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Kinase Fusion Gene:PAK2_PTPN11 |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: PAK2_PTPN11 | KinaseFusionDB ID: KFG4442 | FusionGDB2.0 ID: KFG4442 | Hgene | Tgene | Gene symbol | PAK2 | PTPN11 | Gene ID | 5586 | 5781 | |
Gene name | protein kinase N2 | protein tyrosine phosphatase non-receptor type 11 | ||||||||||
Synonyms | PAK2|PRK2|PRKCL2|PRO2042|Pak-2|STK7 | BPTP3|CFC|JMML|METCDS|NS1|PTP-1D|PTP2C|SH-PTP2|SH-PTP3|SHP2 | ||||||||||
Cytomap | 1p22.2 | 12q24.13 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | serine/threonine-protein kinase N2PKN gammacardiolipin-activated protein kinase Pak2protein kinase C-like 2protein-kinase C-related kinase 2 | tyrosine-protein phosphatase non-receptor type 11SH2 domain-containing protein tyrosine phosphatase 2protein-tyrosine phosphatase 1Dprotein-tyrosine phosphatase 2C | ||||||||||
Modification date | 20240323 | 20240407 | ||||||||||
UniProtAcc | Q13177 | Q06124 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000327134, | ENST00000351677, ENST00000392597, ENST00000531326, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: PAK2 [Title/Abstract] AND PTPN11 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | PAK2(196556219)-PTPN11(112946528), # 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 | PAK2 | GO:0006468 | protein phosphorylation | 17332740 |
Hgene | PAK2 | GO:0010631 | epithelial cell migration | 21754995 |
Tgene | PTPN11 | GO:0032480 | negative regulation of type I interferon production | 26358190 |
Tgene | PTPN11 | GO:0035335 | peptidyl-tyrosine dephosphorylation | 15133037 |
Tgene | PTPN11 | GO:0038127 | ERBB signaling pathway | 15133037 |
Tgene | PTPN11 | GO:0043254 | regulation of protein-containing complex assembly | 7493946 |
Tgene | PTPN11 | GO:0046326 | positive regulation of glucose import | 7493946 |
Tgene | PTPN11 | GO:0046628 | positive regulation of insulin receptor signaling pathway | 7493946 |
Tgene | PTPN11 | GO:0048013 | ephrin receptor signaling pathway | 10655584 |
Kinase Fusion gene breakpoints across PAK2 (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 PTPN11 (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 | AW390149 | PAK2 | chr3 | 196556219 | PTPN11 | chr12 | 112946528 |
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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/:196556219/:112946528) - 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 |
PAK2 | PTPN11 |
FUNCTION: Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation (PubMed:7744004, PubMed:19273597, PubMed:19923322, PubMed:9171063, PubMed:12853446, PubMed:16617111, PubMed:33693784). Acts as a downstream effector of the small GTPases CDC42 and RAC1 (PubMed:7744004). Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues (PubMed:7744004). Full-length PAK2 stimulates cell survival and cell growth (PubMed:7744004). Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration (PubMed:21317288). Phosphorylates JUN and plays an important role in EGF-induced cell proliferation (PubMed:21177766). Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP (PubMed:21724829). Phosphorylates CASP7, thereby preventing its activity (PubMed:21555521, PubMed:27889207). Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis (PubMed:19273597, PubMed:19923322). On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway (PubMed:9171063, PubMed:12853446, PubMed:16617111). Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (PubMed:15234964). {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:15234964, ECO:0000269|PubMed:16617111, ECO:0000269|PubMed:19273597, ECO:0000269|PubMed:19923322, ECO:0000269|PubMed:21177766, ECO:0000269|PubMed:21317288, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:21724829, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:33693784, ECO:0000269|PubMed:7744004, ECO:0000269|PubMed:9171063}. | FUNCTION: Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus (PubMed:10655584, PubMed:18559669, PubMed:18829466, PubMed:26742426, PubMed:28074573). Positively regulates MAPK signal transduction pathway (PubMed:28074573). Dephosphorylates GAB1, ARHGAP35 and EGFR (PubMed:28074573). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its RhoA binding activity (PubMed:18559669). Dephosphorylates CDC73 (PubMed:26742426). Dephosphorylates SOX9 on tyrosine residues, leading to inactivate SOX9 and promote ossification (By similarity). Dephosphorylates tyrosine-phosphorylated NEDD9/CAS-L (PubMed:19275884). {ECO:0000250|UniProtKB:P35235, ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:18559669, ECO:0000269|PubMed:18829466, ECO:0000269|PubMed:19275884, ECO:0000269|PubMed:26742426, ECO:0000269|PubMed:28074573}. |
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 PAK2_PTPN11 |
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 |
PAK2 | Q13177 | human | MYC | P01106 | S388 | RRNELkRsFFALRDQ | HLH |
PAK2 | Q13177 | human | ARHGAP15 | Q53QZ3 | S292 | kVCERENsTVPWFVk | |
PAK2 | Q13177 | human | H4C1 | P62805 | S47 | RGGVKrIsGLIyEEt | CENP-T_C |
PAK2 | Q13177 | human | JUN | P05412 | T2 | ______MtAKMETtF | |
PAK2 | Q13177 | human | CALD1 | Q05682 | S744 | GLKVGVSsRINEWLT | Caldesmon |
PAK2 | Q13177 | human | JUN | P05412 | T286 | RLEEKVKtLKAQNSE | bZIP_1 |
PAK2 | Q13177 | human | MYC | P01106 | T373 | EENVkRRtHNVLERQ | HLH |
PAK2 | Q13177 | human | MICAL1 | Q8TDZ2 | S817 | sPERQRLssLNLtPD | |
PAK2 | Q13177 | human | SORT1 | Q99523 | S793 | RFLVHRYsVLQQHAE | |
PAK2 | Q13177 | human | CASP7 | P55210 | S239 | WRsPGRGsWFVQALC | Peptidase_C14 |
PAK2 | Q13177 | human | ABL1 | P00519 | S619 | PtPPKRsssFREMDG | |
PAK2 | Q13177 | human | PAK2 | Q13177 | S192 | PRPDHTksIytRsVI | |
PAK2 | Q13177 | human | PAK2 | Q13177 | S141 | tVkQKyLsFtPPEkd | |
PAK2 | Q13177 | human | SMAD2 | Q15796 | S467 | sVRCssMs_______ | |
PAK2 | Q13177 | human | NF2 | P35240 | S518 | DTDMKRLsMEIEKEK | ERM_C |
PAK2 | Q13177 | human | SMAD2 | Q15796 | S417 | RMCTIRMsFVkGWGA | MH2 |
PAK2 | Q13177 | human | EIF4G1 | Q04637 | S895 | RDIARRRsLGNIkFI | MIF4G |
PAK2 | Q13177 | human | ARHGAP15 | Q53QZ3 | S4 | ____MQKsTNsDTSV | |
PAK2 | Q13177 | human | ARHGAP15 | Q53QZ3 | S43 | DRLsQsksMILTDVG | |
PAK2 | Q13177 | human | PAK2 | Q13177 | T402 | PEQSkRstMVGtPYW | Pkinase |
PAK2 | Q13177 | human | JUN | P05412 | T8 | MtAKMETtFYDDALN | Jun |
PAK2 | Q13177 | human | SMAD2 | Q15796 | S465 | sPsVRCssMs_____ | |
PAK2 | Q13177 | human | MYC | P01106 | T415 | VVILKkAtAYILsVQ | HLH |
PAK2 | Q13177 | human | PXN | P49023 | S272 | ELDELMAsLsDFkIQ | |
PAK2 | Q13177 | human | CASP7 | P55210 | S30 | DAKPDRssFVPsLFs | |
PAK2 | Q13177 | human | CALD1 | Q05682 | S714 | EGVRNIksMWEkGNV | Caldesmon |
PAK2 | Q13177 | human | ARHGAP15 | Q53QZ3 | S41 | HHDRLsQsksMILTD | |
PAK2 | Q13177 | human | MAPK6 | Q16659 | S189 | ySHKGHLsEGLVTkW | Pkinase |
PAK2 | Q13177 | human | PXN | P49023 | S274 | DELMAsLsDFkIQGL | |
PAK2 | Q13177 | human | PAK2 | Q13177 | S197 | TksIytRsVIDPVPA | |
PAK2 | Q13177 | human | CASP7 | P55210 | T173 | FRGDRCktLLEkPKL | Peptidase_C14 |
PAK2 | Q13177 | human | CTNNB1 | P35222 | S552 | QDtQRRtsMGGtQQQ | |
PAK2 | Q13177 | human | SMAD2 | Q15796 | S464 | GsPsVRCssMs____ | |
PAK2 | Q13177 | human | JUN | P05412 | T89 | QSSNGHItTtPtPtQ | Jun |
PAK2 | Q13177 | human | PREX2 | Q70Z35 | S1107 | DTISNRDsYSDCNSN | |
PAK2 | Q13177 | human | RAF1 | P04049 | S338 | RPRGQRDssyyWEIE | |
PAK2 | Q13177 | human | MICAL1 | Q8TDZ2 | S960 | ELALRRQssSPEQQK | bMERB_dom |
PAK2 | Q13177 | human | HACE1 | Q8IYU2 | S385 | LMKNKRDsTEITsIL | |
PAK2 | Q13177 | human | SLC25A5 | P05141 | T107 | LGGVDkRtQFWLyFA | |
PAK2 | Q13177 | human | JUN | P05412 | T93 | GHItTtPtPtQFLCP | Jun |
PAK2 | Q13177 | human | ABL1 | P00519 | S618 | APtPPKRsssFREMD |
