This gene encodes an N(6)-adenine-specific DNA methyltransferase. The encoded enzyme may be involved in the methylation of release factor I during translation termination. This enzyme is also involved in converting the arsenic metabolite monomethylarsonous acid to the less toxic dimethylarsonic acid. Alternative splicing pf this gene results in multiple transcript variants. A r... See more...

Aliases for N6AMT1 Gene

Aliases for N6AMT1 Gene

  • N-6 Adenine-Specific DNA Methyltransferase 1 2 3 5
  • HemK Methyltransferase Family Member 2 2 3 4
  • N-6 Adenine-Specific DNA Methyltransferase 1 (Putative) 2 3
  • Protein N(5)-Glutamine Methyltransferase 3 4
  • Methylarsonite Methyltransferase N6AMT1 3 4
  • Methyltransferase N6AMT1 3 4
  • M.HsaHemK2P 3 4
  • C21orf127 3 4
  • PRED28 3 4
  • HEMK2 3 4
  • N(6)-Adenine-Specific DNA Methyltransferase 1 4
  • Chromosome 21 Open Reading Frame 127 2
  • N6-DNA-Methyltransferase 3
  • EC 2.1.1.72 4
  • EC 2.1.1.- 4
  • N6AMT 3
  • KMT9 3
  • MTQ2 3
  • PrmC 3

External Ids for N6AMT1 Gene

Previous HGNC Symbols for N6AMT1 Gene

  • C21orf127
  • HEMK2

Previous GeneCards Identifiers for N6AMT1 Gene

  • GC21M026827
  • GC21M029166
  • GC21M030244
  • GC21M015649

Summaries for N6AMT1 Gene

Entrez Gene Summary for N6AMT1 Gene

  • This gene encodes an N(6)-adenine-specific DNA methyltransferase. The encoded enzyme may be involved in the methylation of release factor I during translation termination. This enzyme is also involved in converting the arsenic metabolite monomethylarsonous acid to the less toxic dimethylarsonic acid. Alternative splicing pf this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 11. [provided by RefSeq, Jul 2014]

GeneCards Summary for N6AMT1 Gene

N6AMT1 (N-6 Adenine-Specific DNA Methyltransferase 1) is a Protein Coding gene. Diseases associated with N6AMT1 include Glossitis. Among its related pathways are Gene Expression and Viral mRNA Translation. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and protein methyltransferase activity. An important paralog of this gene is HEMK1.

UniProtKB/Swiss-Prot Summary for N6AMT1 Gene

  • Methyltransferase that can methylate both proteins and DNA, and to a lower extent, arsenic (PubMed:18539146, PubMed:21193388, PubMed:30017583). Catalytic subunit of a heterodimer with TRMT112, which catalyzes N5-methylation of Glu residue of proteins with a Gly-Gln-Xaa-Xaa-Xaa-Arg motif (PubMed:18539146) (By similarity). Methylates ETF1 on 'Gln-185'; ETF1 needs to be complexed to ERF3 in its GTP-bound form to be efficiently methylated (PubMed:18539146, PubMed:20606008). Also acts as a N(6)-adenine-specific DNA methyltransferase by mediating methylation of DNA on the 6th position of adenine (N(6)-methyladenosine) (PubMed:30017583). N(6)-methyladenosine (m6A) DNA is significantly enriched in exonic regions and is associated with gene transcriptional activation (PubMed:30017583). May also play a role in the modulation of arsenic-induced toxicity by mediating the conversion of monomethylarsonous acid (3+) into the less toxic dimethylarsonic acid (PubMed:21193388, PubMed:25997655). It however only plays a limited role in arsenic metabolism compared with AS3MT (PubMed:25997655).

