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Kinase Fusion Gene:POFUT1_HCK |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: POFUT1_HCK | KinaseFusionDB ID: KFG4772 | FusionGDB2.0 ID: KFG4772 | Hgene | Tgene | Gene symbol | POFUT1 | HCK | Gene ID | 23509 | 3055 | |
| Gene name | protein O-fucosyltransferase 1 | HCK proto-oncogene, Src family tyrosine kinase | ||||||||||
| Synonyms | DDD2|FUT12|O-FUT|O-Fuc-T|O-FucT-1|OFUCT1 | AIPCV|JTK9|p59Hck|p61Hck | ||||||||||
| Cytomap | 20q11.21 | 20q11.21 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | GDP-fucose protein O-fucosyltransferase 1o-fucosyltransferase proteinpeptide-O-fucosyltransferase 1 | tyrosine-protein kinase HCKhematopoietic cell kinasehemopoietic cell kinasep59-HCK/p60-HCK | ||||||||||
| Modification date | 20240403 | 20240411 | ||||||||||
| UniProtAcc | Q9H488 | P08631 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000486717, ENST00000539210, ENST00000375749, ENST00000375730, | ENST00000375852, ENST00000375862, ENST00000518730, ENST00000520553, ENST00000534862, ENST00000538448, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: POFUT1 [Title/Abstract] AND HCK [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | POFUT1(30818864)-HCK(30689120), # samples:3 | |||||||||||
| 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 | POFUT1 | GO:0006493 | protein O-linked glycosylation | 9023546|11524432 |
| Hgene | POFUT1 | GO:0036066 | protein O-linked fucosylation | 15653671 |
| Tgene | HCK | GO:0071801 | regulation of podosome assembly | 15998323 |
| Kinase Fusion gene breakpoints across POFUT1 (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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| Kinase Fusion gene breakpoints across HCK (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 |
| ChimerDB4 | TCGA-04-1517-01A | POFUT1 | chr20 | 30795868 | HCK | chr20 | 30671697 |
| ChimerDB4 | TCGA-G3-A25X-01A | POFUT1 | chr20 | 30818864 | HCK | chr20 | 30689120 |
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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) |
| ENST00000375749 | ENST00000534862 | POFUT1 | chr20 | 30795868 | HCK | chr20 | 30671697 | 1568 | 402 |
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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 >ENST00000375749_ENST00000534862_POFUT1_chr20_30795868_HCK_chr20_30671697_length(amino acids)=402 MCAAAGSGSRADMGAAAWARPLSVSFLLLLLPLPGMPAGSWDPAGYLLYCPCMGSYSLSVRDYDPRQGDTVKHYKIRTLDNGGFYISPRS TFSTLQELVDHYKKGNDGLCQKLSVPCMSSKPQKPWEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLA EANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLV CKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPE -------------------------------------------------------------- |
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/chr20:30818864/chr20:30689120) - 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 |
| POFUT1 | HCK |
| FUNCTION: Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines. Specifically uses GDP-fucose as donor substrate and proper disulfide pairing of the substrate EGF domains is required for fucose transfer. Plays a crucial role in NOTCH signaling. Initial fucosylation of NOTCH by POFUT1 generates a substrate for FRINGE/RFNG, an acetylglucosaminyltransferase that can then extend the fucosylation on the NOTCH EGF repeats. This extended fucosylation is required for optimal ligand binding and canonical NOTCH signaling induced by DLL1 or JAGGED1. Fucosylates AGRN and determines its ability to cluster