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Kinase Fusion Gene:CCL5_ZAP70 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: CCL5_ZAP70 | KinaseFusionDB ID: KFG967 | FusionGDB2.0 ID: KFG967 | Hgene | Tgene | Gene symbol | CCL5 | ZAP70 | Gene ID | 6352 | 7535 | |
| Gene name | C-C motif chemokine ligand 5 | zeta chain of T cell receptor associated protein kinase 70 | ||||||||||
| Synonyms | D17S136E|RANTES|SCYA5|SIS-delta|SISd|TCP228|eoCP | ADMIO2|IMD48|SRK|STCD|STD|TZK|ZAP-70 | ||||||||||
| Cytomap | 17q12 | 2q11.2 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | C-C motif chemokine 5T-cell specific protein p288beta-chemokine RANTESchemokine (C-C motif) ligand 5eosinophil chemotactic cytokineregulated upon activation, normally T-expressed, and presumably secretedsmall inducible cytokine subfamily A (Cys-Cys) | tyrosine-protein kinase ZAP-7070 kDa zeta-associated protein70 kDa zeta-chain associated proteinsyk-related tyrosine kinasezeta chain of T cell receptor associated protein kinase 70kDazeta-chain (TCR) associated protein kinase 70kDazeta-chain associ | ||||||||||
| Modification date | 20240411 | 20240411 | ||||||||||
| UniProtAcc | P13501 | P43403 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000293272, ENST00000366113, | ENST00000264972, ENST00000442208, ENST00000451498, ENST00000463643, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: CCL5 [Title/Abstract] AND ZAP70 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | CCL5(34206530)-ZAP70(98351769), # 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 | CCL5 | GO:0006816 | calcium ion transport | 10734056 |
| Hgene | CCL5 | GO:0006874 | intracellular calcium ion homeostasis | 10734056 |
| Hgene | CCL5 | GO:0006887 | exocytosis | 10734056 |
| Hgene | CCL5 | GO:0007159 | leukocyte cell-cell adhesion | 8558019 |
| Hgene | CCL5 | GO:0007186 | G protein-coupled receptor signaling pathway | 17001303|23979485 |
| Hgene | CCL5 | GO:0007267 | cell-cell signaling | 8558019 |
| Hgene | CCL5 | GO:0009636 | response to toxic substance | 10841574 |
| Hgene | CCL5 | GO:0010759 | positive regulation of macrophage chemotaxis | 16778803 |
| Hgene | CCL5 | GO:0010820 | positive regulation of T cell chemotaxis | 1699135|7544376|16778803|18337562 |
| Hgene | CCL5 | GO:0014911 | positive regulation of smooth muscle cell migration | 21297082 |
| Hgene | CCL5 | GO:0030335 | positive regulation of cell migration | 7545673 |
| Hgene | CCL5 | GO:0031328 | positive regulation of cellular biosynthetic process | 18337562 |
| Hgene | CCL5 | GO:0031584 | activation of phospholipase D activity | 9469451 |
| Hgene | CCL5 | GO:0033634 | positive regulation of cell-cell adhesion mediated by integrin | 8558019 |
| Hgene | CCL5 | GO:0034112 | positive regulation of homotypic cell-cell adhesion | 10488085 |
| Hgene | CCL5 | GO:0042102 | positive regulation of T cell proliferation | 18832695 |
| Hgene | CCL5 | GO:0042119 | neutrophil activation | 10488085 |
| Hgene | CCL5 | GO:0042327 | positive regulation of phosphorylation | 18337562 |
| Hgene | CCL5 | GO:0042531 | positive regulation of tyrosine phosphorylation of STAT protein | 9417081 |
| Hgene | CCL5 | GO:0043922 | negative regulation by host of viral transcription | 10841574 |
| Hgene | CCL5 | GO:0045071 | negative regulation of viral genome replication | 10490959 |
