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Protein

Acetylserotonin O-methyltransferase

Gene

ASMT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Isoform 1 catalyzes the transfer of a methyl group onto N-acetylserotonin, producing melatonin (N-acetyl-5-methoxytryptamine). Isoform 2 and isoform 3 lack enzyme activity.1 Publication

Miscellaneous

The gene coding for this protein is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes.

Catalytic activityi

S-adenosyl-L-methionine + N-acetylserotonin = S-adenosyl-L-homocysteine + melatonin.1 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
Binding sitei147S-adenosyl-L-methionine1
Binding sitei164S-adenosyl-L-methionine1
Binding sitei210S-adenosyl-L-methionine1
Binding sitei252S-adenosyl-L-methionine1
Active sitei255Proton donor/acceptor1 Publication1
Binding sitei256Substrate1
Binding sitei302Substrate1
Binding sitei306Substrate1

GO - Molecular functioni

  • acetylserotonin O-methyltransferase activity Source: UniProtKB
  • identical protein binding Source: IntAct
  • O-methyltransferase activity Source: ProtInc
  • protein homodimerization activity Source: UniProtKB
  • S-methyltransferase activity Source: Reactome

GO - Biological processi

  • indolalkylamine biosynthetic process Source: Reactome
  • melatonin biosynthetic process Source: UniProtKB
  • translation Source: ProtInc

Keywordsi

Molecular functionMethyltransferase, Transferase
Biological processMelatonin biosynthesis
LigandS-adenosyl-L-methionine

Enzyme and pathway databases

BioCyciMetaCyc:HS09884-MONOMER.
BRENDAi2.1.1.4. 2681.
ReactomeiR-HSA-209931. Serotonin and melatonin biosynthesis.
UniPathwayiUPA00837; UER00815.

Names & Taxonomyi

Protein namesi
Recommended name:
Acetylserotonin O-methyltransferase (EC:2.1.1.4)
Alternative name(s):
Hydroxyindole O-methyltransferase
Short name:
HIOMT
Gene namesi
Name:ASMT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000196433.12.
HGNCiHGNC:750. ASMT.

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi11L → F: Reduced enzyme activity. 1 Publication1
Mutagenesisi31L → H: No effect on enzyme activity. 1
Mutagenesisi296T → M: Nearly abolishes enzyme activity. 1 Publication1
Mutagenesisi318H → D: Reduced enzyme activity. 1 Publication1

Organism-specific databases

DisGeNETi438.
OpenTargetsiENSG00000196433.
PharmGKBiPA25049.

Chemistry databases

DrugBankiDB01065. Melatonin.

Polymorphism and mutation databases

BioMutaiASMT.
DMDMi1170276.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000839821 – 345Acetylserotonin O-methyltransferaseAdd BLAST345

Proteomic databases

PeptideAtlasiP46597.
PRIDEiP46597.

Expressioni

Tissue specificityi

Expressed in the pineal gland (at protein level). In the retina, very low expression is found at the mRNA level (PubMed:7989373), and not at the protein level (PubMed:8574683).3 Publications

Inductioni

By all-trans-, 9-cis- and 13-cis-retinoic acid and by serum treatment, following starvation, in the retinoblastoma cell line Y79.2 Publications

Gene expression databases

BgeeiENSG00000196433.
ExpressionAtlasiP46597. baseline and differential.
GenevisibleiP46597. HS.

Interactioni

Subunit structurei

Homodimer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-6502097,EBI-6502097

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: UniProtKB

Structurei

Secondary structure

1345
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi7 – 31Combined sources25
Helixi33 – 39Combined sources7
Beta strandi40 – 42Combined sources3
Helixi46 – 53Combined sources8
Helixi57 – 69Combined sources13
Beta strandi72 – 78Combined sources7
Beta strandi81 – 86Combined sources6
Helixi88 – 94Combined sources7
Helixi103 – 111Combined sources9
Helixi113 – 117Combined sources5
Helixi120 – 126Combined sources7
Helixi131 – 135Combined sources5
Helixi142 – 146Combined sources5
Helixi150 – 161Combined sources12
Helixi164 – 173Combined sources10
Helixi177 – 179Combined sources3
Beta strandi181 – 186Combined sources6
Helixi192 – 200Combined sources9
Beta strandi205 – 210Combined sources6
Helixi212 – 221Combined sources10
Beta strandi229 – 235Combined sources7
Turni237 – 239Combined sources3
Beta strandi246 – 253Combined sources8
Helixi254 – 256Combined sources3
Helixi259 – 272Combined sources14
Beta strandi278 – 283Combined sources6
Helixi294 – 305Combined sources12
Beta strandi306 – 308Combined sources3
Helixi314 – 324Combined sources11
Beta strandi327 – 332Combined sources6
Beta strandi335 – 337Combined sources3
Beta strandi339 – 344Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4A6DX-ray2.40A1-345[»]
4A6EX-ray2.70A1-345[»]
ProteinModelPortaliP46597.
SMRiP46597.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni235 – 237S-adenosyl-L-methionine binding3

