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	Kinase Fusion Gene Summary
	Kinase Fusion Gene Sample Information
	Kinase Fusion ORF Analysis
	Kinase Fusion Amino Acid Sequences
	Multiple Sequence Alignment of All Fusion Protein Isoforms
	Kinase Fusion Protein Functional Features
	Kinase Fusion Protein Structures
	Comparison of Fusion Protein Isoforms
	Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB
	pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.
	Ramachandran Plot of Kinase Fusion Protein Structure
	Potential Active Site Information
	Virtual Screening Results
	Kinase-Substrate Information
	Related Drugs with This Kinase Fusion Protein
	Related Disease with This Kinase Fusion Protein
	Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:TP53BP1_PDGFRB

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: TP53BP1_PDGFRB
	KinaseFusionDB ID: KFG6690
	FusionGDB2.0 ID: KFG6690
		Hgene	Tgene
	Gene symbol	TP53BP1	PDGFRB
	Gene ID	7158	5159
	Gene name	tumor protein p53 binding protein 1	platelet derived growth factor receptor beta
	Synonyms	53BP1\|TDRD30\|p202\|p53BP1	CD140B\|IBGC4\|IMF1\|JTK12\|KOGS\|PDGFR\|PDGFR-1\|PDGFR1\|PENTT
	Cytomap	15q15.3	5q32
	Type of gene	protein-coding	protein-coding
	Description	TP53-binding protein 1p53-binding protein 1tumor protein 53-binding protein, 1tumor suppressor p53-binding protein 1	platelet-derived growth factor receptor betaActivated tyrosine kinase PDGFRBCD140 antigen-like family member BNDEL1-PDGFRBPDGF-R-betaPDGFR-betabeta-type platelet-derived growth factor receptorplatelet-derived growth factor receptor 1platelet-deriv
	Modification date	20240416	20240413
	UniProtAcc	Q12888	P09619
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000263801, ENST00000382039, ENST00000382044, ENST00000450115, ENST00000605155,	ENST00000523456, ENST00000261799,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: TP53BP1 [Title/Abstract] AND PDGFRB [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)

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	TP53BP1	GO:0006303	double-strand break repair via nonhomologous end joining	23333306\|23760478\|27153538\|28241136\|31135337
Hgene	TP53BP1	GO:0006974	DNA damage response	17500065
Hgene	TP53BP1	GO:0006974	DNA damage response	27153538\|28241136
Hgene	TP53BP1	GO:0045830	positive regulation of isotype switching	23345425
Hgene	TP53BP1	GO:0051260	protein homooligomerization	23345425
Hgene	TP53BP1	GO:0097680	double-strand break repair via classical nonhomologous end joining	27153538
Hgene	TP53BP1	GO:1990166	protein localization to site of double-strand break	37696958
Hgene	TP53BP1	GO:2000042	negative regulation of double-strand break repair via homologous recombination	23333306\|23345425
Tgene	PDGFRB	GO:0007165	signal transduction	10821867
Tgene	PDGFRB	GO:0010863	positive regulation of phospholipase C activity	1653029
Tgene	PDGFRB	GO:0018108	peptidyl-tyrosine phosphorylation	1653029\|2536956\|2850496
Tgene	PDGFRB	GO:0030335	positive regulation of cell migration	17470632
Tgene	PDGFRB	GO:0032516	positive regulation of phosphoprotein phosphatase activity	7691811
Tgene	PDGFRB	GO:0038091	positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway	17470632
Tgene	PDGFRB	GO:0046777	protein autophosphorylation	2536956\|2850496
Tgene	PDGFRB	GO:0048008	platelet-derived growth factor receptor signaling pathway	1314164\|2536956
Tgene	PDGFRB	GO:0051897	positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1314164
Tgene	PDGFRB	GO:0060326	cell chemotaxis	2554309\|17991872

Kinase Fusion gene breakpoints across TP53BP1 (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 PDGFRB (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
ChimerKB3	.	TP53BP1	chr15	43707791	PDGFRB	chr5	149506177

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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)
ENST00000263801	ENST00000261799	TP53BP1	chr15	43707791	PDGFRB	chr5	149506177	8995	2271

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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

