| UTHEALTH HOME ABOUT SBMI A-Z WEBMAIL INSIDE THE UNIVERSITY |
|
|||||||
|
Kinase Fusion Gene:PAK4_ATP6V0E1 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: PAK4_ATP6V0E1 | KinaseFusionDB ID: KFG4447 | FusionGDB2.0 ID: KFG4447 | Hgene | Tgene | Gene symbol | PAK4 | ATP6V0E1 | Gene ID | 10298 | 8992 | |
| Gene name | p21 (RAC1) activated kinase 4 | ATPase H+ transporting V0 subunit e1 | ||||||||||
| Synonyms | - | ATP6H|ATP6V0E|M9.2|Vma21|Vma21p | ||||||||||
| Cytomap | 19q13.2 | 5q35.1 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | serine/threonine-protein kinase PAK 4p21 protein (Cdc42/Rac)-activated kinase 4p21(CDKN1A)-activated kinase 4protein kinase related to S. cerevisiae STE20, effector for Cdc42Hs | V-type proton ATPase subunit e 1ATPase, H+ transporting, lysosomal 9kDa, V0 subunit e1H(+)-transporting two-sector ATPase, subunit HV-ATPase 9.2 kDa membrane accessory proteinV-ATPase H subunitV-ATPase M9.2 subunitV-ATPase subunit e 1vacuolar ATP s | ||||||||||
| Modification date | 20240408 | 20240305 | ||||||||||
| UniProtAcc | O96013 | O15342 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000321944, ENST00000358301, ENST00000360442, ENST00000435673, ENST00000593690, ENST00000597766, ENST00000599386, ENST00000599470, | ENST00000519374, ENST00000265093, ENST00000517669, ENST00000519911, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: PAK4 [Title/Abstract] AND ATP6V0E1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | PAK4(39639416)-ATP6V0E1(172461895), # 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 |
| Kinase Fusion gene breakpoints across PAK4 (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 ATP6V0E1 (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
Top |
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 | BG222075 | PAK4 | chr19 | 39639416 | ATP6V0E1 | chr5 | 172461895 |
Top |
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) |
Top |
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 |
Top |
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/:39639416/:172461895) - 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. |
 |
| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| PAK4 | ATP6V0E1 |
| FUNCTION: Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN. {ECO:0000269|PubMed:11278822, ECO:0000269|PubMed:11313478, ECO:0000269|PubMed:14560027, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:20507994, ECO:0000269|PubMed:20631255, ECO:0000269|PubMed:20805321, ECO:0000269|PubMed:26607847}. | FUNCTION: Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:33065002). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). {ECO:0000250|UniProtKB:Q2KIB5, ECO:0000269|PubMed:33065002}. |
| 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 |
Top |
Kinase-Substrate Information of PAK4_ATP6V0E1 |
| 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 |
| PAK4 | O96013 | human | NFE2L2 | Q16236 | T369 | ESSSYGDtLLGLsDs | |
| PAK4 | O96013 | human | CTNNB1 | P35222 | S675 | QDykKRLsVELtsSL | |
| PAK4 | O96013 | human | SNAI2 | O43623 | S254 | sKTFsRMsLLHKHEE | zf-C2H2 |
| PAK4 | O96013 | human | WASL | O00401 | S484 | KRSKAIHssDEDEDE | |
| PAK4 | O96013 | human | PXN | P49023-2 | S272 | ELDELMAsLSDFKFM | |
| PAK4 | O96013 | human | MZF1 | P28698 | S27 | VMVkLEDsEEEGEAA | |
| PAK4 | O96013 | human | LIMK2 | P53671 | T505 | NDRKKRYtVVGNPYW | PK_Tyr_Ser-Thr |
| PAK4 | O96013 | human | ARHGEF2 | Q92974-2 | S885 | PVDPRRRsLPAGDAL | |
| PAK4 | O96013 | human | STMN2 | Q93045 | S50 | KQINKRAsGQAFELI | Stathmin |
| PAK4 | O96013 | human | ITGB1BP1 | O14713 | S10 | RKGKKRHssSsSQSS | ICAP-1_inte_bdg |
| PAK4 | O96013 | human | SNAI2 | O43623 | S158 | CDAQSRKsFSCKYCD | |
| PAK4 | O96013 | human | PAK4 | O96013 | S474 | kEVPRRksLVGtPyW | Pkinase |
| PAK4 | O96013 | human | RUNX1 | Q01196 | T207 | ELEQLRrtAMrVsPH | |
| PAK4 | O96013 | human | ITGB5 | P18084 | S759 | REFAkFQsERsRARy | Integrin_b_cyt |
| PAK4 | O96013 | human | WASL | O00401 | S485 | RSKAIHssDEDEDED | |
| PAK4 | O96013 | human | ITGB5 | P18084 | S762 | AkFQsERsRARyEMA | Integrin_b_cyt |
| PAK4 | O96013 | human | FH | P07954 | S46 | PNAARMAsQNSFRIE | |
| PAK4 | O96013 | human | TH | P07101 | S71 | RFIGRRQsLIEDARK | TOH_N |
| PAK4 | O96013 | human | RAN | P62826 | S135 | DRkVKAksIVFHRkk | Ras |
| PAK4 | O96013 | human | TP53 | P04637 | S215 | DrNtFrHsVVVPyEP | P53 |
| PAK4 | O96013 | human | LIMK1 | P53667 | T508 | PDRKKRYtVVGNPYW | PK_Tyr_Ser-Thr |
