AS3MT_HUMAN
ID AS3MT_HUMAN Reviewed; 375 AA.
AC Q9HBK9; A6NP79; Q0VDK3; Q0VDK4; Q5PZ02;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 3.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Arsenite methyltransferase;
DE EC=2.1.1.137 {ECO:0000269|PubMed:16407288, ECO:0000269|PubMed:25997655};
DE AltName: Full=Methylarsonite methyltransferase;
DE AltName: Full=S-adenosyl-L-methionine:arsenic(III) methyltransferase;
GN Name=AS3MT; Synonyms=CYT19;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND VARIANTS TRP-173; THR-287 AND ILE-306.
RX PubMed=16407288; DOI=10.1074/jbc.m512227200;
RA Wood T.C., Salavagionne O.E., Mukherjee B., Wang L., Klumpp A.F.,
RA Thomae B.A., Eckloff B.W., Schaid D.J., Wieben E.D., Weinshilboum R.M.;
RT "Human arsenic methyltransferase (AS3MT) pharmacogenetics: gene
RT resequencing and functional genomics studies.";
RL J. Biol. Chem. 281:7364-7373(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Adrenal tumor;
RA Xiao H., Song H., Gao G., Ren S., Chen Z., Han Z.;
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Yu L., Kalla K., Guthrie E., Vidrine A., Klimecki W.T.;
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-367 (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP ALTERNATIVE SPLICING.
RX PubMed=22005461; DOI=10.1016/j.bbrc.2011.10.008;
RA Sumi D., Fukushima K., Miyataka H., Himeno S.;
RT "Alternative splicing variants of human arsenic (+3 oxidation state)
RT methyltransferase.";
RL Biochem. Biophys. Res. Commun. 415:48-53(2011).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-335, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=25997655; DOI=10.1093/toxsci/kfv101;
RA Zhang H., Ge Y., He P., Chen X., Carina A., Qiu Y., Aga D.S., Ren X.;
RT "Interactive effects of N6AMT1 and As3MT in arsenic biomethylation.";
RL Toxicol. Sci. 146:354-362(2015).
RN [11]
RP VARIANT THR-287.
RX PubMed=18334919; DOI=10.1097/fpc.0b013e3282f7f46b;
RA Hernandez A., Xamena N., Sekaran C., Tokunaga H., Sampayo-Reyes A.,
RA Quinteros D., Creus A., Marcos R.;
RT "High arsenic metabolic efficiency in AS3MT287Thr allele carriers.";
RL Pharmacogenet. Genomics 18:349-355(2008).
CC -!- FUNCTION: Catalyzes the transfer of a methyl group from AdoMet to
CC trivalent arsenicals producing methylated and dimethylated arsenicals
CC (PubMed:16407288, PubMed:25997655). It methylates arsenite to form
CC methylarsonate, Me-AsO(3)H(2), which is reduced by methylarsonate
CC reductase to methylarsonite, Me-As(OH)2 (PubMed:16407288,
CC PubMed:25997655). Methylarsonite is also a substrate and it is
CC converted into the much less toxic compound dimethylarsinate
CC (cacodylate), Me(2)As(O)-OH (PubMed:16407288, PubMed:25997655).
