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Kinase Fusion Gene:RAB21_KSR1 |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: RAB21_KSR1 | KinaseFusionDB ID: KFG5220 | FusionGDB2.0 ID: KFG5220 | Hgene | Tgene | Gene symbol | RAB21 | KSR1 | Gene ID | 23011 | 8844 | |
Gene name | RAB21, member RAS oncogene family | kinase suppressor of ras 1 | ||||||||||
Synonyms | - | KSR|RSU2 | ||||||||||
Cytomap | 12q21.1 | 17q11.2 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | ras-related protein Rab-21GTP-binding protein RAB21 | kinase suppressor of Ras 1 | ||||||||||
Modification date | 20240305 | 20240411 | ||||||||||
UniProtAcc | Q9UL25 | Q8IVT5 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000261263, | ENST00000268763, ENST00000398988, ENST00000578981, ENST00000581975, ENST00000582410, ENST00000319524, ENST00000509603, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: RAB21 [Title/Abstract] AND KSR1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | RAB21(72149068)-KSR1(25877594), # 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 | RAB21 | GO:0008089 | anterograde axonal transport | 22705394 |
Hgene | RAB21 | GO:0017157 | regulation of exocytosis | 22705394 |
Tgene | KSR1 | GO:0043410 | positive regulation of MAPK cascade | 29433126 |
Kinase Fusion gene breakpoints across RAB21 (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 KSR1 (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-A8-A09Q-01A | RAB21 | chr12 | 72149068 | KSR1 | chr17 | 25877594 |
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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) |
ENST00000261263 | ENST00000509603 | RAB21 | chr12 | 72149068 | KSR1 | chr17 | 25877594 | 2815 | 853 |
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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 >ENST00000261263_ENST00000509603_RAB21_chr12_72149068_KSR1_chr17_25877594_length(amino acids)=853 MAAAGGGGGGAAAAGRAYSFKVVLLGEGCVGKTSLVLRYCENKFNDKHITTLQAKLVRYICKQRQCKLSVAPGERTPELNSYPRFSDWLY TFNVRPEVVQEIPRDLTLDALLEMNEAKVKETLRRCGASGDECGRLQYALTCLRKVTGLGGEHKEDSSWSSLDARRESGSGPSTDTLSAA SLPWPPGSSQLGRAGNSAQGPRSISVSALPASDSPTPSFSEGLSDTCIPLHASGRLTPRALHSFITPPTTPQLRRHTKLKPPRTPPPPSR KVFQLLPSFPTLTRSKSHESQLGNRIDDVSSMRFDLSHGSPQMVRRDIGLSVTHRFSTKSWLSQVCHVCQKSMIFGVKCKHCRLKCHNKC TKEAPACRISFLPLTRLRRTESVPSDINNPVDRAAEPHFGTLPKALTKKEHPPAMNHLDSSSNPSSTTSSTPSSPAPFPTSSNPSSATTP PNPSPGQRDSRFNFPAAYFIHHRQQFIFPDISAFAHAAPLPEAADGTRLDDQPKADVLEAHEAEAEEPEAGKSEAEDDEDEVDDLPSSRR PWRGPISRKASQTSVYLQEWDIPFEQVELGEPIGQGRWGRVHRGRWHGEVAIRLLEMDGHNQDHLKLFKKEVMNYRQTRHENVVLFMGAC MNPPHLAIITSFCKGRTLHSFVRDPKTSLDINKTRQIAQEIIKGMGYLHAKGIVHKDLKSKNVFYDNGKVVITDFGLFGISGVVREGRRE NQLKLSHDWLCYLAPEIVREMTPGKDEDQLPFSKAADVYAFGTVWYELQARDWPLKNQAAEASIWQIGSGEGMKRVLTSVSLGKEVSEIL -------------------------------------------------------------- |
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/chr12:72149068/chr17:25877594) - 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 |