Additional gene information for N6AMT1 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for N6AMT1 Gene

Genomics for N6AMT1 Gene

GeneHancer (GH) Regulatory Elements for N6AMT1 Gene

Promoters and enhancers for N6AMT1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around N6AMT1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the N6AMT1 gene promoter:
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • Ik-2
  • NCX
  • Nkx2-2
  • YY1

Genomic Locations for N6AMT1 Gene

Genomic Locations for N6AMT1 Gene
chr21:28,872,191-28,885,373
(GRCh38/hg38)
Size:
13,183 bases
Orientation:
Minus strand
chr21:30,244,513-30,257,693
(GRCh37/hg19)
Size:
13,181 bases
Orientation:
Minus strand

Genomic View for N6AMT1 Gene

Genes around N6AMT1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
N6AMT1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for N6AMT1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for N6AMT1 Gene

Proteins for N6AMT1 Gene

  • Protein details for N6AMT1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y5N5-N6MT1_HUMAN
    Recommended name:
    Methyltransferase N6AMT1
    Protein Accession:
    Q9Y5N5
    Secondary Accessions:
    • B2RA97
    • Q96F73

    Protein attributes for N6AMT1 Gene

    Size:
    214 amino acids
    Molecular mass:
    22957 Da
    Quaternary structure:
    • Heterodimer; heterodimerizes with TRMT112.

    Three dimensional structures from OCA and Proteopedia for N6AMT1 Gene

    Alternative splice isoforms for N6AMT1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for N6AMT1 Gene

Post-translational modifications for N6AMT1 Gene

No Post-translational modifications

Other Protein References for N6AMT1 Gene

No data available for DME Specific Peptides for N6AMT1 Gene

Domains & Families for N6AMT1 Gene

Gene Families for N6AMT1 Gene

Protein Domains for N6AMT1 Gene

Blocks:
  • N-6 Adenine-specific DNA methylase
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for N6AMT1 Gene

GenScript: Design optimal peptide antigens:
  • cDNA, FLJ94785, Homo sapiens putative N6-DNA-methyltransferase (N6AMT1), mRNA (B2RA97_HUMAN)
  • N(6)-adenine-specific DNA methyltransferase 1 (HEMK2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9Y5N5

UniProtKB/Swiss-Prot:

N6MT1_HUMAN :
  • Belongs to the eukaryotic/archaeal PrmC-related family.
Family:
  • Belongs to the eukaryotic/archaeal PrmC-related family.
genes like me logo Genes that share domains with N6AMT1: view

Function for N6AMT1 Gene

Molecular function for N6AMT1 Gene

UniProtKB/Swiss-Prot Function:
Methyltransferase that can methylate both proteins and DNA, and to a lower extent, arsenic (PubMed:18539146, PubMed:21193388, PubMed:30017583). Catalytic subunit of a heterodimer with TRMT112, which catalyzes N5-methylation of Glu residue of proteins with a Gly-Gln-Xaa-Xaa-Xaa-Arg motif (PubMed:18539146) (By similarity). Methylates ETF1 on 'Gln-185'; ETF1 needs to be complexed to ERF3 in its GTP-bound form to be efficiently methylated (PubMed:18539146, PubMed:20606008). Also acts as a N(6)-adenine-specific DNA methyltransferase by mediating methylation of DNA on the 6th position of adenine (N(6)-methyladenosine) (PubMed:30017583). N(6)-methyladenosine (m6A) DNA is significantly enriched in exonic regions and is associated with gene transcriptional activation (PubMed:30017583). May also play a role in the modulation of arsenic-induced toxicity by mediating the conversion of monomethylarsonous acid (3+) into the less toxic dimethylarsonic acid (PubMed:21193388, PubMed:25997655). It however only plays a limited role in arsenic metabolism compared with AS3MT (PubMed:25997655).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=L-glutaminyl-[protein] + S-adenosyl-L-methionine = H(+) + N(5)-methyl-L-glutaminyl-[protein] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:57452, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:14895, ChEBI:CHEBI:15378, ChEBI:CHEBI:30011, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61891; Evidence=. ;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=methylarsonous acid + S-adenosyl-L-methionine = dimethylarsinate + 2 H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:11684, ChEBI:CHEBI:15378, ChEBI:CHEBI:16223, ChEBI:CHEBI:17826, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789; Evidence=. ;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=a 2'-deoxyadenosine in DNA + S-adenosyl-L-methionine = an N(6)-methyl-2'-deoxyadenosine in DNA + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:15197, Rhea:RHEA-COMP:12418, Rhea:RHEA-COMP:12419, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:90615, ChEBI:CHEBI:90616; EC=2.1.1.72; Evidence=. ;.