>ENST00000263801_ENST00000261799_TP53BP1_chr15_43707791_PDGFRB_chr5_149506177_length(amino acids)=2271
MDPTGSQLDSDFSQQDTPCLIIEDSQPESQVLEDDSGSHFSMLSRHLPNLQTHKENPVLDVVSNPEQTAGEERGDGNSGFNEHLKENKVA
DPVDSSNLDTCGSISQVIEQLPQPNRTSSVLGMSVESAPAVEEEKGEELEQKEKEKEEDTSGNTTHSLGAEDTASSQLGFGVLELSQSQD
VEENTVPYEVDKEQLQSVTTNSGYTRLSDVDANTAIKHEEQSNEDIPIAEQSSKDIPVTAQPSKDVHVVKEQNPPPARSEDMPFSPKASV
AAMEAKEQLSAQELMESGLQIQKSPEPEVLSTQEDLFDQSNKTVSSDGCSTPSREEGGCSLASTPATTLHLLQLSGQRSLVQDSLSTNSS
DLVAPSPDAFRSTPFIVPSSPTEQEGRQDKPMDTSVLSEEGGEPFQKKLQSGEPVELENPPLLPESTVSPQASTPISQSTPVFPPGSLPI
PSQPQFSHDIFIPSPSLEEQSNDGKKDGDMHSSSLTVECSKTSEIEPKNSPEDLGLSLTGDSCKLMLSTSEYSQSPKMESLSSHRIDEDG
ENTQIEDTEPMSPVLNSKFVPAENDSILMNPAQDGEVQLSQNDDKTKGDDTDTRDDISILATGCKGREETVAEDVCIDLTCDSGSQAVPS
PATRSEALSSVLDQEEAMEIKEHHPEEGSSGSEVEEIPETPCESQGEELKEENMESVPLHLSLTETQSQGLCLQKEMPKKECSEAMEVET
SVISIDSPQKLAILDQELEHKEQEAWEEATSEDSSVVIVDVKEPSPRVDVSCEPLEGVEKCSDSQSWEDIAPEIEPCAENRLDTKEEKSV
EYEGDLKSGTAETEPVEQDSSQPSLPLVRADDPLRLDQELQQPQTQEKTSNSLTEDSKMANAKQLSSDAEAQKLGKPSAHASQSFCESSS
ETPFHFTLPKEGDIIPPLTGATPPLIGHLKLEPKRHSTPIGISNYPESTIATSDVMSESMVETHDPILGSGKGDSGAAPDVDDKLCLRMK
LVSPETEASEESLQFNLEKPATGERKNGSTAVAESVASPQKTMSVLSCICEARQENEARSEDPPTTPIRGNLLHFPSSQGEEEKEKLEGD
HTIRQSQQPMKPISPVKDPVSPASQKMVIQGPSSPQGEAMVTDVLEDQKEGRSTNKENPSKALIERPSQNNIGIQTMECSLRVPETVSAA
TQTIKNVCEQGTSTVDQNFGKQDATVQTERGSGEKPVSAPGDDTESLHSQGEEEFDMPQPPHGHVLHRHMRTIREVRTLVTRVITDVYYV
DGTEVERKVTEETEEPIVECQECETEVSPSQTGGSSGDLGDISSFSSKASSLHRTSSGTSLSAMHSSGSSGKGAGPLRGKTSGTEPADFA
LPSSRGGPGKLSPRKGVSQTGTPVCEEDGDAGLGIRQGGKAPVTPRGRGRRGRPPSRTTGTRETAVPGPLGIEDISPNLSPDDKSFSRVV
PRVPDSTRRTDVGAGALRRSDSPEIPFQAAAGPSDGLDASSPGNSFVGLRVVAKWSSNGYFYSGKITRDVGAGKYKLLFDDGYECDVLGK
DILLCDPIPLDTEVTALSEDEYFSAGVVKGHRKESGELYYSIEKEGQRKWYKRMAVILSLEQGNRLREQYGLGPYEAVTPLTKAADISLD
NLVEGKRKRRSNVSSPATPTASSSSSTTPTRKITESPRASMGVLSGKRKLITSEEERSPAKRGRKSATVKPALPFKVVVISAILALVVLT
IISLIILIMLWQKKPRYEIRWKVIESVSSDGHEYIYVDPMQLPYDSTWELPRDQLVLGRTLGSGAFGQVVEATAHGLSHSQATMKVAVKM
LKSTARSSEKQALMSELKIMSHLGPHLNVVNLLGACTKGGPIYIITEYCRYGDLVDYLHRNKHTFLQHHSDKRRPPSAELYSNALPVGLP
LPSHVSLTGESDGGYMDMSKDESVDYVPMLDMKGDVKYADIESSNYMAPYDNYVPSAPERTCRATLINESPVLSYMDLVGFSYQVANGME
FLASKNCVHRDLAARNVLICEGKLVKICDFGLARDIMRDSNYISKGSTFLPLKWMAPESIFNSLYTTLSDVWSFGILLWEIFTLGGTPYP
ELPMNEQFYNAIKRGYRMAQPAHASDEIYEIMQKCWEEKFEIRPPFSQLVLLLERLLGEGYKKKYQQVDEEFLRSDHPAILRSQARLPGF
HGLRSPLDTSSVLYTAVQPNEGDNDYIIPLPDPKPEVADEGPLEGSPSLASSTLNEVNTSSTISCDSPLEPQDEPEPEPQLELQVEPEPE

