Q9HBK9 (AS3MT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Arsenite methyltransferase
EC=2.1.1.137

Alternative name(s):
Methylarsonite methyltransferase
S-adenosyl-L-methionine:arsenic(III) methyltransferase

Gene names

Name:	AS3MT
Synonyms:	CYT19

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	375 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the transfer of a methyl group from AdoMet to trivalent arsenicals producing methylated and dimethylated arsenicals. It methylates arsenite to form methylarsonate, Me-AsO3H2, which is reduced by methylarsonate reductase to methylarsonite, Me-As(OH)2. Methylarsonite is also a substrate and it is converted into the much less toxic compound dimethylarsinate (cacodylate), Me2As(O)-OH By similarity.
Catalytic activity	S-adenosyl-L-methionine + arsenite = S-adenosyl-L-homocysteine + methylarsonate. S-adenosyl-L-methionine + methylarsonite = S-adenosyl-L-homocysteine + dimethylarsinate.
Subcellular location	Cytoplasm By similarity.
Sequence similarities	Belongs to the methyltransferase superfamily.
Biophysicochemical properties	Kinetic parameters: KM=4.6 µM for sodium arsenite Ref.1 KM=11.8 µM for AdoMet
Sequence caution	The sequence AAG09731.1 differs from that shown. Reason: Frameshift at position 333.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	arsonoacetate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB toxin metabolic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	arsenite methyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB methylarsonite methyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 375	375	Arsenite methyltransferase		PRO_0000204447
Natural variations
	Natural variant	173	1	R → W Rare polymorphism; frequency in African-Americans 0.008; not detected in Caucasian-Americans; enzyme activity is 31% of wild-type. Ref.1 Corresponds to variant rs35232887 [ dbSNP | Ensembl ].		VAR_027392
	Natural variant	287	1	M → T Common polymorphism; frequency in African-Americans 0.108 and Caucasian-Americans 0.100; enzyme activity is 350% of wild-type. Ref.1 Ref.7 Corresponds to variant rs11191439 [ dbSNP | Ensembl ].		VAR_027393
	Natural variant	306	1	T → I Rare polymorphism; frequency in Caucasian-Americans 0.008; not detected in African-Americans. Ref.1 Corresponds to variant rs34556438 [ dbSNP | Ensembl ].		VAR_027394
Experimental info
	Sequence conflict	132	1	I → F in AAG09731. Ref.2
	Sequence conflict	135	1	Y → N in AAG09731. Ref.2
	Sequence conflict	140	1	G → A in AAG09731. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9HBK9 [UniParc]. Last modified October 14, 2008. Version 3. Checksum: 2E0C758A8597AE33	FASTA	375	41,748
	10 20 30 40 50 60 MAALRDAEIQ KDVQTYYGQV LKRSADLQTN GCVTTARPVP KHIREALQNV HEEVALRYYG 70 80 90 100 110 120 CGLVIPEHLE NCWILDLGSG SGRDCYVLSQ LVGEKGHVTG IDMTKGQVEV AEKYLDYHME 130 140 150 160 170 180 KYGFQASNVT FIHGYIEKLG EAGIKNESHD IVVSNCVINL VPDKQQVLQE AYRVLKHGGE 190 200 210 220 230 240 LYFSDVYTSL ELPEEIRTHK VLWGECLGGA LYWKELAVLA QKIGFCPPRL VTANLITIQN 250 260 270 280 290 300 KELERVIGDC RFVSATFRLF KHSKTGPTKR CQVIYNGGIT GHEKELMFDA NFTFKEGEIV 310 320 330 340 350 360 EVDEETAAIL KNSRFAQDFL IRPIGEKLPT SGGCSALELK DIITDPFKLA EESDSMKSRC 370 VPDAAGGCCG TKKSC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human arsenic methyltransferase (AS3MT) pharmacogenetics: gene resequencing and functional genomics studies." Wood T.C., Salavagionne O.E., Mukherjee B., Wang L., Klumpp A.F., Thomae B.A., Eckloff B.W., Schaid D.J., Wieben E.D., Weinshilboum R.M. J. Biol. Chem. 281:7364-7373(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], BIOPHYSICOCHEMICAL PROPERTIES, VARIANTS TRP-173; THR-287 AND ILE-306.
[2]	Xiao H., Song H., Gao G., Ren S., Chen Z., Han Z. Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Adrenal tumor.
[3]	Yu L., Kalla K., Guthrie E., Vidrine A., Klimecki W.T. Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"High arsenic metabolic efficiency in AS3MT287Thr allele carriers." Hernandez A., Xamena N., Sekaran C., Tokunaga H., Sampayo-Reyes A., Quinteros D., Creus A., Marcos R. Pharmacogenet. Genomics 18:349-355(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT THR-287.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF226730 mRNA. Translation: AAG09731.1. Frameshift. AY817668 Genomic DNA. Translation: AAV68045.1. AL358790 Genomic DNA. Translation: CAI52503.1. CH471066 Genomic DNA. Translation: EAW49668.1.
IPI	IPI00307524.
RefSeq	NP_065733.2. NM_020682.3.
UniGene	Hs.720370.
3D structure databases
ProteinModelPortal	Q9HBK9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9HBK9. 2 interactions.
STRING	9606.ENSP00000358896.
PTM databases
PhosphoSite	Q9HBK9.
Polymorphism databases
DMDM	209572762.
Proteomic databases
PaxDb	Q9HBK9.
PRIDE	Q9HBK9.
Protocols and materials databases
DNASU	57412.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000369880; ENSP00000358896; ENSG00000214435.
GeneID	57412.
KEGG	hsa:57412.
UCSC	uc001kwj.3. human.
Organism-specific databases
CTD	57412.
GeneCards	GC10P104624.
HGNC	HGNC:17452. AS3MT.
HPA	HPA017856. HPA027708.
MIM	611806. gene.
neXtProt	NX_Q9HBK9.
PharmGKB	PA134896392.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG257055.
HOGENOM	HOG000229966.
HOVERGEN	HBG050585.
InParanoid	Q9HBK9.
KO	K07755.
OMA	ARYYGCG.
OrthoDB	EOG415GDK.
Enzyme and pathway databases
BioCyc	MetaCyc:HS01822-MONOMER.
BRENDA	2.1.1.137. 2681.
SABIO-RK	Q9HBK9.
Gene expression databases
Bgee	Q9HBK9.
CleanEx	HS_AS3MT.
Genevestigator	Q9HBK9.
GermOnline	ENSG00000166275. Homo sapiens.
Family and domain databases
InterPro	IPR026669. Arsenite_MeTrfase. IPR025714. Methyltranfer_dom. [Graphical view]
PANTHER	PTHR10108:SF11. PTHR10108:SF11. 1 hit.
Pfam	PF13847. Methyltransf_31. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	57412.
NextBio	63542.
SOURCE	Search...

Entry information

Entry name

AS3MT_HUMAN

Accession

Primary (citable) accession number: Q9HBK9
Secondary accession number(s): A6NP79, Q5PZ02

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 4, 2005
Last sequence update:	October 14, 2008
Last modified:	May 1, 2013
This is version 92 of the entry and version 3 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.