferase"
FT /id="PRO_0000074583"
FT DOMAIN 33..194
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT BINDING 122..124
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q29495"
FT BINDING 122
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q29495"
FT BINDING 130..135
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q29495"
FT BINDING 157
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q29495"
FT BINDING 166..168
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q29495"
FT SITE 118
FT /note="Important for the catalytic mechanism; involved in
FT substrate deprotonation"
FT /evidence="ECO:0000250|UniProtKB:Q29495"
FT SITE 120
FT /note="Important for the catalytic mechanism; involved in
FT substrate deprotonation"
FT /evidence="ECO:0000250|UniProtKB:Q29495"
FT MOD_RES 29
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:O97756"
FT MOD_RES 203
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q29495"
SQ SEQUENCE 205 AA; 23069 MW; D2ECD070998CB643 CRC64;
MLNINSLKPE ALHLPLGTSE FLGCQRRHTL PASEFRCLTP EDATSAFEIE REAFISVSGT
CPLYLDEIRH FLTLCPELSL GWFEEGCLVA FIIGSLWDKE RLTQESLTLH RPGGRTAHLH
VLAVHRTFRQ QGKGSVLLWR YLHHLGSQPA VRRAVLMCED ALVPFYEKFG FQAVGPCAIT
VGSLTFTELQ CSLRCHAFLR RNSGC