--------------------------------------------------------------

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/chr15:/chr5:)
- 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
TP53BP1 Q12888	PDGFRB P09619
FUNCTION: Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:22553214, PubMed:23333306, PubMed:17190600, PubMed:21144835, PubMed:27153538, PubMed:28241136, PubMed:31135337). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23727112, PubMed:23333306, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:23760478, PubMed:27153538, PubMed:28241136, PubMed:17190600). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250\|UniProtKB:P70399, ECO:0000269\|PubMed:12364621, ECO:0000269\|PubMed:17190600, ECO:0000269\|PubMed:21144835, ECO:0000269\|PubMed:22553214, ECO:0000269\|PubMed:23333306, ECO:0000269\|PubMed:23345425, ECO:0000269\|PubMed:23727112, ECO:0000269\|PubMed:23760478, ECO:0000269\|PubMed:27153538, ECO:0000269\|PubMed:28241136, ECO:0000269\|PubMed:31135337}.	FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. {ECO:0000269\|PubMed:11297552, ECO:0000269\|PubMed:11331881, ECO:0000269\|PubMed:1314164, ECO:0000269\|PubMed:1396585, ECO:0000269\|PubMed:1653029, ECO:0000269\|PubMed:1709159, ECO:0000269\|PubMed:1846866, ECO:0000269\|PubMed:20494825, ECO:0000269\|PubMed:20529858, ECO:0000269\|PubMed:21098708, ECO:0000269\|PubMed:21679854, ECO:0000269\|PubMed:21733313, ECO:0000269\|PubMed:2554309, ECO:0000269\|PubMed:26599395, ECO:0000269\|PubMed:2835772, ECO:0000269\|PubMed:2850496, ECO:0000269\|PubMed:7685273, ECO:0000269\|PubMed:7691811, ECO:0000269\|PubMed:7692233, ECO:0000269\|PubMed:8195171}.

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
download page
* 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

