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Protein

Arsenite methyltransferase

Gene

AS3MT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

    Keywordsi

    Molecular functionMethyltransferase, Transferase
    LigandS-adenosyl-L-methionine

    Enzyme and pathway databases

    BioCyciMetaCyc:HS01822-MONOMER
    BRENDAi2.1.1.137 2681
    ReactomeiR-HSA-156581 Methylation
    SABIO-RKiQ9HBK9

    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
    Proteomesi
    • UP000005640 Componenti: Chromosome 10

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000214435.7
    HGNCiHGNC:17452 AS3MT
    MIMi611806 gene
    neXtProtiNX_Q9HBK9

    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

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi57412
    OpenTargetsiENSG00000214435
    PharmGKBiPA134896392

    Polymorphism and mutation databases

    BioMutaiAS3MT
    DMDMi209572762

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002044471 – 375Arsenite methyltransferaseAdd BLAST375

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei335PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiQ9HBK9
    MaxQBiQ9HBK9
    PaxDbiQ9HBK9
    PeptideAtlasiQ9HBK9
    PRIDEiQ9HBK9

    PTM databases

    iPTMnetiQ9HBK9
    PhosphoSitePlusiQ9HBK9

    Expressioni

    Gene expression databases

    BgeeiENSG00000214435
    CleanExiHS_AS3MT
    ExpressionAtlasiQ9HBK9 baseline and differential
    GenevisibleiQ9HBK9 HS

    Organism-specific databases

    HPAiHPA017856
    HPA027708

    Interactioni

    Protein-protein interaction databases

    BioGridi121513, 1 interactor
    IntActiQ9HBK9, 2 interactors
    STRINGi9606.ENSP00000358896

    Structurei

    3D structure databases

    ProteinModelPortaliQ9HBK9
    SMRiQ9HBK9
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG410IFW3 Eukaryota
    ENOG410XSKB LUCA
    GeneTreeiENSGT00390000001742
    HOGENOMiHOG000229966
    HOVERGENiHBG050585
    InParanoidiQ9HBK9
    KOiK07755
    OMAiMTEGQVE
    OrthoDBiEOG091G0BA7
    PhylomeDBiQ9HBK9
    TreeFamiTF343797

    Family and domain databases

    InterProiView protein in InterPro
    IPR025714 Methyltranfer_dom
    IPR029063 SAM-dependent_MTases
    PfamiView protein in Pfam
    PF13847 Methyltransf_31, 1 hit
    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 differs from that shown. Reason: Frameshift at position 333.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti125Q → R in AAI19638 (PubMed:15489334).Curated1
    Sequence conflicti132I → F in AAG09731 (Ref. 2) Curated1
    Sequence conflicti135Y → N in AAG09731 (Ref. 2) Curated1
    Sequence conflicti140G → A in AAG09731 (Ref. 2) Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_027392173R → W Rare polymorphism; frequency in African-Americans 0.008; not detected in Caucasian-Americans; enzyme activity is 31% of wild-type. 1 PublicationCorresponds to variant dbSNP:rs35232887Ensembl.1
    Natural variantiVAR_027393287M → T Common polymorphism; frequency in African-Americans 0.108 and Caucasian-Americans 0.100; enzyme activity is 350% of wild-type. 2 PublicationsCorresponds to variant dbSNP:rs11191439Ensembl.1
    Natural variantiVAR_027394306T → I Rare polymorphism; frequency in Caucasian-Americans 0.008; not detected in African-Americans. 1 PublicationCorresponds to variant dbSNP:rs34556438Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_05349458 – 153Missing in isoform 2. CuratedAdd BLAST96

    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 No translation available.
    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 [Q9HBK9-1]
    GeneIDi57412
    KEGGihsa:57412
    UCSCiuc001kwk.4 human [Q9HBK9-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiAS3MT_HUMAN
    AccessioniPrimary (citable) accession number: Q9HBK9
    Secondary accession number(s): A6NP79
    , Q0VDK3, Q0VDK4, Q5PZ02
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 4, 2005
    Last sequence update: October 14, 2008
    Last modified: May 23, 2018
    This is version 133 of the entry and version 3 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

    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

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