RAB21 | KSR1 |
FUNCTION: Small GTPase involved in membrane trafficking control (PubMed:18804435, PubMed:25648148). During the mitosis of adherent cells, controls the endosomal trafficking of integrins which is required for the successful completion of cytokinesis (PubMed:18804435). Regulates integrin internalization and recycling, but does not influence the traffic of endosomally translocated receptors in general (By similarity). As a result, may regulate cell adhesion and migration (By similarity). Involved in neurite growth (By similarity). Following SBF2/MTMT13-mediated activation in response to starvation-induced autophagy, binds to and regulates SNARE protein VAMP8 endolysosomal transport required for SNARE-mediated autophagosome-lysosome fusion (PubMed:25648148). Modulates protein levels of the cargo receptors TMED2 and TMED10, and required for appropriate Golgi localization of TMED10 (PubMed:31455601). {ECO:0000250|UniProtKB:P35282, ECO:0000250|UniProtKB:Q6AXT5, ECO:0000269|PubMed:18804435, ECO:0000269|PubMed:25648148, ECO:0000269|PubMed:31455601}. | FUNCTION: Part of a multiprotein signaling complex which promotes phosphorylation of Raf family members and activation of downstream MAP kinases (By similarity). Independently of its kinase activity, acts as MAP2K1/MEK1 and MAP2K2/MEK2-dependent allosteric activator of BRAF; upon binding to MAP2K1/MEK1 or MAP2K2/MEK2, dimerizes with BRAF and promotes BRAF-mediated phosphorylation of MAP2K1/MEK1 and/or MAP2K2/MEK2 (PubMed:29433126). Promotes activation of MAPK1 and/or MAPK3, both in response to EGF and to cAMP (By similarity). Its kinase activity is unsure (By similarity). Some protein kinase activity has been detected in vitro, however the physiological relevance of this activity is unknown (By similarity). {ECO:0000250|UniProtKB:Q61097, ECO:0000269|PubMed:29433126}. |
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 | RAB21 | 72149068 | KSR1 | 25877594 | ENST00000261263 | 1 | 22 | 613_883 | 0 | 787 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
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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 >>>401_RAB21_KSR1 | ENST00000261263 | ENST00000509603 | RAB21 | chr12 | 72149068 | KSR1 | chr17 | 25877594 | MAAAGGGGGGAAAAGRAYSFKVVLLGEGCVGKTSLVLRYCENKFNDKHITTLQAKLVRYICKQRQCKLSVAPGERTPELNSYPRFSDWLY TFNVRPEVVQEIPRDLTLDALLEMNEAKVKETLRRCGASGDECGRLQYALTCLRKVTGLGGEHKEDSSWSSLDARRESGSGPSTDTLSAA SLPWPPGSSQLGRAGNSAQGPRSISVSALPASDSPTPSFSEGLSDTCIPLHASGRLTPRALHSFITPPTTPQLRRHTKLKPPRTPPPPSR KVFQLLPSFPTLTRSKSHESQLGNRIDDVSSMRFDLSHGSPQMVRRDIGLSVTHRFSTKSWLSQVCHVCQKSMIFGVKCKHCRLKCHNKC TKEAPACRISFLPLTRLRRTESVPSDINNPVDRAAEPHFGTLPKALTKKEHPPAMNHLDSSSNPSSTTSSTPSSPAPFPTSSNPSSATTP PNPSPGQRDSRFNFPAAYFIHHRQQFIFPDISAFAHAAPLPEAADGTRLDDQPKADVLEAHEAEAEEPEAGKSEAEDDEDEVDDLPSSRR PWRGPISRKASQTSVYLQEWDIPFEQVELGEPIGQGRWGRVHRGRWHGEVAIRLLEMDGHNQDHLKLFKKEVMNYRQTRHENVVLFMGAC MNPPHLAIITSFCKGRTLHSFVRDPKTSLDINKTRQIAQEIIKGMGYLHAKGIVHKDLKSKNVFYDNGKVVITDFGLFGISGVVREGRRE NQLKLSHDWLCYLAPEIVREMTPGKDEDQLPFSKAADVYAFGTVWYELQARDWPLKNQAAEASIWQIGSGEGMKRVLTSVSLGKEVSEIL | 853 |
