| UTHEALTH HOME ABOUT SBMI A-Z WEBMAIL INSIDE THE UNIVERSITY |
|
|||||||
|
Fusion Protein:METTL5-MERTK |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: METTL5-MERTK | FusionPDB ID: 53135 | FusionGDB2.0 ID: 53135 | Hgene | Tgene | Gene symbol | METTL5 | MERTK | Gene ID | 29081 | 10461 |
| Gene name | methyltransferase like 5 | MER proto-oncogene, tyrosine kinase | |
| Synonyms | HSPC133|MRT72 | MER|RP38|Tyro12|c-Eyk|c-mer | |
| Cytomap | 2q31.1 | 2q13 | |
| Type of gene | protein-coding | protein-coding | |
| Description | methyltransferase-like protein 5 | tyrosine-protein kinase MerMER receptor tyrosine kinaseSTK kinasec-mer proto-oncogene tyrosine kinaseproto-oncogene c-Merreceptor tyrosine kinase MerTK | |
| Modification date | 20200327 | 20200329 | |
| UniProtAcc | Q9NRN9 | Q12866 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000260953, ENST00000392640, ENST00000409340, ENST00000409837, ENST00000409965, ENST00000410097, ENST00000308099, | ENST00000295408, ENST00000409780, ENST00000421804, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 4 X 6 X 4=96 | 7 X 10 X 8=560 |
| # samples | 7 | 13 | |
| ** MAII score | log2(7/96*10)=-0.45567948377619 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(13/560*10)=-2.10691520391651 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: METTL5 [Title/Abstract] AND MERTK [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | METTL5(170676071)-MERTK(112785928), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | METTL5-MERTK seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. METTL5-MERTK seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. METTL5-MERTK seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. METTL5-MERTK seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. METTL5-MERTK seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. METTL5-MERTK seems lost the major protein functional domain in Tgene partner, which is a kinase due to the frame-shifted ORF. | ||
| * DoF score (Degree of Frequency) = # partners X # break points X # cancer types ** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10) |
| Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Tgene | MERTK | GO:0050766 | positive regulation of phagocytosis | 18395422 |
| Fusion gene breakpoints across METTL5 (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
 |
| Fusion gene breakpoints across MERTK (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
 |
Top |
Fusion Gene Sample Information |
| Fusion gene information from FusionGDB2.0. |
| Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0) * All genome coordinats were lifted-over on hg19. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
| Source | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| ChimerDB4 | SKCM | TCGA-ER-A3EV-06A | METTL5 | chr2 | 170676071 | - | MERTK | chr2 | 112785928 | + |
Top |
Fusion ORF Analysis |
| Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
| ENST00000409837 | METTL5 | chr2 | 170676071 | - | ENST00000409780 | MERTK | chr2 | 112785928 | + | 1587 | 570 | 511 | 1083 | 190 |
| ENST00000409340 | METTL5 | chr2 | 170676071 | - | ENST00000421804 | MERTK | chr2 | 112785928 | + | 1254 | 268 | 209 | 781 | 190 |
| ENST00000260953 | METTL5 | chr2 | 170676071 | - | ENST00000421804 | MERTK | chr2 | 112785928 | + | 1792 | 806 | 747 | 1319 | 190 |
| ENST00000409965 | METTL5 | chr2 | 170676071 | - | ENST00000421804 | MERTK | chr2 | 112785928 | + | 1662 | 676 | 617 | 1189 | 190 |
| ENST00000392640 | METTL5 | chr2 | 170676071 | - | ENST00000409780 | MERTK | chr2 | 112785928 | + | 1613 | 596 | 537 | 1109 | 190 |
| ENST00000410097 | METTL5 | chr2 | 170676071 | - | ENST00000421804 | MERTK | chr2 | 112785928 | + | 1611 | 625 | 566 | 1138 | 190 |
| DeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
| ENST00000409837 | ENST00000409780 | METTL5 | chr2 | 170676071 | - | MERTK | chr2 | 112785928 | + | 0.002484571 | 0.99751544 |
| ENST00000409340 | ENST00000421804 | METTL5 | chr2 | 170676071 | - | MERTK | chr2 | 112785928 | + | 0.003277651 | 0.9967224 |
| ENST00000260953 | ENST00000421804 | METTL5 | chr2 | 170676071 | - | MERTK | chr2 | 112785928 | + | 0.00361741 | 0.9963826 |
| ENST00000409965 | ENST00000421804 | METTL5 | chr2 | 170676071 | - | MERTK | chr2 | 112785928 | + | 0.001984217 | 0.99801576 |
| ENST00000392640 | ENST00000409780 | METTL5 | chr2 | 170676071 | - | MERTK | chr2 | 112785928 | + | 0.001678341 | 0.9983216 |
| ENST00000410097 | ENST00000421804 | METTL5 | chr2 | 170676071 | - | MERTK | chr2 | 112785928 | + | 0.002347504 | 0.9976525 |
Top |
Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP >53135_53135_1_METTL5-MERTK_METTL5_chr2_170676071_ENST00000260953_MERTK_chr2_112785928_ENST00000421804_length(amino acids)=190AA_BP=20 MLWKWQEQQYIPYTNPQLEKYEIMYSCWRTDPLDRPTFSVLRLQLEKLLESLPDVRNQADVIYVNTQLLESSEGLAQGSTLAPLDLNIDP DSIIASCTPRAAISVVTAEVHDSKPHEGRYILNGGSEEWEDLTSAPSAAVTAEKNSVLPGERLVRNGVSWSHSSMLPLGSSLPDELLFAD -------------------------------------------------------------- >53135_53135_2_METTL5-MERTK_METTL5_chr2_170676071_ENST00000392640_MERTK_chr2_112785928_ENST00000409780_length(amino acids)=190AA_BP=20 MLWKWQEQQYIPYTNPQLEKYEIMYSCWRTDPLDRPTFSVLRLQLEKLLESLPDVRNQADVIYVNTQLLESSEGLAQGSTLAPLDLNIDP DSIIASCTPRAAISVVTAEVHDSKPHEGRYILNGGSEEWEDLTSAPSAAVTAEKNSVLPGERLVRNGVSWSHSSMLPLGSSLPDELLFAD -------------------------------------------------------------- >53135_53135_3_METTL5-MERTK_METTL5_chr2_170676071_ENST00000409340_MERTK_chr2_112785928_ENST00000421804_length(amino acids)=190AA_BP=20 MLWKWQEQQYIPYTNPQLEKYEIMYSCWRTDPLDRPTFSVLRLQLEKLLESLPDVRNQADVIYVNTQLLESSEGLAQGSTLAPLDLNIDP DSIIASCTPRAAISVVTAEVHDSKPHEGRYILNGGSEEWEDLTSAPSAAVTAEKNSVLPGERLVRNGVSWSHSSMLPLGSSLPDELLFAD -------------------------------------------------------------- >53135_53135_4_METTL5-MERTK_METTL5_chr2_170676071_ENST00000409837_MERTK_chr2_112785928_ENST00000409780_length(amino acids)=190AA_BP=20 MLWKWQEQQYIPYTNPQLEKYEIMYSCWRTDPLDRPTFSVLRLQLEKLLESLPDVRNQADVIYVNTQLLESSEGLAQGSTLAPLDLNIDP DSIIASCTPRAAISVVTAEVHDSKPHEGRYILNGGSEEWEDLTSAPSAAVTAEKNSVLPGERLVRNGVSWSHSSMLPLGSSLPDELLFAD -------------------------------------------------------------- >53135_53135_5_METTL5-MERTK_METTL5_chr2_170676071_ENST00000409965_MERTK_chr2_112785928_ENST00000421804_length(amino acids)=190AA_BP=20 MLWKWQEQQYIPYTNPQLEKYEIMYSCWRTDPLDRPTFSVLRLQLEKLLESLPDVRNQADVIYVNTQLLESSEGLAQGSTLAPLDLNIDP DSIIASCTPRAAISVVTAEVHDSKPHEGRYILNGGSEEWEDLTSAPSAAVTAEKNSVLPGERLVRNGVSWSHSSMLPLGSSLPDELLFAD -------------------------------------------------------------- >53135_53135_6_METTL5-MERTK_METTL5_chr2_170676071_ENST00000410097_MERTK_chr2_112785928_ENST00000421804_length(amino acids)=190AA_BP=20 MLWKWQEQQYIPYTNPQLEKYEIMYSCWRTDPLDRPTFSVLRLQLEKLLESLPDVRNQADVIYVNTQLLESSEGLAQGSTLAPLDLNIDP DSIIASCTPRAAISVVTAEVHDSKPHEGRYILNGGSEEWEDLTSAPSAAVTAEKNSVLPGERLVRNGVSWSHSSMLPLGSSLPDELLFAD -------------------------------------------------------------- |
Top |
Fusion Protein Functional Features |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr2:170676071/chr2:112785928) - FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels. - How to search 1. Put your fusion gene symbol. 2. Press the tab key until there will be shown the breakpoint information filled. 4. Go down and press 'Search' tab twice. 4. Go down to have the hyperlink of the search result. 5. Click the hyperlink. 6. See the FGviewer result for your fusion gene. |
 |
| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| METTL5 | MERTK |
| FUNCTION: Catalytic subunit of a heterodimer with TRMT112, which specifically methylates the 6th position of adenine in position 1832 of 18S rRNA (PubMed:31328227, PubMed:32217665). N6-methylation of adenine(1832) in 18S rRNA is required for translation and embryonic stem cells (ESCs) pluripotency and differentiation (By similarity). {ECO:0000250|UniProtKB:Q8K1A0, ECO:0000269|PubMed:31328227, ECO:0000269|PubMed:32217665}. | FUNCTION: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. {ECO:0000269|PubMed:17005688}. |
