UTHEALTH HOME ABOUT SBMI A-Z WEBMAIL INSIDE THE UNIVERSITY |
|
Kinase Fusion Gene:PKN1_GNAS |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: PKN1_GNAS | KinaseFusionDB ID: KFG4703 | FusionGDB2.0 ID: KFG4703 | Hgene | Tgene | Gene symbol | PKN1 | GNAS | Gene ID | 5585 | 2778 | |
Gene name | protein kinase N1 | GNAS complex locus | ||||||||||
Synonyms | DBK|PAK-1|PAK1|PKN|PKN-ALPHA|PRK1|PRKCL1 | AHO|C20orf45|GNAS1|GPSA|GSA|GSP|NESP|PITA3|POH|SCG6|SgVI | ||||||||||
Cytomap | 19p13.12 | 20q13.32 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | serine/threonine-protein kinase N1protease-activated kinase 1protein kinase C-like 1protein kinase C-like PKNprotein kinase C-related kinase 1protein kinase PKN-alphaserine-threonine kinase Nserine/threonine protein kinase N | protein ALEXprotein GNASprotein SCG6 (secretogranin VI)G protein subunit alpha Sadenylate cyclase-stimulating G alpha proteinalternative gene product encoded by XL-exonextra large alphas proteinguanine nucleotide binding protein (G protein), alpha | ||||||||||
Modification date | 20240305 | 20240416 | ||||||||||
UniProtAcc | Q16512 | Q5JWF2 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000242783, ENST00000342216, ENST00000587429, | ENST00000313949, ENST00000371075, ENST00000371098, ENST00000371100, ENST00000464624, ENST00000265620, ENST00000306090, ENST00000306120, ENST00000354359, ENST00000371081, ENST00000371085, ENST00000371095, ENST00000371099, ENST00000371102, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: PKN1 [Title/Abstract] AND GNAS [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | PKN1(14557373)-GNAS(57470667), # 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 | PKN1 | GO:0006357 | regulation of transcription by RNA polymerase II | 12514133 |
Hgene | PKN1 | GO:0006468 | protein phosphorylation | 17332740 |
Hgene | PKN1 | GO:0043687 | post-translational protein modification | 18066052 |
Kinase Fusion gene breakpoints across PKN1 (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 GNAS (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 |
ChimerDB4 | TCGA-CD-8525-01A | PKN1 | chr19 | 14557373 | GNAS | chr20 | 57470667 |
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/:14557373/:57470667) - 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 |
PKN1 | GNAS |
FUNCTION: PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594, ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664, ECO:0000269|PubMed:9175763}. | FUNCTION: Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP. GNAS functions downstream of several GPCRs, including beta-adrenergic receptors. XLas isoforms interact with the same set of receptors as GNAS isoforms (By similarity). {ECO:0000250|UniProtKB:Q6R0H7}. |
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 PKN1_GNAS |
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 |
PKN1 | Q16512 | human | MAPT | P10636-8 | S352 | DFKDrVQskIGsLDN | Tubulin-binding |
PKN1 | Q16512 | human | MAPT | P10636-8 | S320 | VDLskVTskCGsLGN | Tubulin-binding |
PKN1 | Q16512 | human | EGFR | P00533 | T678 | RHIVRKRtLRRLLQE | |
PKN1 | Q16512 | human | HDAC5 | Q9UQL6 | T292 | KDGtVIstFKKRAVE | |
PKN1 | Q16512 | human | H3C1 | P68431 | T11 | kQtArkstGGkAPrk | Histone |
PKN1 | Q16512 | human | MAPT | P10636-8 | S258 | PDLkNVKskIGstEN | Tubulin-binding |
PKN1 | Q16512 | human | MAPT | P10636-8 | S214 | GsRsRtPsLPtPPtR | |
PKN1 | Q16512 | human | HDAC9 | Q9UKV0 | S253 | KDGNVVTsFKKRMFE | |
PKN1 | Q16512 | human | MEFV | O15553 | S208 | VRLRRNAssAGRLQG | |
PKN1 | Q16512 | human | CLIP1 | P30622 | S312 | AsLKRsPsAssLsSM | |
PKN1 | Q16512 | human | PKN1 | Q16512 | T774 | GyGDRtstFCGtPEF | Pkinase |
PKN1 | Q16512 | human | MEFV | O15553 | S242 | SGKMRPRsLEVTIST |
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 |
PKN1 | ID | Description | 0.00e+00 |
