METTL3 methyltransferase like 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: METTL3provided by HGNC
Official Full Name: methyltransferase like 3provided by HGNC
Primary source: HGNC:HGNC:17563
See related: Ensembl:ENSG00000165819 MIM:612472
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: M6A; IME4; Spo8; MT-A70; hMETTL3
Summary: This gene encodes the 70 kDa subunit of MT-A which is part of N6-adenosine-methyltransferase. This enzyme is involved in the posttranscriptional methylation of internal adenosine residues in eukaryotic mRNAs, forming N6-methyladenosine. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in lymph node (RPKM 23.5), testis (RPKM 22.1) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 14q11.2

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
109.20200228	current	GRCh38.p13 (GCF_000001405.39)	14	NC_000014.9 (21498138..21511340, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (21966282..21979517, complement)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

METTL3-mediated m6A methylation is found to be dynamically reversed by the demethylase ALKBH5. In summary, this study highlights the functional importance of METTL3 in osteogenic differentiation and METTL3 may serve as a promising molecular target in regenerative medicine, as well as in the field of bone tissue engineering.
Title: The m6A methyltransferase METTL3 cooperates with demethylase ALKBH5 to regulate osteogenic differentiation through NF-κB signaling.
our findings provide a totally different mechanism of METTL3 in regulating CRC metastasis. Our study demonstrates that aberrant m6A modification in CRC was responsible for the upregulated METTL3 expression, which marks pri-miR-1246 for further processing
Title: Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway.
We conclude that METTL3 plays a vital role in many steps of RNA processing and orchestrates successful execution of oncogenic pathways in glioma stem-like cells .
Title: N⁶-Methyladenosine Landscape of Glioma Stem-Like Cells: METTL3 Is Essential for the Expression of Actively Transcribed Genes and Sustenance of the Oncogenic Signaling.
METTL3 was up-regulated in the breast cancer tissue and cells. And, METTL3 could install the methylation of Bcl-2 and promote its translation, thereby regulating the proliferation and apoptosis of breast cancer.
Title: N6-methyladenosine METTL3 promotes the breast cancer progression via targeting Bcl-2.
METTL3 expression is elevated in bladder cancer.MYC, AFF4, RELA and IKBKB are functionally important target genes of METTL3 in bladder cancer.
Title: The m<sup>6</sup>A methyltransferase METTL3 promotes bladder cancer progression via AFF4/NF-κB/MYC signaling network.
METTL3 might inhibit the LPS-induced inflammatory response of human dental pulp cells by regulating alternative splicing of MyD88.
Title: METTL3 regulates alternative splicing of MyD88 upon the lipopolysaccharide-induced inflammatory response in human dental pulp cells.
we found that METTL3 interacted with viral RNA-dependent RNA polymerase 3D and induced enhanced sumoylation and ubiquitination of the 3D polymerase that boosted viral replication. Taken together, our findings demonstrated that the host m6A modification complex interacts with viral proteins to modulate EV71 replication.
Title: N6-methyladenosine modification and METTL3 modulate enterovirus 71 replication.
An important mechanism for SUMOylation of METTL3 regulating its m6A RNA methyltransferase activity.Lysine 177/211/212/215 are major SUMOylation-sites of METTL3.METTL3 role in tumorigenesis.
Title: SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its function.
Study demonstrates that oncogenic miR-25 in pancreatic duct epithelial cells can be excessively maturated by cigarette smoke condensate (CSC) via enhanced N(6)-methyladenosine modification that is mediated by NF-kappaB associated protein NKAP. This modification is catalyzed by overexpressed METTL3 due to hypomethylation of the METTL3 promoter also caused by CSC.
Title: Excessive miR-25-3p maturation via N<sup>6</sup>-methyladenosine stimulated by cigarette smoke promotes pancreatic cancer progression.
METTL3-eIF3h interaction is required for enhanced translation, formation of densely packed polyribosomes and oncogenic transformation; findings uncover a mechanism of translation control that is based on mRNA looping and identify METTL3-eIF3h as a potential therapeutic target for patients with cancer
Title: mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis.

