SNAT_SHEEP
ID SNAT_SHEEP Reviewed; 207 AA.
AC Q29495;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Serotonin N-acetyltransferase;
DE Short=Serotonin acetylase;
DE EC=2.3.1.87 {ECO:0000269|PubMed:10319816, ECO:0000269|PubMed:11884405, ECO:0000269|PubMed:11902838, ECO:0000269|PubMed:18362150};
DE AltName: Full=Aralkylamine N-acetyltransferase;
DE Short=AA-NAT;
GN Name=AANAT; Synonyms=SNAT;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=Dorsett X Rambouillet; TISSUE=Pineal gland;
RX PubMed=7502081; DOI=10.1126/science.270.5242.1681;
RA Coon S.L., Roseboom P.H., Baler R., Weller J.L., Namboodiri M.A.A.,
RA Koonin E.V., Klein D.C.;
RT "Pineal serotonin N-acetyltransferase: expression cloning and molecular
RT analysis.";
RL Science 270:1681-1683(1995).
RN [2]
RP INDUCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11313340; DOI=10.1074/jbc.m011298200;
RA Coon S.L., Weller J.L., Korf H.-W., Namboodiri M.A., Rollag M., Klein D.C.;
RT "cAMP regulation of arylalkylamine N-acetyltransferase (AANAT, EC
RT 2.3.1.87): a new cell line (1E7) provides evidence of intracellular AANAT
RT activation.";
RL J. Biol. Chem. 276:24097-24107(2001).
RN [3]
RP PHOSPHORYLATION AT THR-31, INTERACTION WITH 14-3-3 PROTEINS, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11427721; DOI=10.1073/pnas.141118798;
RA Ganguly S., Gastel J.A., Weller J.L., Schwartz C., Jaffe H.,
RA Namboodiri M.A., Coon S.L., Hickman A.B., Rollag M., Obsil T.,
RA Beauverger P., Ferry G., Boutin J.A., Klein D.C.;
RT "Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-3-3-
RT binding switch in melatonin synthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:8083-8088(2001).
RN [4]
RP ERRATUM OF PUBMED:11427721.
RA Ganguly S., Gastel J.A., Weller J.L., Schwartz C., Jaffe H.,
RA Namboodiri M.A., Coon S.L., Hickman A.B., Rollag M., Obsil T.,
RA Beauverger P., Ferry G., Boutin J.A., Klein D.C.;
RL Proc. Natl. Acad. Sci. U.S.A. 98:14186-14186(2001).
RN [5]
RP PHOSPHORYLATION AT THR-31, INTERACTION WITH YWHAZ, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=14578935; DOI=10.1038/nsb1005;
RA Zheng W., Zhang Z., Ganguly S., Weller J.L., Klein D.C., Cole P.A.;
RT "Cellular stabilization of the melatonin rhythm enzyme induced by
RT nonhydrolyzable phosphonate incorporation.";
RL Nat. Struct. Biol. 10:1054-1057(2003).
RN [6]
RP FUNCTION, PHOSPHORYLATION AT THR-31 AND SER-205, INDUCTION, INTERACTION
RP WITH YWHAZ, AND MUTAGENESIS OF THR-31 AND SER-205.
RX PubMed=15644438; DOI=10.1073/pnas.0406871102;
RA Ganguly S., Weller J.L., Ho A., Chemineau P., Malpaux B., Klein D.C.;
RT "Melatonin synthesis: 14-3-3-dependent activation and inhibition of
RT arylalkylamine N-acetyltransferase mediated by phosphoserine-205.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:1222-1227(2005).
RN [7]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF ILE-57; VAL-59; PRO-64 AND
RP 63-CYS--LEU-65.
RX PubMed=18362150; DOI=10.1074/jbc.m800593200;
RA Pavlicek J., Coon S.L., Ganguly S., Weller J.L., Hassan S.A., Sackett D.L.,
RA Klein D.C.;
RT "Evidence that proline focuses movement of the floppy loop of
RT arylalkylamine N-acetyltransferase (EC 2.3.1.87).";
RL J. Biol. Chem. 283:14552-14558(2008).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 30-195 IN COMPLEX WITH
RP COA-S-ACETYLTRYPTAMINE, IDENTIFICATION BY MASS SPECTROMETRY, CATALYTIC
RP ACTIVITY, AND MUTAGENESIS OF HIS-120; HIS-122 AND TYR-168.
RX PubMed=10319816; DOI=10.1016/s0092-8674(00)80745-x;
RA Hickman A.B., Namboodiri M.A., Klein D.C., Dyda F.;
RT "The structural basis of ordered substrate binding by serotonin N-
RT acetyltransferase: enzyme complex at 1.8 A resolution with a bisubstrate
RT analog.";
RL Cell 97:361-369(1999).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 28-201, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND MUTAGENESIS OF CYS-160.