Enzyme Numbers (IUBMB) for N6AMT1 Gene

Phenotypes From GWAS Catalog for N6AMT1 Gene

Gene Ontology (GO) - Molecular Function for N6AMT1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003676 nucleic acid binding IEA --
GO:0005515 protein binding IPI 18539146
GO:0008168 methyltransferase activity IEA --
GO:0008276 protein methyltransferase activity IDA 18539146
GO:0008757 S-adenosylmethionine-dependent methyltransferase activity IBA 21873635
genes like me logo Genes that share ontologies with N6AMT1: view
genes like me logo Genes that share phenotypes with N6AMT1: view

Animal Models for N6AMT1 Gene

MGI Knock Outs for N6AMT1:

Animal Model Products

CRISPR Products

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for N6AMT1 Gene

Localization for N6AMT1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for N6AMT1 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for N6AMT1 gene
Compartment Confidence
nucleus 5
cytosol 5
cytoskeleton 2
plasma membrane 1
extracellular 1
mitochondrion 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Centrosome (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for N6AMT1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus ISS --
GO:0005829 cytosol TAS --
GO:0032991 protein-containing complex IDA 18539146
GO:0035657 eRF1 methyltransferase complex IBA 21873635
genes like me logo Genes that share ontologies with N6AMT1: view

Pathways & Interactions for N6AMT1 Gene

genes like me logo Genes that share pathways with N6AMT1: view

Pathways by source for N6AMT1 Gene

Gene Ontology (GO) - Biological Process for N6AMT1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006415 translational termination TAS --
GO:0009404 toxin metabolic process IDA 25997655
GO:0018364 peptidyl-glutamine methylation IDA 18539146
GO:0018872 arsonoacetate metabolic process IDA 25997655
GO:0030307 positive regulation of cell growth IDA 18539146
genes like me logo Genes that share ontologies with N6AMT1: view

No data available for SIGNOR curated interactions for N6AMT1 Gene

Drugs & Compounds for N6AMT1 Gene

(3) Drugs for N6AMT1 Gene - From: PharmGKB and ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Clopidogrel Approved Pharma P2Y12 receptor antagonist 909
Thioguanine Approved Pharma Purine antimetabolite 89
Lomeguatrib Pharma MGMT inhibitor 0

(2) ApexBio Compounds for N6AMT1 Gene

Compound Action Cas Number
Lomeguatrib MGMT inhibitor 192441-08-0
Thioguanine Purine antimetabolite 154-42-7
genes like me logo Genes that share compounds with N6AMT1: view

Drug Products

Transcripts for N6AMT1 Gene

mRNA/cDNA for N6AMT1 Gene

2 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for N6AMT1 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c
SP1:
SP2: -
SP3: -

Relevant External Links for N6AMT1 Gene

GeneLoc Exon Structure for
N6AMT1

Expression for N6AMT1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for N6AMT1 Gene

Protein differential expression in normal tissues from HIPED for N6AMT1 Gene

This gene is overexpressed in Heart (48.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for N6AMT1 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for N6AMT1

SOURCE GeneReport for Unigene cluster for N6AMT1 Gene:

Hs.163846

mRNA Expression by UniProt/SwissProt for N6AMT1 Gene:

Q9Y5N5-N6MT1_HUMAN
Tissue specificity: Widely expressed, with highest expression in parathyroid and pituitary glands, followed by adrenal gland and kidney, and lowest expression in leukocytes and mammary gland.