CC {ECO:0000269|PubMed:16407288, ECO:0000269|PubMed:25997655}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-dithiol + arsenic triglutathione + 2 H2O + S-
CC adenosyl-L-methionine = [thioredoxin]-disulfide + 3 glutathione +
CC H(+) + methylarsonous acid + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:69460, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17826,
CC ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:59789, ChEBI:CHEBI:183640;
CC EC=2.1.1.137; Evidence={ECO:0000269|PubMed:16407288,
CC ECO:0000269|PubMed:25997655};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 [thioredoxin]-dithiol + arsenic triglutathione + H2O + 2 S-
CC adenosyl-L-methionine = 2 [thioredoxin]-disulfide + dimethylarsinous
CC acid + 3 glutathione + 2 H(+) + 2 S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:69464, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:23808,
CC ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:59789, ChEBI:CHEBI:183640;
CC EC=2.1.1.137; Evidence={ECO:0000269|PubMed:16407288,
CC ECO:0000269|PubMed:25997655};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 [thioredoxin]-dithiol + arsenic triglutathione + 3 S-
CC adenosyl-L-methionine = 3 [thioredoxin]-disulfide + 3 glutathione + 3
CC H(+) + 3 S-adenosyl-L-homocysteine + trimethylarsine;
CC Xref=Rhea:RHEA:69432, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:27130, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:50058, ChEBI:CHEBI:57856, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:183640; EC=2.1.1.137;
CC Evidence={ECO:0000269|PubMed:16407288, ECO:0000269|PubMed:25997655};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.6 uM for sodium arsenite {ECO:0000269|PubMed:16407288};
CC KM=11.8 uM for AdoMet {ECO:0000269|PubMed:16407288};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q8VHT6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=An isoform missing exon 3 is produced with a premature stop
CC codon at AA 23 and is targeted to nonsense-mediated mRNA decay
CC (NMD).;
CC Name=1;
CC IsoId=Q9HBK9-1; Sequence=Displayed;
CC Name=2; Synonyms=31.1 kDa, delta4,5;
CC IsoId=Q9HBK9-2; Sequence=VSP_053494;
CC -!- MISCELLANEOUS: [Isoform 2]: Devoid of methyltransferase activity.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. Arsenite
CC methyltransferase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG09731.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF226730; AAG09731.1; ALT_FRAME; mRNA.
DR EMBL; AY817668; AAV68045.1; -; Genomic_DNA.
DR EMBL; AL358790; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49668.1; -; Genomic_DNA.
DR EMBL; BC119637; AAI19638.1; -; mRNA.
DR EMBL; BC119638; AAI19639.2; -; mRNA.
DR CCDS; CCDS41567.1; -. [Q9HBK9-1]
DR RefSeq; NP_065733.2; NM_020682.3. [Q9HBK9-1]
DR AlphaFoldDB; Q9HBK9; -.
DR SMR; Q9HBK9; -.
DR BioGRID; 121513; 8.
DR IntAct; Q9HBK9; 2.
DR STRING; 9606.ENSP00000358896; -.
DR BindingDB; Q9HBK9; -.
DR ChEMBL; CHEMBL4295950; -.
DR DrugBank; DB00118; Ademetionine.
DR iPTMnet; Q9HBK9; -.
DR PhosphoSitePlus; Q9HBK9; -.
DR BioMuta; AS3MT; -.
DR DMDM; 209572762; -.
DR EPD; Q9HBK9; -.
DR jPOST; Q9HBK9; -.
DR MassIVE; Q9HBK9; -.
DR MaxQB; Q9HBK9; -.
DR PaxDb; Q9HBK9; -.
DR PeptideAtlas; Q9HBK9; -.
DR PRIDE; Q9HBK9; -.
DR ProteomicsDB; 81567; -. [Q9HBK9-1]
DR Antibodypedia; 2804; 144 antibodies from 32 providers.
DR DNASU; 57412; -.
DR Ensembl; ENST00000369880.8; ENSP00000358896.3; ENSG00000214435.9. [Q9HBK9-1]
DR GeneID; 57412; -.
DR KEGG; hsa:57412; -.
DR MANE-Select; ENST00000369880.8; ENSP00000358896.3; NM_020682.4; NP_065733.2.
DR UCSC; uc001kwk.4; human. [Q9HBK9-1]
DR CTD; 57412; -.
DR DisGeNET; 57412; -.
DR GeneCards; AS3MT; -.
DR HGNC; HGNC:17452; AS3MT.
DR HPA; ENSG00000214435; Tissue enriched (adrenal).
DR MIM; 611806; gene.
DR neXtProt; NX_Q9HBK9; -.
DR OpenTargets; ENSG00000214435; -.
DR PharmGKB; PA134896392; -.
DR VEuPathDB; HostDB:ENSG00000214435; -.
DR eggNOG; ENOG502QQD6; Eukaryota.
DR GeneTree; ENSGT00390000001742; -.
DR InParanoid; Q9HBK9; -.
