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Protein

Serotonin N-acetyltransferase

Gene

AANAT

Organism
Ovis aries (Sheep)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

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

Kineticsi

  1. KM=0.29 mM for acetyl-CoA2 Publications
  2. KM=0.17 mM for tryptamine2 Publications
  3. KM=0.20 mM for tryptamine2 Publications
  4. KM=0.31 mM for 5-hydroxytryptamine2 Publications
  5. KM=3.4 mM for phenylethylamine2 Publications
  6. KM=3.4 mM for tyramine2 Publications

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei120 – 1201Important for the catalytic mechanism; involved in substrate deprotonation
    Sitei122 – 1221Important for the catalytic mechanism; involved in substrate deprotonation
    Binding sitei124 – 1241Substrate; via carbonyl oxygen

    GO - Molecular functioni

    • aralkylamine N-acetyltransferase activity Source: UniProtKB

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Acyltransferase, Transferase

    Keywords - Biological processi

    Biological rhythms, Melatonin biosynthesis

    Enzyme and pathway databases

    BRENDAi2.3.1.87. 2668.
    UniPathwayiUPA00837; UER00815.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serotonin N-acetyltransferase (EC:2.3.1.87)
    Short name:
    Serotonin acetylase
    Alternative name(s):
    Aralkylamine N-acetyltransferase
    Short name:
    AA-NAT
    Gene namesi
    Name:AANAT
    Synonyms:SNAT
    OrganismiOvis aries (Sheep)
    Taxonomic identifieri9940 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeCaprinaeOvis
    ProteomesiUP000002356 Componenti: Unplaced

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi31 – 311T → A: Loss of PKA-promoted YWHAZ-binding; when associated with G-205. 1 Publication
    Mutagenesisi57 – 571I → A: No effect on enzymatic activity; when associated with A-59. 1 Publication
    Mutagenesisi59 – 591V → A: No effect on enzymatic activity; when associated with A-57. 1 Publication
    Mutagenesisi63 – 653Missing : Drastic loss of enzymatic activity. 1 Publication
    Mutagenesisi64 – 641P → A, G or W: Drastic loss of enzymatic activity. 1 Publication
    Mutagenesisi120 – 1201H → A: Reduces catalytic activity 270-fold and decreases affinity for acetyl-coenzyme A; when associated with A-122. 2 Publications
    Mutagenesisi120 – 1201H → Q: Decreases affinity for acetyl-coenzyme A and for substrate. 2 Publications
    Mutagenesisi122 – 1221H → A: Reduces catalytic activity 270-fold and decreases affinity for acetyl-coenzyme A; when associated with A-120. 2 Publications
    Mutagenesisi122 – 1221H → Q: Decreases affinity for acetyl-coenzyme A and for substrate. 2 Publications
    Mutagenesisi160 – 1601C → A: No effect on catalytic activity. 2 Publications
    Mutagenesisi160 – 1601C → S: Reduces catalytic activity. 2 Publications
    Mutagenesisi161 – 1611E → A: No effect. 1 Publication
    Mutagenesisi168 – 1681Y → F: Reduces catalytic activity 30-fold. 2 Publications
    Mutagenesisi205 – 2051S → G: Loss of PKA-promoted YWHAZ-binding; when associated with A-31. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 207207Serotonin N-acetyltransferasePRO_0000074586Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei31 – 311Phosphothreonine; by PKA3 Publications
    Modified residuei205 – 2051Phosphoserine; by PKA1 Publication

    Post-translational modificationi

    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.By similarity

    Keywords - PTMi

    Phosphoprotein

    Expressioni

    Tissue specificityi

    Highest expression in the pineal gland, followed by retina. Expressed at much lower levels in brainstem and pituitary gland. AANAT activity also detected at low levels in the olfactory lobe.1 Publication

    Inductioni

    Exhibits night/day variations with a 7-fold increased activity at night. At the mRNA level, the nocturnal increase is lower than 2-fold.3 Publications

    Interactioni

    Subunit structurei

    Monomer. 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 a 10-fold lower affinity. The interaction with YWHAZ considerably increases affinity for arylalkylamines and acetyl-CoA and protects the enzyme from dephosphorylation and proteasomal degradation. It may also prevent thiol-dependent inactivation. The physiological stoichiometry of the interaction is not clear. In vitro studies show either 1:2 (i.e. 1 AANAT molecule per YWHAZ dimer) (PubMed:11427721) or 2:2 (PubMed:11336675).6 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    YWHAZP631043EBI-446413,EBI-347088From a different organism.