| PAK4 | O96013 | human | ESR1 | P03372 | S305 | IkRSkkNsLALSLtA |
| 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 |
| PAK4 | ID | Description | 0.00e+00 |
| PAK4 | GO:2001242 | regulation of intrinsic apoptotic signaling pathway | 1.19e-03 |
| PAK4 | GO:0048863 | stem cell differentiation | 1.19e-03 |
| PAK4 | GO:0030038 | contractile actin filament bundle assembly | 1.19e-03 |
| PAK4 | GO:0043149 | stress fiber assembly | 1.19e-03 |
| PAK4 | GO:0007015 | actin filament organization | 1.19e-03 |
| PAK4 | GO:2001243 | negative regulation of intrinsic apoptotic signaling pathway | 1.19e-03 |
| PAK4 | GO:0072089 | stem cell proliferation | 1.48e-03 |
| PAK4 | GO:0097193 | intrinsic apoptotic signaling pathway | 2.51e-03 |
| PAK4 | GO:0051496 | positive regulation of stress fiber assembly | 2.58e-03 |
| PAK4 | GO:0051017 | actin filament bundle assembly | 2.58e-03 |
| PAK4 | GO:0060688 | regulation of morphogenesis of a branching structure | 2.58e-03 |
| PAK4 | GO:0061572 | actin filament bundle organization | 2.58e-03 |
| PAK4 | GO:1902905 | positive regulation of supramolecular fiber organization | 3.00e-03 |
| PAK4 | GO:0032233 | positive regulation of actin filament bundle assembly | 3.16e-03 |
| PAK4 | GO:0051495 | positive regulation of cytoskeleton organization | 3.16e-03 |
| PAK4 | GO:1902903 | regulation of supramolecular fiber organization | 3.23e-03 |
| PAK4 | GO:1905330 | regulation of morphogenesis of an epithelium | 3.23e-03 |
| PAK4 | GO:2001233 | regulation of apoptotic signaling pathway | 3.23e-03 |
| PAK4 | GO:0061418 | regulation of transcription from RNA polymerase II promoter in response to hypoxia | 3.55e-03 |
| PAK4 | GO:0031032 | actomyosin structure organization | 3.83e-03 |
| PAK4 | GO:0006970 | response to osmotic stress | 5.01e-03 |
| PAK4 | GO:0007405 | neuroblast proliferation | 5.01e-03 |
| PAK4 | GO:0009404 | toxin metabolic process | 5.62e-03 |
| PAK4 | GO:2001234 | negative regulation of apoptotic signaling pathway | 5.62e-03 |
| PAK4 | GO:0033627 | cell adhesion mediated by integrin | 5.62e-03 |
| PAK4 | GO:0048145 | regulation of fibroblast proliferation | 5.62e-03 |
| PAK4 | GO:0051492 | regulation of stress fiber assembly | 6.33e-03 |
| PAK4 | GO:0072091 | regulation of stem cell proliferation | 6.33e-03 |
| PAK4 | GO:0003007 | heart morphogenesis | 6.66e-03 |
| PAK4 | GO:1901522 | positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus | 6.77e-03 |
| PAK4 | GO:0036003 | positive regulation of transcription from RNA polymerase II promoter in response to stress | 7.30e-03 |
| PAK4 | GO:0110020 | regulation of actomyosin structure organization | 7.30e-03 |
| PAK4 | GO:0032231 | regulation of actin filament bundle assembly | 7.30e-03 |
| PAK4 | GO:0048144 | fibroblast proliferation | 7.30e-03 |
| PAK4 | GO:0043542 | endothelial cell migration | 7.30e-03 |
| PAK4 | GO:0010721 | negative regulation of cell development | 7.39e-03 |
| PAK4 | GO:0032355 | response to estradiol | 7.80e-03 |
| PAK4 | GO:1904035 | regulation of epithelial cell apoptotic process | 7.80e-03 |
| PAK4 | GO:0002062 | chondrocyte differentiation | 8.21e-03 |
| PAK4 | GO:1903707 | negative regulation of hemopoiesis | 8.42e-03 |
| PAK4 | GO:0062197 | cellular response to chemical stress | 9.50e-03 |
| PAK4 | GO:0009651 | response to salt stress | 9.77e-03 |
| PAK4 | GO:0032331 | negative regulation of chondrocyte differentiation | 1.04e-02 |
| PAK4 | GO:0006929 | substrate-dependent cell migration | 1.05e-02 |
| PAK4 | GO:0007026 | negative regulation of microtubule depolymerization | 1.05e-02 |
| PAK4 | GO:0061311 | cell surface receptor signaling pathway involved in heart development | 1.05e-02 |
| PAK4 | GO:2000647 | negative regulation of stem cell proliferation | 1.16e-02 |
| PAK4 | GO:0045765 | regulation of angiogenesis | 1.16e-02 |
| PAK4 | GO:1901342 | regulation of vasculature development | 1.16e-02 |
Top |
Related Drugs to PAK4_ATP6V0E1 |
| 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 PAK4-ATP6V0E1 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 |
Top |
Related Diseases to PAK4_ATP6V0E1 |
| 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 |
Top |
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 |
Copyright 2024-Present -The University of Texas Health Science Center at Houston
Web File Viewing | Emergency Information |Campus Carry|Site Policies |