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Kinase Fusion Gene:SRD5A1_GRK4 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: SRD5A1_GRK4 | KinaseFusionDB ID: KFG6045 | FusionGDB2.0 ID: KFG6045 | Hgene | Tgene | Gene symbol | SRD5A1 | GRK4 | Gene ID | 6715 | 2868 | |
| Gene name | steroid 5 alpha-reductase 1 | G protein-coupled receptor kinase 4 | ||||||||||
| Synonyms | S5AR 1 | GPRK2L|GPRK4|GRK4a|IT11 | ||||||||||
| Cytomap | 5p15.31 | 4p16.3 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | 3-oxo-5-alpha-steroid 4-dehydrogenase 1SR type 1steroid 5-alpha-reductase type Isteroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 1) | G protein-coupled receptor kinase 4G protein-coupled receptor kinase 2-like | ||||||||||
| Modification date | 20240411 | 20240411 | ||||||||||
| UniProtAcc | P18405 | P32298 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000537411, ENST00000274192, ENST00000538824, ENST00000504286, | ENST00000345167, ENST00000398051, ENST00000398052, ENST00000504933, ENST00000442472, ENST00000503518, ENST00000509545, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: SRD5A1 [Title/Abstract] AND GRK4 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | SRD5A1(6663079)-GRK4(3024140), # samples:2 | |||||||||||
| 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 |
| Tgene | GRK4 | GO:0031623 | receptor internalization | 20074556 |
| Kinase Fusion gene breakpoints across SRD5A1 (5'-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 breakpoints across GRK4 (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-L5-A8NW | SRD5A1 | chr5 | 6663079 | GRK4 | chr4 | 3024140 |
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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) |
| ENST00000274192 | ENST00000398051 | SRD5A1 | chr5 | 6663079 | GRK4 | chr4 | 3024140 | 1716 | 484 |
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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 >ENST00000274192_ENST00000398051_SRD5A1_chr5_6663079_GRK4_chr4_3024140_length(amino acids)=484 MPPRRRPICCPPRPLGHGARCPALAMATATGVAEERLLAALAYLQCAVGCAVFARNRQTNSVYGRHALPSHRLRVPARAAWVVQELPSLA LPLYQYASESAPRLRSAPNCILLAMFLVHYGHRCLIYPFLMRGGKPMPLLACTMAIMFCTCNGYLQSRYLSHCAVYADDWVTDPRFLIGF GLWLTGMLINIHSDHILRNLRKPGDTGYKIPRGGLFEYVTAANYFGEIMEWCGYALASWSVQGAAFAFFTFCFLSGRAKEHHEDLKPENI LLDDRGHIRISDLGLATEIPEGQRVRGRVGTVGYMAPEVVNNEKYTFSPDWWGLGCLIYEMIQGHSPFKKYKEKVKWEEVDQRIKNDTEE YSEKFSEDAKSICRMLLTKNPSKRLGCRGEGAAGVKQHPVFKDINFRRLEANMLEPPFCPDPHAVYCKDVLDIEQFSVVKGIYLDTADED -------------------------------------------------------------- |
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/chr5:6663079/chr4:3024140) - 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 |
| SRD5A1 | GRK4 |
| FUNCTION: Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology. {ECO:0000269|PubMed:2339109}. | FUNCTION: Specifically phosphorylates the activated forms of G protein-coupled receptors. GRK4-alpha can phosphorylate rhodopsin and its activity is inhibited by calmodulin; the other three isoforms do not phosphorylate rhodopsin and do not interact with calmodulin. GRK4-alpha and GRK4-gamma phosphorylate DRD3. Phosphorylates ADRB2. {ECO:0000269|PubMed:19520868, ECO:0000269|PubMed:8626439}. |
| 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 |
| Tgene | SRD5A1 | 6663079 | GRK4 | 3024140 | ENST00000274192 | 7 | 14 | 450_515 | 278 | 501 | Domain | Note=AGC-kinase C-terminal;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00618 |
| Tgene | SRD5A1 | 6663079 | GRK4 | 3024140 | ENST00000274192 | 7 | 15 | 450_515 | 278 | 547 | Domain | Note=AGC-kinase C-terminal;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00618 |
| Tgene | SRD5A1 | 6663079 | GRK4 | 3024140 | ENST00000274192 | 8 | 15 | 450_515 | 310 | 533 | Domain | Note=AGC-kinase C-terminal;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00618 |
| Tgene | SRD5A1 | 6663079 | GRK4 | 3024140 | ENST00000274192 | 8 | 16 | 450_515 | 310 | 579 | Domain | Note=AGC-kinase C-terminal;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00618 |
