UTHEALTH HOME ABOUT SBMI A-Z WEBMAIL INSIDE THE UNIVERSITY |
|
Kinase Fusion Gene:RPS6KA3_PRPH2 |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: RPS6KA3_PRPH2 | KinaseFusionDB ID: KFG5567 | FusionGDB2.0 ID: KFG5567 | Hgene | Tgene | Gene symbol | RPS6KA3 | PRPH2 | Gene ID | 6197 | 5961 | |
Gene name | ribosomal protein S6 kinase A3 | peripherin 2 | ||||||||||
Synonyms | CLS|HU-3|ISPK-1|MAPKAPK1B|MRX19|RSK|RSK2|S6K-alpha3|XLID19|p90-RSK2|pp90RSK2 | AOFMD|AVMD|CACD2|DS|MDBS1|PRPH|RDS|RP7|TSPAN22|rd2 | ||||||||||
Cytomap | Xp22.12 | 6p21.1 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | ribosomal protein S6 kinase alpha-3MAP kinase-activated protein kinase 1bMAPK-activated protein kinase 1bMAPKAP kinase 1bMAPKAPK-1bRSK-2S6K-alpha-3epididymis secretory sperm binding proteininsulin-stimulated protein kinase 1p90-RSK 3ribosomal S6 | peripherin-2choroidal dystrophy, central areolar 2peripherin 2 (retinal degeneration, slow)peripherin 2, homolog of mouseperipherin, photoreceptor typeretinal degeneration slow proteinretinal peripherintetraspanin-22tspan-22 | ||||||||||
Modification date | 20240403 | 20240413 | ||||||||||
UniProtAcc | P51812 | P23942 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000379548, ENST00000379565, ENST00000479809, ENST00000540702, ENST00000544447, | ENST00000230381, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: RPS6KA3 [Title/Abstract] AND PRPH2 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | RPS6KA3(20189615)-PRPH2(42674739), # 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 | RPS6KA3 | GO:0043154 | negative regulation of cysteine-type endopeptidase activity involved in apoptotic process | 18402937 |
Kinase Fusion gene breakpoints across RPS6KA3 (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 PRPH2 (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 | AJ012498 | RPS6KA3 | chrX | 20189615 | PRPH2 | chr6 | 42674739 |
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/:20189615/:42674739) - 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 |
RPS6KA3 | PRPH2 |
FUNCTION: Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:9770464, PubMed:16223362, PubMed:17360704, PubMed:16213824). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:9770464, PubMed:10436156). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity). {ECO:0000250|UniProtKB:P18654, ECO:0000269|PubMed:10436156, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:8250835, ECO:0000269|PubMed:9770464, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}. | FUNCTION: Essential for retina photoreceptor outer segment disk morphogenesis, may also play a role with ROM1 in the maintenance of outer segment disk structure (By similarity). Required for the maintenance of retinal outer nuclear layer thickness (By similarity). Required for the correct development and organization of the photoreceptor inner segment (By similarity). {ECO:0000250|UniProtKB:P15499}. |
