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Kinase Fusion Gene:FGR_SQSTM1 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: FGR_SQSTM1 | KinaseFusionDB ID: KFG2371 | FusionGDB2.0 ID: KFG2371 | Hgene | Tgene | Gene symbol | FGR | SQSTM1 | Gene ID | 2268 | 8878 | |
| Gene name | FGR proto-oncogene, Src family tyrosine kinase | sequestosome 1 | ||||||||||
| Synonyms | SRC2|c-fgr|c-src2|p55-Fgr|p55c-fgr|p58-Fgr|p58c-fgr | A170|DMRV|FTDALS3|NADGP|OSIL|PDB3|ZIP3|p60|p62|p62B | ||||||||||
| Cytomap | 1p35.3 | 5q35.3 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | tyrosine-protein kinase FgrGardner-Rasheed feline sarcoma viral (v-fgr) oncogene homologc-fgr protooncogenec-src-2 proto-oncogenefeline Gardner-Rasheed sarcoma viral oncogene homologp55-c-fgr proteinproto-oncogene c-Fgrproto-oncogene tyrosine-prote | sequestosome-1EBI3-associated protein of 60 kDaEBI3-associated protein p60EBIAPautophagy receptor p62oxidative stress induced likephosphotyrosine independent ligand for the Lck SH2 domain p62phosphotyrosine-independent ligand for the Lck SH2 domain | ||||||||||
| Modification date | 20240411 | 20240411 | ||||||||||
| UniProtAcc | P09769 | Q13501 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000374004, ENST00000374005, ENST00000399173, ENST00000468038, ENST00000545953, | ENST00000376929, ENST00000360718, ENST00000389805, ENST00000402874, ENST00000506690, ENST00000510187, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: FGR [Title/Abstract] AND SQSTM1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | FGR(27942264)-SQSTM1(179252166), # samples:1 | |||||||||||
| 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 | FGR | GO:0018108 | peptidyl-tyrosine phosphorylation | 7519620|8327512 |
| Hgene | FGR | GO:0046777 | protein autophosphorylation | 2181286|8327512 |
| Tgene | SQSTM1 | GO:0000425 | pexophagy | 26344566 |
| Tgene | SQSTM1 | GO:0006914 | autophagy | 20452972 |
| Tgene | SQSTM1 | GO:0007032 | endosome organization | 27368102 |
| Tgene | SQSTM1 | GO:0010508 | positive regulation of autophagy | 28871090 |
| Tgene | SQSTM1 | GO:0030163 | protein catabolic process | 27498865|30612879|32715615|36221902 |
| Tgene | SQSTM1 | GO:0031397 | negative regulation of protein ubiquitination | 20452972 |
| Tgene | SQSTM1 | GO:0034144 | negative regulation of toll-like receptor 4 signaling pathway | 31281713 |
| Tgene | SQSTM1 | GO:0035973 | aggrephagy | 17580304|22017874|29343546|29507397|31857589|37306101|37802024 |
| Tgene | SQSTM1 | GO:0061635 | regulation of protein complex stability | 25127057 |
| Tgene | SQSTM1 | GO:0071211 | protein targeting to vacuole involved in autophagy | 27498865|36221902|37802024 |
| Tgene | SQSTM1 | GO:0140694 | non-membrane-bounded organelle assembly | 29343546|29507397|31857589|37802024 |
| Tgene | SQSTM1 | GO:1905719 | protein localization to perinuclear region of cytoplasm | 27368102 |
| Kinase Fusion gene breakpoints across FGR (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Kinase Fusion gene breakpoints across SQSTM1 (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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Kinase Fusion Gene Sample Information |
| Kinase Fusion gene information. |
| Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE) * 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 | Sample | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp |
| ChiTaRS5.0 | BG314620 | FGR | chr1 | 27942264 | SQSTM1 | chr5 | 179252166 |
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Kinase Fusion ORF Analysis |
| Kinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Seq length (transcript) | Seq length (amino acids) |
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Kinase Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq |
Multiple Sequence Alignment of All Fusion Protein Isoforms |
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Kinase 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/:27942264/:179252166) - 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 |
| FGR | SQSTM1 |
| FUNCTION: Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration. Promotes mast cell degranulation, release of inflammatory cytokines and IgE-mediated anaphylaxis. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as MS4A2/FCER1B, FCGR2A and/or FCGR2B. Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton reorganization, cell spreading and adhesion. Depending on the context, activates or inhibits cellular responses. Functions as a negative regulator of ITGB2 signaling, phagocytosis and SYK activity in monocytes. Required for normal ITGB1 and ITGB2 signaling, normal cell spreading and adhesion in neutrophils and macrophages. Functions as a positive regulator of cell migration and regulates cytoskeleton reorganization via RAC1 activation. Phosphorylates SYK (in vitro) and promotes SYK-dependent activation of AKT1 and MAP kinase signaling. Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 activation and the production of the signaling molecules lysophosphatidic acid and diacylglycerol. Promotes activation of PIK3R1. Phosphorylates FASLG, and thereby regulates its ubiquitination and subsequent internalization. Phosphorylates ABL1. Promotes phosphorylation of CBL, CTTN, PIK3R1, PTK2/FAK1, PTK2B/PYK2 and VAV2. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1. Together with CLNK, it acts as a negative regulator of natural killer cell-activating receptors and inhibits interferon-gamma production (By similarity). {ECO:0000250|UniProtKB:P14234, ECO:0000269|PubMed:10739672, ECO:0000269|PubMed:17164290, ECO:0000269|PubMed:1737799, ECO:0000269|PubMed:7519620}. | FUNCTION: Autophagy receptor required for selective macroautophagy (aggrephagy) (PubMed:34471133, PubMed:16286508, PubMed:20168092, PubMed:24128730, PubMed:28404643, PubMed:22622177, PubMed:33509017). Functions as a bridge between polyubiquitinated cargo and autophagosomes (PubMed:34471133). Interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family (PubMed:16286508, PubMed:20168092, PubMed:24128730, PubMed:28404643, PubMed:22622177). Along with WDFY3, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with WDFY3, required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:24128730, PubMed:20168092). Also involved in autophagy of peroxisomes (pexophagy) in response to reactive oxygen species (ROS) by acting as a bridge between ubiquitinated PEX5 receptor and autophagosomes (PubMed:26344566). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role in titin/TTN downstream signaling in muscle cells. May regulate signaling cascades through ubiquitination. Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels. Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (PubMed:27368102). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (PubMed:29496741). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (PubMed:20452972, PubMed:28380357, PubMed:33393215). Sequesters tensin TNS2 into cytoplasmic puncta, promoting TNS2 ubiquitination and proteasomal degradation (PubMed:25101860). {ECO:0000250|UniProtKB:O08623, ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10747026, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:15340068, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:15953362, ECO:0000269|PubMed:16079148, ECO:0000269|PubMed:16286508, ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:25101860, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:28404643, ECO:0000269|PubMed:29496741, ECO:0000269|PubMed:33393215, ECO:0000269|PubMed:33509017, ECO:0000269|PubMed:34471133}. |
| 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 domain in the 5'-partner of fusion protein (protein functional feature from UniProt). |
| Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
| - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt). |
| Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
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Kinase-Substrate Information of FGR_SQSTM1 |
| Phosphorylation target of the kinase (phosphosite, 03-17-2024) |
| Kinase | Kinase UniProt Acc | Kinase species | Substrate | Substrate UniProt Acc | Substrate phosphorylated residues | Substrate phosphorylated sites (+/-7AA) | Domain |
| FGR | P09769 | human | PTK2 | Q05397 | Y925 | DRsNDkVyENVtGLV | Focal_AT |
| FGR | P09769 | human | ALOX5 | P09917 | Y446 | RAMKDLtyAsLCFPE | Lipoxygenase |
| FGR | P09769 | human | TBK1 | Q9UHD2 | Y354 | SSNQELIyEGRRLVL | TBK1_ULD |
| FGR | P09769 | human | GLO1 | Q04760 | Y136 | GIAVPDVysACkRFE | Glyoxalase |
| FGR | P09769 | human | NFE2L2 | Q16236 | Y576 | RDEDGkPysPSEYSL | |
| FGR | P09769 | human | PTK2 | Q05397 | Y397 | sVsEtDDyAEIIDEE | |
| FGR | P09769 | human | RIPK2 | O43353 | Y474 | DLIMKEDyELVSTkP | CARD |
| FGR | P09769 | human | ALOX5 | P09917 | Y54 | ERGAVDSyDVTVDEE | PLAT |
| FGR | P09769 | human | PTK2 | Q05397 | Y576 | RyMEDstyyKAsKGK | PK_Tyr_Ser-Thr |
| FGR | P09769 | human | TBK1 | Q9UHD2 | Y394 | LNTIGLIyEkISLPk | TBK1_ULD |
| FGR | P09769 | human | ALOX5 | P09917 | Y43 | HLLDKPFyNDFERGA | PLAT |
| FGR | P09769 | human | IKBKG | Q9Y6K9 | Y374 | PLPPAPAyLssPLAL |
| Biological Network Integration of This Kinase and Substrates (GeneMANIA website) |
| Enriched GO biological processes of the phosphorylation target genes of the kinase |
| Kinase | GOID | GO term | P.adjust |
| FGR | ID | Description | 0.00e+00 |
| FGR | GO:0016239 | positive regulation of macroautophagy | 1.19e-03 |
| FGR | GO:0045862 | positive regulation of proteolysis | 1.19e-03 |
| FGR | GO:2000060 | positive regulation of ubiquitin-dependent protein catabolic process | 1.19e-03 |
| FGR | GO:0098792 | xenophagy | 1.19e-03 |
| FGR | GO:0061041 | regulation of wound healing | 1.19e-03 |
| FGR | GO:0002757 | immune response-activating signaling pathway | 1.19e-03 |
| FGR | GO:1903052 | positive regulation of proteolysis involved in protein catabolic process | 1.19e-03 |
| FGR | GO:0002764 | immune response-regulating signaling pathway | 1.19e-03 |
| FGR | GO:0010508 | positive regulation of autophagy | 1.19e-03 |
| FGR | GO:0016241 | regulation of macroautophagy | 1.27e-03 |
| FGR | GO:1903034 | regulation of response to wounding | 1.49e-03 |
| FGR | GO:2000058 | regulation of ubiquitin-dependent protein catabolic process | 1.49e-03 |
| FGR | GO:0032727 | positive regulation of interferon-alpha production | 1.58e-03 |
| FGR | GO:0043123 | positive regulation of canonical NF-kappaB signal transduction | 1.62e-03 |
| FGR | GO:1900407 | regulation of cellular response to oxidative stress | 1.62e-03 |
| FGR | GO:0032607 | interferon-alpha production | 1.91e-03 |
| FGR | GO:0032647 | regulation of interferon-alpha production | 1.91e-03 |
| FGR | GO:1903050 | regulation of proteolysis involved in protein catabolic process | 2.20e-03 |
| FGR | GO:0043276 | anoikis | 2.20e-03 |
| FGR | GO:1902882 | regulation of response to oxidative stress | 2.22e-03 |
| FGR | GO:0032728 | positive regulation of interferon-beta production | 2.65e-03 |
| FGR | GO:0043122 | regulation of canonical NF-kappaB signal transduction | 2.65e-03 |
| FGR | GO:0007249 | canonical NF-kappaB signal transduction | 3.67e-03 |
| FGR | GO:0002429 | immune response-activating cell surface receptor signaling pathway | 4.12e-03 |
| FGR | GO:0042742 | defense response to bacterium | 4.12e-03 |
| FGR | GO:0016236 | macroautophagy | 4.12e-03 |
| FGR | GO:0006749 | glutathione metabolic process | 4.12e-03 |
| FGR | GO:0032608 | interferon-beta production | 4.12e-03 |
| FGR | GO:0032648 | regulation of interferon-beta production | 4.12e-03 |
| FGR | GO:0002768 | immune response-regulating cell surface receptor signaling pathway | 4.12e-03 |
| FGR | GO:0001961 | positive regulation of cytokine-mediated signaling pathway | 4.12e-03 |
| FGR | GO:0070661 | leukocyte proliferation | 4.12e-03 |
| FGR | GO:0010506 | regulation of autophagy | 4.12e-03 |
| FGR | GO:0090303 | positive regulation of wound healing | 4.12e-03 |
| FGR | GO:1901653 | cellular response to peptide | 4.55e-03 |
| FGR | GO:0060760 | positive regulation of response to cytokine stimulus | 4.55e-03 |
| FGR | GO:0032481 | positive regulation of type I interferon production | 5.04e-03 |
| FGR | GO:0031331 | positive regulation of cellular catabolic process | 5.04e-03 |
| FGR | GO:1903036 | positive regulation of response to wounding | 5.55e-03 |
| FGR | GO:0042060 | wound healing | 5.75e-03 |
| FGR | GO:0045088 | regulation of innate immune response | 5.75e-03 |
| FGR | GO:1905897 | regulation of response to endoplasmic reticulum stress | 5.84e-03 |
| FGR | GO:0061912 | selective autophagy | 7.81e-03 |
| FGR | GO:0022407 | regulation of cell-cell adhesion | 8.10e-03 |
| FGR | GO:0018107 | peptidyl-threonine phosphorylation | 8.10e-03 |
| FGR | GO:0033138 | positive regulation of peptidyl-serine phosphorylation | 8.57e-03 |
| FGR | GO:0018210 | peptidyl-threonine modification | 9.37e-03 |
| FGR | GO:0050830 | defense response to Gram-positive bacterium | 1.06e-02 |
| FGR | GO:0032479 | regulation of type I interferon production | 1.10e-02 |
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Related Drugs to FGR_SQSTM1 |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
| Distribution of the number of studies mentioning FGR-SQSTM1 and kinase inhibitors the PubMed Abstract (04-01-2024) |
| Fusion gene - drug pair 1 | Fusion gene - drug pair 2 | PMID | Publication date | DOI | Study title |
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Related Diseases to FGR_SQSTM1 |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Related diseases from the literature mentioned this fusion gene and drug. (PubMed, 04-01-2024) |
| MeSH ID | MeSH term |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
| Tgene | SQSTM1 | C4085252 | PAGET DISEASE OF BONE 3 | 9 | GENOMICS_ENGLAND;UNIPROT |
| Tgene | SQSTM1 | C0002736 | Amyotrophic Lateral Sclerosis | 5 | CTD_human;ORPHANET |
| Tgene | SQSTM1 | C4225326 | FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS 3 | 4 | CTD_human;UNIPROT |
| Tgene | SQSTM1 | C0029463 | Osteosarcoma | 2 | GENOMICS_ENGLAND |
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Clinical Trials of the Found Drugs/Small Molecules |
| Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024) |
| Clinical Trials from clinicaltrials.gov (06-17-2024) |
| Fusion Gene | Kinase Inhibitor | NCT ID | Study Status | Phases | Disease | # Enrolment | Date |
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