    Protein-protein interaction databases

    IntActiQ29495. 1 interaction.
    MINTiMINT-7997059.

    Structurei

    Secondary structure

    1
    207
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi34 – 385Combined sources
    Helixi42 – 443Combined sources
    Helixi45 – 5511Combined sources
    Helixi57 – 604Combined sources
    Helixi67 – 7610Combined sources
    Helixi78 – 803Combined sources
    Beta strandi81 – 866Combined sources
    Beta strandi89 – 9911Combined sources
    Beta strandi101 – 1033Combined sources
    Helixi106 – 1105Combined sources
    Beta strandi118 – 1269Combined sources
    Helixi128 – 1303Combined sources
    Beta strandi132 – 1343Combined sources
    Helixi135 – 14814Combined sources
    Beta strandi150 – 1523Combined sources
    Beta strandi155 – 1606Combined sources
    Helixi162 – 1643Combined sources
    Helixi165 – 1695Combined sources
    Turni170 – 1723Combined sources
    Beta strandi173 – 1786Combined sources
    Beta strandi189 – 1946Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1B6BX-ray2.50A/B28-201[»]
    1CJWX-ray1.80A30-195[»]
    1IB1X-ray2.70E/F/G/H2-201[»]
    1KUVX-ray2.00A1-207[»]
    1KUXX-ray1.80A1-207[»]
    1KUYX-ray2.40A1-207[»]
    1L0CX-ray2.30A1-207[»]
    ProteinModelPortaliQ29495.
    SMRiQ29495. Positions 18-196.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ29495.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini35 – 196162N-acetyltransferasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni28 – 358YWHAZ-binding
    Regioni124 – 1263Acetyl-CoA binding
    Regioni132 – 1376Acetyl-CoA binding
    Regioni168 – 1703Acetyl-CoA binding

    Sequence similaritiesi

    Contains 1 N-acetyltransferase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    HOVERGENiHBG016332.
    KOiK00669.

    Family and domain databases

    Gene3Di3.40.630.30. 1 hit.
    InterProiIPR016181. Acyl_CoA_acyltransferase.
    IPR000182. GNAT_dom.
    [Graphical view]
    PfamiPF00583. Acetyltransf_1. 1 hit.
    [Graphical view]
    SUPFAMiSSF55729. SSF55729. 1 hit.
    PROSITEiPS51186. GNAT. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q29495-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSTPSVHCLK PSPLHLPSGI PGSPGRQRRH TLPANEFRCL TPEDAAGVFE
    60 70 80 90 100
    IEREAFISVS GNCPLNLDEV QHFLTLCPEL SLGWFVEGRL VAFIIGSLWD
    110 120 130 140 150
    EERLTQESLA LHRPRGHSAH LHALAVHRSF RQQGKGSVLL WRYLHHVGAQ
    160 170 180 190 200
    PAVRRAVLMC EDALVPFYQR FGFHPAGPCA IVVGSLTFTE MHCSLRGHAA

    LRRNSDR
    Length:207
    Mass (Da):23,077
    Last modified:November 1, 1996 - v1
    Checksum:iF6752A872F436DF9
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U29663 mRNA. Translation: AAC48690.1.
    RefSeqiNP_001009461.1. NM_001009461.1.
    UniGeneiOar.638.

    Genome annotation databases

    GeneIDi443531.
    KEGGioas:443531.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U29663 mRNA. Translation: AAC48690.1.
    RefSeqiNP_001009461.1. NM_001009461.1.
    UniGeneiOar.638.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1B6BX-ray2.50A/B28-201[»]
    1CJWX-ray1.80A30-195[»]
    1IB1X-ray2.70E/F/G/H2-201[»]
    1KUVX-ray2.00A1-207[»]
    1KUXX-ray1.80A1-207[»]
    1KUYX-ray2.40A1-207[»]
    1L0CX-ray2.30A1-207[»]
    ProteinModelPortaliQ29495.
    SMRiQ29495. Positions 18-196.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiQ29495. 1 interaction.
    MINTiMINT-7997059.

    Chemistry

    BindingDBiQ29495.
    ChEMBLiCHEMBL5452.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    GeneIDi443531.
    KEGGioas:443531.

    Organism-specific databases

    CTDi15.

    Phylogenomic databases

    HOVERGENiHBG016332.
    KOiK00669.

