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Q29495

- SNAT_SHEEP

UniProt

Q29495 - SNAT_SHEEP

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Protein
Serotonin N-acetyltransferase
Gene
AANAT, SNAT
Organism
Ovis aries (Sheep)
Status
Reviewed - 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 tryptamine
  3. KM=0.20 mM for tryptamine
  4. KM=0.31 mM for 5-hydroxytryptamine
  5. KM=3.4 mM for phenylethylamine
  6. KM=3.4 mM for tyramine

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

  1. aralkylamine N-acetyltransferase activity Source: UniProtKB
  2. protein binding Source: IntAct

GO - Biological processi

  1. N-terminal protein amino acid acetylation Source: UniProtKB
  2. cellular response to cAMP Source: UniProtKB
  3. circadian rhythm Source: UniProtKB
  4. melatonin biosynthetic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Transferase

Keywords - Biological processi

Biological rhythms, Melatonin biosynthesis

Enzyme and pathway databases

BRENDAi2.3.1.87. 4472.
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: Unplaced

Subcellular locationi

Cytoplasm By similarity

GO - Cellular componenti

  1. perinuclear region of cytoplasm Source: UniProtKB
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-acetyltransferase
PRO_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) (1 Publication) or 2:2 (1 Publication).3 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

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

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
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.

Miscellaneous databases

EvolutionaryTraceiQ29495.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini35 – 196162N-acetyltransferase
Add
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

Phylogenomic databases

HOVERGENiHBG016332.

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

MSTPSVHCLK PSPLHLPSGI PGSPGRQRRH TLPANEFRCL TPEDAAGVFE    50
IEREAFISVS GNCPLNLDEV QHFLTLCPEL SLGWFVEGRL VAFIIGSLWD 100
EERLTQESLA LHRPRGHSAH LHALAVHRSF RQQGKGSVLL WRYLHHVGAQ 150
PAVRRAVLMC EDALVPFYQR FGFHPAGPCA IVVGSLTFTE MHCSLRGHAA 200
LRRNSDR 207
Length:207
Mass (Da):23,077
Last modified:November 1, 1996 - v1
Checksum:iF6752A872F436DF9
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U29663 mRNA. Translation: AAC48690.1.
RefSeqiNP_001009461.1. NM_001009461.1.
UniGeneiOar.638.

Genome annotation databases

GeneIDi443531.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U29663 mRNA. Translation: AAC48690.1 .
RefSeqi NP_001009461.1. NM_001009461.1.
UniGenei Oar.638.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
ProteinModelPortali Q29495.
SMRi Q29495. Positions 18-196.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q29495. 1 interaction.
MINTi MINT-7997059.

Chemistry

BindingDBi Q29495.
ChEMBLi CHEMBL5452.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 443531.

Organism-specific databases

CTDi 15.

Phylogenomic databases

HOVERGENi HBG016332.

Enzyme and pathway databases

UniPathwayi UPA00837 ; UER00815 .
BRENDAi 2.3.1.87. 4472.

Miscellaneous databases

EvolutionaryTracei Q29495.

Family and domain databases

Gene3Di 3.40.630.30. 1 hit.
InterProi IPR016181. Acyl_CoA_acyltransferase.
IPR000182. GNAT_dom.
[Graphical view ]
Pfami PF00583. Acetyltransf_1. 1 hit.
[Graphical view ]
SUPFAMi SSF55729. SSF55729. 1 hit.
PROSITEi PS51186. GNAT. 1 hit.
[Graphical view ]
ProtoNeti Search...

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 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 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: July 9, 2014
This is version 95 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