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Kinase Fusion Protein Structures |
| CIF files of the predicted kinase fusion proteins * Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB) | Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | AA seq | Len(AA seq) |
| PDB file >>>474_SRD5A1_GRK4 | ENST00000274192 | ENST00000398051 | SRD5A1 | chr5 | 6663079 | GRK4 | chr4 | 3024140 | MPPRRRPICCPPRPLGHGARCPALAMATATGVAEERLLAALAYLQCAVGCAVFARNRQTNSVYGRHALPSHRLRVPARAAWVVQELPSLA LPLYQYASESAPRLRSAPNCILLAMFLVHYGHRCLIYPFLMRGGKPMPLLACTMAIMFCTCNGYLQSRYLSHCAVYADDWVTDPRFLIGF GLWLTGMLINIHSDHILRNLRKPGDTGYKIPRGGLFEYVTAANYFGEIMEWCGYALASWSVQGAAFAFFTFCFLSGRAKEHHEDLKPENI LLDDRGHIRISDLGLATEIPEGQRVRGRVGTVGYMAPEVVNNEKYTFSPDWWGLGCLIYEMIQGHSPFKKYKEKVKWEEVDQRIKNDTEE YSEKFSEDAKSICRMLLTKNPSKRLGCRGEGAAGVKQHPVFKDINFRRLEANMLEPPFCPDPHAVYCKDVLDIEQFSVVKGIYLDTADED | 484 |
| 3D view using mol* of 474_SRD5A1_GRK4 | ||||||||||
| PDB file >>>TKFP_803_SRD5A1_GRK4 | ENST00000274192 | ENST00000398051 | SRD5A1 | chr5 | 6663079 | GRK4 | chr4 | 3024140 | MPPRRRPICCPPRPLGHGARCPALAMATATGVAEERLLAALAYLQCAVGCAVFARNRQTNSVYGRHALPSHRLRVPARAAWVVQELPSLA LPLYQYASESAPRLRSAPNCILLAMFLVHYGHRCLIYPFLMRGGKPMPLLACTMAIMFCTCNGYLQSRYLSHCAVYADDWVTDPRFLIGF GLWLTGMLINIHSDHILRNLRKPGDTGYKIPRGGLFEYVTAANYFGEIMEWCGYALASWSVQGAAFAFFTFCFLSGRAKEHHEDLKPENI LLDDRGHIRISDLGLATEIPEGQRVRGRVGTVGYMAPEVVNNEKYTFSPDWWGLGCLIYEMIQGHSPFKKYKEKVKWEEVDQRIKNDTEE YSEKFSEDAKSICRMLLTKNPSKRLGCRGEGAAGVKQHPVFKDINFRRLEANMLEPPFCPDPHAVYCKDVLDIEQFSVVKGIYLDTADED | 484_SRD5A1_GRK4 |
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Comparison of Fusion Protein Isoforms |
| Superimpose the 3D Structures Among All Fusion Protein Isoforms * Download the pdb file and open it from the molstar online viewer. |
| Comparison of the Secondary Structures of Fusion Protein Isoforms |
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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB |
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pLDDT score distribution |
| pLDDT score distribution of the predicted fusion protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. * The blue color at the bottom marks the best active site residues. |
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Potential Active Site Information |
| The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite. |
| Kinase Fusion AA seq ID in KinaseFusionDB | Site score | Size | Dscore | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
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Ramachandran Plot of Kinase Fusion Protein Structure |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide. |
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Virtual Screening Results |
| Distribution of the average docking score across all approved kinase inhibitors. Distribution of the number of occurrence across all approved kinase inhibitors. |
| 5'-kinase fusion protein case |
| 3'-kinase fusion protein case |
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| Drug information from DrugBank of the top 20 interacting small molecules. * The detailed information of individual kinase inhibitors are available in the download page. |
| Fusion gene name info | Drug | Docking score | Glide g score | Glide energy |
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Kinase-Substrate Information of SRD5A1_GRK4 |
| 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 |
| GRK4 | P32298 | human | GRK4 | P32298 | S10 | LENIVANsLLLkARQ | |
| GRK4 | P32298 | human | GRK4 | P32298 | S430 | MLLtKNPsKRLGCRG | Pkinase |
| GRK4 | P32298 | human | BDKRB2 | P30411 | S366 | EPIQMENsMGTLRTs | |
| GRK4 | P32298 | human | BDKRB2 | P30411 | S375 | GTLRTsIsVERQIHk | |
| GRK4 | P32298 | human | GRK4 | P32298 | S419 | KFSEDAKsICRMLLt | Pkinase |
| GRK4 | P32298 | human | GRK4 | P32298 | S139 | GLKEENPsKKAFEEC | RGS |
| GRK4 | P32298 | human | GRK4 | P32298 | T426 | sICRMLLtKNPsKRL | Pkinase |
| GRK4 | P32298 | human | GRK4 | P32298 | S249 | VQsRFVVsLAYAYEt | Pkinase |