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 RPS6KA3_PRPH2 |
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 |
RPS6KA3 | P51812 | human | NFATC4 | Q14934 | S289 | PALsRRGsLGEEGsE | |
RPS6KA3 | P51812 | human | WWC1 | Q8IX03 | S947 | CRLNRsDsDSSTLSK | |
RPS6KA3 | P51812 | human | NFATC4 | Q14934 | S281 | SGTPSSAsPALsRRG | |
RPS6KA3 | P51812 | human | TH | P07101-4 | S44 | RFIGRRQsLIEDARK | TOH_N |
RPS6KA3 | P51812 | human | RIOK2 | Q9BVS4 | S483 | QYRTRtLsItssGsA | |
RPS6KA3 | P51812 | human | EIF2AK2 | P19525 | T451 | kRtRSKGtLRyMsPE | Pkinase |
RPS6KA3 | P51812 | human | YBX1 | P67809 | S102 | NPRKyLrsVGDGEtV | CSD |
RPS6KA3 | P51812 | human | TINF2 | Q9BSI4 | S295 | FPFRNLGsPtQVISk | |
RPS6KA3 | P51812 | human | H3C1 | P68431 | S10 | tkQtArkstGGkAPr | Histone |
RPS6KA3 | P51812 | human | RRN3 | Q9NYV6 | S649 | PVLYMQPsPL_____ | |
RPS6KA3 | P51812 | human | LCP1 | P13796 | S5 | ___MARGsVsDEEMM | |
RPS6KA3 | P51812 | human | MYL12A | P19105 | S19 | KRPQRAtsNVFAMFD | |
RPS6KA3 | P51812 | human | TBX21 | Q9UL17 | S503 | DSKRRRVsPYPsSGD | |
RPS6KA3 | P51812 | human | TBX21 | Q9UL17 | S507 | RRVsPYPsSGDSsSP | |
RPS6KA3 | P51812 | human | MAP3K5 | Q99683 | T1109 | DRKIIATtLSKLkLE | HisK-N-like |
RPS6KA3 | P51812 | human | DAPK1 | P53355 | S289 | QALSRKAsAVNMEkF | |
RPS6KA3 | P51812 | human | STAT3 | P40763 | S727 | NtIDLPMsPrTLDSL | |
RPS6KA3 | P51812 | human | STMN1 | P16949 | S16 | kELEKrAsGQAFELI | Stathmin |
RPS6KA3 | P51812 | human | EPHA2 | P29317 | S897 | RVsIRLPstsGsEGV | |
RPS6KA3 | P51812 | human | BAD | Q92934 | S99 | PFrGrsRsAPPNLWA | Bcl-2_BAD |
RPS6KA3 | P51812 | human | NFATC4 | Q14934 | S344 | QAVALPRsEEPASCN | |
RPS6KA3 | P51812 | human | WWC1 | Q8IX03 | T929 | stIIRsKtFsPGPQS | |
RPS6KA3 | P51812 | human | NFKBIA | P25963 | S32 | LLDDRHDsGLDsMkD | |
RPS6KA3 | P51812 | human | GSK3A | P49840 | S21 | sGrARtssFAEPGGG | |
RPS6KA3 | P51812 | human | PPP1R3A | Q16821 | S65 | SSGTRRVsFADSFGF | |
RPS6KA3 | P51812 | human | NFATC4 | Q14934 | S676 | SNGRRKRsPTQSFRF | RHD_dimer |
RPS6KA3 | P51812 | human | NFATC4 | Q14934 | S285 | SSAsPALsRRGsLGE | |
RPS6KA3 | P51812 | human | SPRED2 | Q7Z698 | S168 | QPTRTIssPTSCEHR | |
RPS6KA3 | P51812 | human | MAP3K5 | Q99683 | S83 | ATRGRGssVGGGSrR | |
RPS6KA3 | P51812 | human | BAD | Q92934 | S75 | EIRsRHssyPAGtED | Bcl-2_BAD |
RPS6KA3 | P51812 | human | CASP8 | Q14790 | T263 | SIRDRNGtHLDAGAL | Peptidase_C14 |
RPS6KA3 | P51812 | human | CREB1 | P16220 | S119 | EILsRRPsyRkILND | pKID |
RPS6KA3 | P51812 | human | GSK3B | P49841 | S9 | SGRPRttsFAEsCkP | |
RPS6KA3 | P51812 | human | RANBP3 | Q9H6Z4 | S126 | VKRERtssLtQFPPs | |
