P46597 (ASMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Acetylserotonin O-methyltransferase
EC=2.1.1.4

Alternative name(s):
Hydroxyindole O-methyltransferase
Short name=HIOMT

Gene names

Name:

ASMT

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	345 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.9
Catalytic activity	S-adenosyl-L-methionine + N-acetylserotonin = S-adenosyl-L-homocysteine + melatonin. Ref.9
Pathway	Aromatic compound metabolism; melatonin biosynthesis; melatonin from serotonin: step 1/2.
Subunit structure	Homodimer. Ref.9
Tissue specificity	Expressed in the pineal gland (at protein level). In the retina, very low expression is found at the mRNA level (Ref.1), and not at the protein level (Ref.6). Ref.1 Ref.6 Ref.9
Induction	By all-trans-, 9-cis- and 13-cis-retinoic acid and by serum treatment, following starvation, in the retinoblastoma cell line Y79. Ref.7 Ref.8
Miscellaneous	The gene coding for this protein is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes.
Sequence similarities	Belongs to the methyltransferase superfamily.

Ontologies

Keywords
Biological process	Melatonin biosynthesis
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	indolalkylamine biosynthetic process Traceable author statement. Source: Reactome melatonin biosynthetic process Inferred from direct assay Ref.9. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome translation Traceable author statement Ref.2. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	acetylserotonin O-methyltransferase activity Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-6502097,EBI-6502097

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P46597-1)

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.

Isoform 2 (identifier: P46597-2)

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

Isoform 3 (identifier: P46597-3)

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

Note: Includes part of a LINE-1 element.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 345

345

Acetylserotonin O-methyltransferase

PRO_0000083982

Regions

Region

235 – 237

3

S-adenosyl-L-methionine binding

Sites

Active site

255

1

Proton donor/acceptor Probable

Binding site

147

1

S-adenosyl-L-methionine

Binding site

164

1

S-adenosyl-L-methionine

Binding site

210

1

S-adenosyl-L-methionine

Binding site

252

1

S-adenosyl-L-methionine

Binding site

256

1

Substrate

Binding site

302

1

Substrate

Binding site

306

1

Substrate

Natural variations

Alternative sequence

188

1

G → GTWIKLETIILSKLSQGQKT KHRVFSLIG in isoform 3.

VSP_004284

Alternative sequence

189 – 235

47

Missing in isoform 2.

VSP_004285

Natural variant

13

1

N → H Polymorphism with no effect on enzyme activity. Ref.9 Ref.12
Corresponds to variant rs121918819 [ dbSNP | Ensembl ].

VAR_069111

Natural variant

17

1

N → K Functional polymorphism that nearly abolishes enzyme activity. Ref.9 Ref.11 Ref.12 Ref.15
Corresponds to variant rs17149149 [ dbSNP | Ensembl ].

VAR_045991

Natural variant

61

1

E → Q Functional polymorphism with reduced enzyme activity. Ref.9 Ref.12 Ref.14
Corresponds to variant rs121918823 [ dbSNP | Ensembl ].

VAR_069112

Natural variant

81

1

K → E Polymorphism with no effect on enzyme activity. Ref.9 Ref.11
Corresponds to variant rs117343570 [ dbSNP | Ensembl ].

VAR_069113

Natural variant

111

1

R → K Polymorphism with no effect on enzyme activity. Ref.9 Ref.14

VAR_069114

Natural variant

115

1

R → W. Ref.15
Corresponds to variant rs201053197 [ dbSNP | Ensembl ].

VAR_069115

Natural variant

151

1

G → S. Ref.15
Corresponds to variant rs192710293 [ dbSNP | Ensembl ].

VAR_069116

Natural variant

166

1

V → I. Ref.15

VAR_069117

Natural variant

171

1

V → M Functional polymorphism that nearly abolishes enzyme activity. Ref.9 Ref.12
Corresponds to variant rs121918820 [ dbSNP | Ensembl ].

VAR_069118

Natural variant

179

1

V → G. Ref.15

VAR_069119

Natural variant

210

1

D → G Functional polymorphism that nearly abolishes enzyme activity. Ref.9 Ref.12 Ref.13
Corresponds to variant rs121918824 [ dbSNP | Ensembl ].

VAR_069120

Natural variant

211

1

I → M. Ref.15
Corresponds to variant rs201316181 [ dbSNP | Ensembl ].

VAR_069121

Natural variant

217

1

T → M. Ref.15
Corresponds to variant rs148036160 [ dbSNP | Ensembl ].

VAR_069122

Natural variant

219

1

K → R Polymorphism with no effect on enzyme activity. Ref.9 Ref.12 Ref.14
Corresponds to variant rs121918825 [ dbSNP | Ensembl ].