Submit: New GeneRIF Correction See all GeneRIFs (26)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

RH44762 (e-PCR)
- UniSTS:32768

SHGC-64027 (e-PCR)
- UniSTS:31045

SHGC-36315 (e-PCR)
- UniSTS:873

D15S1477 (e-PCR)
- UniSTS:474482

Homology

Homologs of the METTL3 gene: The METTL3 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 254 organisms have orthologs with human gene METTL3
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
RNA methyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
S-adenosyl-L-methionine binding	IDA Inferred from Direct Assay more info	PubMed
mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity	IEA Inferred from Electronic Annotation more info
mRNA (N6-adenosine)-methyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
mRNA (N6-adenosine)-methyltransferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
mRNA binding	IDA Inferred from Direct Assay more info	PubMed
methyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein heterodimerization activity	IDA Inferred from Direct Assay more info	PubMed
protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
RNA metabolic process	TAS Traceable Author Statement more info
RNA methylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
RNA methylation	IMP Inferred from Mutant Phenotype more info	PubMed
adenosine to inosine editing	ISS Inferred from Sequence or Structural Similarity more info
cellular response to DNA damage stimulus	IDA Inferred from Direct Assay more info	PubMed
cellular response to UV	IDA Inferred from Direct Assay more info	PubMed
circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
dosage compensation by inactivation of X chromosome	IDA Inferred from Direct Assay more info	PubMed
endothelial to hematopoietic transition	ISS Inferred from Sequence or Structural Similarity more info
forebrain radial glial cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
gliogenesis	ISS Inferred from Sequence or Structural Similarity more info
innate immune response	IEA Inferred from Electronic Annotation more info
mRNA catabolic process	ISS Inferred from Sequence or Structural Similarity more info
mRNA destabilization	ISS Inferred from Sequence or Structural Similarity more info
mRNA methylation	IDA Inferred from Direct Assay more info	PubMed
mRNA methylation	IMP Inferred from Mutant Phenotype more info	PubMed
mRNA processing	ISS Inferred from Sequence or Structural Similarity more info
mRNA splicing, via spliceosome	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mRNA splicing, via spliceosome	IMP Inferred from Mutant Phenotype more info	PubMed
NOT mRNA splicing, via spliceosome	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of Notch signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of type I interferon-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of cap-independent translational initiation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of translation	IMP Inferred from Mutant Phenotype more info	PubMed
primary miRNA methylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
primary miRNA methylation	IDA Inferred from Direct Assay more info	PubMed
primary miRNA processing	IDA Inferred from Direct Assay more info	PubMed
regulation of T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
regulation of hematopoietic stem cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
regulation of meiotic cell cycle	ISS Inferred from Sequence or Structural Similarity more info
spermatogenesis	ISS Inferred from Sequence or Structural Similarity more info
stem cell population maintenance	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
RNA N6-methyladenosine methyltransferase complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
RNA N6-methyladenosine methyltransferase complex	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IEA Inferred from Electronic Annotation more info
nuclear speck	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nuclear speck	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: N6-adenosine-methyltransferase catalytic subunit

Names: N6-adenosine-methyltransferase 70 kDa subunit; adoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase; mRNA (2'-O-methyladenosine-N(6)-)-methyltransferase; mRNA m(6)A methyltransferase; methyltransferase-like protein 3

NP_062826.2

EC 2.1.1.348

XP_006720269.1

EC 2.1.1.348

XP_011535270.1

EC 2.1.1.348

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_019852.5 → NP_062826.2 N6-adenosine-methyltransferase catalytic subunit

See identical proteins and their annotated locations for NP_062826.2

Status: REVIEWED

Source sequence(s)

AL161747, BC001650, CA311761, DC295053

Consensus CDS

CCDS32044.1

UniProtKB/Swiss-Prot

Q86U44

Related

ENSP00000298717.3, ENST00000298717.9

Conserved Domains (1) summary

pfam05063
Location:389 → 550

MT-A70; MT-A70

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000014.9 Reference GRCh38.p13 Primary Assembly

Range

21498138..21511340 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006720206.4 → XP_006720269.1 N6-adenosine-methyltransferase catalytic subunit isoform X2

Conserved Domains (1) summary

pfam05063
Location:105 → 266

MT-A70; MT-A70
XM_011536968.2 → XP_011535270.1 N6-adenosine-methyltransferase catalytic subunit isoform X1

Conserved Domains (1) summary

cl01947
Location:389 → 528

MT-A70; MT-A70