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Protein

Serotonin N-acetyltransferase

Gene

AANAT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.Curated1 Publication

Catalytic activityi

Acetyl-CoA + a 2-arylethylamine = CoA + an N-acetyl-2-arylethylamine.1 Publication

Kineticsi

  1. KM=0.13 mM for tryptamine1 Publication
  2. KM=2.6 mM for 5-hydroxytryptamine1 Publication
  3. KM=0.55 mM for phenylethylamine1 Publication
  4. KM=10.6 mM for tyramine1 Publication

    Pathwayi: melatonin biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes melatonin from serotonin.
    Proteins known to be involved in the 2 steps of the subpathway in this organism are:
    1. Serotonin N-acetyltransferase (AANAT), Acetylserotonin O-methyltransferase (ASMT)
    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 deprotonationBy similarity1
    Sitei122Important for the catalytic mechanism; involved in substrate deprotonationBy similarity1
    Binding sitei124Substrate; via amide nitrogenBy similarity1
    Binding sitei159Substrate; via carbonyl oxygenBy similarity1

    GO - Molecular functioni

    GO - Biological processi

    • cellular response to cAMP Source: UniProtKB
    • circadian rhythm Source: UniProtKB
    • indolalkylamine biosynthetic process Source: Reactome
    • melatonin biosynthetic process Source: UniProtKB
    • N-terminal protein amino acid acetylation Source: UniProtKB
    • photoperiodism Source: Ensembl
    • response to calcium ion Source: Ensembl
    • response to copper ion Source: Ensembl
    • response to corticosterone Source: Ensembl
    • response to cytokine Source: Ensembl
    • response to insulin Source: Ensembl
    • response to light stimulus Source: GO_Central
    • response to prostaglandin E Source: Ensembl
    • response to zinc ion Source: Ensembl

    Keywordsi

    Molecular functionAcyltransferase, Transferase
    Biological processBiological rhythms, Melatonin biosynthesis

    Enzyme and pathway databases

    BioCyciMetaCyc:HS05303-MONOMER
    BRENDAi2.3.1.87 2681
    ReactomeiR-HSA-209931 Serotonin and melatonin biosynthesis
    SABIO-RKiQ16613
    SIGNORiQ16613
    UniPathwayiUPA00837; UER00815

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serotonin N-acetyltransferase (EC:2.3.1.871 Publication)
    Short name:
    Serotonin acetylase
    Alternative name(s):
    Aralkylamine N-acetyltransferase
    Short name:
    AA-NAT
    Gene namesi
    Name:AANAT
    Synonyms:SNAT
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 17

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000129673.9
    HGNCiHGNC:19 AANAT
    MIMi600950 gene
    neXtProtiNX_Q16613

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi31T → A: Loss of activation by cAMP. 1 Publication1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi15
    OpenTargetsiENSG00000129673
    PharmGKBiPA24366

    Chemistry databases

    DrugBankiDB03341 Coa-S-Acetyl 5-Bromotryptamine
    DB02931 Coa-S-Acetyl Tryptamine
    DB01777 Coa-S-Trimethylene-Acetyl-Tryptamine

    Polymorphism and mutation databases

    BioMutaiAANAT
    DMDMi11387096

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000745801 – 207Serotonin N-acetyltransferaseAdd BLAST207

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei31Phosphothreonine; by PKABy similarity1
    Modified residuei205PhosphoserineBy similarity1

    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.

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiQ16613
    PRIDEiQ16613
    ProteomicsDBi60951

    PTM databases

    iPTMnetiQ16613
    PhosphoSitePlusiQ16613

    Miscellaneous databases

    PMAP-CutDBiQ16613

    Expressioni

    Tissue specificityi

    Highly expressed in pineal gland and at lower levels in the retina. Weak expression in several brain regions and in the pituitary gland.2 Publications

    Gene expression databases

    BgeeiENSG00000129673
    CleanExiHS_AANAT
    ExpressionAtlasiQ16613 baseline and differential
    GenevisibleiQ16613 HS

    Organism-specific databases

    HPAiHPA054321

    Interactioni

    Subunit structurei

    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).By similarity

    Binary interactionsi

    Show more details

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi106533, 3 interactors
    IntActiQ16613, 7 interactors
    MINTiQ16613
    STRINGi9606.ENSP00000250615

    Chemistry databases

    BindingDBiQ16613

    Structurei

    3D structure databases

    ProteinModelPortaliQ16613
    SMRiQ16613
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini35 – 194N-acetyltransferasePROSITE-ProRule annotationAdd BLAST160

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni124 – 126Acetyl-CoA bindingBy similarity3
    Regioni132 – 137Acetyl-CoA bindingBy similarity6
    Regioni168 – 170Acetyl-CoA bindingBy similarity3

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG4144 Eukaryota
    COG0454 LUCA
    GeneTreeiENSGT00390000015579
    HOGENOMiHOG000115812
    HOVERGENiHBG016332
    InParanoidiQ16613
    KOiK00669
    OMAiGRCAITV
    OrthoDBiEOG091G0KJP
    PhylomeDBiQ16613
    TreeFamiTF331622

    Family and domain databases

    InterProiView protein in InterPro
    IPR016181 Acyl_CoA_acyltransferase
    IPR000182 GNAT_dom
    PfamiView protein in Pfam
    PF00583 Acetyltransf_1, 1 hit
    SUPFAMiSSF55729 SSF55729, 1 hit
    PROSITEiView protein in PROSITE
    PS51186 GNAT, 1 hit

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q16613-1) [UniParc]FASTAAdd to basket

    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.

    « Hide

            10         20         30         40         50
    MSTQSTHPLK PEAPRLPPGI PESPSCQRRH TLPASEFRCL TPEDAVSAFE
    60 70 80 90 100
    IEREAFISVL GVCPLYLDEI RHFLTLCPEL SLGWFEEGCL VAFIIGSLWD
    110 120 130 140 150
    KERLMQESLT LHRSGGHIAH LHVLAVHRAF RQQGRGPILL WRYLHHLGSQ
    160 170 180 190 200
    PAVRRAALMC EDALVPFYER FSFHAVGPCA ITVGSLTFME LHCSLRGHPF

    LRRNSGC
    Length:207
    Mass (Da):23,344
    Last modified:November 1, 1996 - v1
    Checksum:i7476612F3661E0D5
    GO
    Isoform 2 (identifier: Q16613-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MEPQSMKGQKRPFGGPWRLKVLGGPPWLRRTLPKLGRPKEAPVARM

    Note: No experimental confirmation available.
    Show »
    Length:252
    Mass (Da):28,432
    Checksum:i112BEFE03782A3D8
    GO

    Sequence cautioni

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

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_04816815R → C. Corresponds to variant dbSNP:rs34470791Ensembl.1
    Natural variantiVAR_055086129A → T Found in individuals with delayed sleep phase syndrome; has higher frequency in affected individuals than in healthy controls; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs28936679Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0541081M → MEPQSMKGQKRPFGGPWRLK VLGGPPWLRRTLPKLGRPKE APVARM in isoform 2. Curated1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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
    CCDSiCCDS11745.1 [Q16613-1]
    CCDS54169.1 [Q16613-2]
    RefSeqiNP_001079.1, NM_001088.2 [Q16613-1]
    NP_001160051.1, NM_001166579.1 [Q16613-2]
    UniGeneiHs.431417

    Genome annotation databases

    EnsembliENST00000250615; ENSP00000250615; ENSG00000129673 [Q16613-2]
    ENST00000392492; ENSP00000376282; ENSG00000129673 [Q16613-1]
    GeneIDi15
    KEGGihsa:15
    UCSCiuc002jro.4 human [Q16613-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiSNAT_HUMAN
    AccessioniPrimary (citable) accession number: Q16613
    Secondary accession number(s): A0AVF2, J3KMZ5, Q562F4
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: November 1, 1996
    Last modified: July 18, 2018
    This is version 156 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. SIMILARITY comments
      Index of protein domains and families

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