VAR_069123

Natural variant

243

1

P → L Functional polymorphism with reduced enzyme activity. Ref.9 Ref.12 Ref.14 Ref.15
Corresponds to variant rs121918826 [ dbSNP | Ensembl ].

VAR_069124

Natural variant

248

1

Y → H Functional polymorphism that nearly abolishes enzyme activity. Ref.9 Ref.14

VAR_069125

Natural variant

269

1

I → M Functional polymorphism with reduced enzyme activity. Ref.9
Corresponds to variant rs146121655 [ dbSNP | Ensembl ].

VAR_069126

Natural variant

273

1

C → S Functional polymorphism with reduced enzyme activity. Ref.9 Ref.12 Ref.14
Corresponds to variant rs121918827 [ dbSNP | Ensembl ].

VAR_069127

Natural variant

278

1

G → A Functional polymorphism with reduced enzyme activity. Ref.9 Ref.11

VAR_069128

Natural variant

288

1

E → D Polymorphism with no effect on enzyme activity. Ref.9 Ref.10 Ref.12 Ref.14
Corresponds to variant rs121918821 [ dbSNP | Ensembl ].

VAR_069129

Natural variant

291

1

R → Q Functional polymorphism that nearly abolishes enzyme activity. Ref.9 Ref.12 Ref.14

VAR_069130

Natural variant

298

1

L → F Functional polymorphism that nearly abolishes enzyme activity. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
Corresponds to variant rs121918822 [ dbSNP | Ensembl ].

VAR_069131

Natural variant

305

1

V → M Functional polymorphism with reduced enzyme activity. Ref.9 Ref.14

VAR_069132

Experimental info

Mutagenesis

11

1

L → F: Reduced enzyme activity. Ref.9

Mutagenesis

31

1

L → H: No effect on enzyme activity.

Mutagenesis

296

1

T → M: Nearly abolishes enzyme activity. Ref.9

Mutagenesis

318

1

H → D: Reduced enzyme activity. Ref.9

Sequence conflict

302

1

N → S in BAG37430. Ref.3

Isoform 3:

Sequence conflict

190

1

W → R in AAA58582. Ref.1

Sequence conflict

190

1

W → R in AAA58583. Ref.1

Sequence conflict

190

1

W → R in AAA75290. Ref.1

Sequence conflict

190

1

W → R in AAA17020. Ref.2

Sequence conflict

190

1

W → R in BAG37430. Ref.3

Secondary structure

1

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345

Helix Strand Turn

Details...

