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Q16613 (SNAT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serotonin N-acetyltransferase

Short name=Serotonin acetylase
EC=2.3.1.87
Alternative name(s):
Aralkylamine N-acetyltransferase
Short name=AA-NAT
Gene names
Name:AANAT
Synonyms:SNAT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length207 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Controls the night/day rhythm of melatonin production in the pineal gland. Catalyzes the N-acetylation of serotonin into N-acetylserotonin, the penultimate step in the synthesis of melatonin.

Catalytic activity

Acetyl-CoA + a 2-arylethylamine = CoA + an N-acetyl-2-arylethylamine.

Pathway

Aromatic compound metabolism; melatonin biosynthesis; melatonin from serotonin: step 1/2.

Subunit structure

Monomer By similarity. Interacts with several 14-3-3 proteins, including YWHAB, YWHAE, YWHAG and YWHAZ, preferentially when phosphorylated at Thr-31. Phosphorylation on Ser-205 also allows binding to YWHAZ, but with lower affinity. The interaction with YWHAZ considerably increases affinity for arylalkylamines and acetyl-CoA and protects the enzyme from dephosphorylation and proteasomal degradation By similarity. It may also prevent thiol-dependent inactivation By similarity. Ref.5

Subcellular location

Cytoplasm Ref.4.

Tissue specificity

Highly expressed in pineal gland and at lower levels in the retina. Weak expression in several brain regions and in the pituitary gland. Ref.1 Ref.6

Post-translational modification

cAMP-dependent phosphorylation on both N-terminal Thr-31 and C-terminal Ser-205 regulates AANAT activity by promoting interaction with 14-3-3 proteins.

Involvement in disease

Delayed sleep phase syndrome (DSPS) [MIM:614163]: A circadian rhythm sleep disorder characterized by sleep-onset insomnia and difficulty in awakening at the desired time. Patients with DSPS have chronic difficulty in adjusting their sleep-onset and wake-up times to occupational, school, and social activities.
Note: Disease susceptibility may be associated with variations affecting the gene represented in this entry. Susceptibility to delayed sleep phase syndrome can be conferred by variant Thr-129. Thr-129 shows a significantly higher frequency in affected individuals than in healthy controls. Ref.7

Sequence similarities

Belongs to the acetyltransferase family. AANAT subfamily.

Contains 1 N-acetyltransferase domain.

Biophysicochemical properties

Kinetic parameters:

KM=0.13 mM for tryptamine Ref.4

KM=2.6 mM for 5-hydroxytryptamine

KM=0.55 mM for phenylethylamine

KM=10.6 mM for tyramine

Sequence caution

The sequence AAH69434.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q16613-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q16613-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MEPQSMKGQKRPFGGPWRLKVLGGPPWLRRTLPKLGRPKEAPVARM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 207207Serotonin N-acetyltransferase
PRO_0000074580

Regions

Domain35 – 194160N-acetyltransferase
Region124 – 1263Acetyl-CoA binding By similarity
Region132 – 1376Acetyl-CoA binding By similarity
Region168 – 1703Acetyl-CoA binding By similarity

Sites

Binding site1241Substrate; via carbonyl oxygen By similarity
Site1201Important for the catalytic mechanism; involved in substrate deprotonation By similarity
Site1221Important for the catalytic mechanism; involved in substrate deprotonation By similarity

Amino acid modifications

Modified residue311Phosphothreonine; by PKA By similarity
Modified residue2051Phosphoserine By similarity

Natural variations

Alternative sequence11M → MEPQSMKGQKRPFGGPWRLK VLGGPPWLRRTLPKLGRPKE APVARM in isoform 2.
VSP_054108
Natural variant151R → C.
Corresponds to variant rs34470791 [ dbSNP | Ensembl ].
VAR_048168
Natural variant1291A → T in DSPS. Ref.7
Corresponds to variant rs28936679 [ dbSNP | Ensembl ].
VAR_055086

Experimental info

Mutagenesis311T → A: Loss of activation by cAMP. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 7476612F3661E0D5

FASTA20723,344
        10         20         30         40         50         60 
MSTQSTHPLK PEAPRLPPGI PESPSCQRRH TLPASEFRCL TPEDAVSAFE IEREAFISVL 

        70         80         90        100        110        120 
GVCPLYLDEI RHFLTLCPEL SLGWFEEGCL VAFIIGSLWD KERLMQESLT LHRSGGHIAH 

       130        140        150        160        170        180 
LHVLAVHRAF RQQGRGPILL WRYLHHLGSQ PAVRRAALMC EDALVPFYER FSFHAVGPCA 

       190        200 
ITVGSLTFME LHCSLRGHPF LRRNSGC 

« Hide

Isoform 2 [UniParc].

