Protein:METTL3 |
Protein Summary |
 Gene summary |
| Gene name: METTL3 | ASpdb.0 ID: 56339 | Gene | Gene symbol | METTL3 | Gene ID | 56339 |
| Gene name | methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit |
| Synonyms | IME4|M6A|MT-A70|Spo8|hMETTL3 |
| Cytomap | 14q11.2 |
| Type of gene | protein-coding |
| Description | N6-adenosine-methyltransferase catalytic subunitN6-adenosine-methyltransferase 70 kDa subunitadoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferasemRNA (2'-O-methyladenosine-N(6)-)-methyltransferasemRNA m(6)A methyltransferasemethy |
| Modification date | 20240416 |
| UniProtAcc | Q86U44 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | METTL3 | GO:0001734 | mRNA m(6)A methyltransferase activity | 24316715|27281194|27373337|27627798 |
| Gene | METTL3 | GO:0003729 | mRNA binding | 27281194|27373337|30559377 |
| Gene | METTL3 | GO:0005634 | nucleus | 9409616|24316715|26458103|29348140|29506078 |
| Gene | METTL3 | GO:0005654 | nucleoplasm | - |
| Gene | METTL3 | GO:0005794 | Golgi apparatus | - |
| Gene | METTL3 | GO:0005829 | cytosol | - |
| Gene | METTL3 | GO:0006974 | DNA damage response | 28297716 |
| Gene | METTL3 | GO:0008173 | RNA methyltransferase activity | 25799998|27602518|29348140|29506078 |
| Gene | METTL3 | GO:0009048 | dosage compensation by inactivation of X chromosome | 27602518 |
| Gene | METTL3 | GO:0016556 | mRNA modification | 24316715|27281194|27373337|27627798|28297716 |
| Gene | METTL3 | GO:0016604 | nuclear body | - |
| Gene | METTL3 | GO:0016607 | nuclear speck | 24407421 |
| Gene | METTL3 | GO:0031053 | primary miRNA processing | 25799998 |
| Gene | METTL3 | GO:0034644 | cellular response to UV | 28297716 |
| Gene | METTL3 | GO:0036396 | RNA N6-methyladenosine methyltransferase complex | 24316715|24407421|24981863|27602518|27627798|29348140|29506078|29507755 |
| Gene | METTL3 | GO:0046982 | protein heterodimerization activity | 27373337 |
| Gene | METTL3 | GO:1904047 | S-adenosyl-L-methionine binding | 27281194|27373337 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| Q86U44-1 | Q86U44-1_5tey_A.pdb | 5TEY | X-ray | 1.8 | A | 367 | 577 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| Q86U44 | METTL3 | Q86U44-1 | Q86U44-2 | 580 | 221 | 1 | 284 | Deletion | none | none | 0 | 0 |
| Q86U44 | METTL3 | Q86U44-1 | Q86U44-2 | 580 | 221 | 486 | 505 | Substitution | GVKGNPQGFNQGLDCDVIVA | SSSGAQFNRWSTKKNHLISY | 202 | 221 |
| Q86U44 | METTL3 | Q86U44-1 | Q86U44-2 | 580 | 221 | 506 | 580 | Deletion | none | none | 221 | 221 |
| Multiple sequence alignment of our canonical and alternatively spliced METTL3 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of METTL3 |
| UniProt-id | ENSG | ENST | ENSP |
| Q86U44-1 | ENSG00000165819.12 | ENST00000298717.9 | ENSP00000298717.3 |
| UniProt-id | NM ID | NP ID |
| Q86U44-1 | NM_019852.4 | NP_062826.2 |
| Amino acid sequences of our canonical and alternatively spliced METTL3 |
| accession_id | Protein sequence |
| Q86U44-1 | MSDTWSSIQAHKKQLDSLRERLQRRRKQDSGHLDLRNPEAALSPTFRSDSPVPTAPTSGGPKPSTASAVPELATDPELEKKLLHHLSDLA LTLPTDAVSICLAISTPDAPATQDGVESLLQKFAAQELIEVKRGLLQDDAHPTLVTYADHSKLSAMMGAVAEKKGPGEVAGTVTGQKRRA EQDSTTVAAFASSLVSGLNSSASEPAKEPAKKSRKHAASDVDLEIESLLNQQSTKEQQSKKVSQEILELLNTTTAKEQSIVEKFRSRGRA QVQEFCDYGTKEECMKASDADRPCRKLHFRRIINKHTDESLGDCSFLNTCFHMDTCKYVHYEIDACMDSEAPGSKDHTPSQELALTQSVG GDSSADRLFPPQWICCDIRYLDVSILGKFAVVMADPPWDIHMELPYGTLTDDEMRRLNIPVLQDDGFLFLWVTGRAMELGRECLNLWGYE RVDEIIWVKTNQLQRIIRTGRTGHWLNHGKEHCLVGVKGNPQGFNQGLDCDVIVAEVRSTSHKPDEIYGMIERLSPGTRKIELFGRPHNV |
| Q86U44-2 | MKASDADRPCRKLHFRRIINKHTDESLGDCSFLNTCFHMDTCKYVHYEIDACMDSEAPGSKDHTPSQELALTQSVGGDSSADRLFPPQWI CCDIRYLDVSILGKFAVVMADPPWDIHMELPYGTLTDDEMRRLNIPVLQDDGFLFLWVTGRAMELGRECLNLWGYERVDEIIWVKTNQLQ |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| METTL3 (go to UniProt):Q86U44 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Q86U44 | Region | 1 | 70 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=284 |
| Q86U44 | Region | 198 | 219 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=284 |
| Q86U44 | Region | 507 | 515 | Note=Gate loop 2;Ontology_term=ECO:0000303;evidence=ECO:0000303|PubMed:27281194;Dbxref=PMID:27281194 | Type=Deletion;Start=506;End=580 |
| Q86U44 | Motif | 210 | 215 | Note=Nuclear localization signal;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29348140;Dbxref=PMID:29348140 | Type=Deletion;Start=1;End=284 |
| Q86U44 | Compositional bias | 13 | 34 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=284 |
| Q86U44 | Compositional bias | 43 | 64 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=284 |
Gene Isoform Structures and Expression Levels for METTL3 |
| Gene structures of our canonical and alternative spliced genes of METTL3 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of Q86U44-1 |
| 3D view using mol* of Q86U44-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of Q86U44-1 |
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| pLDDT distribution across the protein length of Q86U44-2 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of Q86U44-1 |
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| Ramachandran plot of Q86U44-2 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| Q86U44-1 | 1.033 | 273 | 1.006 | 789.929 | 0.533 | 0.747 | 1.033 | 0.407 | 1.173 | 0.347 | 0.553 | 316,319,321,376,377,378,379,393,395,396,397,398,40 2,406,407,409,431,432,433,434,437,457,459,467,469, 472,473,474,475,476,477,478,479,480,481,482,507,50 8,509,510,511,512,513,515,517,518,532,533,534,535, 536,538,539,541,548,549,550 |
| Q86U44-2 | 0.954 | 95 | 0.978 | 317.618 | 0.691 | 0.644 | 0.843 | 0.346 | 0.997 | 0.347 | 0.974 | 111,112,113,114,116,118,120,122,147,148,149,150,15 1,153,175,183,188,189,190,191,192,193,194,195,196, 197,198 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of Q86U44-1_Q86U44-1_5tey_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q86U44-1_5tey_A_Q86U44-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q86U44-1_Q86U44-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q86U44-1_vs_Q86U44-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q86U44-1_vs_Q86U44-2.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to METTL3 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to METTL3 |
| Previous studies relating to the alternative splicing of METTL3 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| METTL3 | 35456475 | An Alternatively Spliced Variant of METTL3 Mediates Tumor Suppression in Hepatocellular Carcinoma. | Many post-transcriptional mRNA processing steps play crucial roles in tumorigenesis and the progression of cancers, such as N6-methyladenosine (m6A) modification and alternative splicing. Upregulation of methyltransferase-like 3 (METTL3), the catalytic core of the m6A methyltransferase complex, increases m6A levels and results in significant effects on the progression of hepatocellular carcinoma (HCC). However, alternative splicing of METTL3 has not been fully investigated, and the functions of its splice variants remain unclear. Here, we analyzed both our and online transcriptomic data, obtaining 13 splice variants of METTL3 in addition to canonical full-length METTL3-A in HCC cell lines and tissues. Validated by RT-qPCR and Western blotting, we found that METTL3-D, one of the splice variants expressing a truncated METTL3 protein, exhibits higher levels than METTL3-A in normal human livers but lower levels than METTL3-A in HCC tumor tissues and cell lines. Further functional assays demonstrated that METTL3-D expression decreased cellular m6A modification, inhibited the proliferation, migration, and invasion of HCC cells, and was negatively associated with the malignancy of patient tumors, exhibiting functions opposite to those of full-length METTL3-A. This study demonstrates that the METTL3-D splice variant is a tumor suppressor that could potentially be used as a target for HCC therapy. | D006528 | Carcinoma, Hepatocellular |
| METTL3 | 35456475 | An Alternatively Spliced Variant of METTL3 Mediates Tumor Suppression in Hepatocellular Carcinoma. | Many post-transcriptional mRNA processing steps play crucial roles in tumorigenesis and the progression of cancers, such as N6-methyladenosine (m6A) modification and alternative splicing. Upregulation of methyltransferase-like 3 (METTL3), the catalytic core of the m6A methyltransferase complex, increases m6A levels and results in significant effects on the progression of hepatocellular carcinoma (HCC). However, alternative splicing of METTL3 has not been fully investigated, and the functions of its splice variants remain unclear. Here, we analyzed both our and online transcriptomic data, obtaining 13 splice variants of METTL3 in addition to canonical full-length METTL3-A in HCC cell lines and tissues. Validated by RT-qPCR and Western blotting, we found that METTL3-D, one of the splice variants expressing a truncated METTL3 protein, exhibits higher levels than METTL3-A in normal human livers but lower levels than METTL3-A in HCC tumor tissues and cell lines. Further functional assays demonstrated that METTL3-D expression decreased cellular m6A modification, inhibited the proliferation, migration, and invasion of HCC cells, and was negatively associated with the malignancy of patient tumors, exhibiting functions opposite to those of full-length METTL3-A. This study demonstrates that the METTL3-D splice variant is a tumor suppressor that could potentially be used as a target for HCC therapy. | D008113 | Liver Neoplasms |
Clinically important variants in METTL3 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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