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Kinase Fusion Gene:GRK5_PDZD8 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: GRK5_PDZD8 | KinaseFusionDB ID: KFG2566 | FusionGDB2.0 ID: KFG2566 | Hgene | Tgene | Gene symbol | GRK5 | PDZD8 | Gene ID | 2869 | 118987 | |
| Gene name | G protein-coupled receptor kinase 5 | PDZ domain containing 8 | ||||||||||
| Synonyms | FP2025|GPRK5 | IDDADF|PDZK8 | ||||||||||
| Cytomap | 10q26.11 | 10q25.3-q26.11 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | G protein-coupled receptor kinase 5g protein-coupled receptor kinase GRK5 | PDZ domain-containing protein 8sarcoma antigen NY-SAR-84/NY-SAR-104 | ||||||||||
| Modification date | 20240305 | 20240411 | ||||||||||
| UniProtAcc | P34947 | Q8NEN9 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000369108, ENST00000392870, ENST00000473264, | ENST00000482496, ENST00000334464, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: GRK5 [Title/Abstract] AND PDZD8 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | GRK5(121156284)-PDZD8(119078485), # samples:2 PDZD8(119078382)-GRK5(121189886), # 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 | GRK5 | GO:0007217 | tachykinin receptor signaling pathway | 17986524 |
| Hgene | GRK5 | GO:0043066 | negative regulation of apoptotic process | 20124405 |
| Hgene | GRK5 | GO:0046777 | protein autophosphorylation | 14976207 |
| Tgene | PDZD8 | GO:0051560 | mitochondrial calcium ion homeostasis | 29097544 |
| Tgene | PDZD8 | GO:1990456 | mitochondrion-endoplasmic reticulum membrane tethering | 29097544 |
| Kinase Fusion gene breakpoints across GRK5 (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 PDZD8 (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-BA-4075-01A | GRK5 | chr10 | 121156284 | PDZD8 | chr10 | 119078485 |
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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/:121156284/:119078485) - 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 | PDZD8 |
| 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}. | FUNCTION: Molecular tethering protein that connects endoplasmic reticulum and mitochondria membranes (PubMed:29097544). PDZD8-dependent endoplasmic reticulum-mitochondria membrane tethering is essential for endoplasmic reticulum-mitochondria Ca(2+) transfer (PubMed:29097544). In neurons, involved in the regulation of dendritic Ca(2+) dynamics by regulating mitochondrial Ca(2+) uptake in neurons (PubMed:29097544). Plays an indirect role in the regulation of cell morphology and cytoskeletal organization (PubMed:21834987). May inhibit herpes simplex virus 1 infection at an early stage (PubMed:21549406). {ECO:0000269|PubMed:21549406, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:29097544}. |
| 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 GRK5_PDZD8 |
| 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 |
| GRK5 | P34947 | human | ADRB2 | P07550 | S396 | GHQGtVPsDNIDsQG | |
| GRK5 | P34947 | human | MSN | P26038 | T66 | LkLNKkVtAQDVrkE | FERM_N |
| GRK5 | P34947 | human | GRK5 | P34947 | T485 | LDIEQFstVkGVNLD | |
| GRK5 | P34947 | human | GPBAR1 | Q8TDU6 | S324 | YHPSsQssVDLDLN_ | |
| GRK5 | P34947 | human | ST13 | P50502 | S346 | AQNPANMskYQsNPk | STI1 |
| GRK5 | P34947 | human | GPBAR1 | Q8TDU6 | S323 | AYHPSsQssVDLDLN | |
| GRK5 | P34947 | human | ADRB2 | P07550 | S407 | DsQGRNCstNDsLL_ | |
| GRK5 | P34947 | human | FZD6 | O60353 | S648 | sVSESARsEGRIsPK | |
| GRK5 | P34947 | human | GRK5 | P34947 | T10 | LENIVANtVLLkARE | |
| GRK5 | P34947 | human | SNCA | P37840 | S129 | NEAyEMPsEEGyQDy | Synuclein |
| GRK5 | P34947 | human | ADRB2 | P07550 | S411 | RNCstNDsLL_____ | |
| GRK5 | P34947 | human | ADRB2 | P07550 | S355 | KAyGNGyssNGNtGE | |
| GRK5 | P34947 | human | ADRB2 | P07550 | T393 | DFVGHQGtVPsDNID | |
| GRK5 | P34947 | human | GPBAR1 | Q8TDU6 | S321 | SIAYHPSsQssVDLD | |
| GRK5 | P34947 | human | GPBAR1 | Q8TDU6 | S310 | WGRASRDsPGPSIAY | |
| GRK5 | P34947 | human | ADRB2 | P07550 | S401 | VPsDNIDsQGRNCst | |
| GRK5 | P34947 | human | ADRB2 | P07550 | S356 | AyGNGyssNGNtGEQ | |
| GRK5 | P34947 | human | ADRB2 | P07550 | T384 | LCEDLPGtEDFVGHQ | |
| GRK5 | P34947 | human | GRK5 | P34947 | S484 | VLDIEQFstVkGVNL | |