3D view using mol* of 401_RAB21_KSR1 | ||||||||||
PDB file >>>TKFP_681_RAB21_KSR1 | ENST00000261263 | ENST00000509603 | RAB21 | chr12 | 72149068 | KSR1 | chr17 | 25877594 | MAAAGGGGGGAAAAGRAYSFKVVLLGEGCVGKTSLVLRYCENKFNDKHITTLQAKLVRYICKQRQCKLSVAPGERTPELNSYPRFSDWLY TFNVRPEVVQEIPRDLTLDALLEMNEAKVKETLRRCGASGDECGRLQYALTCLRKVTGLGGEHKEDSSWSSLDARRESGSGPSTDTLSAA SLPWPPGSSQLGRAGNSAQGPRSISVSALPASDSPTPSFSEGLSDTCIPLHASGRLTPRALHSFITPPTTPQLRRHTKLKPPRTPPPPSR KVFQLLPSFPTLTRSKSHESQLGNRIDDVSSMRFDLSHGSPQMVRRDIGLSVTHRFSTKSWLSQVCHVCQKSMIFGVKCKHCRLKCHNKC TKEAPACRISFLPLTRLRRTESVPSDINNPVDRAAEPHFGTLPKALTKKEHPPAMNHLDSSSNPSSTTSSTPSSPAPFPTSSNPSSATTP PNPSPGQRDSRFNFPAAYFIHHRQQFIFPDISAFAHAAPLPEAADGTRLDDQPKADVLEAHEAEAEEPEAGKSEAEDDEDEVDDLPSSRR PWRGPISRKASQTSVYLQEWDIPFEQVELGEPIGQGRWGRVHRGRWHGEVAIRLLEMDGHNQDHLKLFKKEVMNYRQTRHENVVLFMGAC MNPPHLAIITSFCKGRTLHSFVRDPKTSLDINKTRQIAQEIIKGMGYLHAKGIVHKDLKSKNVFYDNGKVVITDFGLFGISGVVREGRRE NQLKLSHDWLCYLAPEIVREMTPGKDEDQLPFSKAADVYAFGTVWYELQARDWPLKNQAAEASIWQIGSGEGMKRVLTSVSLGKEVSEIL | 853_RAB21_KSR1 |
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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. |
401_RAB21_KSR1.png |
401_RAB21_KSR1.png |
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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. |
401_RAB21_KSR1_ramachandran.png |
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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 RAB21_KSR1 |
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 |
KSR1 | Q8IVT5 | human | RAF1 | P04049 | T269 | NVHMVsttLPVDSRM |
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 |
KSR1 | ID | Description | 0.00e+00 |
KSR1 | GO:0007190 | activation of adenylate cyclase activity | 1.46e-02 |
KSR1 | GO:0035994 | response to muscle stretch | 1.46e-02 |
KSR1 | GO:0048011 | neurotrophin TRK receptor signaling pathway | 1.46e-02 |
KSR1 | GO:0060333 | type II interferon-mediated signaling pathway | 1.46e-02 |
KSR1 | GO:0044342 | type B pancreatic cell proliferation | 1.46e-02 |
KSR1 | GO:0030878 | thyroid gland development | 1.46e-02 |
KSR1 | GO:0045762 | positive regulation of adenylate cyclase activity | 1.46e-02 |
KSR1 | GO:1902042 | negative regulation of extrinsic apoptotic signaling pathway via death domain receptors | 1.46e-02 |
KSR1 | GO:0031281 | positive regulation of cyclase activity | 1.46e-02 |
KSR1 | GO:0038179 | neurotrophin signaling pathway | 1.46e-02 |
KSR1 | GO:0051349 | positive regulation of lyase activity | 1.46e-02 |
KSR1 | GO:0045761 | regulation of adenylate cyclase activity | 1.46e-02 |
KSR1 | GO:0048538 | thymus development | 1.46e-02 |
KSR1 | GO:1902041 | regulation of extrinsic apoptotic signaling pathway via death domain receptors | 1.46e-02 |
KSR1 | GO:0043154 | negative regulation of cysteine-type endopeptidase activity involved in apoptotic process | 1.46e-02 |
