Serotonin N-acetyltransferase - Ovis aries (Sheep)

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Q29495 (SNAT_SHEEP) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 89. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names 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

Name:	AANAT
Synonyms:	SNAT

Organism

Ovis aries (Sheep)

Taxonomic identifier

9940 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Caprinae › Ovis

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. 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: K_M=0.29 mM for acetyl-CoA Ref.2 Ref.11 K_M=0.17 mM for tryptamine K_M=0.20 mM for tryptamine K_M=0.31 mM for 5-hydroxytryptamine K_M=3.4 mM for phenylethylamine K_M=3.4 mM for tyramine

Ontologies

Keywords
Biological process	Biological rhythms Melatonin biosynthesis
Cellular component	Cytoplasm
Molecular function	Acyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological_process	N-terminal protein amino acid acetylation Inferred from sequence or structural similarity. Source: UniProtKB cellular response to cAMP Inferred from sequence or structural similarity. Source: UniProtKB circadian rhythm Inferred from sequence or structural similarity. Source: UniProtKB melatonin biosynthetic process Inferred from direct assay Ref.2. Source: UniProtKB
Cellular_component	perinuclear region of cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	aralkylamine N-acetyltransferase activity Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
YWHAZ	P63104	3	EBI-446413,EBI-347088	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 207

207

Serotonin N-acetyltransferase

PRO_0000074586

Regions

Domain

35 – 196

162

N-acetyltransferase

Region

28 – 35

YWHAZ-binding

Region

124 – 126

Acetyl-CoA binding

Region

132 – 137

Acetyl-CoA binding

Region

168 – 170

Acetyl-CoA binding

Sites

Binding site

124

Substrate; via carbonyl oxygen

Site

120

Important for the catalytic mechanism; involved in substrate deprotonation

Site

122

Important for the catalytic mechanism; involved in substrate deprotonation

Amino acid modifications

Modified residue

Phosphothreonine; by PKA Ref.3 Ref.5 Ref.6

Modified residue

205

Phosphoserine; by PKA Ref.6

Experimental info

Mutagenesis

T → A: Loss of PKA-promoted YWHAZ-binding; when associated with G-205. Ref.6

Mutagenesis

I → A: No effect on enzymatic activity; when associated with A-59. Ref.7

Mutagenesis

V → A: No effect on enzymatic activity; when associated with A-57. Ref.7

Mutagenesis

63 – 65

Missing: Drastic loss of enzymatic activity. Ref.7

Mutagenesis

P → A, G or W: Drastic loss of enzymatic activity. Ref.7

Mutagenesis

120

H → A: Reduces catalytic activity 270-fold and decreases affinity for acetyl-coenzyme A; when associated with A-122. Ref.8 Ref.11

Mutagenesis

120

H → Q: Decreases affinity for acetyl-coenzyme A and for substrate. Ref.8 Ref.11

Mutagenesis

122

H → A: Reduces catalytic activity 270-fold and decreases affinity for acetyl-coenzyme A; when associated with A-120. Ref.8 Ref.11

Mutagenesis

122

H → Q: Decreases affinity for acetyl-coenzyme A and for substrate. Ref.8 Ref.11

Mutagenesis

160

C → A: No effect on catalytic activity. Ref.9 Ref.12

Mutagenesis

160

C → S: Reduces catalytic activity. Ref.9 Ref.12

Mutagenesis

161

E → A: No effect. Ref.12

Mutagenesis

168

Y → F: Reduces catalytic activity 30-fold. Ref.8 Ref.11

Mutagenesis

205

S → G: Loss of PKA-promoted YWHAZ-binding; when associated with A-31. Ref.6

Secondary structure

207

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

Q29495 [UniParc].

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

207

23,077

        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, 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, 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, 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, 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.

RefSeq

NP_001009461.1. NM_001009461.1.

UniGene

Oar.638.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B6B	X-ray	2.50	A/B	28-201	[»]
1CJW	X-ray	1.80	A	30-195	[»]
1IB1	X-ray	2.70	E/F/G/H	2-201	[»]
1KUV	X-ray	2.00	A	1-207	[»]
1KUX	X-ray	1.80	A	1-207	[»]
1KUY	X-ray	2.40	A	1-207	[»]
1L0C	X-ray	2.30	A	1-207	[»]

ProteinModelPortal

Q29495.

SMR

Q29495. Positions 18-196.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q29495. 1 interaction.

MINT

MINT-7997059.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

443531.

Organism-specific databases

CTD

15.

Phylogenomic databases

HOVERGEN

HBG016332.

Enzyme and pathway databases

BRENDA

2.3.1.87. 4472.

UniPathway

UPA00837; UER00815.

Family and domain databases

Gene3D

3.40.630.30. 1 hit.

InterPro

IPR016181. Acyl_CoA_acyltransferase.
IPR000182. GNAT_dom.
[Graphical view]

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

BindingDB

Q29495.

ChEMBL

CHEMBL5452.

EvolutionaryTrace

Q29495.

Entry information

Entry name

SNAT_SHEEP

Accession

Primary (citable) accession number: Q29495

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 1, 1996
Last modified:	May 29, 2013
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Other

Entry information

Relevant documents