    Enzyme and pathway databases

    UniPathwayiUPA00837; UER00815.
    BRENDAi2.3.1.87. 2668.

    Miscellaneous databases

    EvolutionaryTraceiQ29495.
    PROiQ29495.

    Family and domain databases

    Gene3Di3.40.630.30. 1 hit.
    InterProiIPR016181. Acyl_CoA_acyltransferase.
    IPR000182. GNAT_dom.
    [Graphical view]
    PfamiPF00583. Acetyltransf_1. 1 hit.
    [Graphical view]
    SUPFAMiSSF55729. SSF55729. 1 hit.
    PROSITEiPS51186. GNAT. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    1. "Pineal serotonin N-acetyltransferase: expression cloning and molecular analysis."
      Coon S.L., Roseboom P.H., Baler R., Weller J.L., Namboodiri M.A.A., Koonin E.V., Klein D.C.
      Science 270:1681-1683(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION.
      Strain: Dorsett X Rambouillet.
      Tissue: Pineal gland.
    2. "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: INDUCTION, BIOPHYSICOCHEMICAL PROPERTIES.
    3. "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: PHOSPHORYLATION AT THR-31, INTERACTION WITH 14-3-3 PROTEINS, IDENTIFICATION BY MASS SPECTROMETRY.
    4. "Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable phosphonate incorporation."
      Zheng W., Zhang Z., Ganguly S., Weller J.L., Klein D.C., Cole P.A.
      Nat. Struct. Biol. 10:1054-1057(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-31, INTERACTION WITH YWHAZ, IDENTIFICATION BY MASS SPECTROMETRY.
    5. "Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205."
      Ganguly S., Weller J.L., Ho A., Chemineau P., Malpaux B., Klein D.C.
      Proc. Natl. Acad. Sci. U.S.A. 102:1222-1227(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION AT THR-31 AND SER-205, INDUCTION, INTERACTION WITH YWHAZ, MUTAGENESIS OF THR-31 AND SER-205.
    6. "Evidence that proline focuses movement of the floppy loop of arylalkylamine N-acetyltransferase (EC 2.3.1.87)."
      Pavlicek J., Coon S.L., Ganguly S., Weller J.L., Hassan S.A., Sackett D.L., Klein D.C.
      J. Biol. Chem. 283:14552-14558(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF ILE-57; VAL-59; PRO-64 AND 63-CYS--LEU-65.
    7. "The structural basis of ordered substrate binding by serotonin N-acetyltransferase: enzyme complex at 1.8 A resolution with a bisubstrate analog."
      Hickman A.B., Namboodiri M.A., Klein D.C., Dyda F.
      Cell 97:361-369(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 30-195 IN COMPLEX WITH COA-S-ACETYLTRYPTAMINE, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF HIS-120; HIS-122 AND TYR-168.
    8. "Melatonin biosynthesis: the structure of serotonin N-acetyltransferase at 2.5 A resolution suggests a catalytic mechanism."
      Hickman A.B., Klein D.C., Dyda F.
      Mol. Cell 3:23-32(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 28-201, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF CYS-160.
    9. "Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase complex. a role for scaffolding in enzyme regulation."
      Obsil T., Ghirlando R., Klein D.C., Ganguly S., Dyda F.
      Cell 105:257-267(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-201 IN COMPLEX WITH THE ACETYL-COA AND SUBSTRATE ANALOG COA-S-ACETYLTRYPTAMINE AND YWHAZ, AFFINITY FOR ACETYL-COA AND SEROTONIN.
    10. "Investigation of the roles of catalytic residues in serotonin N-acetyltransferase."
      Scheibner K.A., De Angelis J., Burley S.K., Cole P.A.
      J. Biol. Chem. 277:18118-18126(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT PHE-168 IN COMPLEX WITH SUBSTRATE ANALOG, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF HIS-120; HIS-122 AND TYR-168.
    11. "X-ray crystallographic studies of serotonin N-acetyltransferase catalysis and inhibition."
      Wolf E., De Angelis J., Khalil E.M., Cole P.A., Burley S.K.
      J. Mol. Biol. 317:215-224(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEXES WITH ACETYL-COA AND SUBSTRATE ANALOGS, MUTAGENESIS OF CYS-160 AND GLU-161.

    Entry informationi

    Entry nameiSNAT_SHEEP
    AccessioniPrimary (citable) accession number: Q29495
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: November 1, 1996
    Last modified: April 29, 2015
    This is version 101 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.