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Fusion Protein:MARK2-PLA2G16 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: MARK2-PLA2G16 | FusionPDB ID: 51755 | FusionGDB2.0 ID: 51755 | Hgene | Tgene | Gene symbol | MARK2 | PLA2G16 | Gene ID | 2011 | 11145 |
| Gene name | microtubule affinity regulating kinase 2 | phospholipase A and acyltransferase 3 | |
| Synonyms | EMK-1|EMK1|PAR-1|Par-1b|Par1b | AdPLA|H-REV107|H-REV107-1|HRASLS3|HREV107|HREV107-1|HREV107-3|HRSL3|PLA2G16|PLAAT-3 | |
| Cytomap | 11q13.1 | 11q12.3-q13.1 | |
| Type of gene | protein-coding | protein-coding | |
| Description | serine/threonine-protein kinase MARK2ELKL motif kinase 1MAP/microtubule affinity-regulating kinase 2PAR1 homolog bSer/Thr protein kinase PAR-1Bserine/threonine protein kinase EMKtesticular tissue protein Li 117 | phospholipase A and acyltransferase 3Ca-independent phospholipase A1/2H-rev 107 protein homologHRAS-like suppressor 1HRAS-like suppressor 3adipose-specific PLA2adipose-specific phospholipase A2group XVI phospholipase A1/A2group XVI phospholipase A | |
| Modification date | 20200329 | 20200313 | |
| UniProtAcc | Q7KZI7 Main function of 5'-partner protein: FUNCTION: Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:12429843, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15158914, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:15365179, ECO:0000269|PubMed:16775013, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:18626018, ECO:0000269|PubMed:20194617, ECO:0000269|PubMed:23666762}. | . | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000315032, ENST00000350490, ENST00000361128, ENST00000377809, ENST00000402010, ENST00000413835, ENST00000502399, ENST00000508192, ENST00000377810, ENST00000408948, ENST00000425897, ENST00000509502, ENST00000513765, | ENST00000394613, ENST00000323646, ENST00000415826, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 13 X 9 X 11=1287 | 8 X 7 X 4=224 |
| # samples | 21 | 8 | |
| ** MAII score | log2(21/1287*10)=-2.61555082055458 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(8/224*10)=-1.48542682717024 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: MARK2 [Title/Abstract] AND PLA2G16 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: MARK2 [Title/Abstract] AND PLA2G16 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | MARK2(63607032)-PLA2G16(63342518), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | MARK2-PLA2G16 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. MARK2-PLA2G16 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. MARK2-PLA2G16 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. MARK2-PLA2G16 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF. MARK2-PLA2G16 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF. MARK2-PLA2G16 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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 |
| Hgene | MARK2 | GO:0006468 | protein phosphorylation | 14976552 |
| Hgene | MARK2 | GO:0010976 | positive regulation of neuron projection development | 12429843 |
| Hgene | MARK2 | GO:0018105 | peptidyl-serine phosphorylation | 10542369|16717194 |
| Hgene | MARK2 | GO:0030010 | establishment of cell polarity | 12429843 |
| Hgene | MARK2 | GO:0035556 | intracellular signal transduction | 14976552 |
| Hgene | MARK2 | GO:0045197 | establishment or maintenance of epithelial cell apical/basal polarity | 15324659 |
| Hgene | MARK2 | GO:0070507 | regulation of microtubule cytoskeleton organization | 10542369 |
| Tgene | PLA2G16 | GO:0006644 | phospholipid metabolic process | 20100577 |
| Tgene | PLA2G16 | GO:0070292 | N-acylphosphatidylethanolamine metabolic process | 22825852 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr11:63607032/chr11:63342518) - 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. |
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| Retention analysis results 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, are available here. |
| Fusion gene breakpoints across MARK2 (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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| Fusion gene breakpoints across PLA2G16 (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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Fusion Amino Acid Sequences |
| 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) |
| ENST00000377809 | MARK2 | chr11 | 63607032 | + | ENST00000415826 | PLA2G16 | chr11 | 63342518 | - | 1206 | 633 | 68 | 493 | 141 |
| ENST00000402010 | MARK2 | chr11 | 63607032 | + | ENST00000415826 | PLA2G16 | chr11 | 63342518 | - | 1206 | 633 | 68 | 493 | 141 |
| ENST00000413835 | MARK2 | chr11 | 63607032 | + | ENST00000415826 | PLA2G16 | chr11 | 63342518 | - | 1206 | 633 | 68 | 493 | 141 |
| ENST00000315032 | MARK2 | chr11 | 63607032 | + | ENST00000415826 | PLA2G16 | chr11 | 63342518 | - | 1206 | 633 | 68 | 493 | 141 |
| ENST00000508192 | MARK2 | chr11 | 63607032 | + | ENST00000415826 | PLA2G16 | chr11 | 63342518 | - | 1129 | 556 | 15 | 416 | 133 |
| ENST00000361128 | MARK2 | chr11 | 63607032 | + | ENST00000415826 | PLA2G16 | chr11 | 63342518 | - | 1129 | 556 | 15 | 416 | 133 |