DR OMA; PVCGNTW; -.
DR OrthoDB; 1025394at2759; -.
DR PhylomeDB; Q9HBK9; -.
DR TreeFam; TF343797; -.
DR BioCyc; MetaCyc:HS01822-MON; -.
DR BRENDA; 2.1.1.137; 2681.
DR PathwayCommons; Q9HBK9; -.
DR Reactome; R-HSA-156581; Methylation.
DR SABIO-RK; Q9HBK9; -.
DR SignaLink; Q9HBK9; -.
DR BioGRID-ORCS; 57412; 8 hits in 1081 CRISPR screens.
DR GeneWiki; AS3MT; -.
DR GenomeRNAi; 57412; -.
DR Pharos; Q9HBK9; Tbio.
DR PRO; PR:Q9HBK9; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9HBK9; protein.
DR Bgee; ENSG00000214435; Expressed in right adrenal gland and 97 other tissues.
DR ExpressionAtlas; Q9HBK9; baseline and differential.
DR Genevisible; Q9HBK9; HS.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0030791; F:arsenite methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0030792; F:methylarsonite methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0008168; F:methyltransferase activity; IBA:GO_Central.
DR GO; GO:0018872; P:arsonoacetate metabolic process; IDA:UniProtKB.
DR GO; GO:0032259; P:methylation; IDA:UniProtKB.
DR GO; GO:0009404; P:toxin metabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR026669; Arsenite_MeTrfase-like.
DR InterPro; IPR025714; Methyltranfer_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR43675; PTHR43675; 1.
DR Pfam; PF13847; Methyltransf_31; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Methyltransferase; Phosphoprotein;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..375
FT /note="Arsenite methyltransferase"
FT /id="PRO_0000204447"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 58..153
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_053494"
FT VARIANT 173
FT /note="R -> W (frequency in African-Americans 0.008; not
FT detected in Caucasian-Americans; enzyme activity is 31% of
FT wild-type; dbSNP:rs35232887)"
FT /evidence="ECO:0000269|PubMed:16407288"
FT /id="VAR_027392"
FT VARIANT 287
FT /note="M -> T (frequency in African-Americans 0.108 and
FT Caucasian-Americans 0.100; enzyme activity is 350% of wild-
FT type; dbSNP:rs11191439)"
FT /evidence="ECO:0000269|PubMed:16407288,
FT ECO:0000269|PubMed:18334919"
FT /id="VAR_027393"
FT VARIANT 306
FT /note="T -> I (frequency in Caucasian-Americans 0.008; not
FT detected in African-Americans; dbSNP:rs34556438)"
FT /evidence="ECO:0000269|PubMed:16407288"
FT /id="VAR_027394"
FT CONFLICT 125
FT /note="Q -> R (in Ref. 6; AAI19638)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="I -> F (in Ref. 2; AAG09731)"
FT /evidence="ECO:0000305"
FT CONFLICT 135
FT /note="Y -> N (in Ref. 2; AAG09731)"
FT /evidence="ECO:0000305"
FT CONFLICT 140
FT /note="G -> A (in Ref. 2; AAG09731)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 375 AA; 41748 MW; 2E0C758A8597AE33 CRC64;
MAALRDAEIQ KDVQTYYGQV LKRSADLQTN GCVTTARPVP KHIREALQNV HEEVALRYYG
CGLVIPEHLE NCWILDLGSG SGRDCYVLSQ LVGEKGHVTG IDMTKGQVEV AEKYLDYHME
KYGFQASNVT FIHGYIEKLG EAGIKNESHD IVVSNCVINL VPDKQQVLQE AYRVLKHGGE
LYFSDVYTSL ELPEEIRTHK VLWGECLGGA LYWKELAVLA QKIGFCPPRL VTANLITIQN
KELERVIGDC RFVSATFRLF KHSKTGPTKR CQVIYNGGIT GHEKELMFDA NFTFKEGEIV
EVDEETAAIL KNSRFAQDFL IRPIGEKLPT SGGCSALELK DIITDPFKLA EESDSMKSRC
VPDAAGGCCG TKKSC