Sequence similaritiesi

Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-independent O-methyltransferase family.PROSITE-ProRule annotation

Phylogenomic databases

GeneTreeiENSGT00530000064032.
HOGENOMiHOG000247024.
HOVERGENiHBG001526.
InParanoidiP46597.
KOiK00543.
OMAiFWPYVFG.
PhylomeDBiP46597.
TreeFamiTF314574.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiView protein in InterPro
IPR031725. ASMT_dimerisation.
IPR016461. O-MeTrfase_COMT.
IPR001077. O_MeTrfase_2.
IPR029063. SAM-dependent_MTases.
IPR011991. WHTH_DNA-bd_dom.
PfamiView protein in Pfam
PF16864. Dimerisation2. 1 hit.
PF00891. Methyltransf_2. 1 hit.
PIRSFiPIRSF005739. O-mtase. 1 hit.
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF53335. SSF53335. 1 hit.
PROSITEiView protein in PROSITE
PS51683. SAM_OMT_II. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P46597-1) [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
MGSSEDQAYR LLNDYANGFM VSQVLFAACE LGVFDLLAEA PGPLDVAAVA
60 70 80 90 100
AGVRASAHGT ELLLDICVSL KLLKVETRGG KAFYRNTELS SDYLTTVSPT
110 120 130 140 150
SQCSMLKYMG RTSYRCWGHL ADAVREGRNQ YLETFGVPAE ELFTAIYRSE
160 170 180 190 200
GERLQFMQAL QEVWSVNGRS VLTAFDLSVF PLMCDLGGGA GALAKECMSL
210 220 230 240 250
YPGCKITVFD IPEVVWTAKQ HFSFQEEEQI DFQEGDFFKD PLPEADLYIL
260 270 280 290 300
ARVLHDWADG KCSHLLERIY HTCKPGGGIL VIESLLDEDR RGPLLTQLYS
310 320 330 340
LNMLVQTEGQ ERTPTHYHML LSSAGFRDFQ FKKTGAIYDA ILARK
Length:345
Mass (Da):38,453
Last modified:November 1, 1995 - v1
Checksum:i187A375E1E2940B7
GO
Isoform 2 (identifier: P46597-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     189-235: Missing.

Show »
Length:298
Mass (Da):33,192
Checksum:iAAFC60D1F8D70E5A
GO
Isoform 3 (identifier: P46597-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     188-188: G → GTWIKLETIILSKLSQGQKTKHRVFSLIG