RPS6KA3 | P51812 | human | ESR1 | P03372 | S167 | GGRERLAsTNDkGSM | Oest_recep |
RPS6KA3 | P51812 | human | H2AX | P16104 | S16 | kARAkAksRSsrAGL | Histone |
RPS6KA3 | P51812 | human | RPS6 | P62753 | S236 | AKRRRLssLRAstsK | |
RPS6KA3 | P51812 | human | VGLL1 | Q99990 | S84 | PNQWRYSsPWTKPQP | |
RPS6KA3 | P51812 | human | RELA | Q04206 | S276 | sMQLRRPsDRELsEP | RHD_dimer |
RPS6KA3 | P51812 | human | TINF2 | Q9BSI4 | S330 | ASTGKSKsPCQTLGG | |
RPS6KA3 | P51812 | human | TH | P07101-2 | S67 | RFIGRRQsLIEDARK | TOH_N |
RPS6KA3 | P51812 | human | MAP3K5 | Q99683 | T1326 | VNGADEDtISRFLAE | |
RPS6KA3 | P51812 | human | TH | P07101 | S71 | RFIGRRQsLIEDARK | TOH_N |
RPS6KA3 | P51812 | human | PPP1R3A | Q16821 | S46 | PQPSRRGsDssEDIY | |
RPS6KA3 | P51812 | human | ATF4 | P18848 | S245 | TrGSPNRsLPsPGVL | |
RPS6KA3 | P51812 | human | FOXN2 | P32314 | S369 | LGDsGYAsQPCAKIS | |
RPS6KA3 | P51812 | human | FOXN2 | P32314 | S365 | EDDPLGDsGYAsQPC | |
RPS6KA3 | P51812 | human | SPRED2 | Q7Z698 | S167 | EQPTRTIssPTSCEH | |
RPS6KA3 | P51812 | human | H2BC3 | P33778 | S32 | DGKkRKRsRkEsysI | Histone |
RPS6KA3 | P51812 | human | FGFR1 | P11362 | S789 | DTRSSTCsSGEDSVF | |
RPS6KA3 | P51812 | human | RPS6 | P62753 | S235 | IAKRRRLssLRAsts | |
RPS6KA3 | P51812 | human | SLC9A3 | P48764 | S663 | TMRKRLEsFKSTKLG | |
RPS6KA3 | P51812 | human | TH | P07101-3 | S40 | RFIGRRQsLIEDARK | TOH_N |
RPS6KA3 | P51812 | human | CIC | Q96RK0 | S173 | PGKRRtQsLsALPKE | |
RPS6KA3 | P51812 | human | EIF2S1 | P05198 | S52 | MILLsELsRRRIRsI | S1 |
RPS6KA3 | P51812 | human | KCNK3 | O14649 | S393 | GLMKRRssV______ |
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 |
RPS6KA3 | ID | Description | 0.00e+00 |
RPS6KA3 | GO:0071248 | cellular response to metal ion | 2.28e-04 |
RPS6KA3 | GO:0071241 | cellular response to inorganic substance | 2.28e-04 |
RPS6KA3 | GO:0097191 | extrinsic apoptotic signaling pathway | 2.28e-04 |
RPS6KA3 | GO:0010038 | response to metal ion | 2.56e-04 |
RPS6KA3 | GO:0071287 | cellular response to manganese ion | 3.40e-04 |
RPS6KA3 | GO:0034198 | cellular response to amino acid starvation | 1.04e-03 |
RPS6KA3 | GO:1990928 | response to amino acid starvation | 1.04e-03 |
RPS6KA3 | GO:0002064 | epithelial cell development | 1.04e-03 |
RPS6KA3 | GO:0010042 | response to manganese ion | 1.15e-03 |
RPS6KA3 | GO:0045862 | positive regulation of proteolysis | 1.15e-03 |
RPS6KA3 | GO:0038034 | signal transduction in absence of ligand | 1.59e-03 |
RPS6KA3 | GO:0097192 | extrinsic apoptotic signaling pathway in absence of ligand | 1.59e-03 |
RPS6KA3 | GO:1902893 | regulation of miRNA transcription | 1.71e-03 |
RPS6KA3 | GO:0061614 | miRNA transcription | 1.71e-03 |
RPS6KA3 | GO:2001233 | regulation of apoptotic signaling pathway | 1.71e-03 |
RPS6KA3 | GO:0003323 | type B pancreatic cell development | 1.71e-03 |