acetylcholine receptors (AChRs). {ECO:0000269|PubMed:11524432, ECO:0000269|PubMed:28334865, ECO:0000269|PubMed:8358148}. | FUNCTION: Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS. {ECO:0000269|PubMed:10092522, ECO:0000269|PubMed:10779760, ECO:0000269|PubMed:10973280, ECO:0000269|PubMed:11741929, ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:12411494, ECO:0000269|PubMed:15010462, ECO:0000269|PubMed:15952790, ECO:0000269|PubMed:15998323, ECO:0000269|PubMed:17310994, ECO:0000269|PubMed:17535448, ECO:0000269|PubMed:19114024, ECO:0000269|PubMed:19903482, ECO:0000269|PubMed:20452982, ECO:0000269|PubMed:21338576, ECO:0000269|PubMed:7535819, ECO:0000269|PubMed:8132624, ECO:0000269|PubMed:9406996, ECO:0000269|PubMed:9407116}. |
| 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 |
| Tgene | POFUT1 | 30795868 | HCK | 30671697 | ENST00000375749 | 5 | 13 | 262_515 | 155 | 505 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Tgene | POFUT1 | 30795868 | HCK | 30671697 | ENST00000375749 | 5 | 13 | 262_515 | 156 | 506 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Tgene | POFUT1 | 30795868 | HCK | 30671697 | ENST00000375749 | 6 | 14 | 262_515 | 156 | 506 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
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Kinase Fusion Protein Structures |
| CIF files of the predicted kinase fusion proteins * Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB) | Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | AA seq | Len(AA seq) |
| PDB file >>>382_POFUT1_HCK | ENST00000375749 | ENST00000534862 | POFUT1 | chr20 | 30795868 | HCK | chr20 | 30671697 | MCAAAGSGSRADMGAAAWARPLSVSFLLLLLPLPGMPAGSWDPAGYLLYCPCMGSYSLSVRDYDPRQGDTVKHYKIRTLDNGGFYISPRS TFSTLQELVDHYKKGNDGLCQKLSVPCMSSKPQKPWEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLA EANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLV CKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPE | 402 |
| 3D view using mol* of 382_POFUT1_HCK | ||||||||||
| PDB file >>>TKFP_655_POFUT1_HCK | ENST00000375749 | ENST00000534862 | POFUT1 | chr20 | 30795868 | HCK | chr20 | 30671697 | MCAAAGSGSRADMGAAAWARPLSVSFLLLLLPLPGMPAGSWDPAGYLLYCPCMGSYSLSVRDYDPRQGDTVKHYKIRTLDNGGFYISPRS TFSTLQELVDHYKKGNDGLCQKLSVPCMSSKPQKPWEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLA EANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLV CKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPE | 402_POFUT1_HCK |
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Comparison of Fusion Protein Isoforms |
| Superimpose the 3D Structures Among All Fusion Protein Isoforms * Download the pdb file and open it from the molstar online viewer. |
| Comparison of the Secondary Structures of Fusion Protein Isoforms |
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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB |
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pLDDT score distribution |
| pLDDT score distribution of the predicted fusion protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. * The blue color at the bottom marks the best active site residues. |
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Potential Active Site Information |
| The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite. |
| Kinase Fusion AA seq ID in KinaseFusionDB | Site score | Size | Dscore | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
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Ramachandran Plot of Kinase Fusion Protein Structure |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide. |
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Virtual Screening Results |
| Distribution of the average docking score across all approved kinase inhibitors. Distribution of the number of occurrence across all approved kinase inhibitors. |
| 5'-kinase fusion protein case |
| 3'-kinase fusion protein case |
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| Drug information from DrugBank of the top 20 interacting small molecules. * The detailed information of individual kinase inhibitors are available in the download page. |
| Fusion gene name info | Drug | Docking score | Glide g score | Glide energy |
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Kinase-Substrate Information of POFUT1_HCK |
| 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 |
| HCK | P08631 | human | ABL1 | P00519 | Y393 | RLMtGDtytAHAGAk | PK_Tyr_Ser-Thr |
| HCK | P08631 | human | ELMO1 | Q92556 | Y216 | VLNSHDLyQKVAQEI | ELMO_ARM |
| HCK | P08631 | human | STAT5A | P42229 | Y694 | LAkAVDGyVkPQIkQ | |
| HCK | P08631 | human | ADAM15 | Q13444 | Y715 | LVMLGASyWYRARLH | TM |
| HCK | P08631 | human | ELMO1 | Q92556 | Y18 | AIEWPGAyPkLMEID | |
| HCK | P08631 | human | RAPGEF1 | Q13905 | Y504 | APIPSVPyAPFAAIL | |
| HCK | P08631 | human | TP73 | O15350 | Y28 | SLEPDStyFDLPQSS | |
| HCK | P08631 | human | ABL1 | P00519 | Y128 | SLEKHSWyHGPVSRN | SH2 |
| HCK | P08631 | human | ALOX5 | P09917 | Y95 | LKTPHGDyIEFPCyR | PLAT |
| HCK | P08631 | human | ABL1 | P00519 | Y226 | KRNKPtVyGVsPNyD | |
| HCK | P08631 | human | ABL1 | P00519 | Y115 | QGWVPsNyItPVNSL | |
| HCK | P08631 | human | ABL1 | P00519 | Y215 | GLITTLHyPAPKRNK | |
| HCK | P08631 | human | ABL1 | P00519 | Y70 | PNLFVALyDFVAsGD | SH3_1 |
| HCK | P08631 | human | TBK1 | Q9UHD2 | Y354 | SSNQELIyEGRRLVL | TBK1_ULD |
| HCK | P08631 | human | BCR | P11274 | Y177 | ADAEKPFyVNVEFHH | |
| HCK | P08631 | human | ELMO1 | Q92556 | Y720 | IPKEPsNyDFVyDCN | |
| HCK | P08631 | human | ABL1 | P00519 | Y139 | VSRNAAEyLLsSGIN | SH2 |
| HCK | P08631 | human | HCK | P08631 | Y411 | RVIEDNEytAREGAk | PK_Tyr_Ser-Thr |
| HCK | P08631 | human | STAT5B | P51692 | Y699 | tAkAVDGyVkPQIkQ | |
| HCK | P08631 | human | ABL1 | P00519 | Y172 | LRyEGRVyHyRINTA | SH2 |
| HCK | P08631 | human | ALOX5 | P09917 | Y54 | ERGAVDSyDVTVDEE | PLAT |
| HCK | P08631 | human | ABL1 | P00519 | Y185 | TAsDGKLyVsSESRF | SH2 |
| HCK | P08631 | human | ELMO1 | Q92556 | Y395 | AKHHQDAyIRIVLEN | ELMO_CED12 |
| HCK | P08631 | human | ELMO1 | Q92556 | Y511 | SkLQNLSytEILkIR | |
| HCK | P08631 | human | HCK | P08631 | Y522 | YTATEsQyQQQP___ | |
| HCK | P08631 | human | TBK1 | Q9UHD2 | Y394 | LNTIGLIyEkISLPk | TBK1_ULD |
| HCK | P08631 | human | ALOX5 | P09917 | Y43 | HLLDKPFyNDFERGA | PLAT |
| HCK | P08631 | human | PLCG2 | P16885 | Y1217 | LNNQLFLyDtHQNLR | |
| HCK | P08631 | human | GRB2 | P62993 | Y160 | QVPQQPtyVQALFDF |
| 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 |
| HCK | ID | Description | 0.00e+00 |
| HCK | GO:0006909 | phagocytosis | 3.63e-04 |
| HCK | GO:0032743 | positive regulation of interleukin-2 production | 6.11e-04 |
| HCK | GO:0007265 | Ras protein signal transduction | 6.11e-04 |
| HCK | GO:2000377 | regulation of reactive oxygen species metabolic process | 6.11e-04 |
| HCK | GO:0050900 | leukocyte migration | 9.09e-04 |
| HCK | GO:0050727 | regulation of inflammatory response | 1.01e-03 |
| HCK | GO:0038093 | Fc receptor signaling pathway | 1.01e-03 |
| HCK | GO:0032623 | interleukin-2 production | 1.08e-03 |