Note: Includes part of a LINE-1 element.Curated
Show »
Length:373
Mass (Da):41,661
Checksum:i8CA134BD0BA50FDD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti302N → S in BAG37430 (PubMed:14702039).Curated1
Isoform 3 (identifier: P46597-3)
Sequence conflicti190W → R in AAA58582 (PubMed:7989373).Curated1
Sequence conflicti190W → R in AAA58583 (PubMed:7989373).Curated1
Sequence conflicti190W → R in AAA75290 (PubMed:7989373).Curated1
Sequence conflicti190W → R in AAA17020 (PubMed:8397829).Curated1
Sequence conflicti190W → R in BAG37430 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06911113N → H Polymorphism; no effect on enzyme activity. 2 PublicationsCorresponds to variant dbSNP:rs121918819Ensembl.1
Natural variantiVAR_04599117N → K Functional polymorphism; nearly abolishes enzyme activity. 4 PublicationsCorresponds to variant dbSNP:rs17149149Ensembl.1
Natural variantiVAR_06911261E → Q Functional polymorphism; reduced enzyme activity. 3 PublicationsCorresponds to variant dbSNP:rs121918823Ensembl.1
Natural variantiVAR_06911381K → E Polymorphism; no effect on enzyme activity. 2 PublicationsCorresponds to variant dbSNP:rs117343570Ensembl.1
Natural variantiVAR_069114111R → K Polymorphism; no effect on enzyme activity. 2 Publications1
Natural variantiVAR_069115115R → W1 PublicationCorresponds to variant dbSNP:rs201053197Ensembl.1
Natural variantiVAR_069116151G → S1 PublicationCorresponds to variant dbSNP:rs192710293Ensembl.1
Natural variantiVAR_069117166V → I1 PublicationCorresponds to variant dbSNP:rs373339042Ensembl.1
Natural variantiVAR_069118171V → M Functional polymorphism; nearly abolishes enzyme activity. 2 PublicationsCorresponds to variant dbSNP:rs121918820Ensembl.1
Natural variantiVAR_069119179V → G1 Publication1
Natural variantiVAR_069120210D → G Functional polymorphism; nearly abolishes enzyme activity. 3 PublicationsCorresponds to variant dbSNP:rs121918824Ensembl.1
Natural variantiVAR_069121211I → M1 PublicationCorresponds to variant dbSNP:rs201316181Ensembl.1
Natural variantiVAR_069122217T → M1 PublicationCorresponds to variant dbSNP:rs148036160Ensembl.1
Natural variantiVAR_069123219K → R Polymorphism; no effect on enzyme activity. 3 PublicationsCorresponds to variant dbSNP:rs121918825Ensembl.1
Natural variantiVAR_069124243P → L Functional polymorphism; reduced enzyme activity. 4 PublicationsCorresponds to variant dbSNP:rs121918826Ensembl.1
Natural variantiVAR_069125248Y → H Functional polymorphism; nearly abolishes enzyme activity. 2 Publications1
Natural variantiVAR_069126269I → M Functional polymorphism; reduced enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs146121655Ensembl.1
Natural variantiVAR_069127273C → S Functional polymorphism; reduced enzyme activity. 3 PublicationsCorresponds to variant dbSNP:rs121918827Ensembl.1
Natural variantiVAR_069128278G → A Functional polymorphism; reduced enzyme activity. 2 Publications1
Natural variantiVAR_069129288E → D Polymorphism; no effect on enzyme activity. 4 PublicationsCorresponds to variant dbSNP:rs121918821Ensembl.1
Natural variantiVAR_069130291R → Q Functional polymorphism; nearly abolishes enzyme activity. 3 PublicationsCorresponds to variant dbSNP:rs121918828Ensembl.1
Natural variantiVAR_069131298L → F Functional polymorphism; nearly abolishes enzyme activity. 6 PublicationsCorresponds to variant dbSNP:rs121918822Ensembl.1
Natural variantiVAR_069132305V → M Functional polymorphism; reduced enzyme activity. 2 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004284188G → GTWIKLETIILSKLSQGQKT KHRVFSLIG in isoform 3. 2 Publications1
Alternative sequenceiVSP_004285189 – 235Missing in isoform 2. 1 PublicationAdd BLAST47

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U11098
, U11089, U11093, U11094, U11095, U11096, U11092, U11097 Genomic DNA. Translation: AAA75291.1.
U11098
, U11089, U11093, U11094, U11095, U11096, U11097 Genomic DNA. Translation: AAA75289.1.
U11098
, U11089, U11093, U11094, U11095, U11096, U11092, U11097 Genomic DNA. Translation: AAA75290.1.
U11090 mRNA. Translation: AAA58582.1.
U11091 mRNA. Translation: AAA58583.1.
M83779 mRNA. Translation: AAA17020.1.
AK314922 mRNA. Translation: BAG37430.1.
AL683807 Genomic DNA. No translation available.
BC001620 mRNA. Translation: AAH01620.1.
CCDSiCCDS14117.1. [P46597-3]
CCDS55364.1. [P46597-2]
PIRiI37463.
RefSeqiNP_001164509.1. NM_001171038.1. [P46597-3]
NP_001164510.1. NM_001171039.1. [P46597-2]
NP_004034.2. NM_004043.2. [P46597-3]
UniGeneiHs.522572.

Genome annotation databases

EnsembliENST00000381229; ENSP00000370627; ENSG00000196433. [P46597-1]
ENST00000381233; ENSP00000370631; ENSG00000196433. [P46597-2]
ENST00000381241; ENSP00000370639; ENSG00000196433. [P46597-3]
GeneIDi438.
KEGGihsa:438.
UCSCiuc010ncy.4. human. [P46597-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiASMT_HUMAN
AccessioniPrimary (citable) accession number: P46597
Secondary accession number(s): B2RC33
, Q16598, Q5JQ72, Q5JQ73
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: September 27, 2017
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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families