Q16613 (SNAT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	207 AA.
Sequence status	Complete.
Protein existence	Evidence 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.4
Subcellular location	Cytoplasm Ref.3.
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.5
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	Defects in AANAT are a cause of susceptibility to 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=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.6
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.3 KM=2.6 mM for 5-hydroxytryptamine KM=0.55 mM for phenylethylamine KM=10.6 mM for tyramine

Ontologies

Keywords
Biological process	Biological rhythms Melatonin biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Molecular function	Acyltransferase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	circadian rhythm Traceable author statement. Source: ProtInc melatonin biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	aralkylamine N-acetyltransferase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 207	207	Serotonin N-acetyltransferase		PRO_0000074580
Regions
	Domain	35 – 194	160	N-acetyltransferase
	Region	124 – 126	3	Acetyl-CoA binding By similarity
	Region	132 – 137	6	Acetyl-CoA binding By similarity
	Region	168 – 170	3	Acetyl-CoA binding By similarity
Sites
	Binding site	124	1	Substrate; via carbonyl oxygen By similarity
	Site	120	1	Important for the catalytic mechanism; involved in substrate deprotonation By similarity
	Site	122	1	Important for the catalytic mechanism; involved in substrate deprotonation By similarity
Amino acid modifications
	Modified residue	31	1	Phosphothreonine; by PKA By similarity
	Modified residue	205	1	Phosphoserine By similarity
Natural variations
	Natural variant	15	1	R → C. Corresponds to variant rs34470791 [ dbSNP | Ensembl ].		VAR_048168
	Natural variant	129	1	A → T in DSPS. Ref.6 Corresponds to variant rs28936679 [ dbSNP | Ensembl ].		VAR_055086
Experimental info
	Mutagenesis	31	1	T → A: Loss of activation by cAMP. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q16613 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 7476612F3661E0D5	FASTA	207	23,344
	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

References

	« Hide 'large scale' referencesShow '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: 8661026] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], INDUCTION, TISSUE SPECIFICITY.
[2]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Testis.
[3]	"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: 11313340] [Abstract] Cited for: SUBCELLULAR LOCATION, INDUCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[4]	"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: 11427721] [Abstract] Cited for: INTERACTION WITH 14-3-3 PROTEINS, MUTAGENESIS OF THR-31.
[5]	"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: 18212399] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"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: 12736803] [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	U40391 Genomic DNA. Translation: AAC50555.1. U40347 mRNA. Translation: AAC50554.1. BC069434 mRNA. Translation: AAH69434.1. BC092430 mRNA. Translation: AAH92430.1. BC126332 mRNA. Translation: AAI26333.1. BC126334 mRNA. Translation: AAI26335.1.
IPI	IPI00003354.
RefSeq	NP_001079.1. NM_001088.2. NP_001160051.1. NM_001166579.1.
UniGene	Hs.431417.
3D structure databases
ProteinModelPortal	Q16613.
SMR	Q16613. Positions 30-195.
ModBase	Search...
Protein-protein interaction databases
STRING	Q16613.
PTM databases
PhosphoSite	Q16613.
Polymorphism databases
DMDM	11387096.
Proteomic databases
PRIDE	Q16613.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000250615; ENSP00000250615; ENSG00000129673. ENST00000392492; ENSP00000376282; ENSG00000129673.
GeneID	15.
KEGG	hsa:15.
UCSC	uc002jro.1. human.
Organism-specific databases
CTD	15.
GeneCards	GC17P074449.
H-InvDB	HIX0039129.
HGNC	HGNC:19. AANAT.
MIM	600950. gene. 614163. phenotype.
neXtProt	NX_Q16613.
PharmGKB	PA24366.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15095.
HOGENOM	HBG715289.
HOVERGEN	HBG016332.
InParanoid	Q16613.
OMA	VPFYERF.
OrthoDB	EOG4M0F2N.
PhylomeDB	Q16613.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q16613.
Bgee	Q16613.
CleanEx	HS_AANAT.
Genevestigator	Q16613.
GermOnline	ENSG00000129673. Homo sapiens.
Family and domain databases
InterPro	IPR000182. AcTrfase_GCN5-related_dom. IPR016181. Acyl_CoA_acyltransferase. [Graphical view]
Gene3D	G3DSA:3.40.630.30. Acyl_CoA_acyltransferase. 1 hit.
KO	K00669.
Pfam	PF00583. Acetyltransf_1. 1 hit. [Graphical view]
SUPFAM	SSF55729. Acyl_CoA_acyltransferase. 1 hit.
PROSITE	PS51186. GNAT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	35.
PMAP-CutDB	Q16613.
SOURCE	Search...

Entry information

Entry name

SNAT_HUMAN

Accession

Primary (citable) accession number: Q16613
Secondary accession number(s): A0AVF2, Q562F4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.