KSR1 | GO:0048009 | insulin-like growth factor receptor signaling pathway | 1.46e-02 |
KSR1 | GO:0060324 | face development | 1.46e-02 |
KSR1 | GO:0031279 | regulation of cyclase activity | 1.46e-02 |
KSR1 | GO:0051339 | regulation of lyase activity | 1.49e-02 |
KSR1 | GO:0035773 | insulin secretion involved in cellular response to glucose stimulus | 1.51e-02 |
KSR1 | GO:2000117 | negative regulation of cysteine-type endopeptidase activity | 1.51e-02 |
KSR1 | GO:0035019 | somatic stem cell population maintenance | 1.53e-02 |
KSR1 | GO:0035023 | regulation of Rho protein signal transduction | 1.70e-02 |
KSR1 | GO:0008625 | extrinsic apoptotic signaling pathway via death domain receptors | 1.70e-02 |
KSR1 | GO:0045104 | intermediate filament cytoskeleton organization | 1.70e-02 |
KSR1 | GO:0045103 | intermediate filament-based process | 1.70e-02 |
KSR1 | GO:0048534 | hematopoietic or lymphoid organ development | 1.70e-02 |
KSR1 | GO:2001237 | negative regulation of extrinsic apoptotic signaling pathway | 1.70e-02 |
KSR1 | GO:0033138 | positive regulation of peptidyl-serine phosphorylation | 1.70e-02 |
KSR1 | GO:0140888 | interferon-mediated signaling pathway | 1.70e-02 |
KSR1 | GO:0071346 | cellular response to type II interferon | 1.70e-02 |
KSR1 | GO:0008286 | insulin receptor signaling pathway | 1.70e-02 |
KSR1 | GO:0010951 | negative regulation of endopeptidase activity | 1.70e-02 |
KSR1 | GO:0071333 | cellular response to glucose stimulus | 1.70e-02 |
KSR1 | GO:0007266 | Rho protein signal transduction | 1.70e-02 |
KSR1 | GO:0010466 | negative regulation of peptidase activity | 1.70e-02 |
KSR1 | GO:0033135 | regulation of peptidyl-serine phosphorylation | 1.70e-02 |
KSR1 | GO:0071331 | cellular response to hexose stimulus | 1.70e-02 |
KSR1 | GO:0035270 | endocrine system development | 1.70e-02 |
KSR1 | GO:0071326 | cellular response to monosaccharide stimulus | 1.70e-02 |
KSR1 | GO:0034341 | response to type II interferon | 1.70e-02 |
KSR1 | GO:0031333 | negative regulation of protein-containing complex assembly | 1.71e-02 |
KSR1 | GO:0071322 | cellular response to carbohydrate stimulus | 1.71e-02 |
KSR1 | GO:0001678 | intracellular glucose homeostasis | 1.71e-02 |
KSR1 | GO:2001236 | regulation of extrinsic apoptotic signaling pathway | 1.71e-02 |
KSR1 | GO:0043281 | regulation of cysteine-type endopeptidase activity involved in apoptotic process | 1.73e-02 |
KSR1 | GO:0019827 | stem cell population maintenance | 1.79e-02 |
KSR1 | GO:0046578 | regulation of Ras protein signal transduction | 1.79e-02 |
KSR1 | GO:0098727 | maintenance of cell number | 1.79e-02 |
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Related Drugs to RAB21_KSR1 |
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 RAB21-KSR1 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 RAB21_KSR1 |
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 |