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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.4 Publications

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: melatonin biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes melatonin from serotonin.Curated
    Proteins known to be involved in the 2 steps of the subpathway in this organism are:
    1. Serotonin N-acetyltransferase (AANAT)
    2. no protein annotated in this organism
    This subpathway is part of the pathway melatonin biosynthesis, which is itself part of Aromatic compound metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes melatonin from serotonin, the pathway melatonin biosynthesis and in Aromatic compound metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei120Important for the catalytic mechanism; involved in substrate deprotonation2 Publications1
    Sitei122Important for the catalytic mechanism; involved in substrate deprotonation2 Publications1
    Binding sitei124Substrate; via amide nitrogen3 Publications1
    Binding sitei159Substrate; via carbonyl oxygen3 Publications1

    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:2.3.1.874 Publications)
    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
    Proteomesi
    • UP000002356 Componenti: Unplaced

    Subcellular locationi

    • Cytoplasm By similarity

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi31T → A: Loss of PKA-promoted YWHAZ-binding; when associated with G-205. 1 Publication1
    Mutagenesisi57I → A: No effect on enzymatic activity; when associated with A-59. 1 Publication1
    Mutagenesisi59V → A: No effect on enzymatic activity; when associated with A-57. 1 Publication1
    Mutagenesisi63 – 65Missing : Drastic loss of enzymatic activity. 1 Publication3
    Mutagenesisi64P → A, G or W: Drastic loss of enzymatic activity. 1 Publication1
    Mutagenesisi120H → A: Reduces catalytic activity 270-fold and decreases affinity for acetyl-coenzyme A; when associated with A-122. 2 Publications1
    Mutagenesisi120H → Q: Decreases affinity for acetyl-coenzyme A and for substrate. 2 Publications1
    Mutagenesisi122H → A: Reduces catalytic activity 270-fold and decreases affinity for acetyl-coenzyme A; when associated with A-120. 2 Publications1
    Mutagenesisi122H → Q: Decreases affinity for acetyl-coenzyme A and for substrate. 2 Publications1
    Mutagenesisi160C → A: No effect on catalytic activity. 2 Publications1
    Mutagenesisi160C → S: Reduces catalytic activity. 2 Publications1
    Mutagenesisi161E → A: No effect. 1 Publication1
    Mutagenesisi168Y → F: Reduces catalytic activity 30-fold. 2 Publications1
    Mutagenesisi205S → G: Loss of PKA-promoted YWHAZ-binding; when associated with A-31. 1 Publication1

    Chemistry databases

    ChEMBLiCHEMBL5452.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000745861 – 207Serotonin N-acetyltransferaseAdd BLAST207

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei31Phosphothreonine; by PKA3 Publications1
    Modified residuei205Phosphoserine; by PKA1 Publication1

    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

    PTM databases

    iPTMnetiQ29495.

    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 interactor.
    MINTiMINT-7997059.

    Chemistry databases

    BindingDBiQ29495.

    Structurei

    Secondary structure

    1207
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi34 – 38Combined sources5
    Helixi42 – 44Combined sources3
    Helixi45 – 55Combined sources11
    Helixi57 – 60Combined sources4
    Helixi67 – 76Combined sources10
    Helixi78 – 80Combined sources3
    Beta strandi81 – 86Combined sources6
    Beta strandi89 – 99Combined sources11
    Beta strandi101 – 103Combined sources3
    Helixi106 – 110Combined sources5
    Beta strandi118 – 126Combined sources9
    Helixi128 – 130Combined sources3
    Beta strandi132 – 134Combined sources3
    Helixi135 – 148Combined sources14
    Beta strandi150 – 152Combined sources3
    Beta strandi155 – 160Combined sources6
    Helixi162 – 164Combined sources3
    Helixi165 – 169Combined sources5
    Turni170 – 172Combined sources3
    Beta strandi173 – 178Combined sources6
    Beta strandi189 – 194Combined sources6

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ29495.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini35 – 196N-acetyltransferasePROSITE-ProRule annotationAdd BLAST162

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni28 – 35YWHAZ-binding8
    Regioni124 – 126Acetyl-CoA binding3 Publications3
    Regioni132 – 137Acetyl-CoA binding3 Publications6
    Regioni168 – 170Acetyl-CoA binding3 Publications3

    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
    PDB 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiQ29495. 1 interactor.
    MINTiMINT-7997059.

    Chemistry databases

    BindingDBiQ29495.
    ChEMBLiCHEMBL5452.

    PTM databases

    iPTMnetiQ29495.

    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...

    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: November 2, 2016
    This is version 108 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

    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 one 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.