| Retention analysis result of each fusion partner 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. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | METTL5 | chr2:170676071 | chr2:112785928 | ENST00000260953 | - | 4 | 7 | 108_109 | 163.0 | 210.0 | Region | S-adenosyl-L-methionine binding |
| Hgene | METTL5 | chr2:170676071 | chr2:112785928 | ENST00000392640 | - | 5 | 8 | 108_109 | 163.0 | 210.0 | Region | S-adenosyl-L-methionine binding |
| Hgene | METTL5 | chr2:170676071 | chr2:112785928 | ENST00000409965 | - | 5 | 8 | 108_109 | 163.0 | 210.0 | Region | S-adenosyl-L-methionine binding |
| - Not-retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000295408 | 17 | 19 | 197_273 | 828.6666666666666 | 1000.0 | Domain | Note=Ig-like C2-type 2 | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000295408 | 17 | 19 | 286_381 | 828.6666666666666 | 1000.0 | Domain | Fibronectin type-III 1 | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000295408 | 17 | 19 | 386_484 | 828.6666666666666 | 1000.0 | Domain | Fibronectin type-III 2 | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000295408 | 17 | 19 | 587_858 | 828.6666666666666 | 1000.0 | Domain | Protein kinase | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000295408 | 17 | 19 | 81_186 | 828.6666666666666 | 1000.0 | Domain | Note=Ig-like C2-type 1 | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000421804 | 17 | 20 | 197_273 | 828.6666666666666 | 951.3333333333334 | Domain | Note=Ig-like C2-type 2 | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000421804 | 17 | 20 | 286_381 | 828.6666666666666 | 951.3333333333334 | Domain | Fibronectin type-III 1 | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000421804 | 17 | 20 | 386_484 | 828.6666666666666 | 951.3333333333334 | Domain | Fibronectin type-III 2 | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000421804 | 17 | 20 | 587_858 | 828.6666666666666 | 951.3333333333334 | Domain | Protein kinase | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000421804 | 17 | 20 | 81_186 | 828.6666666666666 | 951.3333333333334 | Domain | Note=Ig-like C2-type 1 | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000295408 | 17 | 19 | 593_601 | 828.6666666666666 | 1000.0 | Nucleotide binding | ATP | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000421804 | 17 | 20 | 593_601 | 828.6666666666666 | 951.3333333333334 | Nucleotide binding | ATP | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000295408 | 17 | 19 | 21_505 | 828.6666666666666 | 1000.0 | Topological domain | Extracellular | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000295408 | 17 | 19 | 527_999 | 828.6666666666666 | 1000.0 | Topological domain | Cytoplasmic | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000421804 | 17 | 20 | 21_505 | 828.6666666666666 | 951.3333333333334 | Topological domain | Extracellular | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000421804 | 17 | 20 | 527_999 | 828.6666666666666 | 951.3333333333334 | Topological domain | Cytoplasmic | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000295408 | 17 | 19 | 506_526 | 828.6666666666666 | 1000.0 | Transmembrane | Helical | |
| Tgene | MERTK | chr2:170676071 | chr2:112785928 | ENST00000421804 | 17 | 20 | 506_526 | 828.6666666666666 | 951.3333333333334 | Transmembrane | Helical |
Top |
Fusion Protein-Protein Interaction |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in |
| Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160) |
| Gene | PPI interactors |
| Protein-protein interactors based on sequence similarity (STRING) |
| Gene | STRING network |
| METTL5 | |
| MERTK |
| - Retained interactions in fusion protein (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost interactions due to fusion (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
Top |
Related Drugs to METTL5-MERTK |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
Top |
Related Diseases to METTL5-MERTK |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
Copyright 2021-Present -The University of Texas Health Science Center at Houston (UTHealth)
Web File Viewing | Emergency Information |Campus Carry|Site Policies