METTL3
N(6)-adenosine-methyltransferase catalytic subunit METTL3
Also known as: M6A, MT-A70, MTA70_HUMAN, Spo8
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q86U44
- Gene
- METTL3
- Ensembl
- ENSG00000165819
- Chromosome
- 14
- Canonical length
- 580 aa
- Protein class
- Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Nuclear bodies,Golgi apparatus,Cytosol
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
580 residues, UniProt reviewed canonical sequence.
>Q86U44|METTL3
1 MSDTWSSIQA HKKQLDSLRE RLQRRRKQDS GHLDLRNPEA ALSPTFRSDS PVPTAPTSGG
61 PKPSTASAVP ELATDPELEK KLLHHLSDLA LTLPTDAVSI CLAISTPDAP ATQDGVESLL
121 QKFAAQELIE VKRGLLQDDA HPTLVTYADH SKLSAMMGAV AEKKGPGEVA GTVTGQKRRA
181 EQDSTTVAAF ASSLVSGLNS SASEPAKEPA KKSRKHAASD VDLEIESLLN QQSTKEQQSK
241 KVSQEILELL NTTTAKEQSI VEKFRSRGRA QVQEFCDYGT KEECMKASDA DRPCRKLHFR
301 RIINKHTDES LGDCSFLNTC FHMDTCKYVH YEIDACMDSE APGSKDHTPS QELALTQSVG
361 GDSSADRLFP PQWICCDIRY LDVSILGKFA VVMADPPWDI HMELPYGTLT DDEMRRLNIP
421 VLQDDGFLFL WVTGRAMELG RECLNLWGYE RVDEIIWVKT NQLQRIIRTG RTGHWLNHGK
481 EHCLVGVKGN PQGFNQGLDC DVIVAEVRST SHKPDEIYGM IERLSPGTRK IELFGRPHNV
541 QPNWITLGNQ LDGIHLLDPD VVARFKQRYP DGIISKPKNLLocalizationUniProt · AlphaFold · HPA
Whether an antibody against METTL3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.43
- Highest tissue expression
- 20 nTPM
Expression across tissuesHPA
Tissue
- tonsil: 20 nTPM
- testis: 20 nTPM
- parathyroid gland: 18 nTPM
- lymph node: 18 nTPM
- fallopian tube: 18 nTPM
- adrenal gland: 18 nTPM
Single-cell type
- late primary spermatocytes: 177 nCPM
- early spermatids: 177 nCPM
- tuft cells: 58 nCPM
- syncytiotrophoblasts: 54 nCPM
- cytotrophoblasts: 47 nCPM
- migrating cytotrophoblasts: 39 nCPM
Immune cell
- NK-cell: 16 nTPM
- T-reg: 16 nTPM
- memory B-cell: 14 nTPM
- plasmacytoid DC: 13 nTPM
- MAIT T-cell: 13 nTPM
- intermediate monocyte: 12 nTPM
Brain region
- medulla oblongata: 9.7 nTPM
- pons: 8.8 nTPM
- thalamus: 8.5 nTPM
- white matter: 8.4 nTPM
- cerebral cortex: 8.1 nTPM
- midbrain: 7.8 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.79
- gnomAD pLI
- 0
- gnomAD missense Z
- 3.05
- DepMap mean gene effect
- -0.57
- DepMap dependency class
- common
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cellular response to UV
- circadian rhythm
- DNA damage response
- dosage compensation by inactivation of X chromosome
- endothelial to hematopoietic transition
- forebrain radial glial cell differentiation
- gliogenesis
- innate immune response
- mRNA destabilization
- mRNA modification
- mRNA processing
- mRNA splicing, via spliceosome
- negative regulation of Notch signaling pathway
- negative regulation of type I interferon-mediated signaling pathway
- oogenesis
- positive regulation of cap-independent translational initiation
- positive regulation of translation
- primary miRNA processing
- regulation of hematopoietic stem cell differentiation
- regulation of meiotic cell cycle
- regulation of T cell differentiation
- RNA methylation
- spermatogenesis
- stem cell population maintenance
Molecular functions
- mRNA binding
- mRNA m(6)A methyltransferase activity
- protein heterodimerization activity
- RNA methyltransferase activity
- S-adenosyl-L-methionine binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- MT-A70-like
- S-adenosyl-L-methionine-dependent methyltransferase superfamily
- MT-A70
- N6-adenosine-methyltransferase MT-A70-like
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of METTL3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads METTL3 as an antibody target. Whether an autoantibody or antibody against METTL3 could matter depends on whether native METTL3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
METTL3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label METTL3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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