Helix

7 – 31

25

Helix

33 – 39

7

Beta strand

40 – 42

3

Helix

46 – 53

8

Helix

57 – 69

13

Beta strand

72 – 78

7

Beta strand

81 – 86

6

Helix

88 – 94

7

Helix

103 – 111

9

Helix

113 – 117

5

Helix

120 – 126

7

Helix

131 – 135

5

Helix

142 – 146

5

Helix

150 – 161

12

Helix

164 – 173

10

Helix

177 – 179

3

Beta strand

181 – 186

6

Helix

192 – 200

9

Beta strand

205 – 210

6

Helix

212 – 221

10

Beta strand

229 – 235

7

Turn

237 – 239

3

Beta strand

246 – 253

8

Helix

254 – 256

3

Helix

259 – 272

14

Beta strand

278 – 283

6

Helix

294 – 305

12

Beta strand

306 – 308

3

Helix

314 – 324

11

Beta strand

327 – 332

6

Beta strand

335 – 337

3

Beta strand

339 – 344

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 187A375E1E2940B7	FASTA	345	38,453
	10 20 30 40 50 60 MGSSEDQAYR LLNDYANGFM VSQVLFAACE LGVFDLLAEA PGPLDVAAVA AGVRASAHGT 70 80 90 100 110 120 ELLLDICVSL KLLKVETRGG KAFYRNTELS SDYLTTVSPT SQCSMLKYMG RTSYRCWGHL 130 140 150 160 170 180 ADAVREGRNQ YLETFGVPAE ELFTAIYRSE GERLQFMQAL QEVWSVNGRS VLTAFDLSVF 190 200 210 220 230 240 PLMCDLGGGA GALAKECMSL YPGCKITVFD IPEVVWTAKQ HFSFQEEEQI DFQEGDFFKD 250 260 270 280 290 300 PLPEADLYIL ARVLHDWADG KCSHLLERIY HTCKPGGGIL VIESLLDEDR RGPLLTQLYS 310 320 330 340 LNMLVQTEGQ ERTPTHYHML LSSAGFRDFQ FKKTGAIYDA ILARK
	Isoform 2 [UniParc]. Checksum: AAFC60D1F8D70E5A	FASTA	298	33,192
	10 20 30 40 50 60 MGSSEDQAYR LLNDYANGFM VSQVLFAACE LGVFDLLAEA PGPLDVAAVA AGVRASAHGT 70 80 90 100 110 120 ELLLDICVSL KLLKVETRGG KAFYRNTELS SDYLTTVSPT SQCSMLKYMG RTSYRCWGHL 130 140 150 160 170 180 ADAVREGRNQ YLETFGVPAE ELFTAIYRSE GERLQFMQAL QEVWSVNGRS VLTAFDLSVF 190 200 210 220 230 240 PLMCDLGGDF FKDPLPEADL YILARVLHDW ADGKCSHLLE RIYHTCKPGG GILVIESLLD 250 260 270 280 290 EDRRGPLLTQ LYSLNMLVQT EGQERTPTHY HMLLSSAGFR DFQFKKTGAI YDAILARK
	Isoform 3 [UniParc]. Checksum: 8CA134BD0BA50FDD	FASTA	373	41,661
	10 20 30 40 50 60 MGSSEDQAYR LLNDYANGFM VSQVLFAACE LGVFDLLAEA PGPLDVAAVA AGVRASAHGT 70 80 90 100 110 120 ELLLDICVSL KLLKVETRGG KAFYRNTELS SDYLTTVSPT SQCSMLKYMG RTSYRCWGHL 130 140 150 160 170 180 ADAVREGRNQ YLETFGVPAE ELFTAIYRSE GERLQFMQAL QEVWSVNGRS VLTAFDLSVF 190 200 210 220 230 240 PLMCDLGGTW IKLETIILSK LSQGQKTKHR VFSLIGGAGA LAKECMSLYP GCKITVFDIP 250 260 270 280 290 300 EVVWTAKQHF SFQEEEQIDF QEGDFFKDPL PEADLYILAR VLHDWADGKC SHLLERIYHT 310 320 330 340 350 360 CKPGGGILVI ESLLDEDRRG PLLTQLYSLN MLVQTEGQER TPTHYHMLLS SAGFRDFQFK 370 KTGAIYDAIL ARK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structural analysis of the human hydroxyindole-O-methyltransferase gene. Presence of two distinct promoters." Rodriguez I.R., Mazuruk K., Schoen T.J., Chader G.J. J. Biol. Chem. 269:31969-31977(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY.
[2]	"Human hydroxyindole-O-methyltransferase: presence of LINE-1 fragment in a cDNA clone and pineal mRNA." Donohue S.J., Roseboom P.H., Illnerova H., Weller J.L., Klein D.C. DNA Cell Biol. 12:715-727(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Pineal gland.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Subthalamic nucleus.
[4]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Eye.
[6]	"Human hydroxyindole-O-methyltransferase in pineal gland, retina and Y79 retinoblastoma cells." Bernard M., Donohue S.J., Klein D.C. Brain Res. 696:37-48(1995) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Hydroxyindole-O-methyltransferase in Y-79 cells: regulation by serum." Bernard M., Voisin P., Klein D.C. Brain Res. 727:118-124(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY SERUM TREATMENT.
[8]	"Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in human Y-79 retinoblastoma cells." Bernard M., Klein D.C. J. Neurochem. 67:1032-1038(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY RETINOIC ACID.
[9]	"Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway." Botros H.G., Legrand P., Pagan C., Bondet V., Weber P., Ben-Abdallah M., Lemiere N., Huguet G., Bellalou J., Maronde E., Beguin P., Haouz A., Shepard W., Bourgeron T. J. Pineal Res. 0:0-0(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEXES WITH S-ADENOSYL-L-METHIONINE; N-ACETYL SEROTONIN AND ZINC IONS, CATALYTIC ACTIVITY, FUNCTION, ACTIVE SITE, CHARACTERIZATION OF ISOFORMS 1; 2 AND 3, SUBUNIT, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANTS HIS-13; LYS-17; GLN-61; GLU-81; LYS-111; MET-171; GLY-210; ARG-219; LEU-243; HIS-248; MET-269; SER-273; ALA-278; ASP-288; GLN-291; PHE-298 AND MET-305, MUTAGENESIS OF LEU-11; THR-296 AND HIS-318.
[10]	"Is ASMT a susceptibility gene for autism spectrum disorders? A replication study in European populations." Toma C., Rossi M., Sousa I., Blasi F., Bacchelli E., Alen R., Vanhala R., Monaco A.P., Jarvela I., Maestrini E. Mol. Psychiatry 12:977-979(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ASP-288 AND PHE-298.
[11]	"Abnormal melatonin synthesis in autism spectrum disorders." Melke J., Goubran Botros H., Chaste P., Betancur C., Nygren G., Anckarsater H., Rastam M., Stahlberg O., Gillberg I.C., Delorme R., Chabane N., Mouren-Simeoni M.C., Fauchereau F., Durand C.M., Chevalier F., Drouot X., Collet C., Launay J.M. , Leboyer M., Gillberg C., Bourgeron T. Mol. Psychiatry 13:90-98(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LYS-17; GLU-81; ALA-278 AND PHE-298.
[12]	"Mutation screening of ASMT, the last enzyme of the melatonin pathway, in a large sample of patients with intellectual disability." Pagan C., Botros H.G., Poirier K., Dumaine A., Jamain S., Moreno S., de Brouwer A., Van Esch H., Delorme R., Launay J.M., Tzschach A., Kalscheuer V., Lacombe D., Briault S., Laumonnier F., Raynaud M., van Bon B.W., Willemsen M.H. , Leboyer M., Chelly J., Bourgeron T. BMC Med. Genet. 12:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HIS-13; LYS-17; GLN-61; MET-171; GLY-210; ARG-219; LEU-243; SER-273; ASP-288; GLN-291 AND PHE-298.
[13]	"Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders." Chaste P., Clement N., Botros H.G., Guillaume J.L., Konyukh M., Pagan C., Scheid I., Nygren G., Anckarsater H., Rastam M., Stahlberg O., Gillberg I.C., Melke J., Delorme R., Leblond C., Toro R., Huguet G., Fauchereau F. , Durand C., Boudarene L., Serrano E., Lemiere N., Launay J.M., Leboyer M., Jockers R., Gillberg C., Bourgeron T. J. Pineal Res. 51:394-399(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GLY-210 AND PHE-298.
[14]	"Genetic and functional abnormalities of the melatonin biosynthesis pathway in patients with bipolar disorder." Etain B., Dumaine A., Bellivier F., Pagan C., Francelle L., Goubran-Botros H., Moreno S., Deshommes J., Moustafa K., Le Dudal K., Mathieu F., Henry C., Kahn J.P., Launay J.M., Muhleisen T.W., Cichon S., Bourgeron T., Leboyer M., Jamain S. Hum. Mol. Genet. 21:4030-4037(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GLN-61; LYS-111; ARG-219; LEU-243; HIS-248; SER-273; ASP-288; GLN-291; PHE-298 AND MET-305.
[15]	"Sequencing ASMT identifies rare mutations in Chinese Han patients with autism." Wang L., Li J., Ruan Y., Lu T., Liu C., Jia M., Yue W., Liu J., Bourgeron T., Zhang D. PLoS ONE 8:E53727-E53727(2013) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LYS-17; TRP-115; SER-151; ILE-166; GLY-179; MET-211; MET-217 AND LEU-243.
+	Additional computationally mapped references.