TP53BP1

43707791

PDGFRB

149506177

ENST00000263801

600_962

526

1107

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 >>>515_TP53BP1_PDGFRB	ENST00000263801	ENST00000261799	TP53BP1	chr15	43707791	PDGFRB	chr5	149506177	MDPTGSQLDSDFSQQDTPCLIIEDSQPESQVLEDDSGSHFSMLSRHLPNLQTHKENPVLDVVSNPEQTAGEERGDGNSGFNEHLKENKVA DPVDSSNLDTCGSISQVIEQLPQPNRTSSVLGMSVESAPAVEEEKGEELEQKEKEKEEDTSGNTTHSLGAEDTASSQLGFGVLELSQSQD VEENTVPYEVDKEQLQSVTTNSGYTRLSDVDANTAIKHEEQSNEDIPIAEQSSKDIPVTAQPSKDVHVVKEQNPPPARSEDMPFSPKASV AAMEAKEQLSAQELMESGLQIQKSPEPEVLSTQEDLFDQSNKTVSSDGCSTPSREEGGCSLASTPATTLHLLQLSGQRSLVQDSLSTNSS DLVAPSPDAFRSTPFIVPSSPTEQEGRQDKPMDTSVLSEEGGEPFQKKLQSGEPVELENPPLLPESTVSPQASTPISQSTPVFPPGSLPI PSQPQFSHDIFIPSPSLEEQSNDGKKDGDMHSSSLTVECSKTSEIEPKNSPEDLGLSLTGDSCKLMLSTSEYSQSPKMESLSSHRIDEDG ENTQIEDTEPMSPVLNSKFVPAENDSILMNPAQDGEVQLSQNDDKTKGDDTDTRDDISILATGCKGREETVAEDVCIDLTCDSGSQAVPS PATRSEALSSVLDQEEAMEIKEHHPEEGSSGSEVEEIPETPCESQGEELKEENMESVPLHLSLTETQSQGLCLQKEMPKKECSEAMEVET SVISIDSPQKLAILDQELEHKEQEAWEEATSEDSSVVIVDVKEPSPRVDVSCEPLEGVEKCSDSQSWEDIAPEIEPCAENRLDTKEEKSV EYEGDLKSGTAETEPVEQDSSQPSLPLVRADDPLRLDQELQQPQTQEKTSNSLTEDSKMANAKQLSSDAEAQKLGKPSAHASQSFCESSS ETPFHFTLPKEGDIIPPLTGATPPLIGHLKLEPKRHSTPIGISNYPESTIATSDVMSESMVETHDPILGSGKGDSGAAPDVDDKLCLRMK LVSPETEASEESLQFNLEKPATGERKNGSTAVAESVASPQKTMSVLSCICEARQENEARSEDPPTTPIRGNLLHFPSSQGEEEKEKLEGD HTIRQSQQPMKPISPVKDPVSPASQKMVIQGPSSPQGEAMVTDVLEDQKEGRSTNKENPSKALIERPSQNNIGIQTMECSLRVPETVSAA TQTIKNVCEQGTSTVDQNFGKQDATVQTERGSGEKPVSAPGDDTESLHSQGEEEFDMPQPPHGHVLHRHMRTIREVRTLVTRVITDVYYV DGTEVERKVTEETEEPIVECQECETEVSPSQTGGSSGDLGDISSFSSKASSLHRTSSGTSLSAMHSSGSSGKGAGPLRGKTSGTEPADFA LPSSRGGPGKLSPRKGVSQTGTPVCEEDGDAGLGIRQGGKAPVTPRGRGRRGRPPSRTTGTRETAVPGPLGIEDISPNLSPDDKSFSRVV PRVPDSTRRTDVGAGALRRSDSPEIPFQAAAGPSDGLDASSPGNSFVGLRVVAKWSSNGYFYSGKITRDVGAGKYKLLFDDGYECDVLGK DILLCDPIPLDTEVTALSEDEYFSAGVVKGHRKESGELYYSIEKEGQRKWYKRMAVILSLEQGNRLREQYGLGPYEAVTPLTKAADISLD NLVEGKRKRRSNVSSPATPTASSSSSTTPTRKITESPRASMGVLSGKRKLITSEEERSPAKRGRKSATVKPALPFKVVVISAILALVVLT IISLIILIMLWQKKPRYEIRWKVIESVSSDGHEYIYVDPMQLPYDSTWELPRDQLVLGRTLGSGAFGQVVEATAHGLSHSQATMKVAVKM LKSTARSSEKQALMSELKIMSHLGPHLNVVNLLGACTKGGPIYIITEYCRYGDLVDYLHRNKHTFLQHHSDKRRPPSAELYSNALPVGLP LPSHVSLTGESDGGYMDMSKDESVDYVPMLDMKGDVKYADIESSNYMAPYDNYVPSAPERTCRATLINESPVLSYMDLVGFSYQVANGME FLASKNCVHRDLAARNVLICEGKLVKICDFGLARDIMRDSNYISKGSTFLPLKWMAPESIFNSLYTTLSDVWSFGILLWEIFTLGGTPYP ELPMNEQFYNAIKRGYRMAQPAHASDEIYEIMQKCWEEKFEIRPPFSQLVLLLERLLGEGYKKKYQQVDEEFLRSDHPAILRSQARLPGF HGLRSPLDTSSVLYTAVQPNEGDNDYIIPLPDPKPEVADEGPLEGSPSLASSTLNEVNTSSTISCDSPLEPQDEPEPEPQLELQVEPEPE	2271
3D view using mol* of 515_TP53BP1_PDGFRB

