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Protein

Arsenite methyltransferase

Gene

AS3MT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

S-adenosyl-L-methionine + arsenite = S-adenosyl-L-homocysteine + methylarsonate.
S-adenosyl-L-methionine + methylarsonite = S-adenosyl-L-homocysteine + dimethylarsinate.

Kineticsi

  1. KM=4.6 µM for sodium arsenite1 Publication
  2. KM=11.8 µM for AdoMet1 Publication

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Methyltransferase, Transferase

    Keywords - Ligandi

    S-adenosyl-L-methionine

    Enzyme and pathway databases

    BioCyciMetaCyc:HS01822-MONOMER.
    BRENDAi2.1.1.137. 2681.
    SABIO-RKQ9HBK9.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Arsenite methyltransferase (EC:2.1.1.137)
    Alternative name(s):
    Methylarsonite methyltransferase
    S-adenosyl-L-methionine:arsenic(III) methyltransferase
    Gene namesi
    Name:AS3MT
    Synonyms:CYT19
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:17452. AS3MT.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134896392.

    Polymorphism and mutation databases

    BioMutaiAS3MT.
    DMDMi209572762.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 375375Arsenite methyltransferasePRO_0000204447Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei335 – 3351Phosphoserine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9HBK9.
    PaxDbiQ9HBK9.
    PRIDEiQ9HBK9.

    PTM databases

    PhosphoSiteiQ9HBK9.

    Expressioni

    Gene expression databases

    BgeeiQ9HBK9.
    CleanExiHS_AS3MT.
    ExpressionAtlasiQ9HBK9. baseline.
    GenevisibleiQ9HBK9. HS.

    Organism-specific databases

    HPAiHPA017856.
    HPA027708.

    Interactioni

    Protein-protein interaction databases

    IntActiQ9HBK9. 2 interactions.
    STRINGi9606.ENSP00000358896.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9HBK9.
    SMRiQ9HBK9. Positions 39-321.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the methyltransferase superfamily.Curated

    Phylogenomic databases

    eggNOGiNOG257055.
    GeneTreeiENSGT00390000001742.
    HOGENOMiHOG000229966.
    HOVERGENiHBG050585.
    InParanoidiQ9HBK9.
    KOiK07755.
    OMAiARYYGCG.
    OrthoDBiEOG7V49ZQ.
    PhylomeDBiQ9HBK9.
    TreeFamiTF343797.

    Family and domain databases

    Gene3Di3.40.50.150. 1 hit.
    InterProiIPR026669. Arsenite_MeTrfase.
    IPR025714. Methyltranfer_dom.
    IPR029063. SAM-dependent_MTases.
    [Graphical view]
    PANTHERiPTHR10108:SF11. PTHR10108:SF11. 1 hit.
    PfamiPF13847. Methyltransf_31. 1 hit.
    [Graphical view]
    SUPFAMiSSF53335. SSF53335. 2 hits.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Note: An isoform missing exon 3 is produced with a premature stop codon at AA 23 and is targeted to nonsense-mediated mRNA decay (NMD).

    Isoform 1 (identifier: Q9HBK9-1) [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
    MAALRDAEIQ KDVQTYYGQV LKRSADLQTN GCVTTARPVP KHIREALQNV
    60 70 80 90 100
    HEEVALRYYG CGLVIPEHLE NCWILDLGSG SGRDCYVLSQ LVGEKGHVTG
    110 120 130 140 150
    IDMTKGQVEV AEKYLDYHME KYGFQASNVT FIHGYIEKLG EAGIKNESHD
    160 170 180 190 200
    IVVSNCVINL VPDKQQVLQE AYRVLKHGGE LYFSDVYTSL ELPEEIRTHK
    210 220 230 240 250
    VLWGECLGGA LYWKELAVLA QKIGFCPPRL VTANLITIQN KELERVIGDC
    260 270 280 290 300
    RFVSATFRLF KHSKTGPTKR CQVIYNGGIT GHEKELMFDA NFTFKEGEIV
    310 320 330 340 350
    EVDEETAAIL KNSRFAQDFL IRPIGEKLPT SGGCSALELK DIITDPFKLA
    360 370
    EESDSMKSRC VPDAAGGCCG TKKSC
    Length:375
    Mass (Da):41,748
    Last modified:October 14, 2008 - v3
    Checksum:i2E0C758A8597AE33
    GO
    Isoform 2 (identifier: Q9HBK9-2) [UniParc]FASTAAdd to basket

    Also known as: 31.1 kDa, delta4,5

    The sequence of this isoform differs from the canonical sequence as follows:
         58-153: Missing.

    Note: Devoid of methyltransferase activity.
    Show »
    Length:279
    Mass (Da):31,098
    Checksum:i50160483AE264D85
    GO

    Sequence cautioni

    The sequence AAG09731.1 differs from that shown. Reason: Frameshift at position 333. Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti125 – 1251Q → R in AAI19638 (PubMed:15489334).Curated
    Sequence conflicti132 – 1321I → F in AAG09731 (Ref. 2) Curated
    Sequence conflicti135 – 1351Y → N in AAG09731 (Ref. 2) Curated
    Sequence conflicti140 – 1401G → A in AAG09731 (Ref. 2) Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti173 – 1731R → W Rare polymorphism; frequency in African-Americans 0.008; not detected in Caucasian-Americans; enzyme activity is 31% of wild-type. 1 Publication
    Corresponds to variant rs35232887 [ dbSNP | Ensembl ].
    VAR_027392
    Natural varianti287 – 2871M → T Common polymorphism; frequency in African-Americans 0.108 and Caucasian-Americans 0.100; enzyme activity is 350% of wild-type. 2 Publications
    Corresponds to variant rs11191439 [ dbSNP | Ensembl ].
    VAR_027393
    Natural varianti306 – 3061T → I Rare polymorphism; frequency in Caucasian-Americans 0.008; not detected in African-Americans. 1 Publication
    Corresponds to variant rs34556438 [ dbSNP | Ensembl ].
    VAR_027394