RX PubMed=10024876; DOI=10.1016/s1097-2765(00)80171-9;
RA Hickman A.B., Klein D.C., Dyda F.;
RT "Melatonin biosynthesis: the structure of serotonin N-acetyltransferase at
RT 2.5 A resolution suggests a catalytic mechanism.";
RL Mol. Cell 3:23-32(1999).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-201 IN COMPLEX WITH THE
RP ACETYL-COA AND SUBSTRATE ANALOG COA-S-ACETYLTRYPTAMINE AND YWHAZ, AND
RP AFFINITY FOR ACETYL-COA AND SEROTONIN.
RX PubMed=11336675; DOI=10.1016/s0092-8674(01)00316-6;
RA Obsil T., Ghirlando R., Klein D.C., Ganguly S., Dyda F.;
RT "Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase complex.
RT a role for scaffolding in enzyme regulation.";
RL Cell 105:257-267(2001).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT PHE-168 IN COMPLEX WITH
RP SUBSTRATE ANALOG, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF HIS-120; HIS-122 AND TYR-168.
RX PubMed=11884405; DOI=10.1074/jbc.m200595200;
RA Scheibner K.A., De Angelis J., Burley S.K., Cole P.A.;
RT "Investigation of the roles of catalytic residues in serotonin N-
RT acetyltransferase.";
RL J. Biol. Chem. 277:18118-18126(2002).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEXES WITH ACETYL-COA AND
RP SUBSTRATE ANALOGS, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-160 AND
RP GLU-161.
RX PubMed=11902838; DOI=10.1006/jmbi.2001.5371;
RA Wolf E., De Angelis J., Khalil E.M., Cole P.A., Burley S.K.;
RT "X-ray crystallographic studies of serotonin N-acetyltransferase catalysis
RT and inhibition.";
RL J. Mol. Biol. 317:215-224(2002).
CC -!- FUNCTION: Controls the night/day rhythm of melatonin production in the
CC pineal gland. Catalyzes the N-acetylation of serotonin into N-
CC acetylserotonin, the penultimate step in the synthesis of melatonin.
CC {ECO:0000269|PubMed:15644438}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-arylethylamine + acetyl-CoA = CoA + H(+) + N-acetyl-2-
CC arylethylamine; Xref=Rhea:RHEA:20497, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:55469, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:77827; EC=2.3.1.87;
CC Evidence={ECO:0000269|PubMed:10319816, ECO:0000269|PubMed:11884405,
CC ECO:0000269|PubMed:11902838, ECO:0000269|PubMed:18362150};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.29 mM for acetyl-CoA {ECO:0000269|PubMed:11313340,
CC ECO:0000269|PubMed:11884405};
CC KM=0.17 mM for tryptamine {ECO:0000269|PubMed:11313340,
CC ECO:0000269|PubMed:11884405};
CC KM=0.20 mM for tryptamine {ECO:0000269|PubMed:11313340,
CC ECO:0000269|PubMed:11884405};
CC KM=0.31 mM for 5-hydroxytryptamine {ECO:0000269|PubMed:11313340,
CC ECO:0000269|PubMed:11884405};
CC KM=3.4 mM for phenylethylamine {ECO:0000269|PubMed:11313340,
CC ECO:0000269|PubMed:11884405};
CC KM=3.4 mM for tyramine {ECO:0000269|PubMed:11313340,
CC ECO:0000269|PubMed:11884405};
CC -!- PATHWAY: Aromatic compound metabolism; melatonin biosynthesis;
CC melatonin from serotonin: step 1/2. {ECO:0000305}.
CC -!- SUBUNIT: Monomer. Interacts with several 14-3-3 proteins, including
CC YWHAB, YWHAE, YWHAG and YWHAZ, preferentially when phosphorylated at
CC Thr-31. Phosphorylation on Ser-205 also allows binding to YWHAZ, but
CC with a 10-fold lower affinity. The interaction with YWHAZ considerably
CC increases affinity for arylalkylamines and acetyl-CoA and protects the
CC enzyme from dephosphorylation and proteasomal degradation. It may also
CC prevent thiol-dependent inactivation. The physiological stoichiometry
CC of the interaction is not clear. In vitro studies show either 1:2 (i.e.
CC 1 AANAT molecule per YWHAZ dimer) (PubMed:11427721) or 2:2
CC (PubMed:11336675). {ECO:0000269|PubMed:10319816,
CC ECO:0000269|PubMed:11336675, ECO:0000269|PubMed:11427721,
CC ECO:0000269|PubMed:11884405, ECO:0000269|PubMed:14578935,
CC ECO:0000269|PubMed:15644438}.
