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Fusion Protein:PRKCA-IGF2BP1 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: PRKCA-IGF2BP1 | FusionPDB ID: 68703 | FusionGDB2.0 ID: 68703 | Hgene | Tgene | Gene symbol | PRKCA | IGF2BP1 | Gene ID | 5578 | 10642 |
| Gene name | protein kinase C alpha | insulin like growth factor 2 mRNA binding protein 1 | |
| Synonyms | AAG6|PKC-alpha|PKCA|PKCI+/-|PKCalpha|PRKACA | CRD-BP|CRDBP|IMP-1|IMP1|VICKZ1|ZBP1 | |
| Cytomap | 17q24.2 | 17q21.32 | |
| Type of gene | protein-coding | protein-coding | |
| Description | protein kinase C alpha typePKC-Aaging-associated gene 6 | insulin-like growth factor 2 mRNA-binding protein 1IGF-II mRNA-binding protein 1IGF2 mRNA-binding protein 1VICKZ family member 1ZBP-1coding region determinant-binding proteininsulin-like growth factor 2 mRNA binding protein 1 deltaN CRDBPzipcode-bi | |
| Modification date | 20200327 | 20200315 | |
| UniProtAcc | PICK1 Main function of 5'-partner protein: 415 | Q9NZI8 Main function of 5'-partner protein: FUNCTION: RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Plays a direct role in the transport and translation of transcripts required for axonal regeneration in adult sensory neurons (By similarity). Regulates localized beta-actin/ACTB mRNA translation, a crucial process for cell polarity, cell migration and neurite outgrowth. Co-transcriptionally associates with the ACTB mRNA in the nucleus. This binding involves a conserved 54-nucleotide element in the ACTB mRNA 3'-UTR, known as the 'zipcode'. The RNP thus formed is exported to the cytoplasm, binds to a motor protein and is transported along the cytoskeleton to the cell periphery. During transport, prevents ACTB mRNA from being translated into protein. When the RNP complex reaches its destination near the plasma membrane, IGF2BP1 is phosphorylated. This releases the mRNA, allowing ribosomal 40S and 60S subunits to assemble and initiate ACTB protein synthesis. Monomeric ACTB then assembles into the subcortical actin cytoskeleton (By similarity). During neuronal development, key regulator of neurite outgrowth, growth cone guidance and neuronal cell migration, presumably through the spatiotemporal fine tuning of protein synthesis, such as that of ACTB (By similarity). May regulate mRNA transport to activated synapses (By similarity). Binds to and stabilizes ABCB1/MDR-1 mRNA (By similarity). During interstinal wound repair, interacts with and stabilizes PTGS2 transcript. PTGS2 mRNA stabilization may be crucial for colonic mucosal wound healing (By similarity). Binds to the 3'-UTR of IGF2 mRNA by a mechanism of cooperative and sequential dimerization and regulates IGF2 mRNA subcellular localization and translation. Binds to MYC mRNA, in the coding region instability determinant (CRD) of the open reading frame (ORF), hence prevents MYC cleavage by endonucleases and possibly microRNA targeting to MYC-CRD. Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells. Binds to the oncofetal H19 transcript and to the neuron-specific TAU mRNA and regulates their localizations. Binds to and stabilizes BTRC/FBW1A mRNA. Binds to the adenine-rich autoregulatory sequence (ARS) located in PABPC1 mRNA and represses its translation. PABPC1 mRNA-binding is stimulated by PABPC1 protein. Prevents BTRC/FBW1A mRNA degradation by disrupting microRNA-dependent interaction with AGO2. Promotes the directed movement of tumor-derived cells by fine-tuning intracellular signaling networks. Binds to MAPK4 3'-UTR and inhibits its translation. Interacts with PTEN transcript open reading frame (ORF) and prevents mRNA decay. This combined action on MAPK4 (down-regulation) and PTEN (up-regulation) antagonizes HSPB1 phosphorylation, consequently it prevents G-actin sequestration by phosphorylated HSPB1, allowing F-actin polymerization. Hence enhances the velocity of cell migration and stimulates directed cell migration by PTEN-modulated polarization. Interacts with Hepatitis C virus (HCV) 5'-UTR and 3'-UTR and specifically enhances translation at the HCV IRES, but not 5'-cap-dependent translation, possibly by recruiting eIF3. Interacts with HIV-1 GAG protein and blocks the formation of infectious HIV-1 particles. Reduces HIV-1 assembly by inhibiting viral RNA packaging, as well as assembly and processing of GAG protein on cellular membranes. During cellular stress, such as oxidative stress or heat shock, stabilizes target mRNAs that are recruited to stress granules, including CD44, IGF2, MAPK4, MYC, PTEN, RAPGEF2 and RPS6KA5 transcripts. {ECO:0000250, ECO:0000269|PubMed:10875929, ECO:0000269|PubMed:16356927, ECO:0000269|PubMed:16541107, ECO:0000269|PubMed:16778892, ECO:0000269|PubMed:17101699, ECO:0000269|PubMed:17255263, ECO:0000269|PubMed:17893325, ECO:0000269|PubMed:18385235, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:19541769, ECO:0000269|PubMed:19647520, ECO:0000269|PubMed:20080952, ECO:0000269|PubMed:22279049, ECO:0000269|PubMed:8132663, ECO:0000269|PubMed:9891060}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000583361, ENST00000413366, | ENST00000290341, ENST00000431824, ENST00000515586, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 44 X 23 X 14=14168 | 9 X 10 X 3=270 |
| # samples | 46 | 10 | |
| ** MAII score | log2(46/14168*10)=-4.94485844580754 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(10/270*10)=-1.43295940727611 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: PRKCA [Title/Abstract] AND IGF2BP1 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: PRKCA [Title/Abstract] AND IGF2BP1 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | PRKCA(64302245)-IGF2BP1(47126714), # samples:2 | ||
| Anticipated loss of major functional domain due to fusion event. | PRKCA-IGF2BP1 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. PRKCA-IGF2BP1 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. PRKCA-IGF2BP1 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. PRKCA-IGF2BP1 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. PRKCA-IGF2BP1 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF. PRKCA-IGF2BP1 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF. PRKCA-IGF2BP1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. PRKCA-IGF2BP1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. PRKCA-IGF2BP1 seems lost the major protein functional domain in Hgene 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 |
| Hgene | PRKCA | GO:0006468 | protein phosphorylation | 10770950 |
| Hgene | PRKCA | GO:0035408 | histone H3-T6 phosphorylation | 20228790 |
| Hgene | PRKCA | GO:0043536 | positive regulation of blood vessel endothelial cell migration | 20011604 |
| Hgene | PRKCA | GO:0090330 | regulation of platelet aggregation | 12724315 |
| Tgene | IGF2BP1 | GO:0017148 | negative regulation of translation | 9891060 |
| Tgene | IGF2BP1 | GO:0070934 | CRD-mediated mRNA stabilization | 19029303 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr17:64302245/chr17:47126714) - 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 PRKCA (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 IGF2BP1 (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) |
| ENST00000413366 | PRKCA | chr17 | 64302245 | + | ENST00000290341 | IGF2BP1 | chr17 | 47126714 | + | 6530 | 231 | 2899 | 3315 | 138 |
| 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 |
| ENST00000413366 | ENST00000290341 | PRKCA | chr17 | 64302245 | + | IGF2BP1 | chr17 | 47126714 | + | 0.40770778 | 0.5922922 |
| 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 PRKCA-IGF2BP1 |
| +/-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 PRKCA-IGF2BP1 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 PRKCA-IGF2BP1 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 PRKCA-IGF2BP1 |
| 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 PRKCA-IGF2BP1 |
| 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 PRKCA-IGF2BP1 |
| 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 PRKCA-IGF2BP1 |
| 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 PRKCA-IGF2BP1 |
| 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 |
| 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 PRKCA-IGF2BP1 |
| 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 PRKCA-IGF2BP1 |
| 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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