ID SNAT_RAT Reviewed; 205 AA.
AC Q64666; Q4JL74; Q64553;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 24-JAN-2024, entry version 160.
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 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], TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Pineal gland;
RX PubMed=8770929; DOI=10.1210/endo.137.7.8770929;
RA Roseboom P.H., Coon S.L., Baler R., McCune S.K., Weller J.L., Klein D.C.;
RT "Melatonin synthesis: analysis of the more than 150-fold nocturnal increase
RT in serotonin N-acetyltransferase messenger ribonucleic acid in the rat
RT pineal gland.";
RL Endocrinology 137:3033-3045(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Pineal gland;
RX PubMed=8524412; DOI=10.1038/378783a0;
RA Borjigin J., Wang M.M., Snyder S.H.;
RT "Diurnal variation in mRNA encoding serotonin N-acetyltransferase in pineal
RT gland.";
RL Nature 378:783-785(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Pineal gland;
RA Kim T.-D., Kim K.-T.;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 33-205, AND INDUCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Pineal gland;
RX PubMed=7502081; DOI=10.1126/science.270.5242.1681;
RA Coon S.L., Roseboom P.H., Baler R., Weller J.L., Namboodiri M.A.A.,
RA Koonin E.V., Klein D.C.;
RT "Pineal serotonin N-acetyltransferase: expression cloning and molecular
RT analysis.";
RL Science 270:1681-1683(1995).
RN [5]
RP INTERACTION WITH 14-3-3 PROTEINS.
RX PubMed=11427721; DOI=10.1073/pnas.141118798;
RA Ganguly S., Gastel J.A., Weller J.L., Schwartz C., Jaffe H.,
RA Namboodiri M.A., Coon S.L., Hickman A.B., Rollag M., Obsil T.,
RA Beauverger P., Ferry G., Boutin J.A., Klein D.C.;
RT "Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-3-3-
RT binding switch in melatonin synthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:8083-8088(2001).
RN [6]
RP PROTEASOMAL PROTEOLYSIS.
RX PubMed=16099857; DOI=10.1210/en.2005-0642;
RA Terriff D.L., Chik C.L., Price D.M., Ho A.K.;
RT "Proteasomal proteolysis in the adrenergic induction of arylalkylamine-N-
RT acetyltransferase in rat pinealocytes.";
RL Endocrinology 146:4795-4803(2005).
RN [7]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=19103603; DOI=10.1074/jbc.m808394200;
RA Bailey M.J., Coon S.L., Carter D.A., Humphries A., Kim J.S., Shi Q.,
RA Gaildrat P., Morin F., Ganguly S., Hogenesch J.B., Weller J.L., Rath M.F.,
RA Moller M., Baler R., Sugden D., Rangel Z.G., Munson P.J., Klein D.C.;
RT "Night/day changes in pineal expression of >600 genes: central role of
RT adrenergic/cAMP signaling.";
RL J. Biol. Chem. 284:7606-7622(2009).
RN [8]
RP INDUCTION, PROTEASOMAL PROTEOLYSIS, AND MUTAGENESIS OF LEU-2; LYS-8;
RP CYS-37; CYS-61; LYS-99; LYS-133 AND LYS-168.
RX PubMed=20210853; DOI=10.1111/j.1600-079x.2010.00753.x;
RA Huang Z., Liu T., Borjigin J.;
RT "N-terminal residues regulate proteasomal degradation of AANAT.";
RL J. Pineal Res. 48:290-296(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=a 2-arylethylamine + acetyl-CoA = an N-acetyl-2-arylethylamine
CC + CoA + H(+); 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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=1.5 nmol/h/mg enzyme in day;
CC Vmax=175 nmol/h/mg enzyme in night;
CC Vmax=22.2 nmol/h/mg enzyme in day in presence of bisubstrate
CC inhibitor;
CC Vmax=0.46 nmol/h/mg enzyme in night in presence of bisubstrate
CC inhibitor;
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 increases affinity for arylalkylamines and
CC acetyl-CoA and protects the enzyme from dephosphorylation and
CC proteasomal degradation. It may also prevent thiol-dependent
CC inactivation (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q16613}.