Evidence on tissue expression from TISSUES for N6AMT1 Gene

  • Skin(4.3)
  • Nervous system(4.2)
genes like me logo Genes that share expression patterns with N6AMT1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for N6AMT1 Gene

Orthologs for N6AMT1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for N6AMT1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia N6AMT1 31 30
  • 98.75 (n)
OneToOne
dog
(Canis familiaris)
Mammalia LOC487715 30
  • 89.25 (n)
N6AMT1 31
  • 60 (a)
OneToOne
cow
(Bos Taurus)
Mammalia N6AMT1 31
  • 89 (a)
OneToOne
LOC615200 30
  • 87.69 (n)
mouse
(Mus musculus)
Mammalia N6amt1 17 31 30
  • 84.11 (n)
rat
(Rattus norvegicus)
Mammalia N6amt1 30
  • 83.8 (n)
oppossum
(Monodelphis domestica)
Mammalia N6AMT1 31
  • 73 (a)
OneToOne
chicken
(Gallus gallus)
Aves N6AMT1 31 30
  • 71.36 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia N6AMT1 31
  • 58 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia n6amt1 30
  • 66.99 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.21286 30
zebrafish
(Danio rerio)
Actinopterygii n6amt1 31 30
  • 59.97 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG9960 31 30
  • 49.1 (n)
OneToOne
snapin 32
  • 39 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009458 30
  • 47.99 (n)
worm
(Caenorhabditis elegans)
Secernentea CELE_C33C12.9 30
  • 50.09 (n)
C33C12.9 31 32
  • 41 (a)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MTQ2 33 31
  • 34 (a)
thale cress
(Arabidopsis thaliana)
eudicotyledons AT3G13440 30
  • 48.56 (n)
rice
(Oryza sativa)
Liliopsida Os03g0824200 30
  • 50.6 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 50 (a)
OneToOne
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPAC323.05c 30
  • 47.09 (n)
Species where no ortholog for N6AMT1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for N6AMT1 Gene

ENSEMBL:
Gene Tree for N6AMT1 (if available)
TreeFam:
Gene Tree for N6AMT1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for N6AMT1: view image

Paralogs for N6AMT1 Gene

Paralogs for N6AMT1 Gene

(1) SIMAP similar genes for N6AMT1 Gene using alignment to 1 proteins:

  • HEMK2_HUMAN

Pseudogenes.org Pseudogenes for N6AMT1 Gene

genes like me logo Genes that share paralogs with N6AMT1: view

Variants for N6AMT1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for N6AMT1 Gene

SNP ID Clinical significance and condition Chr 21 pos Variation AA Info Type
rs1997607 - p.Asp34Asn
rs2205446 - p.Arg166Lys
rs2205447 - p.Arg146Lys

Additional dbSNP identifiers (rs#s) for N6AMT1 Gene

Structural Variations from Database of Genomic Variants (DGV) for N6AMT1 Gene

Variant ID Type Subtype PubMed ID
esv2758818 CNV gain 17122850
esv3646788 CNV gain 21293372
nsv1062470 CNV loss 25217958
nsv9862 CNV gain 18304495

Variation tolerance for N6AMT1 Gene

Residual Variation Intolerance Score: 88% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.79; 79.04% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for N6AMT1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
N6AMT1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for N6AMT1 Gene

Disorders for N6AMT1 Gene

MalaCards: The human disease database

(1) MalaCards diseases for N6AMT1 Gene - From: DISEASES

Disorder Aliases PubMed IDs
glossitis
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for N6AMT1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with N6AMT1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for N6AMT1 Gene

Publications for N6AMT1 Gene

  1. Involvement of N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) in arsenic biomethylation and its role in arsenic-induced toxicity. (PMID: 21193388) Ren X … Zhang L (Environmental health perspectives 2011) 2 3 4 54
  2. HemK2 protein, encoded on human chromosome 21, methylates translation termination factor eRF1. (PMID: 18539146) Figaro S … Heurgué-Hamard V (FEBS letters 2008) 3 4 23 54
  3. KMT9 monomethylates histone H4 lysine 12 and controls proliferation of prostate cancer cells. (PMID: 31061526) Metzger E … Schüle R (Nature structural & molecular biology 2019) 2 3 54
  4. N6-Methyladenine DNA Modification in the Human Genome. (PMID: 30017583) Xiao CL … Yan GR (Molecular cell 2018) 3 4 54
  5. Interactive Effects of N6AMT1 and As3MT in Arsenic Biomethylation. (PMID: 25997655) Zhang H … Ren X (Toxicological sciences : an official journal of the Society of Toxicology 2015) 3 4 54

Products for N6AMT1 Gene

Sources for N6AMT1 Gene