| GRK5 | P34947 | human | HDAC6 | Q9UBN7 | S22 | RsRQNPQsPPQDSsV | |
| GRK5 | P34947 | human | TP53 | P04637 | T55 | DDIEQWFtEDPGPDE | TAD2 |
| 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 |
| GRK5 | ID | Description | 0.00e+00 |
| GRK5 | GO:0061912 | selective autophagy | 6.42e-03 |
| GRK5 | GO:0010506 | regulation of autophagy | 6.42e-03 |
| GRK5 | GO:0043254 | regulation of protein-containing complex assembly | 6.42e-03 |
| GRK5 | GO:0010310 | regulation of hydrogen peroxide metabolic process | 6.42e-03 |
| GRK5 | GO:0008277 | regulation of G protein-coupled receptor signaling pathway | 6.42e-03 |
| GRK5 | GO:2000377 | regulation of reactive oxygen species metabolic process | 6.42e-03 |
| GRK5 | GO:0016241 | regulation of macroautophagy | 6.96e-03 |
| GRK5 | GO:0051354 | negative regulation of oxidoreductase activity | 9.57e-03 |
| GRK5 | GO:0031334 | positive regulation of protein-containing complex assembly | 9.57e-03 |
| GRK5 | GO:2000273 | positive regulation of signaling receptor activity | 9.57e-03 |
| GRK5 | GO:0031111 | negative regulation of microtubule polymerization or depolymerization | 1.07e-02 |
| GRK5 | GO:0000423 | mitophagy | 1.07e-02 |
| GRK5 | GO:0072593 | reactive oxygen species metabolic process | 1.07e-02 |
| GRK5 | GO:0045861 | negative regulation of proteolysis | 1.07e-02 |
| GRK5 | GO:1903146 | regulation of autophagy of mitochondrion | 1.07e-02 |
| GRK5 | GO:0045926 | negative regulation of growth | 1.07e-02 |
| GRK5 | GO:0045444 | fat cell differentiation | 1.07e-02 |
| GRK5 | GO:0034599 | cellular response to oxidative stress | 1.10e-02 |
| GRK5 | GO:1900542 | regulation of purine nucleotide metabolic process | 1.10e-02 |
| GRK5 | GO:0006140 | regulation of nucleotide metabolic process | 1.10e-02 |
| GRK5 | GO:0031648 | protein destabilization | 1.10e-02 |
| GRK5 | GO:2000378 | negative regulation of reactive oxygen species metabolic process | 1.10e-02 |
| GRK5 | GO:0042743 | hydrogen peroxide metabolic process | 1.22e-02 |
| GRK5 | GO:0045744 | negative regulation of G protein-coupled receptor signaling pathway | 1.22e-02 |
| GRK5 | GO:0062197 | cellular response to chemical stress | 1.50e-02 |
| GRK5 | GO:0031647 | regulation of protein stability | 1.55e-02 |
| GRK5 | GO:0016236 | macroautophagy | 1.58e-02 |
| GRK5 | GO:2000379 | positive regulation of reactive oxygen species metabolic process | 1.66e-02 |
| GRK5 | GO:0010639 | negative regulation of organelle organization | 1.92e-02 |
| GRK5 | GO:0051341 | regulation of oxidoreductase activity | 2.25e-02 |
| GRK5 | GO:0006979 | response to oxidative stress | 2.39e-02 |
| GRK5 | GO:0010507 | negative regulation of autophagy | 2.46e-02 |
| GRK5 | GO:0051262 | protein tetramerization | 2.46e-02 |
| GRK5 | GO:0001738 | morphogenesis of a polarized epithelium | 2.50e-02 |
| GRK5 | GO:0031110 | regulation of microtubule polymerization or depolymerization | 2.58e-02 |
| GRK5 | GO:0000422 | autophagy of mitochondrion | 2.60e-02 |
| GRK5 | GO:0061726 | mitochondrion disassembly | 2.60e-02 |
| GRK5 | GO:0033138 | positive regulation of peptidyl-serine phosphorylation | 2.85e-02 |
| GRK5 | GO:0060079 | excitatory postsynaptic potential | 2.94e-02 |
| GRK5 | GO:0010469 | regulation of signaling receptor activity | 2.96e-02 |
| GRK5 | GO:0043086 | negative regulation of catalytic activity | 2.96e-02 |
| GRK5 | GO:0048640 | negative regulation of developmental growth | 2.96e-02 |
| GRK5 | GO:0099565 | chemical synaptic transmissio | 1.29e-03 |
| GRK5 | GO:0099177 | regulation of trans-synaptic signaling | 2.96e-02 |
| GRK5 | GO:0022411 | cellular component disassembly | 3.02e-02 |
| GRK5 | GO:0007006 | mitochondrial membrane organization | 3.06e-02 |
| GRK5 | GO:0043244 | regulation of protein-containing complex disassembly | 3.14e-02 |
| GRK5 | GO:0031109 | microtubule polymerization or depolymerization | 3.65e-02 |
| GRK5 | GO:0033135 | regulation of peptidyl-serine phosphorylation | 3.75e-02 |
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Related Drugs to GRK5_PDZD8 |
| 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 GRK5-PDZD8 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 GRK5_PDZD8 |
| 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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