| GRK4 | P32298 | human | GRK4 | P32298 | S244 | RILEKVQsRFVVsLA | Pkinase |
| GRK4 | P32298 | human | BDKRB2 | P30411 | S373 | sMGTLRTsIsVERQI | |
| GRK4 | P32298 | human | GRK4 | P32298 | S485 | VLDIEQFsVVKGIYL | |
| GRK4 | P32298 | human | GRK4 | P32298 | T256 | sLAYAYEtKDALCLV | Pkinase |
| 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 |
| GRK4 | escriptio | 0.00e+00 | |
| GRK4 | O:007121 | ellular response to abiotic stimulu | 1.06e-02 |
| GRK4 | O:010400 | ellular response to environmental stimulu | 1.06e-02 |
| GRK4 | O:000862 | ntrinsic apoptotic signaling pathway in response to osmotic stres | 1.65e-02 |
| GRK4 | O:002240 | egulation of rhodopsin mediated signaling pathwa | 1.65e-02 |
| GRK4 | O:010604 | egulation of cellular response to osmotic stres | 1.65e-02 |
| GRK4 | O:001605 | hodopsin mediated signaling pathwa | 1.65e-02 |
| GRK4 | O:004748 | egulation of response to osmotic stres | 1.65e-02 |
| GRK4 | O:000760 | phototransductio | 2.12e-03 |
| GRK4 | O:000965 | esponse to salt stres | 1.68e-02 |
| GRK4 | O:003313 | egative regulation of peptidyl-serine phosphorylatio | 1.68e-02 |
| GRK4 | O:005048 | rachidonic acid secretio | 1.68e-02 |
| GRK4 | O:190396 | rachidonate transpor | 1.68e-02 |
| GRK4 | O:190179 | egative regulation of signal transduction by p53 class mediato | 1.68e-02 |
| GRK4 | O:190225 | egulation of intrinsic apoptotic signaling pathway by p53 class mediato | 1.68e-02 |
| GRK4 | O:003230 | cosanoid secretio | 1.82e-02 |
| GRK4 | O:004231 | asodilatio | 1.82e-02 |
| GRK4 | O:000760 | hototransductio | 1.82e-02 |
| GRK4 | O:004311 | egulation of vascular permeabilit | 1.82e-02 |
| GRK4 | O:007147 | ellular response to osmotic stres | 1.82e-02 |
| GRK4 | O:000958 | etection of visible ligh | 1.82e-02 |
| GRK4 | O:007171 | cosanoid transpor | 1.99e-02 |
| GRK4 | O:001922 | egulation of vasoconstrictio | 1.99e-02 |
| GRK4 | O:001590 | ong-chain fatty acid transpor | 1.99e-02 |
| GRK4 | O:000958 | etection of light stimulu | 1.99e-02 |
| GRK4 | O:000697 | esponse to osmotic stres | 2.16e-02 |
| GRK4 | O:004231 | asoconstrictio | 2.16e-02 |
| GRK4 | O:007233 | ntrinsic apoptotic signaling pathway by p53 class mediato | 2.16e-02 |
| GRK4 | O:190179 | egulation of signal transduction by p53 class mediato | 2.57e-02 |
| GRK4 | O:000693 | mooth muscle contractio | 2.57e-02 |
| GRK4 | O:200124 | egative regulation of intrinsic apoptotic signaling pathwa | 2.57e-02 |
| GRK4 | O:001590 | atty acid transpor | 2.57e-02 |
| GRK4 | O:007148 | ellular response to light stimulu | 2.57e-02 |
| GRK4 | O:003162 | eceptor internalizatio | 2.57e-02 |
| GRK4 | O:000958 | etection of external stimulu | 2.57e-02 |
| GRK4 | O:003313 | egulation of peptidyl-serine phosphorylatio | 2.57e-02 |
| GRK4 | O:000827 | egulation of G protein-coupled receptor signaling pathwa | 2.57e-02 |
| GRK4 | O:000958 | etection of abiotic stimulu | 2.57e-02 |
| GRK4 | O:003529 | egulation of tube diamete | 2.57e-02 |
| GRK4 | O:009774 | lood vessel diameter maintenanc | 2.57e-02 |
| GRK4 | O:003515 | egulation of tube siz | 2.57e-02 |
| GRK4 | O:000720 | ositive regulation of cytosolic calcium ion concentratio | 2.89e-02 |
| GRK4 | O:007233 | ignal transduction by p53 class mediato | 2.89e-02 |
| GRK4 | O:001571 | onocarboxylic acid transpor | 2.89e-02 |
| GRK4 | O:007147 | ellular response to radiatio | 2.89e-02 |
| GRK4 | O:200124 | egulation of intrinsic apoptotic signaling pathwa | 2.96e-02 |
| GRK4 | O:200123 | egative regulation of apoptotic signaling pathwa | 3.70e-02 |
| GRK4 | O:000689 | eceptor-mediated endocytosi | 3.77e-02 |
| GRK4 | O:190352 | egulation of blood circulatio | 3.77e-02 |
| GRK4 | O:000301 | ascular process in circulatory syste | 3.85e-02 |
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Related Drugs to SRD5A1_GRK4 |
| 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 SRD5A1-GRK4 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 SRD5A1_GRK4 |
| 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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