Checksum: 112BEFE03782A3D8
Show »

FASTA25228,432

References

« Hide 'large scale' references
[1]"The human serotonin N-acetyltransferase (EC 2.3.1.87) gene (AANAT): structure, chromosomal localization, and tissue expression."
Coon S.L., Mazuruk K., Bernard M., Roseboom P., Klein D.C., Rodriguez I.R.
Genomics 34:76-84(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), INDUCTION, TISSUE SPECIFICITY.
[2]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain and Testis.
[4]"cAMP regulation of arylalkylamine N-acetyltransferase (AANAT, EC 2.3.1.87): a new cell line (1E7) provides evidence of intracellular AANAT activation."
Coon S.L., Weller J.L., Korf H.-W., Namboodiri M.A., Rollag M., Klein D.C.
J. Biol. Chem. 276:24097-24107(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INDUCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[5]"Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-3-3-binding switch in melatonin synthesis."
Ganguly S., Gastel J.A., Weller J.L., Schwartz C., Jaffe H., Namboodiri M.A., Coon S.L., Hickman A.B., Rollag M., Obsil T., Beauverger P., Ferry G., Boutin J.A., Klein D.C.
Proc. Natl. Acad. Sci. U.S.A. 98:8083-8088(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH 14-3-3 PROTEINS, MUTAGENESIS OF THR-31.
[6]"Role of melatonin in upper gastrointestinal tract."
Konturek S.J., Konturek P.C., Brzozowski T., Bubenik G.A.
J. Physiol. Pharmacol. 58:23-52(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[7]"Significant association of the arylalkylamine N-acetyltransferase (AA-NAT) gene with delayed sleep phase syndrome."
Hohjoh H., Takasu M., Shishikura K., Takahashi Y., Honda Y., Tokunaga K.
Neurogenetics 4:151-153(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DSPS THR-129.
+Additional computationally mapped references.

Web resources

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U40347 mRNA. Translation: AAC50554.1.
U40391 Genomic DNA. Translation: AAC50555.1.
AC015802 Genomic DNA. No translation available.
BC069434 mRNA. Translation: AAH69434.1. Different initiation.
BC092430 mRNA. Translation: AAH92430.1.
BC126332 mRNA. Translation: AAI26333.1.
BC126334 mRNA. Translation: AAI26335.1.
CCDSCCDS11745.1.
RefSeqNP_001079.1. NM_001088.2. [Q16613-1]
NP_001160051.1. NM_001166579.1. [Q16613-2]
UniGeneHs.431417.

3D structure databases

ProteinModelPortalQ16613.
SMRQ16613. Positions 30-195.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106533. 1 interaction.
IntActQ16613. 1 interaction.
MINTMINT-1559914.
STRING9606.ENSP00000250615.

Chemistry

BindingDBQ16613.

Polymorphism databases

DMDM11387096.

Proteomic databases

PaxDbQ16613.
PRIDEQ16613.

Protocols and materials databases

DNASU15.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000250615; ENSP00000250615; ENSG00000129673.
ENST00000392492; ENSP00000376282; ENSG00000129673.
GeneID15.
KEGGhsa:15.
UCSCuc002jro.3. human. [Q16613-1]

Organism-specific databases

CTD15.
GeneCardsGC17P074449.
HGNCHGNC:19. AANAT.
HPAHPA050784.
MIM600950. gene.
614163. phenotype.
neXtProtNX_Q16613.
PharmGKBPA24366.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG324206.
HOGENOMHOG000115812.
HOVERGENHBG016332.
InParanoidQ16613.
KOK00669.
OMALRRNSGC.
OrthoDBEOG7C2R2B.
PhylomeDBQ16613.
TreeFamTF331622.

Enzyme and pathway databases

BioCycMetaCyc:HS05303-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00837; UER00815.

Gene expression databases

ArrayExpressQ16613.
BgeeQ16613.
CleanExHS_AANAT.
GenevestigatorQ16613.

Family and domain databases

Gene3D3.40.630.30. 1 hit.
InterProIPR016181. Acyl_CoA_acyltransferase.
IPR000182. GNAT_dom.
[Graphical view]
PfamPF00583. Acetyltransf_1. 1 hit.
[Graphical view]
SUPFAMSSF55729. SSF55729. 1 hit.
PROSITEPS51186. GNAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi15.
NextBio35534776.
PMAP-CutDBQ16613.
PROQ16613.
SOURCESearch...

Entry information

Entry nameSNAT_HUMAN
AccessionPrimary (citable) accession number: Q16613
Secondary accession number(s): A0AVF2, J3KMZ5, Q562F4
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM