Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q29495 (SNAT_SHEEP) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismOvis aries (Sheep) [Complete proteome]
Taxonomic identifier9940 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeCaprinaeOvis

Protein attributes

Sequence length207 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Ref.6

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. 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) (Ref.3) or 2:2 (Ref.10). Ref.3 Ref.5 Ref.6

Subcellular location

Cytoplasm By similarity.

Tissue specificity

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. Ref.1

Induction

Exhibits night/day variations with a 7-fold increased activity at night. At the mRNA level, the nocturnal increase is lower than 2-fold. Ref.1 Ref.2 Ref.6

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 By similarity.

Sequence similarities

Belongs to the acetyltransferase family. AANAT subfamily.

Contains 1 N-acetyltransferase domain.

Biophysicochemical properties

Kinetic parameters:

KM=0.29 mM for acetyl-CoA Ref.2 Ref.11

KM=0.17 mM for tryptamine

KM=0.20 mM for tryptamine

KM=0.31 mM for 5-hydroxytryptamine

KM=3.4 mM for phenylethylamine

KM=3.4 mM for tyramine

Binary interactions

With

Entry

#Exp.

IntAct

Notes

YWHAZP631043EBI-446413,EBI-347088From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 207207Serotonin N-acetyltransferase
PRO_0000074586

Regions

Domain35 – 196162N-acetyltransferase
Region28 – 358YWHAZ-binding
Region124 – 1263Acetyl-CoA binding
Region132 – 1376Acetyl-CoA binding
Region168 – 1703Acetyl-CoA binding

Sites

Binding site1241Substrate; via carbonyl oxygen
Site1201Important for the catalytic mechanism; involved in substrate deprotonation
Site1221Important for the catalytic mechanism; involved in substrate deprotonation

Amino acid modifications

Modified residue311Phosphothreonine; by PKA Ref.3 Ref.5 Ref.6
Modified residue2051Phosphoserine; by PKA Ref.6

Experimental info

Mutagenesis311T → A: Loss of PKA-promoted YWHAZ-binding; when associated with G-205. Ref.6
Mutagenesis571I → A: No effect on enzymatic activity; when associated with A-59. Ref.7
Mutagenesis591V → A: No effect on enzymatic activity; when associated with A-57. Ref.7
Mutagenesis63 – 653Missing: Drastic loss of enzymatic activity. Ref.7
Mutagenesis641P → A, G or W: Drastic loss of enzymatic activity. Ref.7
Mutagenesis1201H → A: Reduces catalytic activity 270-fold and decreases affinity for acetyl-coenzyme A; when associated with A-122. Ref.8 Ref.11
Mutagenesis1201H → Q: Decreases affinity for acetyl-coenzyme A and for substrate. Ref.8 Ref.11
Mutagenesis1221H → A: Reduces catalytic activity 270-fold and decreases affinity for acetyl-coenzyme A; when associated with A-120. Ref.8 Ref.11
Mutagenesis1221H → Q: Decreases affinity for acetyl-coenzyme A and for substrate. Ref.8 Ref.11
Mutagenesis1601C → A: No effect on catalytic activity. Ref.9 Ref.12
Mutagenesis1601C → S: Reduces catalytic activity. Ref.9 Ref.12
Mutagenesis1611E → A: No effect. Ref.12
Mutagenesis1681Y → F: Reduces catalytic activity 30-fold. Ref.8 Ref.11
Mutagenesis2051S → G: Loss of PKA-promoted YWHAZ-binding; when associated with A-31. Ref.6

Secondary structure

..................................... 207
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q29495 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: F6752A872F436DF9

FASTA20723,077
        10         20         30         40         50         60 
MSTPSVHCLK PSPLHLPSGI PGSPGRQRRH TLPANEFRCL TPEDAAGVFE IEREAFISVS 

        70         80         90        100        110        120 
GNCPLNLDEV QHFLTLCPEL SLGWFVEGRL VAFIIGSLWD EERLTQESLA LHRPRGHSAH 

       130        140        150        160        170        180 
LHALAVHRSF RQQGKGSVLL WRYLHHVGAQ PAVRRAVLMC EDALVPFYQR FGFHPAGPCA 

       190        200 
IVVGSLTFTE MHCSLRGHAA LRRNSDR 

« Hide

References

[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]Erratum
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. 98:14186-14186(2001)
[5]"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.
[6]"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.
[7]"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.
[8]"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.
[9]"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.
[10]"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 COA-S-ACETYLTRYPTAMINE AND YWHAZ, AFFINITY FOR ACETYL-COA AND SEROTONIN.
[11]"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.
[12]"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 SUBSTRATE ANALOGS, MUTAGENESIS OF CYS-160 AND GLU-161.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U29663 mRNA. Translation: AAC48690.1.
RefSeqNP_001009461.1. NM_001009461.1.
UniGeneOar.638.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalQ29495.
SMRQ29495. Positions 18-196.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ29495. 1 interaction.
MINTMINT-7997059.

Chemistry

BindingDBQ29495.
ChEMBLCHEMBL5452.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID443531.

Organism-specific databases

CTD15.

Phylogenomic databases

HOVERGENHBG016332.

Enzyme and pathway databases

BRENDA2.3.1.87. 4472.
UniPathwayUPA00837; UER00815.

Family and domain databases

Gene3D3.40.630.30. 1 hit.
InterProIPR016181. Acyl_CoA_acyltransferase.
IPR000182. GNAT_dom.
[Graphical view]
PfamPF00583. Acetyltransf_1. 1 hit.
[Graphical view]
SUPFAMSSF55729. SSF55729. 1 hit.
PROSITEPS51186. GNAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ29495.

Entry information

Entry nameSNAT_SHEEP
AccessionPrimary (citable) accession number: Q29495
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways