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Fusion Protein:FAM45A-GRK5 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: FAM45A-GRK5 | FusionPDB ID: 29041 | FusionGDB2.0 ID: 29041 | Hgene | Tgene | Gene symbol | FAM45A | GRK5 | Gene ID | 404636 | 2869 |
| Gene name | DENN domain containing 10 | G protein-coupled receptor kinase 5 | |
| Synonyms | FAM45A | FP2025|GPRK5 | |
| Cytomap | 10q26.11 | 10q26.11 | |
| Type of gene | protein-coding | protein-coding | |
| Description | DENN domain-containing protein 10family with sequence similarity 45 member Aprotein FAM45A | G protein-coupled receptor kinase 5g protein-coupled receptor kinase GRK5 | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | . | P34947 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000489988, ENST00000535029, ENST00000361432, ENST00000544016, | ENST00000369108, ENST00000392870, ENST00000473264, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 3 X 3 X 2=18 | 19 X 19 X 6=2166 |
| # samples | 3 | 19 | |
| ** MAII score | log2(3/18*10)=0.736965594166206 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0 | log2(19/2166*10)=-3.51096191927738 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: FAM45A [Title/Abstract] AND GRK5 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | FAM45A(120892121)-GRK5(121207634), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | FAM45A-GRK5 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. FAM45A-GRK5 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. FAM45A-GRK5 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. FAM45A-GRK5 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. | ||
| * 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 | GRK5 | GO:0007217 | tachykinin receptor signaling pathway | 17986524 |
| Tgene | GRK5 | GO:0043066 | negative regulation of apoptotic process | 20124405 |
| Tgene | GRK5 | GO:0046777 | protein autophosphorylation | 14976207 |
| Fusion gene breakpoints across FAM45A (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 GRK5 (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 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 | STAD | TCGA-VQ-A928 | FAM45A | chr10 | 120892121 | + | GRK5 | chr10 | 121207634 | + |
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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) |
| ENST00000544016 | FAM45A | chr10 | 120892121 | + | ENST00000392870 | GRK5 | chr10 | 121207634 | + | 1853 | 794 | 350 | 1300 | 316 |
| ENST00000544016 | FAM45A | chr10 | 120892121 | + | ENST00000369108 | GRK5 | chr10 | 121207634 | + | 1352 | 794 | 350 | 1300 | 316 |
| ENST00000361432 | FAM45A | chr10 | 120892121 | + | ENST00000392870 | GRK5 | chr10 | 121207634 | + | 1982 | 923 | 26 | 1429 | 467 |
| ENST00000361432 | FAM45A | chr10 | 120892121 | + | ENST00000369108 | GRK5 | chr10 | 121207634 | + | 1481 | 923 | 26 | 1429 | 467 |
| 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 |
| ENST00000544016 | ENST00000392870 | FAM45A | chr10 | 120892121 | + | GRK5 | chr10 | 121207634 | + | 0.000893103 | 0.9991068 |
| ENST00000544016 | ENST00000369108 | FAM45A | chr10 | 120892121 | + | GRK5 | chr10 | 121207634 | + | 0.002214909 | 0.9977851 |
| ENST00000361432 | ENST00000392870 | FAM45A | chr10 | 120892121 | + | GRK5 | chr10 | 121207634 | + | 0.00121168 | 0.9987883 |
| ENST00000361432 | ENST00000369108 | FAM45A | chr10 | 120892121 | + | GRK5 | chr10 | 121207634 | + | 0.002795266 | 0.9972047 |
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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 >29041_29041_1_FAM45A-GRK5_FAM45A_chr10_120892121_ENST00000361432_GRK5_chr10_121207634_ENST00000369108_length(amino acids)=467AA_BP=0 MAAAEVADTQLMLGVGLIEKDTNGEVLWVWCYPSTTATLRNLLLRKCCLTDENKLLHPFVFGQYRRTWFYITTIEVPDSSILKKVTHFSI VLTAKDFNPEKYAAFTRILCRMYLKHGSPVKMMESYIAVLTKGICQSEENGSFLSKDFDARKAYLAGSIKDIVSQFGMETVILHTALMLK KRIVVYHPKIEAVQEFTRTLPALVWHRQDWTILHSYVHLNADELEALQMCTGYVAGFVDLEVSNRPDLYDVFVNLAESEITIAPLAKEAM AMGKLHKEMGQLIVQSAEDPEKSESHVIQLLTKDAKQRLGCQEEGAAEVKRHPFFRNMNFKRLEAGMLDPPFVPDPRAVYCKDVLDIEQF STVKGVNLDHTDDDFYSKFSTGSVSIPWQNEMIETECFKELNVFGPNGTLPPDLNRNHPPEPPKKGLLQRLFKRQHQNNSKSSPSSKTSF -------------------------------------------------------------- >29041_29041_2_FAM45A-GRK5_FAM45A_chr10_120892121_ENST00000361432_GRK5_chr10_121207634_ENST00000392870_length(amino acids)=467AA_BP=0 MAAAEVADTQLMLGVGLIEKDTNGEVLWVWCYPSTTATLRNLLLRKCCLTDENKLLHPFVFGQYRRTWFYITTIEVPDSSILKKVTHFSI VLTAKDFNPEKYAAFTRILCRMYLKHGSPVKMMESYIAVLTKGICQSEENGSFLSKDFDARKAYLAGSIKDIVSQFGMETVILHTALMLK KRIVVYHPKIEAVQEFTRTLPALVWHRQDWTILHSYVHLNADELEALQMCTGYVAGFVDLEVSNRPDLYDVFVNLAESEITIAPLAKEAM AMGKLHKEMGQLIVQSAEDPEKSESHVIQLLTKDAKQRLGCQEEGAAEVKRHPFFRNMNFKRLEAGMLDPPFVPDPRAVYCKDVLDIEQF STVKGVNLDHTDDDFYSKFSTGSVSIPWQNEMIETECFKELNVFGPNGTLPPDLNRNHPPEPPKKGLLQRLFKRQHQNNSKSSPSSKTSF -------------------------------------------------------------- >29041_29041_3_FAM45A-GRK5_FAM45A_chr10_120892121_ENST00000544016_GRK5_chr10_121207634_ENST00000369108_length(amino acids)=316AA_BP=0 MLPSLGYCVDIVSQFGMETVILHTALMLKKRIVVYHPKIEAVQEFTRTLPALVWHRQDWTILHSYVHLNADELEALQMCTGYVAGFVDLE VSNRPDLYDVFVNLAESEITIAPLAKEAMAMGKLHKEMGQLIVQSAEDPEKSESHVIQLLTKDAKQRLGCQEEGAAEVKRHPFFRNMNFK RLEAGMLDPPFVPDPRAVYCKDVLDIEQFSTVKGVNLDHTDDDFYSKFSTGSVSIPWQNEMIETECFKELNVFGPNGTLPPDLNRNHPPE -------------------------------------------------------------- >29041_29041_4_FAM45A-GRK5_FAM45A_chr10_120892121_ENST00000544016_GRK5_chr10_121207634_ENST00000392870_length(amino acids)=316AA_BP=0 MLPSLGYCVDIVSQFGMETVILHTALMLKKRIVVYHPKIEAVQEFTRTLPALVWHRQDWTILHSYVHLNADELEALQMCTGYVAGFVDLE VSNRPDLYDVFVNLAESEITIAPLAKEAMAMGKLHKEMGQLIVQSAEDPEKSESHVIQLLTKDAKQRLGCQEEGAAEVKRHPFFRNMNFK RLEAGMLDPPFVPDPRAVYCKDVLDIEQFSTVKGVNLDHTDDDFYSKFSTGSVSIPWQNEMIETECFKELNVFGPNGTLPPDLNRNHPPE -------------------------------------------------------------- |
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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/chr10:120892121/chr10:121207634) - 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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| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| . | GRK5 |
| FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes. | FUNCTION: Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro). {ECO:0000269|PubMed:19661922, ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:20038610, ECO:0000269|PubMed:20124405, ECO:0000269|PubMed:21728385}. |
| 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 | FAM45A | chr10:120892121 | chr10:121207634 | ENST00000361432 | + | 8 | 9 | 165_299 | 299.0 | 358.0 | Domain | cDENN |
| Hgene | FAM45A | chr10:120892121 | chr10:121207634 | ENST00000361432 | + | 8 | 9 | 1_140 | 299.0 | 358.0 | Domain | uDENN |
| Tgene | GRK5 | chr10:120892121 | chr10:121207634 | ENST00000392870 | 11 | 16 | 449_514 | 422.0 | 591.0 | Domain | AGC-kinase C-terminal | |
| Tgene | GRK5 | chr10:120892121 | chr10:121207634 | ENST00000392870 | 11 | 16 | 546_565 | 422.0 | 591.0 | Region | Note=Sufficient for membrane localization |
| - 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 |
| Hgene | FAM45A | chr10:120892121 | chr10:121207634 | ENST00000361432 | + | 8 | 9 | 301_357 | 299.0 | 358.0 | Domain | dDENN |
| Tgene | GRK5 | chr10:120892121 | chr10:121207634 | ENST00000392870 | 11 | 16 | 186_448 | 422.0 | 591.0 | Domain | Protein kinase | |
| Tgene | GRK5 | chr10:120892121 | chr10:121207634 | ENST00000392870 | 11 | 16 | 53_171 | 422.0 | 591.0 | Domain | RGS | |
| Tgene | GRK5 | chr10:120892121 | chr10:121207634 | ENST00000392870 | 11 | 16 | 388_395 | 422.0 | 591.0 | Motif | Nuclear localization signal | |
| Tgene | GRK5 | chr10:120892121 | chr10:121207634 | ENST00000392870 | 11 | 16 | 192_200 | 422.0 | 591.0 | Nucleotide binding | ATP | |
| Tgene | GRK5 | chr10:120892121 | chr10:121207634 | ENST00000392870 | 11 | 16 | 1_185 | 422.0 | 591.0 | Region | Note=N-terminal |
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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 |
| FAM45A | |
| GRK5 |
| - 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 |
| Tgene | GRK5 | chr10:120892121 | chr10:121207634 | ENST00000392870 | 11 | 16 | 20_39 | 422.0 | 591.0 | calmodulin |
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Related Drugs to FAM45A-GRK5 |
| 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 FAM45A-GRK5 |
| 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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