METTL3 methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit [Homo sapiens (human)] - Gene

Summary

Official Symbol: METTL3provided by HGNC
Official Full Name: methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunitprovided 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
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Genomic context

Location:: 14q11.2

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
109.20211119	current	GRCh38.p13 (GCF_000001405.39)	14	NC_000014.9 (21498138..21511340, complement)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (21966282..21979482, complement)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

METTL3 enhances the stability of MALAT1 with the assistance of HuR via m6A modification and activates NF-kappaB to promote the malignant progression of IDH-wildtype glioma.
Title: METTL3 enhances the stability of MALAT1 with the assistance of HuR via m6A modification and activates NF-κB to promote the malignant progression of IDH-wildtype glioma.
MicroRNA-1269b inhibits gastric cancer development through regulating methyltransferase-like 3 (METTL3).
Title: MicroRNA-1269b inhibits gastric cancer development through regulating methyltransferase-like 3 (METTL3).
Tumor-Associated Macrophages Promote Oxaliplatin Resistance via METTL3-Mediated m(6)A of TRAF5 and Necroptosis in Colorectal Cancer.
Title: Tumor-Associated Macrophages Promote Oxaliplatin Resistance via METTL3-Mediated m6A of TRAF5 and Necroptosis in Colorectal Cancer.
Long noncoding RNA SNHG4 remits lipopolysaccharide-engendered inflammatory lung damage by inhibiting METTL3 - Mediated m(6)A level of STAT2 mRNA.
Title: Long noncoding RNA SNHG4 remits lipopolysaccharide-engendered inflammatory lung damage by inhibiting METTL3 - Mediated m6A level of STAT2 mRNA.
METTL3-mediated m(6)A methylation of SPHK2 promotes gastric cancer progression by targeting KLF2.
Title: METTL3-mediated m6A methylation of SPHK2 promotes gastric cancer progression by targeting KLF2.
YTHDF2 facilitates UBXN1 mRNA decay by recognizing METTL3-mediated m(6)A modification to activate NF-kappaB and promote the malignant progression of glioma.
Title: YTHDF2 facilitates UBXN1 mRNA decay by recognizing METTL3-mediated m6A modification to activate NF-κB and promote the malignant progression of glioma.
Inhibiting PP2Acalpha Promotes the Malignant Phenotype of Gastric Cancer Cells through the ATM/METTL3 Axis.
Title: Inhibiting PP2Acα Promotes the Malignant Phenotype of Gastric Cancer Cells through the ATM/METTL3 Axis.
METTL3-mediated m(6)A mRNA modification of FBXW7 suppresses lung adenocarcinoma.
Title: METTL3-mediated m6A mRNA modification of FBXW7 suppresses lung adenocarcinoma.
HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3-mediated m6A modification of HIF-1alpha.
Title: HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3-mediated m6A modification of HIF-1α.
RNA methyltransferase METTL3 induces intrinsic resistance to gefitinib by combining with MET to regulate PI3K/AKT pathway in lung adenocarcinoma.
Title: RNA methyltransferase METTL3 induces intrinsic resistance to gefitinib by combining with MET to regulate PI3K/AKT pathway in lung adenocarcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (109)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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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: 352 organisms have orthologs with human gene METTL3
Orthologs

Gene Ontology Provided by GOA

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

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

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

General protein information

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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 3; 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)

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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

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20211119

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
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