PDB file >>>TKFP_876_TP53BP1_PDGFRB	ENST00000263801	ENST00000261799	TP53BP1	chr15	43707791	PDGFRB	chr5	149506177	MDPTGSQLDSDFSQQDTPCLIIEDSQPESQVLEDDSGSHFSMLSRHLPNLQTHKENPVLDVVSNPEQTAGEERGDGNSGFNEHLKENKVA DPVDSSNLDTCGSISQVIEQLPQPNRTSSVLGMSVESAPAVEEEKGEELEQKEKEKEEDTSGNTTHSLGAEDTASSQLGFGVLELSQSQD VEENTVPYEVDKEQLQSVTTNSGYTRLSDVDANTAIKHEEQSNEDIPIAEQSSKDIPVTAQPSKDVHVVKEQNPPPARSEDMPFSPKASV AAMEAKEQLSAQELMESGLQIQKSPEPEVLSTQEDLFDQSNKTVSSDGCSTPSREEGGCSLASTPATTLHLLQLSGQRSLVQDSLSTNSS DLVAPSPDAFRSTPFIVPSSPTEQEGRQDKPMDTSVLSEEGGEPFQKKLQSGEPVELENPPLLPESTVSPQASTPISQSTPVFPPGSLPI PSQPQFSHDIFIPSPSLEEQSNDGKKDGDMHSSSLTVECSKTSEIEPKNSPEDLGLSLTGDSCKLMLSTSEYSQSPKMESLSSHRIDEDG ENTQIEDTEPMSPVLNSKFVPAENDSILMNPAQDGEVQLSQNDDKTKGDDTDTRDDISILATGCKGREETVAEDVCIDLTCDSGSQAVPS PATRSEALSSVLDQEEAMEIKEHHPEEGSSGSEVEEIPETPCESQGEELKEENMESVPLHLSLTETQSQGLCLQKEMPKKECSEAMEVET SVISIDSPQKLAILDQELEHKEQEAWEEATSEDSSVVIVDVKEPSPRVDVSCEPLEGVEKCSDSQSWEDIAPEIEPCAENRLDTKEEKSV EYEGDLKSGTAETEPVEQDSSQPSLPLVRADDPLRLDQELQQPQTQEKTSNSLTEDSKMANAKQLSSDAEAQKLGKPSAHASQSFCESSS ETPFHFTLPKEGDIIPPLTGATPPLIGHLKLEPKRHSTPIGISNYPESTIATSDVMSESMVETHDPILGSGKGDSGAAPDVDDKLCLRMK LVSPETEASEESLQFNLEKPATGERKNGSTAVAESVASPQKTMSVLSCICEARQENEARSEDPPTTPIRGNLLHFPSSQGEEEKEKLEGD HTIRQSQQPMKPISPVKDPVSPASQKMVIQGPSSPQGEAMVTDVLEDQKEGRSTNKENPSKALIERPSQNNIGIQTMECSLRVPETVSAA TQTIKNVCEQGTSTVDQNFGKQDATVQTERGSGEKPVSAPGDDTESLHSQGEEEFDMPQPPHGHVLHRHMRTIREVRTLVTRVITDVYYV DGTEVERKVTEETEEPIVECQECETEVSPSQTGGSSGDLGDISSFSSKASSLHRTSSGTSLSAMHSSGSSGKGAGPLRGKTSGTEPADFA LPSSRGGPGKLSPRKGVSQTGTPVCEEDGDAGLGIRQGGKAPVTPRGRGRRGRPPSRTTGTRETAVPGPLGIEDISPNLSPDDKSFSRVV PRVPDSTRRTDVGAGALRRSDSPEIPFQAAAGPSDGLDASSPGNSFVGLRVVAKWSSNGYFYSGKITRDVGAGKYKLLFDDGYECDVLGK DILLCDPIPLDTEVTALSEDEYFSAGVVKGHRKESGELYYSIEKEGQRKWYKRMAVILSLEQGNRLREQYGLGPYEAVTPLTKAADISLD NLVEGKRKRRSNVSSPATPTASSSSSTTPTRKITESPRASMGVLSGKRKLITSEEERSPAKRGRKSATVKPALPFKVVVISAILALVVLT IISLIILIMLWQKKPRYEIRWKVIESVSSDGHEYIYVDPMQLPYDSTWELPRDQLVLGRTLGSGAFGQVVEATAHGLSHSQATMKVAVKM LKSTARSSEKQALMSELKIMSHLGPHLNVVNLLGACTKGGPIYIITEYCRYGDLVDYLHRNKHTFLQHHSDKRRPPSAELYSNALPVGLP LPSHVSLTGESDGGYMDMSKDESVDYVPMLDMKGDVKYADIESSNYMAPYDNYVPSAPERTCRATLINESPVLSYMDLVGFSYQVANGME FLASKNCVHRDLAARNVLICEGKLVKICDFGLARDIMRDSNYISKGSTFLPLKWMAPESIFNSLYTTLSDVWSFGILLWEIFTLGGTPYP ELPMNEQFYNAIKRGYRMAQPAHASDEIYEIMQKCWEEKFEIRPPFSQLVLLLERLLGEGYKKKYQQVDEEFLRSDHPAILRSQARLPGF HGLRSPLDTSSVLYTAVQPNEGDNDYIIPLPDPKPEVADEGPLEGSPSLASSTLNEVNTSSTISCDSPLEPQDEPEPEPQLELQVEPEPE	2271_TP53BP1_PDGFRB