CC -!- INTERACTION:
CC Q29495; P63104: YWHAZ; Xeno; NbExp=3; IntAct=EBI-446413, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q16613}.
CC -!- TISSUE SPECIFICITY: Highest expression in the pineal gland, followed by
CC retina. Expressed at much lower levels in brainstem and pituitary
CC gland. AANAT activity also detected at low levels in the olfactory
CC lobe. {ECO:0000269|PubMed:7502081}.
CC -!- INDUCTION: Exhibits night/day variations with a 7-fold increased
CC activity at night. At the mRNA level, the nocturnal increase is lower
CC than 2-fold. {ECO:0000269|PubMed:11313340, ECO:0000269|PubMed:15644438,
CC ECO:0000269|PubMed:7502081}.
CC -!- PTM: cAMP-dependent phosphorylation on both N-terminal Thr-31 and C-
CC terminal Ser-205 regulates AANAT activity by promoting interaction with
CC 14-3-3 proteins. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the acetyltransferase family. AANAT subfamily.
CC {ECO:0000305}.
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DR EMBL; U29663; AAC48690.1; -; mRNA.
DR RefSeq; NP_001009461.1; NM_001009461.1.
DR PDB; 1B6B; X-ray; 2.50 A; A/B=28-201.
DR PDB; 1CJW; X-ray; 1.80 A; A=30-195.
DR PDB; 1IB1; X-ray; 2.70 A; E/F/G/H=2-201.
DR PDB; 1KUV; X-ray; 2.00 A; A=1-207.
DR PDB; 1KUX; X-ray; 1.80 A; A=1-207.
DR PDB; 1KUY; X-ray; 2.40 A; A=1-207.
DR PDB; 1L0C; X-ray; 2.30 A; A=1-207.
DR PDBsum; 1B6B; -.
DR PDBsum; 1CJW; -.
DR PDBsum; 1IB1; -.
DR PDBsum; 1KUV; -.
DR PDBsum; 1KUX; -.
DR PDBsum; 1KUY; -.
DR PDBsum; 1L0C; -.
DR AlphaFoldDB; Q29495; -.
DR SMR; Q29495; -.
DR IntAct; Q29495; 1.
DR MINT; Q29495; -.
DR STRING; 9940.ENSOARP00000007675; -.
DR BindingDB; Q29495; -.
DR ChEMBL; CHEMBL5452; -.
DR iPTMnet; Q29495; -.
DR Ensembl; ENSOART00020022881; ENSOARP00020018976; ENSOARG00020014913.
DR GeneID; 443531; -.
DR KEGG; oas:443531; -.
DR CTD; 15; -.
DR eggNOG; KOG4144; Eukaryota.
DR OrthoDB; 1528352at2759; -.
DR BRENDA; 2.3.1.87; 2668.
DR SABIO-RK; Q29495; -.
DR UniPathway; UPA00837; UER00815.
DR EvolutionaryTrace; Q29495; -.
DR PRO; PR:Q29495; -.
DR Proteomes; UP000002356; Unplaced.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0004059; F:aralkylamine N-acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR GO; GO:0030187; P:melatonin biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006474; P:N-terminal protein amino acid acetylation; ISS:UniProtKB.
DR IDEAL; IID50013; -.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR000182; GNAT_dom.
DR Pfam; PF00583; Acetyltransf_1; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR PROSITE; PS51186; GNAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Biological rhythms; Cytoplasm;
KW Melatonin biosynthesis; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..207
FT /note="Serotonin N-acetyltransferase"
FT /id="PRO_0000074586"
FT DOMAIN 35..196
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 28..35
FT /note="YWHAZ-binding"
FT BINDING 124..126
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:10319816,
FT ECO:0000269|PubMed:11336675, ECO:0000269|PubMed:11902838"
FT BINDING 124
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11336675,
FT ECO:0000269|PubMed:11884405, ECO:0000269|PubMed:11902838"
FT BINDING 132..137
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:10319816,
FT ECO:0000269|PubMed:11336675, ECO:0000269|PubMed:11902838"
FT BINDING 159
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11336675,
FT ECO:0000269|PubMed:11884405, ECO:0000269|PubMed:11902838"
FT BINDING 168..170
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:10319816,
FT ECO:0000269|PubMed:11336675, ECO:0000269|PubMed:11902838"
FT SITE 120
FT /note="Important for the catalytic mechanism; involved in
FT substrate deprotonation"
FT /evidence="ECO:0000269|PubMed:10319816,
FT ECO:0000269|PubMed:11884405"
FT SITE 122
FT /note="Important for the catalytic mechanism; involved in
FT substrate deprotonation"
FT /evidence="ECO:0000269|PubMed:10319816,
FT ECO:0000269|PubMed:11884405"
FT MOD_RES 31
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000269|PubMed:11427721,
FT ECO:0000269|PubMed:14578935, ECO:0000269|PubMed:15644438"
FT MOD_RES 205
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:15644438"
FT MUTAGEN 31
FT /note="T->A: Loss of PKA-promoted YWHAZ-binding; when
FT associated with G-205."
