SNAT_HUMAN
ID SNAT_HUMAN Reviewed; 207 AA.
AC Q16613; A0AVF2; J3KMZ5; Q562F4;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Serotonin N-acetyltransferase;
DE Short=Serotonin acetylase;
DE EC=2.3.1.87 {ECO:0000269|PubMed:11313340};
DE AltName: Full=Aralkylamine N-acetyltransferase;
DE Short=AA-NAT;
GN Name=AANAT; Synonyms=SNAT;
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 / MRNA] (ISOFORM 1), INDUCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=8661026; DOI=10.1006/geno.1996.0243;
RA Coon S.L., Mazuruk K., Bernard M., Roseboom P., Klein D.C., Rodriguez I.R.;
RT "The human serotonin N-acetyltransferase (EC 2.3.1.87) gene (AANAT):
RT structure, chromosomal localization, and tissue expression.";
RL Genomics 34:76-84(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Testis;
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 [4]
RP SUBCELLULAR LOCATION, INDUCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=11313340; DOI=10.1074/jbc.m011298200;
RA Coon S.L., Weller J.L., Korf H.-W., Namboodiri M.A., Rollag M., Klein D.C.;
RT "cAMP regulation of arylalkylamine N-acetyltransferase (AANAT, EC
RT 2.3.1.87): a new cell line (1E7) provides evidence of intracellular AANAT
RT activation.";
RL J. Biol. Chem. 276:24097-24107(2001).
RN [5]
RP INTERACTION WITH 14-3-3 PROTEINS, AND MUTAGENESIS OF THR-31.
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 TISSUE SPECIFICITY.
RX PubMed=18212399;
RA Konturek S.J., Konturek P.C., Brzozowski T., Bubenik G.A.;
RT "Role of melatonin in upper gastrointestinal tract.";
RL J. Physiol. Pharmacol. 58:23-52(2007).
RN [7]
RP VARIANT THR-129.
RX PubMed=12736803; DOI=10.1007/s10048-002-0141-9;
RA Hohjoh H., Takasu M., Shishikura K., Takahashi Y., Honda Y., Tokunaga K.;
RT "Significant association of the arylalkylamine N-acetyltransferase (AA-NAT)
RT gene with delayed sleep phase syndrome.";
RL Neurogenetics 4:151-153(2003).
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:0000269|PubMed:11313340, ECO:0000305}.
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:0000269|PubMed:11313340};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.13 mM for tryptamine {ECO:0000269|PubMed:11313340};
CC KM=2.6 mM for 5-hydroxytryptamine {ECO:0000269|PubMed:11313340};
CC KM=0.55 mM for phenylethylamine {ECO:0000269|PubMed:11313340};
CC KM=10.6 mM for tyramine {ECO:0000269|PubMed:11313340};
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-31. Phosphorylation on Ser-205 also allows
CC binding to YWHAZ, but with lower affinity. The interaction with YWHAZ
CC considerably increases affinity for arylalkylamines and acetyl-CoA and
CC protects the enzyme from dephosphorylation and proteasomal degradation
CC (By similarity). It may also prevent thiol-dependent inactivation (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q16613; O14503: BHLHE40; NbExp=6; IntAct=EBI-7451846, EBI-711810;
CC Q16613; Q8N5X7-2: EIF4E3; NbExp=3; IntAct=EBI-7451846, EBI-17933598;
CC Q16613; Q13322-4: GRB10; NbExp=3; IntAct=EBI-7451846, EBI-12353035;
CC Q16613; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-7451846, EBI-10261141;
CC Q16613; Q99750: MDFI; NbExp=6; IntAct=EBI-7451846, EBI-724076;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11313340}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q16613-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16613-2; Sequence=VSP_054108;
CC -!- TISSUE SPECIFICITY: Highly expressed in pineal gland and at lower
CC levels in the retina. Weak expression in several brain regions and in
CC the pituitary gland. {ECO:0000269|PubMed:18212399,
CC ECO:0000269|PubMed:8661026}.
CC -!- PTM: cAMP-dependent phosphorylation on both N-terminal Thr-31 and C-
CC terminal Ser-205 regulates AANAT activity by promoting interaction with
CC 14-3-3 proteins.
CC -!- SIMILARITY: Belongs to the acetyltransferase family. AANAT subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH69434.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U40347; AAC50554.1; -; mRNA.
DR EMBL; U40391; AAC50555.1; -; Genomic_DNA.
DR EMBL; AC015802; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069434; AAH69434.1; ALT_INIT; mRNA.
DR EMBL; BC092430; AAH92430.1; -; mRNA.
DR EMBL; BC126332; AAI26333.1; -; mRNA.
DR EMBL; BC126334; AAI26335.1; -; mRNA.
DR CCDS; CCDS11745.1; -. [Q16613-1]
DR CCDS; CCDS54169.1; -. [Q16613-2]
DR RefSeq; NP_001079.1; NM_001088.2. [Q16613-1]
DR RefSeq; NP_001160051.1; NM_001166579.1. [Q16613-2]
DR PDB; 6T80; X-ray; 2.99 A; E/F/G/H=197-207.
DR PDBsum; 6T80; -.
DR AlphaFoldDB; Q16613; -.
DR SMR; Q16613; -.
DR BioGRID; 106533; 13.
DR IntAct; Q16613; 6.
DR MINT; Q16613; -.
DR STRING; 9606.ENSP00000250615; -.
DR BindingDB; Q16613; -.
DR DrugBank; DB03341; CoA-S-acetyl 5-bromotryptamine.
