METTL3 [The Human Chemical-Genetic Interaction Map Project]

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======= METTL3 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: METTL3
  * **<color #00a2e8>Official Name</color>**: methyltransferase like 3
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=56339|56339]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q86U44|Q86U44]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=METTL3&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20METTL3|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/612472|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  The METTL3-METTL14 heterodimer forms a N6- methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, differentiation of embryonic and haematopoietic stem cells, cortical neurogenesis, response to DNA damage, differentiation of T-cells and primary miRNA processing (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:27627798, PubMed:27373337, PubMed:27281194, PubMed:28297716, PubMed:9409616). In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core (PubMed:27627798, PubMed:27373337, PubMed:27281194). N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability, processing, translation efficiency and editing (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:28297716, PubMed:9409616). M6A acts as a key regulator of mRNA stability: methylation is completed upon the release of mRNA into the nucleoplasm and promotes mRNA destabilization and degradation (PubMed:28637692). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization, promoting differentiation of ESCs (By similarity). M6A regulates the length of the circadian clock: acts as an early pace-setter in the circadian loop by putting mRNA production on a fast-track for facilitating nuclear processing, thereby providing an early point of control in setting the dynamics of the feedback loop (By similarity). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (By similarity). Involved in the response to DNA damage: in response to ultraviolet irradiation, METTL3 rapidly catalyzes the formation of m6A on poly(A) transcripts at DNA damage sites, leading to the recruitment of POLK to DNA damage sites (PubMed:28297716). M6A is also required for T-cell homeostasis and differentiation: m6A methylation of transcripts of SOCS family members (SOCS1, SOCS3 and CISH) in naive T-cells promotes mRNA destabilization and degradation, promoting T-cell differentiation (By similarity). M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs) (PubMed:25799998). M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells (By similarity). METTL3 mediates methylation of pri-miRNAs, marking them for recognition and processing by DGCR8 (PubMed:25799998). Acts as a positive regulator of mRNA translation independently of the methyltransferase activity: promotes translation by interacting with the translation initiation machinery in the cytoplasm (PubMed:27117702). Its overexpression in a number of cancer cells suggests that it may participate to cancer cell proliferation by promoting mRNA translation (PubMed:27117702). {ECO:0000250|UniProtKB:Q8C3P7, ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:25719671, ECO:0000269|PubMed:25799998, ECO:0000269|PubMed:26321680, ECO:0000269|PubMed:26593424, ECO:0000269|PubMed:27117702, ECO:0000269|PubMed:27281194, ECO:0000269|PubMed:27373337, ECO:0000269|PubMed:27627798, ECO:0000269|PubMed:28297716, ECO:0000269|PubMed:28637692, ECO:0000269|PubMed:9409616}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|MT-A70|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|primary miRNA methylation|
|primary miRNA modification|
|mRNA (N6-adenosine)-methyltransferase activity|
|endothelial to hematopoietic transition|
|positive regulation of cap-independent translational initiation|
|regulation of cap-independent translational initiation|
|mRNA (2-O-methyladenosine-N6-)-methyltransferase activity|
|positive regulation of cytoplasmic translational initiation|
|regulation of cytoplasmic translational initiation|
|delamination|
|RNA methyltransferase activity|
|forebrain radial glial cell differentiation|
|RNA N6-methyladenosine methyltransferase complex|
|primary miRNA processing|
|adenosine to inosine editing|
|S-adenosyl-L-methionine binding|
|positive regulation of cytoplasmic translation|
|radial glial cell differentiation|
|mRNA methylation|
|negative regulation of type I interferon-mediated signaling pathway|
|dosage compensation by inactivation of X chromosome|
|dosage compensation|
|base conversion or substitution editing|
|mRNA modification|
|production of miRNAs involved in gene silencing by miRNA|
|regulation of cytoplasmic translation|
|mRNA destabilization|
|positive regulation of translational initiation|
|RNA destabilization|
|production of small RNA involved in gene silencing by RNA|
|dsRNA processing|
|regulation of type I interferon-mediated signaling pathway|
|negative regulation of Notch signaling pathway|
|gene silencing by miRNA|
|positive regulation of mRNA catabolic process|
|regulation of meiotic cell cycle|
|negative regulation of innate immune response|
|posttranscriptional gene silencing by RNA|
|posttranscriptional gene silencing|
|negative regulation of cytokine-mediated signaling pathway|
|negative regulation of response to cytokine stimulus|
|forebrain generation of neurons|
|regulation of hematopoietic stem cell differentiation|
|positive regulation of mRNA metabolic process|
|regulation of translational initiation|
|RNA methylation|
|cellular response to UV|
|regulation of hematopoietic progenitor cell differentiation|
|gene silencing by RNA|
|negative regulation of response to biotic stimulus|
|regulation of Notch signaling pathway|
|cellular response to light stimulus|
