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Database: UniProt
Entry: Q16613
LinkDB: Q16613
Original site: Q16613 
ID   SNAT_HUMAN              Reviewed;         207 AA.
AC   Q16613; A0AVF2; Q562F4;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   19-FEB-2014, entry version 117.
DE   RecName: Full=Serotonin N-acetyltransferase;
DE            Short=Serotonin acetylase;
DE            EC=2.3.1.87;
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], 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.,
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 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   [3]
RP   SUBCELLULAR LOCATION, INDUCTION, AND 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   [4]
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   [5]
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   [6]
RP   VARIANT DSPS 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.
CC   -!- CATALYTIC ACTIVITY: Acetyl-CoA + a 2-arylethylamine = CoA + an N-
CC       acetyl-2-arylethylamine.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.13 mM for tryptamine;
CC         KM=2.6 mM for 5-hydroxytryptamine;
CC         KM=0.55 mM for phenylethylamine;
CC         KM=10.6 mM for tyramine;
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).
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
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.
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   -!- DISEASE: Delayed sleep phase syndrome (DSPS) [MIM:614163]: A
CC       circadian rhythm sleep disorder characterized by sleep-onset
CC       insomnia and difficulty in awakening at the desired time. Patients
CC       with DSPS have chronic difficulty in adjusting their sleep-onset
CC       and wake-up times to occupational, school, and social activities.
CC       Note=Disease susceptibility may be associated with variations
CC       affecting the gene represented in this entry. Susceptibility to
CC       delayed sleep phase syndrome can be conferred by variant Thr-129.
CC       Thr-129 shows a significantly higher frequency in affected
CC       individuals than in healthy controls.
CC   -!- SIMILARITY: Belongs to the acetyltransferase family. AANAT
CC       subfamily.
CC   -!- SIMILARITY: Contains 1 N-acetyltransferase domain.
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";
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DR   EMBL; U40391; AAC50555.1; -; Genomic_DNA.
DR   EMBL; U40347; AAC50554.1; -; mRNA.
DR   EMBL; BC069434; AAH69434.1; -; mRNA.
DR   EMBL; BC092430; AAH92430.1; -; mRNA.
DR   EMBL; BC126332; AAI26333.1; -; mRNA.
DR   EMBL; BC126334; AAI26335.1; -; mRNA.
DR   RefSeq; NP_001079.1; NM_001088.2.
DR   RefSeq; NP_001160051.1; NM_001166579.1.
DR   UniGene; Hs.431417; -.
DR   ProteinModelPortal; Q16613; -.
DR   SMR; Q16613; 30-195.
DR   BioGrid; 106533; 1.
DR   IntAct; Q16613; 1.
DR   MINT; MINT-1559914; -.
DR   STRING; 9606.ENSP00000250615; -.
DR   BindingDB; Q16613; -.
DR   DMDM; 11387096; -.
DR   PaxDb; Q16613; -.
DR   PRIDE; Q16613; -.
DR   DNASU; 15; -.
DR   Ensembl; ENST00000392492; ENSP00000376282; ENSG00000129673.
DR   GeneID; 15; -.
DR   KEGG; hsa:15; -.
DR   UCSC; uc002jro.3; human.
DR   CTD; 15; -.
DR   GeneCards; GC17P074449; -.
DR   HGNC; HGNC:19; AANAT.
DR   HPA; HPA050784; -.
DR   MIM; 600950; gene.
DR   MIM; 614163; phenotype.
DR   neXtProt; NX_Q16613; -.
DR   PharmGKB; PA24366; -.
DR   eggNOG; NOG324206; -.
DR   HOGENOM; HOG000115812; -.
DR   HOVERGEN; HBG016332; -.
DR   InParanoid; Q16613; -.
DR   KO; K00669; -.
DR   PhylomeDB; Q16613; -.
DR   BioCyc; MetaCyc:HS05303-MONOMER; -.
DR   Reactome; REACT_111217; Metabolism.
DR   UniPathway; UPA00837; UER00815.
DR   GenomeRNAi; 15; -.
DR   NextBio; 35; -.
DR   PMAP-CutDB; Q16613; -.
DR   PRO; PR:Q16613; -.
DR   ArrayExpress; Q16613; -.
DR   Bgee; Q16613; -.
DR   CleanEx; HS_AANAT; -.
DR   Genevestigator; Q16613; -.
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: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:0044281; P:small molecule metabolic process; TAS:Reactome.
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; Biological rhythms; Complete proteome; Cytoplasm;
KW   Disease mutation; Melatonin biosynthesis; Phosphoprotein;
KW   Polymorphism; Reference proteome; Transferase.
FT   CHAIN         1    207       Serotonin N-acetyltransferase.
FT                                /FTId=PRO_0000074580.
FT   DOMAIN       35    194       N-acetyltransferase.
FT   REGION      124    126       Acetyl-CoA binding (By similarity).
FT   REGION      132    137       Acetyl-CoA binding (By similarity).
FT   REGION      168    170       Acetyl-CoA binding (By similarity).
FT   BINDING     124    124       Substrate; via carbonyl oxygen (By
FT                                similarity).
FT   SITE        120    120       Important for the catalytic mechanism;
FT                                involved in substrate deprotonation (By
FT                                similarity).
FT   SITE        122    122       Important for the catalytic mechanism;
FT                                involved in substrate deprotonation (By
FT                                similarity).
FT   MOD_RES      31     31       Phosphothreonine; by PKA (By similarity).
FT   MOD_RES     205    205       Phosphoserine (By similarity).
FT   VARIANT      15     15       R -> C (in dbSNP:rs34470791).
FT                                /FTId=VAR_048168.
FT   VARIANT     129    129       A -> T (in DSPS; dbSNP:rs28936679).
FT                                /FTId=VAR_055086.
FT   MUTAGEN      31     31       T->A: Loss of activation by cAMP.
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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