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei58 – 15396Missing in isoform 2. CuratedVSP_053494Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF226730 mRNA. Translation: AAG09731.1. Frameshift.
    AY817668 Genomic DNA. Translation: AAV68045.1.
    AL358790 Genomic DNA. Translation: CAI52503.1.
    CH471066 Genomic DNA. Translation: EAW49668.1.
    BC119637 mRNA. Translation: AAI19638.1.
    BC119638 mRNA. Translation: AAI19639.2.
    CCDSiCCDS41567.1. [Q9HBK9-1]
    RefSeqiNP_065733.2. NM_020682.3. [Q9HBK9-1]
    UniGeneiHs.720370.

    Genome annotation databases

    EnsembliENST00000369880; ENSP00000358896; ENSG00000214435.
    GeneIDi57412.
    KEGGihsa:57412.
    UCSCiuc001kwj.3. human. [Q9HBK9-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF226730 mRNA. Translation: AAG09731.1. Frameshift.
    AY817668 Genomic DNA. Translation: AAV68045.1.
    AL358790 Genomic DNA. Translation: CAI52503.1.
    CH471066 Genomic DNA. Translation: EAW49668.1.
    BC119637 mRNA. Translation: AAI19638.1.
    BC119638 mRNA. Translation: AAI19639.2.
    CCDSiCCDS41567.1. [Q9HBK9-1]
    RefSeqiNP_065733.2. NM_020682.3. [Q9HBK9-1]
    UniGeneiHs.720370.

    3D structure databases

    ProteinModelPortaliQ9HBK9.
    SMRiQ9HBK9. Positions 39-321.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiQ9HBK9. 2 interactions.
    STRINGi9606.ENSP00000358896.

    PTM databases

    PhosphoSiteiQ9HBK9.

    Polymorphism and mutation databases

    BioMutaiAS3MT.
    DMDMi209572762.

    Proteomic databases

    MaxQBiQ9HBK9.
    PaxDbiQ9HBK9.
    PRIDEiQ9HBK9.

    Protocols and materials databases

    DNASUi57412.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000369880; ENSP00000358896; ENSG00000214435.
    GeneIDi57412.
    KEGGihsa:57412.
    UCSCiuc001kwj.3. human. [Q9HBK9-1]

    Organism-specific databases

    CTDi57412.
    GeneCardsiGC10P104629.
    HGNCiHGNC:17452. AS3MT.
    HPAiHPA017856.
    HPA027708.
    MIMi611806. gene.
    neXtProtiNX_Q9HBK9.
    PharmGKBiPA134896392.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiNOG257055.
    GeneTreeiENSGT00390000001742.
    HOGENOMiHOG000229966.
    HOVERGENiHBG050585.
    InParanoidiQ9HBK9.
    KOiK07755.
    OMAiARYYGCG.
    OrthoDBiEOG7V49ZQ.
    PhylomeDBiQ9HBK9.
    TreeFamiTF343797.

    Enzyme and pathway databases

    BioCyciMetaCyc:HS01822-MONOMER.
    BRENDAi2.1.1.137. 2681.
    SABIO-RKQ9HBK9.

    Miscellaneous databases

    GeneWikiiAS3MT.
    GenomeRNAii57412.
    NextBioi63542.
    PROiQ9HBK9.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ9HBK9.
    CleanExiHS_AS3MT.
    ExpressionAtlasiQ9HBK9. baseline.
    GenevisibleiQ9HBK9. HS.

    Family and domain databases

    Gene3Di3.40.50.150. 1 hit.
    InterProiIPR026669. Arsenite_MeTrfase.
    IPR025714. Methyltranfer_dom.
    IPR029063. SAM-dependent_MTases.
    [Graphical view]
    PANTHERiPTHR10108:SF11. PTHR10108:SF11. 1 hit.
    PfamiPF13847. Methyltransf_31. 1 hit.
    [Graphical view]
    SUPFAMiSSF53335. SSF53335. 2 hits.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    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] (ISOFORM 1), 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] (ISOFORM 1).
      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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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] OF 1-367 (ISOFORM 1).
    7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    8. "Alternative splicing variants of human arsenic (+3 oxidation state) methyltransferase."
      Sumi D., Fukushima K., Miyataka H., Himeno S.
      Biochem. Biophys. Res. Commun. 415:48-53(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE SPLICING.
    9. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-335, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    10. Cited for: VARIANT THR-287.

    Entry informationi

    Entry nameiAS3MT_HUMAN
    AccessioniPrimary (citable) accession number: Q9HBK9
    Secondary accession number(s): A6NP79
    , Q0VDK3, Q0VDK4, Q5PZ02
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 4, 2005
    Last sequence update: October 14, 2008
    Last modified: July 22, 2015
    This is version 113 of the entry and version 3 of the sequence. [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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 10
      Human chromosome 10: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.