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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

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

General annotation (Comments)

Function	Produces melatonin (N-acetyl-5-methoxytryptamine) from N-acetylserotonin.
Catalytic activity	S-adenosyl-L-methionine + N-acetylserotonin = S-adenosyl-L-homocysteine + N-acetyl-5-methoxytryptamine.
Pathway	Aromatic compound metabolism; melatonin biosynthesis; melatonin from serotonin: step 1/2.
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
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 encoding 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	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	melatonin biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW translation Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	acetylserotonin O-methyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

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
	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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 345	345	Acetylserotonin O-methyltransferase		PRO_0000083982
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	17	1	N → K. Corresponds to variant rs17149149 [ dbSNP | Ensembl ].		VAR_045991
Experimental info
	Sequence conflict	302	1	N → S in BAG37430. Ref.3

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: 7989373] [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: 8397829] [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: 14702039] [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: 15772651] [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: 15489334] [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: 8574683] [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: 8842389] [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: 8752109] [Abstract] Cited for: INDUCTION BY RETINOIC ACID.
+	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
ProteinModelPortal	P46597.
SMR	P46597. Positions 3-345.
ModBase	Search...
Protein-protein interaction databases
STRING	P46597.
Polymorphism databases
DMDM	1170276.
Proteomic databases
PRIDE	P46597.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000381229; ENSP00000370627; ENSG00000196433.
GeneID	438.
KEGG	hsa:438.
UCSC	uc004cqd.1. human. uc004cqe.1. 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	prNOG20311.
GeneTree	ENSGT00530000064032.
HOVERGEN	HBG001526.
OMA	LFTAIYR.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P46597.
Bgee	P46597.
Genevestigator	P46597.
GermOnline	ENSG00000196433. Homo sapiens.
Family and domain databases
InterPro	IPR016461. O-MeTrfase_COMT_euk. IPR001077. O_MeTrfase_2. IPR011991. WHTH_trsnscrt_rep_DNA-bd. [Graphical view]
Gene3D	G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
KO	K00543.
Pfam	PF00891. Methyltransf_2. 1 hit. [Graphical view]
PIRSF	PIRSF005739. O-mtase. 1 hit.
ProtoNet	Search...
Other
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:	January 25, 2012
This is version 103 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.