CC -!- TISSUE SPECIFICITY: Highly expressed at night in pinealocytes and in
CC the retina. Expressed at very low levels in the hindbrain and midbrain.
CC {ECO:0000269|PubMed:19103603, ECO:0000269|PubMed:8770929}.
CC -!- INDUCTION: Exhibits night/day variations with an up to 150-fold
CC increased expression at night. Up-regulation is due to a large degree
CC to the release of norepinephrine from nerve terminals in the pineal
CC gland and cAMP signaling pathway. Down-regulated by light-induced
CC proteasomal degradation. In the retina, 10-fold increased expression at
CC night. {ECO:0000269|PubMed:19103603, ECO:0000269|PubMed:20210853,
CC ECO:0000269|PubMed:7502081, ECO:0000269|PubMed:8524412,
CC ECO:0000269|PubMed:8770929}.
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 -!- SIMILARITY: Belongs to the acetyltransferase family. AANAT subfamily.
CC {ECO:0000305}.
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DR EMBL; U38306; AAB38484.1; -; mRNA.
DR EMBL; U40803; AAA92711.1; -; mRNA.
DR EMBL; DQ075321; AAY86767.1; -; mRNA.
DR EMBL; U29664; AAC52330.1; -; mRNA.
DR PIR; S68435; S68435.
DR RefSeq; NP_036950.1; NM_012818.2.
DR RefSeq; XP_006247854.1; XM_006247792.2.
DR RefSeq; XP_006247855.1; XM_006247793.2.
DR AlphaFoldDB; Q64666; -.
DR SMR; Q64666; -.
DR STRING; 10116.ENSRNOP00000015221; -.
DR BindingDB; Q64666; -.
DR ChEMBL; CHEMBL1075242; -.
DR iPTMnet; Q64666; -.
DR PhosphoSitePlus; Q64666; -.
DR PaxDb; 10116-ENSRNOP00000015221; -.
DR Ensembl; ENSRNOT00000015221.5; ENSRNOP00000015221.2; ENSRNOG00000011182.7.
DR Ensembl; ENSRNOT00055051954; ENSRNOP00055042891; ENSRNOG00055029977.
DR Ensembl; ENSRNOT00060053316; ENSRNOP00060044328; ENSRNOG00060030684.
DR Ensembl; ENSRNOT00065006605; ENSRNOP00065004594; ENSRNOG00065004543.
DR GeneID; 25120; -.
DR KEGG; rno:25120; -.
DR AGR; RGD:2006; -.
DR CTD; 15; -.
DR RGD; 2006; Aanat.
DR eggNOG; KOG4144; Eukaryota.
DR GeneTree; ENSGT00390000015579; -.
DR HOGENOM; CLU_061829_3_1_1; -.
DR InParanoid; Q64666; -.
DR OMA; HFLNLCP; -.
DR OrthoDB; 1327238at2759; -.
DR PhylomeDB; Q64666; -.
DR TreeFam; TF331622; -.
DR BRENDA; 2.3.1.87; 5301.
DR Reactome; R-RNO-209931; Serotonin and melatonin biosynthesis.
DR SABIO-RK; Q64666; -.
DR UniPathway; UPA00837; UER00815.
DR PRO; PR:Q64666; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000011182; Expressed in pancreas and 4 other cell types or tissues.
DR Genevisible; Q64666; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; IDA:UniProtKB.
DR GO; GO:0004059; F:aralkylamine N-acetyltransferase activity; IDA:RGD.
DR GO; GO:0004060; F:arylamine N-acetyltransferase activity; ISO:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; TAS:RGD.
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; IDA:RGD.