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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

TP53BP1_PDGFRB does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/515_TP53BP1_PDGFRB.png

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.

515_TP53BP1_PDGFRB.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.

515_TP53BP1_PDGFRB_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
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Nilotinib	-5.79663	-5.93623	-44.9815
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Nilotinib	-5.79663	-5.93623	-44.9815
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Larotrectinib	-5.29758	-5.29758	-38.3285
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Lapatinib	-5.2759	-5.3647	-55.2762
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Neratinib	-5.19335	-5.37925	-47.544
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Neratinib	-5.16309	-5.34539	-48.6644
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Neratinib	-5.16309	-5.34539	-48.6644
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Larotrectinib	-4.9281	-4.9281	-34.957
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Larotrectinib	-4.86841	-4.86841	-38.8524
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Lapatinib	-4.8621	-4.9509	-48.2889
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Ruxolitinib	-4.76628	-4.76628	-26.9669
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Upadacitinib	-4.758319999999999	-4.75932	-31.1345
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Afatinib	-4.6663	-4.8486	-32.0839
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Afatinib	-4.6663	-4.8486	-32.0839
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Afatinib	-4.6649	-4.8486	-32.0839
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Dacomitinib	-4.63754	-4.74654	-36.5442
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Crizotinib	-4.58047	-4.91667	-41.6677
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Crizotinib	-4.58047	-4.91667	-41.6677
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Tucatinib	-4.5724	-5.0352	-37.9893
515_TP53BP1_PDGFRB-DOCK_HTVS_1-001	Tucatinib	-4.56989	-5.0326900000000006	-37.881

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Kinase-Substrate Information of TP53BP1_PDGFRB