PKN1 | GO:0031116 | positive regulation of microtubule polymerization | 1.66e-02 |
PKN1 | GO:0040029 | epigenetic regulation of gene expression | 1.66e-02 |
PKN1 | GO:0031112 | positive regulation of microtubule polymerization or depolymerization | 1.66e-02 |
PKN1 | GO:0042113 | B cell activation | 1.66e-02 |
PKN1 | GO:0010830 | regulation of myotube differentiation | 1.66e-02 |
PKN1 | GO:0006476 | protein deacetylation | 1.66e-02 |
PKN1 | GO:0031122 | cytoplasmic microtubule organization | 1.66e-02 |
PKN1 | GO:0031113 | regulation of microtubule polymerization | 1.66e-02 |
PKN1 | GO:0035601 | protein deacylation | 1.66e-02 |
PKN1 | GO:0098732 | macromolecule deacylation | 1.66e-02 |
PKN1 | GO:0010631 | epithelial cell migration | 1.66e-02 |
PKN1 | GO:0090132 | epithelium migration | 1.66e-02 |
PKN1 | GO:0090130 | tissue migration | 1.66e-02 |
PKN1 | GO:0060191 | regulation of lipase activity | 1.68e-02 |
PKN1 | GO:0090049 | regulation of cell migration involved in sprouting angiogenesis | 1.68e-02 |
PKN1 | GO:0043254 | regulation of protein-containing complex assembly | 1.76e-02 |
PKN1 | GO:0032273 | positive regulation of protein polymerization | 1.76e-02 |
PKN1 | GO:0046785 | microtubule polymerization | 1.76e-02 |
PKN1 | GO:0031110 | regulation of microtubule polymerization or depolymerization | 1.76e-02 |
PKN1 | GO:0002042 | cell migration involved in sprouting angiogenesis | 1.76e-02 |
PKN1 | GO:0051153 | regulation of striated muscle cell differentiation | 1.76e-02 |
PKN1 | GO:0001667 | ameboidal-type cell migration | 2.15e-02 |
PKN1 | GO:0045814 | negative regulation of gene expressio | 1.10e-03 |
PKN1 | GO:0014902 | myotube differentiation | 2.64e-02 |
PKN1 | GO:0031109 | microtubule polymerization or depolymerization | 2.69e-02 |
PKN1 | GO:0030183 | B cell differentiation | 3.13e-02 |
PKN1 | GO:0043535 | regulation of blood vessel endothelial cell migration | 3.13e-02 |
PKN1 | GO:0034614 | cellular response to reactive oxygen species | 3.13e-02 |
PKN1 | GO:0010950 | positive regulation of endopeptidase activity | 3.13e-02 |
PKN1 | GO:0070507 | regulation of microtubule cytoskeleton organization | 3.13e-02 |
PKN1 | GO:0051147 | regulation of muscle cell differentiation | 3.13e-02 |
PKN1 | GO:0030307 | positive regulation of cell growth | 3.13e-02 |
PKN1 | GO:0010952 | positive regulation of peptidase activity | 3.30e-02 |
PKN1 | GO:1902905 | positive regulation of supramolecular fiber organization | 3.39e-02 |
PKN1 | GO:0043534 | blood vessel endothelial cell migration | 3.52e-02 |
PKN1 | GO:0051495 | positive regulation of cytoskeleton organization | 3.54e-02 |
PKN1 | GO:0002040 | sprouting angiogenesis | 3.67e-02 |
PKN1 | GO:2000116 | regulation of cysteine-type endopeptidase activity | 3.76e-02 |
PKN1 | GO:0031334 | positive regulation of protein-containing complex assembly | 3.78e-02 |
PKN1 | GO:0032271 | regulation of protein polymerization | 3.80e-02 |
PKN1 | GO:0000302 | response to reactive oxygen species | 3.80e-02 |
PKN1 | GO:0032869 | cellular response to insulin stimulus | 3.80e-02 |
PKN1 | GO:0010594 | regulation of endothelial cell migration | 4.65e-02 |
PKN1 | GO:0048742 | regulation of skeletal muscle fiber development | 4.65e-02 |
PKN1 | GO:0034599 | cellular response to oxidative stress | 4.65e-02 |
PKN1 | GO:0045927 | positive regulation of growth | 4.65e-02 |
PKN1 | GO:0032886 | regulation of microtubule-based process | 4.65e-02 |
PKN1 | GO:0010749 | regulation of nitric oxide mediated signal transduction | 4.65e-02 |
PKN1 | GO:0010917 | negative regulation of mitochondrial membrane potential | 4.65e-02 |
Top |
Related Drugs to PKN1_GNAS |
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 PKN1-GNAS 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 PKN1_GNAS |
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 |