DR GO; GO:0051592; P:response to calcium ion; IEP:RGD.
DR GO; GO:0051591; P:response to cAMP; IEP:RGD.
DR GO; GO:0046688; P:response to copper ion; IDA:RGD.
DR GO; GO:0051412; P:response to corticosterone; IEP:RGD.
DR GO; GO:0034097; P:response to cytokine; IEP:RGD.
DR GO; GO:0032868; P:response to insulin; IDA:RGD.
DR GO; GO:0009416; P:response to light stimulus; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IDA:RGD.
DR GO; GO:1901652; P:response to peptide; IEP:RGD.
DR GO; GO:0034695; P:response to prostaglandin E; IDA:RGD.
DR GO; GO:0010043; P:response to zinc ion; IDA:RGD.
DR Gene3D; 3.40.630.30; -; 1.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR000182; GNAT_dom.
DR PANTHER; PTHR10908; SEROTONIN N-ACETYLTRANSFERASE; 1.
DR PANTHER; PTHR10908:SF0; SEROTONIN N-ACETYLTRANSFERASE; 1.
DR Pfam; PF00583; Acetyltransf_1; 1.
DR SUPFAM; SSF55729; Acyl-CoA N-acyltransferases (Nat); 1.
DR PROSITE; PS51186; GNAT; 1.
PE 1: Evidence at protein 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_0000074585"
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 SITE 122
FT /note="Important for the catalytic mechanism; involved in
FT substrate deprotonation"
FT /evidence="ECO:0000250"
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"
FT MUTAGEN 2
FT /note="Missing: Impaired light-induced proteasomal
FT degradation."
FT /evidence="ECO:0000269|PubMed:20210853"
FT MUTAGEN 8
FT /note="K->R: No effect on light-induced proteasomal
FT degradation; when associated with R-99, R-133 and R-168."
FT /evidence="ECO:0000269|PubMed:20210853"
FT MUTAGEN 37
FT /note="C->A: No effect on light-induced proteasomal
FT degradation."
FT /evidence="ECO:0000269|PubMed:20210853"
FT MUTAGEN 61
FT /note="C->A: No effect on light-induced proteasomal
FT degradation."
FT /evidence="ECO:0000269|PubMed:20210853"
FT MUTAGEN 99
FT /note="K->R: No effect onlight-induced proteasomal
FT degradation; when associated with R-8, R-133 and R-168."
FT /evidence="ECO:0000269|PubMed:20210853"
FT MUTAGEN 133
FT /note="K->R: No effect on light-induced proteasomal
FT degradation; when associated with R-8, R-99 and R-168."
FT /evidence="ECO:0000269|PubMed:20210853"
FT MUTAGEN 168
FT /note="K->R: No effect on proteasomal degradation; when
FT associated with R-8, R-99 and R-133."
FT /evidence="ECO:0000269|PubMed:20210853"
FT CONFLICT 33
FT /note="S -> N (in Ref. 4; AAC52330)"
FT /evidence="ECO:0000305"
FT CONFLICT 153
FT /note="R -> P (in Ref. 4; AAC52330)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="T -> A (in Ref. 4; AAC52330)"
FT /evidence="ECO:0000305"
FT CONFLICT 204..205
FT /note="GC -> DR (in Ref. 4; AAC52330)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 205 AA; 23142 MW; 2504E3082A26BF8E CRC64;
MLSIHPLKPE ALHLPLGTSE FLGCQRRHTL PASEFRCLTP EDATSAFEIE REAFISVSGT
CPLHLDEIRH FLTLCPELSL GWFEEGCLVA FIIGSLWDKE RLTQESLTLH RPGGRTAHLH
VLAVHRTFRQ QGKGSVLLWR YLHHLGSQPA VRRAVLMCEN ALVPFYEKFG FQAMGPCAIT
MGSLTFTELQ CSLRCHTFLR RNSGC
//