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
PDGFRB	P09619	human	PDGFRB	P09619	Y1021	PNEGDNDyIIPLPDP
PDGFRB	P09619	human	PDGFRA	P16234	Y754	ERKEVsKysDIQRsL	PK_Tyr_Ser-Thr
PDGFRB	P09619	human	PDGFRB	P09619	Y1009	LDTSSVLyTAVQPNE
PDGFRB	P09619	human	PTK2	Q05397	Y5	___MAAAyLDPNLNH
PDGFRB	P09619	human	ABL2	P42684	Y272	KCNKPTVyGVsPIHD
PDGFRB	P09619	human	PDGFRB	P09619	Y579	VSSDGHEyIyVDPMQ
PDGFRB	P09619	human	PDGFRB	P09619	Y562	LWQKKPRyEIRWKVI
PDGFRB	P09619	human	THOC5	Q13769	Y225	EIEVKKEyLSSLQPR	FmiP_Thoc5
PDGFRB	P09619	human	ABL2	P42684	Y139	EKLRVLGyNQNGEWS	SH3_1
PDGFRB	P09619	human	PLCG1	P19174	Y783	EGRNPGFyVEANPMP
PDGFRB	P09619	human	PDGFRB	P09619	Y740	TGESDGGyMDMSKDE	PK_Tyr_Ser-Thr
PDGFRB	P09619	human	ABL2	P42684	Y439	RLMtGDtytAHAGAk	PK_Tyr_Ser-Thr
PDGFRB	P09619	human	FYN	P06241	Y28	sLNQssGyRyGTDPT
PDGFRB	P09619	human	ETV6	P41212	Y17	IkQERIsytPPEsPV
PDGFRB	P09619	human	PTK2	Q05397	Y194	ALEKKSNyEVLEkDV	FERM_M
PDGFRB	P09619	human	PDGFRB	P09619	Y763	DMKGDVKyADIESSN	PK_Tyr_Ser-Thr
PDGFRB	P09619	human	TNK2	Q07912	Y635	PLPPPPAyDDVAQDE
PDGFRB	P09619	human	PDGFRB	P09619	Y581	SDGHEyIyVDPMQLP
PDGFRB	P09619	human	ABL2	P42684	Y116	PNLFVALyDFVAsGD	SH3_1
PDGFRB	P09619	human	ABL2	P42684	Y303	GGQyGEVyVGVWKKy	PK_Tyr_Ser-Thr
PDGFRB	P09619	human	MUC1	P15941	Y1218	tyHtHGRyVPPsstD
PDGFRB	P09619	human	ABL2	P42684	Y310	yVGVWKKysLtVAVK	PK_Tyr_Ser-Thr
PDGFRB	P09619	human	PDGFRB	P09619	Y857	DIMRDSNyISKGSTF	PK_Tyr_Ser-Thr
PDGFRB	P09619	human	PDGFRB	P09619	Y775	SSNyMAPyDNyVPSA	PK_Tyr_Ser-Thr
PDGFRB	P09619	human	MUC1	P15941	Y1203	IFPARDtyHPMsEyP
PDGFRB	P09619	human	PDGFRB	P09619	Y771	ADIESSNyMAPyDNy	PK_Tyr_Ser-Thr
PDGFRB	P09619	human	ABL2	P42684	Y161	QGWVPsNyItPVNSL
PDGFRB	P09619	human	ETV6	P41212	Y27	PEsPVPsyAsstPLH
PDGFRB	P09619	human	SRC	P12931	Y419	RLIEDNEytARQGAk	PK_Tyr_Ser-Thr
PDGFRB	P09619	human	PDGFRB	P09619	Y751	SKDESVDyVPMLDMK	PK_Tyr_Ser-Thr
PDGFRB	P09619	human	ABL2	P42684	Y299	HKLGGGQyGEVyVGV	PK_Tyr_Ser-Thr
PDGFRB	P09619	human	PDGFRB	P09619	Y778	yMAPyDNyVPSAPER	PK_Tyr_Ser-Thr