DR DrugBank; DB02931; CoA-s-acetyl tryptamine.
DR DrugBank; DB01777; CoA-S-trimethylene-acetyl-tryptamine.
DR iPTMnet; Q16613; -.
DR PhosphoSitePlus; Q16613; -.
DR BioMuta; AANAT; -.
DR DMDM; 11387096; -.
DR PaxDb; Q16613; -.
DR PeptideAtlas; Q16613; -.
DR PRIDE; Q16613; -.
DR Antibodypedia; 32420; 299 antibodies from 30 providers.
DR DNASU; 15; -.
DR Ensembl; ENST00000250615.7; ENSP00000250615.2; ENSG00000129673.10. [Q16613-2]
DR Ensembl; ENST00000392492.8; ENSP00000376282.2; ENSG00000129673.10. [Q16613-1]
DR GeneID; 15; -.
DR KEGG; hsa:15; -.
DR MANE-Select; ENST00000392492.8; ENSP00000376282.2; NM_001088.3; NP_001079.1.
DR UCSC; uc002jro.4; human. [Q16613-1]
DR CTD; 15; -.
DR DisGeNET; 15; -.
DR GeneCards; AANAT; -.
DR HGNC; HGNC:19; AANAT.
DR HPA; ENSG00000129673; Tissue enhanced (retina, testis).
DR MIM; 600950; gene.
DR neXtProt; NX_Q16613; -.
DR OpenTargets; ENSG00000129673; -.
DR PharmGKB; PA24366; -.
DR VEuPathDB; HostDB:ENSG00000129673; -.
DR eggNOG; KOG4144; Eukaryota.
DR GeneTree; ENSGT00390000015579; -.
DR HOGENOM; CLU_061829_3_1_1; -.
DR InParanoid; Q16613; -.
DR OrthoDB; 1528352at2759; -.
DR PhylomeDB; Q16613; -.
DR TreeFam; TF331622; -.
DR BioCyc; MetaCyc:HS05303-MON; -.
DR BRENDA; 2.3.1.87; 2681.
DR PathwayCommons; Q16613; -.
DR Reactome; R-HSA-209931; Serotonin and melatonin biosynthesis.
DR SABIO-RK; Q16613; -.
DR SignaLink; Q16613; -.
DR SIGNOR; Q16613; -.
DR UniPathway; UPA00837; UER00815.
DR BioGRID-ORCS; 15; 8 hits in 1067 CRISPR screens.
DR ChiTaRS; AANAT; human.
DR GenomeRNAi; 15; -.
DR Pharos; Q16613; Tbio.
DR PRO; PR:Q16613; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q16613; protein.
DR Bgee; ENSG00000129673; Expressed in granulocyte and 95 other tissues.
DR ExpressionAtlas; Q16613; baseline and differential.
DR Genevisible; Q16613; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; IEA:Ensembl.
DR GO; GO:0004059; F:aralkylamine N-acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0004060; F:arylamine N-acetyltransferase activity; IEA:Ensembl.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IMP:UniProtKB.
DR GO; GO:0046219; P:indolalkylamine biosynthetic process; TAS:Reactome.
DR GO; GO:0030187; P:melatonin biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006474; P:N-terminal protein amino acid acetylation; IDA:UniProtKB.
DR GO; GO:0009648; P:photoperiodism; IEA:Ensembl.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0046688; P:response to copper ion; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0009416; P:response to light stimulus; IBA:GO_Central.
DR GO; GO:0034695; P:response to prostaglandin E; IEA:Ensembl.
DR GO; GO:0010043; P:response to zinc ion; IEA:Ensembl.
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 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Alternative splicing; Biological rhythms;
KW Cytoplasm; Disease variant; Melatonin biosynthesis; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..207
FT /note="Serotonin N-acetyltransferase"
FT /id="PRO_0000074580"
FT DOMAIN 35..194
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 124..126
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q29495"
FT BINDING 124
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q29495"
FT BINDING 132..137
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q29495"
FT BINDING 159
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q29495"
FT BINDING 168..170
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
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|UniProtKB:Q29495"
FT MOD_RES 31
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:O97756"
FT MOD_RES 205
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q29495"
FT VAR_SEQ 1
FT /note="M -> MEPQSMKGQKRPFGGPWRLKVLGGPPWLRRTLPKLGRPKEAPVARM
FT (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_054108"
FT VARIANT 15
FT /note="R -> C (in dbSNP:rs34470791)"
FT /id="VAR_048168"
FT VARIANT 129
FT /note="A -> T (found in individuals with delayed sleep
FT phase syndrome; has higher frequency in affected
FT individuals than in healthy controls; unknown pathological
FT significance; dbSNP:rs28936679)"
FT /evidence="ECO:0000269|PubMed:12736803"
FT /id="VAR_055086"
FT MUTAGEN 31
FT /note="T->A: Loss of activation by cAMP."
FT /evidence="ECO:0000269|PubMed:11427721"
SQ SEQUENCE 207 AA; 23344 MW; 7476612F3661E0D5 CRC64;
MSTQSTHPLK PEAPRLPPGI PESPSCQRRH TLPASEFRCL TPEDAVSAFE IEREAFISVL
GVCPLYLDEI RHFLTLCPEL SLGWFEEGCL VAFIIGSLWD KERLMQESLT LHRSGGHIAH
LHVLAVHRAF RQQGRGPILL WRYLHHLGSQ PAVRRAALMC EDALVPFYER FSFHAVGPCA
ITVGSLTFME LHCSLRGHPF LRRNSGC