RPS6KA3 | GO:0010950 | positive regulation of endopeptidase activity | 1.71e-03 |
RPS6KA3 | GO:1902894 | negative regulation of miRNA transcription | 1.77e-03 |
RPS6KA3 | GO:2000629 | negative regulation of miRNA metabolic process | 1.89e-03 |
RPS6KA3 | GO:0010952 | positive regulation of peptidase activity | 2.20e-03 |
RPS6KA3 | GO:0008625 | extrinsic apoptotic signaling pathway via death domain receptors | 2.33e-03 |
RPS6KA3 | GO:2000628 | regulation of miRNA metabolic process | 2.33e-03 |
RPS6KA3 | GO:0003309 | type B pancreatic cell differentiation | 2.43e-03 |
RPS6KA3 | GO:0005979 | regulation of glycogen biosynthetic process | 2.47e-03 |
RPS6KA3 | GO:0010962 | regulation of glucan biosynthetic process | 2.47e-03 |
RPS6KA3 | GO:0140747 | regulation of ncRNA transcription | 2.57e-03 |
RPS6KA3 | GO:0006109 | regulation of carbohydrate metabolic process | 2.64e-03 |
RPS6KA3 | GO:0062197 | cellular response to chemical stress | 2.74e-03 |
RPS6KA3 | GO:0097193 | intrinsic apoptotic signaling pathway | 2.74e-03 |
RPS6KA3 | GO:0046777 | protein autophosphorylation | 3.02e-03 |
RPS6KA3 | GO:0002068 | glandular epithelial cell development | 3.02e-03 |
RPS6KA3 | GO:0071214 | cellular response to abiotic stimulus | 3.02e-03 |
RPS6KA3 | GO:0104004 | cellular response to environmental stimulus | 3.02e-03 |
RPS6KA3 | GO:0035883 | enteroendocrine cell differentiation | 3.02e-03 |
RPS6KA3 | GO:0070306 | lens fiber cell differentiation | 3.02e-03 |
RPS6KA3 | GO:0001819 | positive regulation of cytokine production | 3.02e-03 |
RPS6KA3 | GO:0010586 | miRNA metabolic process | 3.02e-03 |
RPS6KA3 | GO:0070873 | regulation of glycogen metabolic process | 3.02e-03 |
RPS6KA3 | GO:0032885 | regulation of polysaccharide biosynthetic process | 3.12e-03 |
RPS6KA3 | GO:0071496 | cellular response to external stimulus | 3.12e-03 |
RPS6KA3 | GO:0043280 | positive regulation of cysteine-type endopeptidase activity involved in apoptotic process | 3.40e-03 |
RPS6KA3 | GO:0032355 | response to estradiol | 3.56e-03 |
RPS6KA3 | GO:0005978 | glycogen biosynthetic process | 4.15e-03 |
RPS6KA3 | GO:0006984 | ER-nucleus signaling pathway | 4.15e-03 |
RPS6KA3 | GO:0009250 | glucan biosynthetic process | 4.15e-03 |
RPS6KA3 | GO:0031018 | endocrine pancreas development | 4.15e-03 |
RPS6KA3 | GO:0032881 | regulation of polysaccharide metabolic process | 4.15e-03 |
RPS6KA3 | GO:0042789 | mRNA transcription by RNA polymerase II | 4.15e-03 |
RPS6KA3 | GO:0002286 | T cell activation involved in immune response | 4.15e-03 |
Top |
Related Drugs to RPS6KA3_PRPH2 |
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 RPS6KA3-PRPH2 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 RPS6KA3_PRPH2 |
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 |