|regulation of stem cell differentiation|
|positive regulation of translation|
|negative regulation of translation|
|stem cell population maintenance|
|maintenance of cell number|
|regulation of T cell differentiation|
|circadian rhythm|
|response to UV|
|negative regulation of cellular amide metabolic process|
|negative regulation of immune response|
|positive regulation of cellular amide metabolic process|
|gene silencing|
|regulation of reproductive process|
|mRNA binding|
|regulation of cytokine-mediated signaling pathway|
|RNA modification|
|regulation of lymphocyte differentiation|
|glial cell differentiation|
|negative regulation of cell-cell adhesion|
|cellular response to radiation|
|regulation of response to cytokine stimulus|
|regulation of mRNA stability|
|regulation of RNA stability|
|regulation of mRNA catabolic process|
|negative regulation of defense response|
|gliogenesis|
|negative regulation of multi-organism process|
|mRNA catabolic process|
|regulation of gene expression, epigenetic|
|RNA catabolic process|
|macromolecule methylation|
|negative regulation of cell adhesion|
|regulation of leukocyte differentiation|
|rhythmic process|
|mRNA splicing, via spliceosome|
|RNA splicing, via transesterification reactions with bulged adenosine as nucleophile|
|RNA splicing, via transesterification reactions|
|response to light stimulus|
|methylation|
|cellular response to abiotic stimulus|
|cellular response to environmental stimulus|
|regulation of T cell activation|
|regulation of mRNA metabolic process|
|regulation of translation|
|positive regulation of cellular catabolic process|
|negative regulation of response to external stimulus|
|nucleobase-containing compound catabolic process|
|ncRNA processing|
|forebrain development|
|regulation of cell-cell adhesion|
|RNA splicing|
|nuclear speck|
|regulation of cellular amide metabolic process|
|positive regulation of catabolic process|
|heterocycle catabolic process|
|cellular nitrogen compound catabolic process|
|response to radiation|
|negative regulation of immune system process|
|aromatic compound catabolic process|
|regulation of hemopoiesis|
|regulation of innate immune response|
|ncRNA metabolic process|
|mRNA processing|
|organic cyclic compound catabolic process|
|protein heterodimerization activity|
|regulation of lymphocyte activation|
|regulation of response to biotic stimulus|
|posttranscriptional regulation of gene expression|
|spermatogenesis|
|cell morphogenesis involved in differentiation|
|male gamete generation|
|regulation of leukocyte activation|
|regulation of cell activation|
|regulation of cell adhesion|
|gamete generation|
|mRNA metabolic process|
|cell morphogenesis|
|brain development|
|regulation of defense response|
|regulation of multi-organism process|
|cellular response to DNA damage stimulus|
|head development|
|cellular component morphogenesis|
|multicellular organismal reproductive process|
|sexual reproduction|
|regulation of cellular catabolic process|
|multicellular organism reproduction|
|RNA processing|
|cellular macromolecule catabolic process|
|central nervous system development|
|regulation of catabolic process|
|multi-organism reproductive process|
|negative regulation of cellular protein metabolic process|
|macromolecule catabolic process|
|regulation of response to external stimulus|
|negative regulation of protein metabolic process|
|regulation of immune response|
|response to abiotic stimulus|
|regulation of cell cycle|
|negative regulation of signal transduction|
|negative regulation of cell communication|
|negative regulation of signaling|
|negative regulation of cellular macromolecule biosynthetic process|
|reproductive process|
|reproduction|
|negative regulation of macromolecule biosynthetic process|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|generation of neurons|
|negative regulation of biosynthetic process|
|positive regulation of cellular protein metabolic process|
|negative regulation of response to stimulus|
|neurogenesis|
|cell development|
|regulation of immune system process|
|RNA metabolic process|
|cellular response to stress|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|organic substance catabolic process|
|cellular catabolic process|
|regulation of cell differentiation|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp147|Resveratrol 16μM R03 exp147]]|-1.77|
|[[:results:exp485|GSK626616 14μM R08 exp485]]|1.7|
|[[:results:exp458|Bisphenol S 100μM R08 exp458]]|1.72|
|[[:results:exp519|RS-1 10μM R08 exp519]]|1.73|
|[[:results:exp3|Actinomycin-D 0.001μM R00 exp3]]|1.88|
|[[:results:exp439|QNZ 0.01μM R08 exp439]]|2.17|
|[[:results:exp183|IU1-C 25μM R04 exp183]]|2.2|
|[[:results:exp48|Mubritinib 0.2μM R01 exp48]]|2.26|
|[[:results:exp374|Latrunculin-B 10μM R07 exp374]]|2.57|
|[[:results:exp274|Citral 50μM R06 exp274]]|2.99|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:m:mettl14|METTL14]]|0.494|
|[[:human genes:m:midn|MIDN]]|0.444|
|[[:human genes:y:ythdf2|YTHDF2]]|0.439|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 265/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|12/28|
|blood|14/28|
|bone|7/26|
|breast|12/33|
|central nervous system|20/56|
|cervix|0/4|
|colorectal|8/17|
|esophagus|4/13|
|fibroblast|0/1|
|gastric|4/16|
|kidney|13/21|
|liver|7/20|
|lung|24/75|
|lymphocyte|10/16|
|ovary|8/26|
|pancreas|7/24|
|peripheral nervous system|3/16|
|plasma cell|9/15|
|prostate|0/1|
|skin|7/24|
|soft tissue|3/9|
|thyroid|0/2|
|upper aerodigestive|8/22|
|urinary tract|10/29|
|uterus|2/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 1705
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.12 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='METTL3 Expression in NALM6 Cells: 7.12'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>