| ENST00000350490 | MARK2 | chr11 | 63607032 | + | ENST00000415826 | PLA2G16 | chr11 | 63342518 | - | 1041 | 468 | 610 | 233 | 125 |
| ENST00000502399 | MARK2 | chr11 | 63607032 | + | ENST00000415826 | PLA2G16 | chr11 | 63342518 | - | 839 | 266 | 408 | 31 | 125 |
| 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 |
| ENST00000377809 | ENST00000415826 | MARK2 | chr11 | 63607032 | + | PLA2G16 | chr11 | 63342518 | - | 0.5288704 | 0.47112957 |
| ENST00000402010 | ENST00000415826 | MARK2 | chr11 | 63607032 | + | PLA2G16 | chr11 | 63342518 | - | 0.5288704 | 0.47112957 |
| ENST00000413835 | ENST00000415826 | MARK2 | chr11 | 63607032 | + | PLA2G16 | chr11 | 63342518 | - | 0.5288704 | 0.47112957 |
| ENST00000315032 | ENST00000415826 | MARK2 | chr11 | 63607032 | + | PLA2G16 | chr11 | 63342518 | - | 0.5288704 | 0.47112957 |
| ENST00000508192 | ENST00000415826 | MARK2 | chr11 | 63607032 | + | PLA2G16 | chr11 | 63342518 | - | 0.21254049 | 0.78745955 |
| ENST00000361128 | ENST00000415826 | MARK2 | chr11 | 63607032 | + | PLA2G16 | chr11 | 63342518 | - | 0.21254049 | 0.78745955 |
| ENST00000350490 | ENST00000415826 | MARK2 | chr11 | 63607032 | + | PLA2G16 | chr11 | 63342518 | - | 0.23851985 | 0.76148015 |
| ENST00000502399 | ENST00000415826 | MARK2 | chr11 | 63607032 | + | PLA2G16 | chr11 | 63342518 | - | 0.27537215 | 0.72462785 |
| Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones. |
Get the fusion protein sequences from here. |
| Fusion protein sequence information is available in the fasta format. >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP |
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Fusion Protein Breakpoint Sequences for MARK2-PLA2G16 |
| +/-13 AA sequence from the breakpoints of the fusion protein sequences. |
| Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Length(fusion protein) | BP in fusion protein | Peptide |
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Potential FusionNeoAntigen Information of MARK2-PLA2G16 in HLA I |
| Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific. |
| Potential FusionNeoAntigen Information * We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5) |
| Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA I | FusionNeoAntigen peptide | Binding score | Immunogenic score | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
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Potential FusionNeoAntigen Information of MARK2-PLA2G16 in HLA II |
| Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific. |
| Potential FusionNeoAntigen Information * We used NetMHCIIpan v4.1 (%rank<0.5). |
| Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA II | FusionNeoAntigen peptide | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
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Fusion breakpoint peptide structures of MARK2-PLA2G16 |
| 3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens * The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA. |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MARK2-PLA2G16 |
| Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens * We used Glide to predict the interaction between HLAs and neoantigens. |
| HLA allele | PDB ID | File name | BPseq | Docking score | Glide score |
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Vaccine Design for the FusionNeoAntigens of MARK2-PLA2G16 |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide sequence | FusionNeoAntigen RNA sequence |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide | FusionNEoAntigen RNA sequence |
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Information of the samples that have these potential fusion neoantigens of MARK2-PLA2G16 |
| These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens. |
| Cancer type | Fusion gene | Hchr | Hbp | Henst | Tchr | Tbp | Tenst | Sample |
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Potential target of CAR-T therapy development for MARK2-PLA2G16 |
| Predicted 3D structure. We used RoseTTAFold. |
| 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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features * Minus value of BPloci means that the break point is located before the CDS. |
| - In-frame and retained 'Transmembrane'. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Tgene | PLA2G16 | chr11:63607032 | chr11:63342518 | ENST00000323646 | 2 | 4 | 134_154 | 0 | 163.0 | Transmembrane | Helical | |
| Tgene | PLA2G16 | chr11:63607032 | chr11:63342518 | ENST00000415826 | 3 | 5 | 134_154 | 0 | 163.0 | Transmembrane | Helical |
| Subcellular localization prediction of the transmembrane domain retained fusion proteins * We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image. |
| Hgene | Hchr | Hbp | Henst | Tgene | Tchr | Tbp | Tenst | DeepLoc result |
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Related Drugs to MARK2-PLA2G16 |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to MARK2-PLA2G16 |
| 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 |
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