Q16613 (SNAT_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 95.
History...
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames 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 |
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| 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 | |
| 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 processInferred 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
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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: 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 |
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| 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. | ||||||||
Relevant documents
| Human chromosome 17 Human chromosome 17: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| SIMILARITY comments Index of protein domains and families |

Clusters with