| HCK | GO:0032663 | regulation of interleukin-2 production | 1.08e-03 |
| HCK | GO:0002757 | immune response-activating signaling pathway | 1.08e-03 |
| HCK | GO:0007264 | small GTPase mediated signal transduction | 1.09e-03 |
| HCK | GO:0071222 | cellular response to lipopolysaccharide | 1.09e-03 |
| HCK | GO:0002764 | immune response-regulating signaling pathway | 1.09e-03 |
| HCK | GO:0072593 | reactive oxygen species metabolic process | 1.10e-03 |
| HCK | GO:0071219 | cellular response to molecule of bacterial origin | 1.12e-03 |
| HCK | GO:0050853 | B cell receptor signaling pathway | 1.16e-03 |
| HCK | GO:0060397 | growth hormone receptor signaling pathway via JAK-STAT | 1.18e-03 |
| HCK | GO:0070669 | response to interleukin-2 | 1.32e-03 |
| HCK | GO:0071216 | cellular response to biotic stimulus | 1.32e-03 |
| HCK | GO:0070672 | response to interleukin-15 | 1.47e-03 |
| HCK | GO:0030100 | regulation of endocytosis | 1.73e-03 |
| HCK | GO:0050764 | regulation of phagocytosis | 1.85e-03 |
| HCK | GO:0002429 | immune response-activating cell surface receptor signaling pathway | 2.23e-03 |
| HCK | GO:0007229 | integrin-mediated signaling pathway | 2.31e-03 |
| HCK | GO:0048638 | regulation of developmental growth | 2.31e-03 |
| HCK | GO:0045089 | positive regulation of innate immune response | 2.60e-03 |
| HCK | GO:0002768 | immune response-regulating cell surface receptor signaling pathway | 2.60e-03 |
| HCK | GO:0032496 | response to lipopolysaccharide | 2.60e-03 |
| HCK | GO:0002237 | response to molecule of bacterial origin | 3.05e-03 |
| HCK | GO:0002833 | positive regulation of response to biotic stimulus | 3.05e-03 |
| HCK | GO:0060396 | growth hormone receptor signaling pathway | 4.12e-03 |
| HCK | GO:0030183 | B cell differentiation | 4.12e-03 |
| HCK | GO:0002433 | immune response-regulating cell surface receptor signaling pathway involved in phagocytosis | 4.12e-03 |
| HCK | GO:0038096 | Fc-gamma receptor signaling pathway involved in phagocytosis | 4.12e-03 |
| HCK | GO:0071378 | cellular response to growth hormone stimulus | 4.12e-03 |
| HCK | GO:0043254 | regulation of protein-containing complex assembly | 4.15e-03 |
| HCK | GO:0045088 | regulation of innate immune response | 4.26e-03 |
| HCK | GO:0030041 | actin filament polymerization | 4.91e-03 |
| HCK | GO:1902905 | positive regulation of supramolecular fiber organization | 5.26e-03 |
| HCK | GO:0010634 | positive regulation of epithelial cell migration | 5.26e-03 |
| HCK | GO:0002431 | Fc receptor mediated stimulatory signaling pathway | 5.26e-03 |
| HCK | GO:0007015 | actin filament organization | 5.26e-03 |
| HCK | GO:0038094 | Fc-gamma receptor signaling pathway | 5.43e-03 |
| HCK | GO:0051495 | positive regulation of cytoskeleton organization | 5.59e-03 |
| HCK | GO:0031349 | positive regulation of defense response | 5.59e-03 |
| HCK | GO:0006298 | mismatch repair | 5.72e-03 |
| HCK | GO:0070670 | response to interleukin-4 | 5.92e-03 |
| HCK | GO:0001819 | positive regulation of cytokine production | 6.08e-03 |
| HCK | GO:0008154 | actin polymerization or depolymerization | 6.09e-03 |
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Related Drugs to POFUT1_HCK |
| 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 POFUT1-HCK 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 POFUT1_HCK |
| 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 |
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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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