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
PDGFRB	ID	Description	0.00e+00
PDGFRB	GO:0018108	peptidyl-tyrosine phosphorylation	1.87e-08
PDGFRB	GO:0018212	peptidyl-tyrosine modification	1.87e-08
PDGFRB	GO:0038093	Fc receptor signaling pathway	6.42e-06
PDGFRB	GO:0036120	cellular response to platelet-derived growth factor stimulus	4.63e-05
PDGFRB	GO:0036119	response to platelet-derived growth factor	4.63e-05
PDGFRB	GO:0002433	immune response-regulating cell surface receptor signaling pathway involved in phagocytosis	4.63e-05
PDGFRB	GO:0038096	Fc-gamma receptor signaling pathway involved in phagocytosis	4.63e-05
PDGFRB	GO:0002431	Fc receptor mediated stimulatory signaling pathway	6.79e-05
PDGFRB	GO:0002862	negative regulation of inflammatory response to antigenic stimulus	6.79e-05
PDGFRB	GO:0038094	Fc-gamma receptor signaling pathway	6.79e-05
PDGFRB	GO:0010863	positive regulation of phospholipase C activity	8.77e-05
PDGFRB	GO:1900274	regulation of phospholipase C activity	9.45e-05
PDGFRB	GO:0051897	positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1.34e-04
PDGFRB	GO:0002861	regulation of inflammatory response to antigenic stimulus	1.52e-04
PDGFRB	GO:0010518	positive regulation of phospholipase activity	1.52e-04
PDGFRB	GO:0048013	ephrin receptor signaling pathway	1.61e-04
PDGFRB	GO:0046777	protein autophosphorylation	1.87e-04
PDGFRB	GO:0048008	platelet-derived growth factor receptor signaling pathway	2.11e-04
PDGFRB	GO:0010517	regulation of phospholipase activity	2.11e-04
PDGFRB	GO:0060193	positive regulation of lipase activity	2.11e-04
PDGFRB	GO:0048010	vascular endothelial growth factor receptor signaling pathway	2.11e-04
PDGFRB	GO:0051896	regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	3.46e-04
PDGFRB	GO:0060191	regulation of lipase activity	4.05e-04
PDGFRB	GO:0002437	inflammatory response to antigenic stimulus	4.19e-04
PDGFRB	GO:0043491	phosphatidylinositol 3-kinase/protein kinase B signal transduction	5.64e-04
PDGFRB	GO:0002429	immune response-activating cell surface receptor signaling pathway	7.80e-04
PDGFRB	GO:0035791	platelet-derived growth factor receptor-beta signaling pathway	8.61e-04
PDGFRB	GO:0007173	epidermal growth factor receptor signaling pathway	8.61e-04
PDGFRB	GO:0033674	positive regulation of kinase activity	8.77e-04
PDGFRB	GO:0002768	immune response-regulating cell surface receptor signaling pathway	9.40e-04
PDGFRB	GO:2001243	negative regulation of intrinsic apoptotic signaling pathway	9.40e-04
PDGFRB	GO:0072224	metanephric glomerulus development	1.11e-03
PDGFRB	GO:0038127	ERBB signaling pathway	1.14e-03
PDGFRB	GO:2000811	negative regulation of anoikis	1.18e-03
PDGFRB	GO:0055003	cardiac myofibril assembly	1.24e-03
PDGFRB	GO:0061298	retina vasculature development in camera-type eye	1.24e-03
PDGFRB	GO:0050900	leukocyte migration	1.29e-03
PDGFRB	GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity	1.45e-03
PDGFRB	GO:0051347	positive regulation of transferase activity	1.46e-03
PDGFRB	GO:0050921	positive regulation of chemotaxis	1.49e-03
PDGFRB	GO:0002223	stimulatory C-type lectin receptor signaling pathway	1.54e-03
PDGFRB	GO:1990840	response to lectin	1.54e-03
PDGFRB	GO:1990858	cellular response to lectin	1.54e-03
PDGFRB	GO:0034614	cellular response to reactive oxygen species	1.60e-03
PDGFRB	GO:2000209	regulation of anoikis	1.60e-03
PDGFRB	GO:0090218	positive regulation of lipid kinase activity	1.85e-03
PDGFRB	GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation	1.97e-03
PDGFRB	GO:0002757	immune response-activating signaling pathway	1.99e-03
PDGFRB	GO:0032102	negative regulation of response to external stimulus	2.07e-03

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Related Drugs to TP53BP1_PDGFRB

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 TP53BP1-PDGFRB and kinase inhibitors the PubMed Abstract (04-01-2024)

all structure sitemap plddt TP53BP1-PDGFRB

Fusion gene - drug pair 1	Fusion gene - drug pair 2	PMID	Publication date	DOI	Study title
TP53BP1-PDGFRB AND Imatinib		15492236	2004-10-15	10.1158/0008-5472.can-04-2005	p53-Binding protein 1 is fused to the platelet-derived growth factor receptor beta in a patient with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic myeloproliferative disorder.

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Related Diseases to TP53BP1_PDGFRB

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
Tgene	PDGFRB	C3554321	BASAL GANGLIA CALCIFICATION, IDIOPATHIC, 4	6	CTD_human;GENOMICS_ENGLAND;UNIPROT
Tgene	PDGFRB	C0393590	Fahr's syndrome (disorder)	3	GENOMICS_ENGLAND;ORPHANET
Tgene	PDGFRB	C4225270	Kosaki overgrowth syndrome	3	CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
Tgene	PDGFRB	C4551572	MYOFIBROMATOSIS, INFANTILE, 1	3	GENOMICS_ENGLAND;UNIPROT
Tgene	PDGFRB	C0013421	Dystonia	2	GENOMICS_ENGLAND
Tgene	PDGFRB	C0023480	Leukemia, Myelomonocytic, Chronic	2	ORPHANET
Tgene	PDGFRB	C0023893	Liver Cirrhosis, Experimental	2	CTD_human
Tgene	PDGFRB	C0036341	Schizophrenia	2	PSYGENET
Tgene	PDGFRB	C0432284	Infantile myofibromatosis	2	CTD_human;GENOMICS_ENGLAND;ORPHANET

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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