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Database: UniProt
Entry: Q16613
LinkDB: Q16613
Original site: Q16613 
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   07-SEP-2016, entry version 141.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), INDUCTION, AND
RP   TISSUE SPECIFICITY.
RX   PubMed=8661026; DOI=10.1006/geno.1996.0243;
RA   Coon S.L., Mazuruk K., Bernard M., Roseboom P., Klein D.C.,
RA   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.,
RA   Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA   Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA   Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA   Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA   Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA   Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA   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
RT   the 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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   SUBCELLULAR LOCATION, INDUCTION, CATALYTIC ACTIVITY, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=11313340; DOI=10.1074/jbc.M011298200;
RA   Coon S.L., Weller J.L., Korf H.-W., Namboodiri M.A., Rollag M.,
RA   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
RT   AANAT 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-
RT   3-3-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;
RA   Hohjoh H., Takasu M., Shishikura K., Takahashi Y., Honda Y.,
RA   Tokunaga K.;
RT   "Significant association of the arylalkylamine N-acetyltransferase
RT   (AA-NAT) gene with delayed sleep phase syndrome.";
RL   Neurogenetics 4:151-153(2003).
CC   -!- FUNCTION: Controls the night/day rhythm of melatonin production in
CC       the pineal gland. Catalyzes the N-acetylation of serotonin into N-
CC       acetylserotonin, the penultimate step in the synthesis of
CC       melatonin. {ECO:0000269|PubMed:11313340, ECO:0000305}.
CC   -!- CATALYTIC ACTIVITY: Acetyl-CoA + a 2-arylethylamine = CoA + an N-
CC       acetyl-2-arylethylamine. {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
CC       when phosphorylated at Thr-31. Phosphorylation on Ser-205 also
CC       allows binding to YWHAZ, but with lower affinity. The interaction
CC       with YWHAZ considerably increases affinity for arylalkylamines and
CC       acetyl-CoA and protects the enzyme from dephosphorylation and
CC       proteasomal degradation (By similarity). It may also prevent
CC       thiol-dependent inactivation (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       O14503:BHLHE40; NbExp=3; IntAct=EBI-7451846, EBI-711810;
CC       Q99750:MDFI; NbExp=3; 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         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Highly expressed in pineal gland and at lower
CC       levels in the retina. Weak expression in several brain regions and
CC       in the pituitary gland. {ECO:0000269|PubMed:18212399,
CC       ECO:0000269|PubMed:8661026}.
CC   -!- PTM: cAMP-dependent phosphorylation on both N-terminal Thr-31 and
CC       C-terminal Ser-205 regulates AANAT activity by promoting
CC       interaction with 14-3-3 proteins.
CC   -!- SIMILARITY: Belongs to the acetyltransferase family. AANAT
CC       subfamily. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 N-acetyltransferase domain.
CC       {ECO:0000255|PROSITE-ProRule:PRU00532}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH69434.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and
CC       polymorphism database;
CC       URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=AANAT";
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   UniGene; Hs.431417; -.
DR   ProteinModelPortal; Q16613; -.
DR   SMR; Q16613; 30-195.
DR   BioGrid; 106533; 3.
DR   IntAct; Q16613; 3.
DR   MINT; MINT-1559914; -.
DR   STRING; 9606.ENSP00000250615; -.
DR   BindingDB; Q16613; -.
DR   iPTMnet; Q16613; -.
DR   PhosphoSite; Q16613; -.
DR   BioMuta; AANAT; -.
DR   DMDM; 11387096; -.
DR   PaxDb; Q16613; -.
DR   PRIDE; Q16613; -.
DR   DNASU; 15; -.
DR   Ensembl; ENST00000250615; ENSP00000250615; ENSG00000129673. [Q16613-2]
DR   Ensembl; ENST00000392492; ENSP00000376282; ENSG00000129673. [Q16613-1]
DR   GeneID; 15; -.
DR   KEGG; hsa:15; -.
DR   UCSC; uc002jro.4; human. [Q16613-1]
DR   CTD; 15; -.
DR   GeneCards; AANAT; -.