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 |
PAK2 | ID | Description | 0.00e+00 |
PAK2 | GO:0051017 | actin filament bundle assembly | 9.20e-06 |
PAK2 | GO:0061572 | actin filament bundle organization | 9.20e-06 |
PAK2 | GO:0051492 | regulation of stress fiber assembly | 7.93e-04 |
PAK2 | GO:0110020 | regulation of actomyosin structure organization | 7.93e-04 |
PAK2 | GO:0031400 | negative regulation of protein modification process | 7.93e-04 |
PAK2 | GO:0032231 | regulation of actin filament bundle assembly | 7.93e-04 |
PAK2 | GO:0030038 | contractile actin filament bundle assembly | 7.93e-04 |
PAK2 | GO:0043149 | stress fiber assembly | 7.93e-04 |
PAK2 | GO:0007015 | actin filament organization | 8.86e-04 |
PAK2 | GO:0071560 | cellular response to transforming growth factor beta stimulus | 1.30e-03 |
PAK2 | GO:0071559 | response to transforming growth factor beta | 1.31e-03 |
PAK2 | GO:0001933 | negative regulation of protein phosphorylation | 1.43e-03 |
PAK2 | GO:0048538 | thymus development | 1.75e-03 |
PAK2 | GO:0042326 | negative regulation of phosphorylation | 1.75e-03 |
PAK2 | GO:0051496 | positive regulation of stress fiber assembly | 1.76e-03 |
PAK2 | GO:0032233 | positive regulation of actin filament bundle assembly | 2.69e-03 |
PAK2 | GO:0045936 | negative regulation of phosphate metabolic process | 2.69e-03 |
PAK2 | GO:0010563 | negative regulation of phosphorus metabolic process | 2.69e-03 |
PAK2 | GO:0007440 | foregut morphogenesis | 3.13e-03 |
PAK2 | GO:2001233 | regulation of apoptotic signaling pathway | 3.13e-03 |
PAK2 | GO:0031032 | actomyosin structure organization | 3.71e-03 |
PAK2 | GO:0009950 | dorsal/ventral axis specification | 4.07e-03 |
PAK2 | GO:0051346 | negative regulation of hydrolase activity | 4.07e-03 |
PAK2 | GO:0034333 | adherens junction assembly | 4.44e-03 |
PAK2 | GO:0016358 | dendrite development | 4.84e-03 |
PAK2 | GO:0048145 | regulation of fibroblast proliferation | 5.40e-03 |
PAK2 | GO:0007264 | small GTPase mediated signal transduction | 5.67e-03 |
PAK2 | GO:0045638 | negative regulation of myeloid cell differentiation | 5.67e-03 |
PAK2 | GO:0060192 | negative regulation of lipase activity | 5.67e-03 |
PAK2 | GO:0001657 | ureteric bud development | 5.67e-03 |
PAK2 | GO:0048534 | hematopoietic or lymphoid organ development | 5.67e-03 |
PAK2 | GO:0051098 | regulation of binding | 5.67e-03 |
PAK2 | GO:0072163 | mesonephric epithelium development | 5.67e-03 |
PAK2 | GO:0072164 | mesonephric tubule development | 5.67e-03 |
PAK2 | GO:0001823 | mesonephros development | 6.19e-03 |
PAK2 | GO:0110053 | regulation of actin filament organization | 6.19e-03 |
PAK2 | GO:0048144 | fibroblast proliferation | 6.56e-03 |
PAK2 | GO:0051056 | regulation of small GTPase mediated signal transduction | 7.89e-03 |
PAK2 | GO:0007398 | ectoderm development | 8.04e-03 |
PAK2 | GO:0002065 | columnar/cuboidal epithelial cell differentiation | 9.15e-03 |
PAK2 | GO:0002053 | positive regulation of mesenchymal cell proliferation | 9.35e-03 |
PAK2 | GO:0035994 | response to muscle stretch | 9.35e-03 |
PAK2 | GO:0048011 | neurotrophin TRK receptor signaling pathway | 9.35e-03 |
PAK2 | GO:0001704 | formation of primary germ layer | 9.35e-03 |
PAK2 | GO:0044346 | fibroblast apoptotic process | 9.78e-03 |
PAK2 | GO:0032956 | regulation of actin cytoskeleton organization | 1.08e-02 |
PAK2 | GO:0031589 | cell-substrate adhesion | 1.30e-02 |
PAK2 | GO:0033688 | regulation of osteoblast proliferation | 1.31e-02 |
PAK2 | GO:0072073 | kidney epithelium development | 1.34e-02 |
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Related Drugs to PAK2_PTPN11 |
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 PAK2-PTPN11 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 PAK2_PTPN11 |
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 |