FT /evidence="ECO:0000269|PubMed:15644438"
FT MUTAGEN 57
FT /note="I->A: No effect on enzymatic activity; when
FT associated with A-59."
FT /evidence="ECO:0000269|PubMed:18362150"
FT MUTAGEN 59
FT /note="V->A: No effect on enzymatic activity; when
FT associated with A-57."
FT /evidence="ECO:0000269|PubMed:18362150"
FT MUTAGEN 63..65
FT /note="Missing: Drastic loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18362150"
FT MUTAGEN 64
FT /note="P->A,G,W: Drastic loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18362150"
FT MUTAGEN 120
FT /note="H->A: Reduces catalytic activity 270-fold and
FT decreases affinity for acetyl-coenzyme A; when associated
FT with A-122."
FT /evidence="ECO:0000269|PubMed:10319816,
FT ECO:0000269|PubMed:11884405"
FT MUTAGEN 120
FT /note="H->Q: Decreases affinity for acetyl-coenzyme A and
FT for substrate."
FT /evidence="ECO:0000269|PubMed:10319816,
FT ECO:0000269|PubMed:11884405"
FT MUTAGEN 122
FT /note="H->A: Reduces catalytic activity 270-fold and
FT decreases affinity for acetyl-coenzyme A; when associated
FT with A-120."
FT /evidence="ECO:0000269|PubMed:10319816,
FT ECO:0000269|PubMed:11884405"
FT MUTAGEN 122
FT /note="H->Q: Decreases affinity for acetyl-coenzyme A and
FT for substrate."
FT /evidence="ECO:0000269|PubMed:10319816,
FT ECO:0000269|PubMed:11884405"
FT MUTAGEN 160
FT /note="C->A: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:10024876,
FT ECO:0000269|PubMed:11902838"
FT MUTAGEN 160
FT /note="C->S: Reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:10024876,
FT ECO:0000269|PubMed:11902838"
FT MUTAGEN 161
FT /note="E->A: No effect."
FT /evidence="ECO:0000269|PubMed:11902838"
FT MUTAGEN 168
FT /note="Y->F: Reduces catalytic activity 30-fold."
FT /evidence="ECO:0000269|PubMed:10319816,
FT ECO:0000269|PubMed:11884405"
FT MUTAGEN 205
FT /note="S->G: Loss of PKA-promoted YWHAZ-binding; when
FT associated with A-31."
FT /evidence="ECO:0000269|PubMed:15644438"
FT STRAND 34..38
FT /evidence="ECO:0007829|PDB:1CJW"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:1CJW"
FT HELIX 45..55
FT /evidence="ECO:0007829|PDB:1CJW"
FT HELIX 57..60
FT /evidence="ECO:0007829|PDB:1CJW"
FT HELIX 67..76
FT /evidence="ECO:0007829|PDB:1CJW"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:1CJW"
FT STRAND 81..86
FT /evidence="ECO:0007829|PDB:1CJW"
FT STRAND 89..99
FT /evidence="ECO:0007829|PDB:1CJW"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:1CJW"
FT HELIX 106..110
FT /evidence="ECO:0007829|PDB:1CJW"
FT STRAND 118..126
FT /evidence="ECO:0007829|PDB:1CJW"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:1KUX"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:1KUX"
FT HELIX 135..148
FT /evidence="ECO:0007829|PDB:1CJW"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:1L0C"
FT STRAND 155..160
FT /evidence="ECO:0007829|PDB:1CJW"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:1CJW"
FT HELIX 165..169
FT /evidence="ECO:0007829|PDB:1CJW"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:1CJW"
FT STRAND 173..178
FT /evidence="ECO:0007829|PDB:1CJW"
FT STRAND 189..194
FT /evidence="ECO:0007829|PDB:1CJW"
SQ SEQUENCE 207 AA; 23077 MW; F6752A872F436DF9 CRC64;
MSTPSVHCLK PSPLHLPSGI PGSPGRQRRH TLPANEFRCL TPEDAAGVFE IEREAFISVS
GNCPLNLDEV QHFLTLCPEL SLGWFVEGRL VAFIIGSLWD EERLTQESLA LHRPRGHSAH
LHALAVHRSF RQQGKGSVLL WRYLHHVGAQ PAVRRAVLMC EDALVPFYQR FGFHPAGPCA
IVVGSLTFTE MHCSLRGHAA LRRNSDR