| Hgene | CCL5 | GO:0045744 | negative regulation of G protein-coupled receptor signaling pathway | 10734056 |
| Hgene | CCL5 | GO:0045785 | positive regulation of cell adhesion | 10910894 |
| Hgene | CCL5 | GO:0048245 | eosinophil chemotaxis | 16778803 |
| Hgene | CCL5 | GO:0048661 | positive regulation of smooth muscle cell proliferation | 21297082 |
| Hgene | CCL5 | GO:0050796 | regulation of insulin secretion | 23979485 |
| Hgene | CCL5 | GO:0050863 | regulation of T cell activation | 10488085 |
| Hgene | CCL5 | GO:0051897 | positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 7544376 |
| Hgene | CCL5 | GO:0051928 | positive regulation of calcium ion transport | 8699119 |
| Hgene | CCL5 | GO:0070098 | chemokine-mediated signaling pathway | 17001303 |
| Hgene | CCL5 | GO:0070233 | negative regulation of T cell apoptotic process | 10488085 |
| Hgene | CCL5 | GO:0070234 | positive regulation of T cell apoptotic process | 10488085 |
| Hgene | CCL5 | GO:0090026 | positive regulation of monocyte chemotaxis | 1699135|19779041 |
| Hgene | CCL5 | GO:2000406 | positive regulation of T cell migration | 23620790 |
| Hgene | CCL5 | GO:2000503 | positive regulation of natural killer cell chemotaxis | 7545673 |
| Tgene | ZAP70 | GO:0006468 | protein phosphorylation | 12447358 |
| Tgene | ZAP70 | GO:0006955 | immune response | 1423621 |
| Tgene | ZAP70 | GO:0018108 | peptidyl-tyrosine phosphorylation | 22732588 |
| Tgene | ZAP70 | GO:0045059 | positive thymic T cell selection | 7630421 |
| Tgene | ZAP70 | GO:0045582 | positive regulation of T cell differentiation | 7630421 |
| Tgene | ZAP70 | GO:0050852 | T cell receptor signaling pathway | 9489702 |
| Kinase Fusion gene breakpoints across CCL5 (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 ZAP70 (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 | AG266142 | CCL5 | chr17 | 34206530 | ZAP70 | chr2 | 98351769 |
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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/:34206530/:98351769) - 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 |
| CCL5 | ZAP70 |
| FUNCTION: Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. May activate several chemokine receptors including CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second processed form RANTES(4-68) exhibits reduced chemotactic and HIV-suppressive activity compared with RANTES(1-68) and RANTES(3-68) (PubMed:16791620, PubMed:1380064, PubMed:8525373, PubMed:9516414, PubMed:15923218). May also be an agonist of the G protein-coupled receptor GPR75, stimulating inositol trisphosphate production and calcium mobilization through its activation. Together with GPR75, may play a role in neuron survival through activation of a downstream signaling pathway involving the PI3, Akt and MAP kinases. By activating GPR75 may also play a role in insulin secretion by islet cells (PubMed:23979485). {ECO:0000269|PubMed:1380064, ECO:0000269|PubMed:15923218, ECO:0000269|PubMed:16791620, ECO:0000269|PubMed:17001303, ECO:0000269|PubMed:23979485, ECO:0000269|PubMed:8525373, ECO:0000269|PubMed:9516414}. | FUNCTION: Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR). {ECO:0000269|PubMed:11353765, ECO:0000269|PubMed:12051764, ECO:0000269|PubMed:1423621, ECO:0000269|PubMed:20135127, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:8124727, ECO:0000269|PubMed:8702662, ECO:0000269|PubMed:9489702}. |
| 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 CCL5_ZAP70 |
| 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 |
| ZAP70 | P43403 | human | LAT | O43561-2 | Y226 | EEEGAPDyENLQELN | LAT |
| ZAP70 | P43403 | human | GAB2 | Q9UQC2 | Y614 | KSTGsVDyLALDFQP | |
| ZAP70 | P43403 | human | ZAP70 | P43403 | Y315 | MPMDtsVyEsPysDP | |
| ZAP70 | P43403 | human | SHC1 | P29353-2 | Y239 | EEPPDHQyyNDFPGK | |
| ZAP70 | P43403 | human | DBNL | Q9UJU6 | Y334 | QAEEEAVyEEPPEQE | |
| ZAP70 | P43403 | human | AGO2 | Q9UKV8 | Y529 | LPGKtPVyAEVkRVG | Piwi |
| ZAP70 | P43403 | human | LAT | O43561-2 | Y171 | SMESIDDyVNVPESG | LAT |
| ZAP70 | P43403 | human | ZAP70 | P43403 | Y319 | tsVyEsPysDPEELk | |
| ZAP70 | P43403 | human | LAT | O43561-2 | Y132 | DDyHNPGyLVVLPDS | LAT |
| ZAP70 | P43403 | human | SHC1 | P29353-2 | Y240 | EPPDHQyyNDFPGKE | |
| ZAP70 | P43403 | human | DBNL | Q9UJU6 | Y344 | PPEQETFyEQPPLVQ | |
| ZAP70 | P43403 | human | THEMIS | Q8N1K5 | Y429 | EAALLPLyMEGGFVE | CABIT |
| ZAP70 | P43403 | human | DUSP3 | P51452 | Y38 | NEVTPRIyVGNASVA | DSPc |
| ZAP70 | P43403 | human | THEMIS | Q8N1K5 | Y540 | EEITEEQyyMMRRYE | |
| ZAP70 | P43403 | human | THEMIS | Q8N1K5 | Y95 | IVADkTPyLTMEEIT | CABIT |
| ZAP70 | P43403 | human | LCP2 | Q13094 | Y128 | DGEDDGDyEsPNEEE | |
| ZAP70 | P43403 | human | SHC1 | P29353-2 | Y317 | ELFDDPSyVNVQNLD | |
| ZAP70 | P43403 | human | ZAP70 | P43403 | Y493 | LGADDsyytARsAGk | PK_Tyr_Ser-Thr |
| ZAP70 | P43403 | human | LCP2 | Q13094 | Y145 | PVEDDADyEPPPSND | |
| ZAP70 | P43403 | human | LAT | O43561-2 | Y191 | SLDGSREyVNVSQEL | LAT |
| ZAP70 | P43403 | human | THEMIS | Q8N1K5 | Y541 | EITEEQyyMMRRYES | |
| ZAP70 | P43403 | human | MAPK14 | Q16539 | Y323 | DEPVADPyDQsFESR | |
| ZAP70 | P43403 | human | ZAP70 | P43403 | Y598 | QRMRACyysLASkVE | |
| ZAP70 | P43403 | human | ZAP70 | P43403 | Y492 | ALGADDsyytARsAG | PK_Tyr_Ser-Thr |
| ZAP70 | P43403 | human | THEMIS | Q8N1K5 | Y174 | LsQEGEFyECEDERI | CABIT |
| ZAP70 | P43403 | human | ZAP70 | P43403 | Y597 | EQRMRACyysLASkV | |
| ZAP70 | P43403 | human | DUSP3 | P51452 | Y138 | SPTLVIAyLMMRQKM | DSPc |
| ZAP70 | P43403 | human | MAPT | P10636-8 | Y29 | DRKDQGGytMHQDQE | |
| ZAP70 | P43403 | human | LAT | O43561-2 | Y127 | ADEDEDDyHNPGyLV | LAT |
| ZAP70 | P43403 | human | MAPT | P10636-8 | Y197 | KsGDRsGyssPGsPG | |
| ZAP70 | P43403 | human | ZAP70 | P43403 | Y126 | RDAMVRDyVRQTWkL | |
| ZAP70 | P43403 | human | ZAP70 | P43403 | Y292 | DtLNsDGytPEPARI | |
| ZAP70 | P43403 | human | LCP2 | Q13094 | Y113 | ssFEEDDyESPNDDQ | |
| ZAP70 | P43403 | human | THEMIS | Q8N1K5 | Y353 | PREFPTAyDLEIAkS | CABIT |
| 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 |
| ZAP70 | ID | Description | 0.00e+00 |
| ZAP70 | GO:0050852 | T cell receptor signaling pathway | 6.43e-06 |
| ZAP70 | GO:0050851 | antigen receptor-mediated signaling pathway | 1.89e-05 |
| ZAP70 | GO:0002429 | immune response-activating cell surface receptor signaling pathway | 1.12e-04 |
| ZAP70 | GO:0002768 | immune response-regulating cell surface receptor signaling pathway | 1.27e-04 |
| ZAP70 | GO:0002757 | immune response-activating signaling pathway | 4.73e-04 |
| ZAP70 | GO:0002764 | immune response-regulating signaling pathway | 5.17e-04 |
| ZAP70 | GO:0045576 | mast cell activation | 5.97e-04 |
| ZAP70 | GO:0002274 | myeloid leukocyte activation | 5.97e-04 |
| ZAP70 | GO:0043383 | negative T cell selection | 1.60e-03 |
| ZAP70 | GO:0019722 | calcium-mediated signaling | 1.26e-02 |
| ZAP70 | GO:0043368 | positive T cell selection | 1.29e-02 |
| ZAP70 | GO:0045058 | T cell selection | 1.93e-02 |
| ZAP70 | GO:0043303 | mast cell degranulation | 1.93e-02 |
| ZAP70 | GO:0002279 | mast cell activation involved in immune response | 1.93e-02 |
| ZAP70 | GO:0002448 | mast cell mediated immunity | 1.93e-02 |
| ZAP70 | GO:0019932 | second-messenger-mediated signaling | 2.42e-02 |
| ZAP70 | GO:2000379 | positive regulation of reactive oxygen species metabolic process | 2.42e-02 |
| ZAP70 | GO:0033674 | positive regulation of kinase activity | 2.78e-02 |
| ZAP70 | GO:0043299 | leukocyte degranulation | 2.99e-02 |
| ZAP70 | GO:0050848 | regulation of calcium-mediated signaling | 2.99e-02 |
| ZAP70 | GO:0032418 | lysosome localization | 2.99e-02 |
| ZAP70 | GO:1990849 | vacuolar localization | 2.99e-02 |
| ZAP70 | GO:0050863 | regulation of T cell activation | 3.11e-02 |
| ZAP70 | GO:0002275 | myeloid cell activation involved in immune response | 3.55e-02 |
| ZAP70 | GO:0051347 | positive regulation of transferase activity | 3.63e-02 |
| ZAP70 | GO:0030316 | osteoclast differentiation | 3.75e-02 |
| ZAP70 | GO:0007173 | epidermal growth factor receptor signaling pathway | 3.75e-02 |
| ZAP70 | GO:0002444 | myeloid leukocyte mediated immunity | 3.82e-02 |
| ZAP70 | GO:0051656 | establishment of organelle localization | 4.47e-02 |
| ZAP70 | GO:0038127 | ERBB signaling pathway | 4.52e-02 |
| ZAP70 | GO:0050808 | synapse organization | 4.55e-02 |
| ZAP70 | GO:0022407 | regulation of cell-cell adhesion | 4.67e-02 |
| ZAP70 | GO:2000377 | regulation of reactive oxygen species metabolic process | 5.74e-02 |
| ZAP70 | GO:0048639 | positive regulation of developmental growth | 7.15e-02 |
| ZAP70 | GO:0033673 | negative regulation of kinase activity | 7.86e-02 |
| ZAP70 | GO:0070391 | response to lipoteichoic acid | 7.86e-02 |
| ZAP70 | GO:0070922 | RISC complex assembly | 7.86e-02 |
| ZAP70 | GO:0071223 | cellular response to lipoteichoic acid | 7.86e-02 |
| ZAP70 | GO:0010917 | negative regulation of mitochondrial membrane potential | 7.86e-02 |
| ZAP70 | GO:0045060 | negative thymic T cell selection | 7.86e-02 |
| ZAP70 | GO:0045837 | negative regulation of membrane potential | 7.86e-02 |
| ZAP70 | GO:0071493 | cellular response to UV-B | 7.86e-02 |
| ZAP70 | GO:0051348 | negative regulation of transferase activity | 7.86e-02 |
| ZAP70 | GO:0045055 | regulated exocytosis | 7.86e-02 |
| ZAP70 | GO:0035331 | negative regulation of hippo signaling | 7.86e-02 |
| ZAP70 | GO:0060213 | positive regulation of nuclear-transcribed mRNA poly(A) tail shortening | 7.86e-02 |
| ZAP70 | GO:0070486 | leukocyte aggregation | 7.86e-02 |
| ZAP70 | GO:0051403 | stress-activated MAPK cascade | 7.86e-02 |
| ZAP70 | GO:0072593 | reactive oxygen species metabolic process | 7.86e-02 |
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Related Drugs to CCL5_ZAP70 |
| 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 CCL5-ZAP70 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 CCL5_ZAP70 |
| 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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