Web resources

Wikipedia

5-hydroxyindole-O-methyltransferase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00007218.
IPI00219431.
IPI00219432.

PIR

I37463.

RefSeq

NP_001164509.1. NM_001171038.1.
NP_001164510.1. NM_001171039.1.
NP_004034.2. NM_004043.2.

UniGene

Hs.522572.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4A6D	X-ray	2.40	A	1-345	[»]
4A6E	X-ray	2.70	A	1-345	[»]

ProteinModelPortal

P46597.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000370639.

Polymorphism databases

DMDM

1170276.

Proteomic databases

PaxDb

P46597.

PRIDE

P46597.

Protocols and materials databases

DNASU

438.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000381229; ENSP00000370627; ENSG00000196433.
ENST00000381233; ENSP00000370631; ENSG00000196433.
ENST00000381241; ENSP00000370639; ENSG00000196433.

GeneID

438.

KEGG

hsa:438.

UCSC

uc004cqd.3. human.
uc004cqe.3. human.

Organism-specific databases

CTD

438.

GeneCards

GC0XP001674.

HGNC

HGNC:750. ASMT.

MIM

300015. gene.
402500. gene.

neXtProt

NX_P46597.

PharmGKB

PA25049.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0500.

HOGENOM

HOG000247024.

HOVERGEN

HBG001526.

KO

K00543.

OMA

AIVISEL.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00837; UER00815.

Gene expression databases

Bgee

P46597.

Genevestigator

P46597.

GermOnline

ENSG00000196433. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.10. 1 hit.

InterPro

IPR025781. AS_MeTrfase.
IPR016461. COMT.
IPR001077. O_MeTrfase_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

Pfam

PF00891. Methyltransf_2. 1 hit.
[Graphical view]

PIRSF

PIRSF005739. O-mtase. 1 hit.

ProtoNet

Search...

Other

GenomeRNAi

438.

NextBio

1835.

SOURCE

Search...

Entry information

Entry name

ASMT_HUMAN

Accession

Primary (citable) accession number: P46597
Secondary accession number(s): B2RC33 , Q16598, Q5JQ72, Q5JQ73

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 29, 2013
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.