DR   HGNC; HGNC:19; AANAT.
DR   HPA; HPA050784; -.
DR   MalaCards; AANAT; -.
DR   MIM; 600950; gene.
DR   neXtProt; NX_Q16613; -.
DR   PharmGKB; PA24366; -.
DR   eggNOG; KOG4144; Eukaryota.
DR   eggNOG; COG0454; LUCA.
DR   GeneTree; ENSGT00390000015579; -.
DR   HOGENOM; HOG000115812; -.
DR   HOVERGEN; HBG016332; -.
DR   InParanoid; Q16613; -.
DR   KO; K00669; -.
DR   OMA; TFTELHC; -.
DR   OrthoDB; EOG091G0KJP; -.
DR   PhylomeDB; Q16613; -.
DR   TreeFam; TF331622; -.
DR   BioCyc; MetaCyc:HS05303-MONOMER; -.
DR   BRENDA; 2.3.1.87; 2681.
DR   Reactome; R-HSA-209931; Serotonin and melatonin biosynthesis.
DR   UniPathway; UPA00837; UER00815.
DR   GenomeRNAi; 15; -.
DR   PMAP-CutDB; Q16613; -.
DR   PRO; PR:Q16613; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   Bgee; ENSG00000129673; -.
DR   CleanEx; HS_AANAT; -.
DR   ExpressionAtlas; Q16613; baseline and differential.
DR   Genevisible; Q16613; HS.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
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:0034695; P:response to prostaglandin E; IEA:Ensembl.
DR   GO; GO:0010043; P:response to zinc ion; IEA:Ensembl.
DR   Gene3D; 3.40.630.30; -; 1.
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   Acyltransferase; Alternative splicing; Biological rhythms;
KW   Complete proteome; Cytoplasm; Disease mutation;
KW   Melatonin biosynthesis; Phosphoprotein; Polymorphism;
KW   Reference proteome; Transferase.
FT   CHAIN         1    207       Serotonin N-acetyltransferase.
FT                                /FTId=PRO_0000074580.
FT   DOMAIN       35    194       N-acetyltransferase.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00532}.
FT   REGION      124    126       Acetyl-CoA binding.
FT                                {ECO:0000250|UniProtKB:Q29495}.
FT   REGION      132    137       Acetyl-CoA binding.
FT                                {ECO:0000250|UniProtKB:Q29495}.
FT   REGION      168    170       Acetyl-CoA binding.
FT                                {ECO:0000250|UniProtKB:Q29495}.
FT   BINDING     124    124       Substrate; via amide nitrogen.
FT                                {ECO:0000250|UniProtKB:Q29495}.
FT   BINDING     159    159       Substrate; via carbonyl oxygen.
FT                                {ECO:0000250|UniProtKB:Q29495}.
FT   SITE        120    120       Important for the catalytic mechanism;
FT                                involved in substrate deprotonation.
FT                                {ECO:0000250|UniProtKB:Q29495}.
FT   SITE        122    122       Important for the catalytic mechanism;
FT                                involved in substrate deprotonation.
FT                                {ECO:0000250|UniProtKB:Q29495}.
FT   MOD_RES      31     31       Phosphothreonine; by PKA. {ECO:0000250}.
FT   MOD_RES     205    205       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q29495}.
FT   VAR_SEQ       1      1       M -> MEPQSMKGQKRPFGGPWRLKVLGGPPWLRRTLPKLG
FT                                RPKEAPVARM (in isoform 2). {ECO:0000305}.
FT                                /FTId=VSP_054108.
FT   VARIANT      15     15       R -> C (in dbSNP:rs34470791).
FT                                /FTId=VAR_048168.
FT   VARIANT     129    129       A -> T (found in individuals with delayed
FT                                sleep phase syndrome; has higher
FT                                frequency in affected individuals than in
FT                                healthy controls; unknown pathological
FT                                significance; dbSNP:rs28936679).
FT                                {ECO:0000269|PubMed:12736803}.
FT                                /FTId=VAR_055086.
FT   MUTAGEN      31     31       T->A: Loss of activation by cAMP.
FT                                {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
//
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