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Fusion Protein:PTK2-RNF139

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: PTK2-RNF139
	FusionPDB ID: 70052
	FusionGDB2.0 ID: 70052
		Hgene	Tgene
	Gene symbol	PTK2	RNF139
	Gene ID	5747	11236
	Gene name	protein tyrosine kinase 2	ring finger protein 139
	Synonyms	FADK\|FAK\|FAK1\|FRNK\|PPP1R71\|p125FAK\|pp125FAK	HRCA1\|RCA1\|TRC8
	Cytomap	8q24.3	8q24.13
	Type of gene	protein-coding	protein-coding
	Description	focal adhesion kinase 1FADK 1FAK-related non-kinase polypeptidePTK2 protein tyrosine kinase 2focal adhesion kinase isoform FAK-Del33focal adhesion kinase-related nonkinaseprotein phosphatase 1 regulatory subunit 71	E3 ubiquitin-protein ligase RNF139RING-type E3 ubiquitin transferase RNF139multiple membrane spanning receptor TRC8patched related protein translocated in renal cancertranslocation in renal carcinoma on chromosome 8 proteintranslocation in renal carc
	Modification date	20200327	20200313
	UniProtAcc	.	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000340930, ENST00000395218, ENST00000430260, ENST00000519419, ENST00000522684, ENST00000517887, ENST00000519465, ENST00000521059, ENST00000535192, ENST00000538769, ENST00000517712, ENST00000519635, ENST00000519881, ENST00000520151, ENST00000520892, ENST00000522950,	ENST00000303545,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	39 X 32 X 15=18720	4 X 3 X 4=48
	# samples	57	5
	** MAII score	log2(57/18720*10)=-5.03747470541866 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(5/48*10)=0.0588936890535686 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0
Fusion gene context	PubMed: PTK2 [Title/Abstract] AND RNF139 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: PTK2 [Title/Abstract] AND RNF139 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	PTK2(141696731)-RNF139(125498072), # samples:3
Anticipated loss of major functional domain due to fusion event.	PTK2-RNF139 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. PTK2-RNF139 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. PTK2-RNF139 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. PTK2-RNF139 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. PTK2-RNF139 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. PTK2-RNF139 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF. PTK2-RNF139 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.

* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

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	PTK2	GO:0007179	transforming growth factor beta receptor signaling pathway	24036928
Hgene	PTK2	GO:0007229	integrin-mediated signaling pathway	24036928
Hgene	PTK2	GO:0010763	positive regulation of fibroblast migration	26763945
Hgene	PTK2	GO:0018108	peptidyl-tyrosine phosphorylation	10655584\|11331870
Hgene	PTK2	GO:0022408	negative regulation of cell-cell adhesion	21703394
Hgene	PTK2	GO:0030335	positive regulation of cell migration	11331870\|21703394
Hgene	PTK2	GO:0033628	regulation of cell adhesion mediated by integrin	10655584
Hgene	PTK2	GO:0046777	protein autophosphorylation	10655584\|11331870
Hgene	PTK2	GO:0048013	ephrin receptor signaling pathway	10655584
Hgene	PTK2	GO:0060396	growth hormone receptor signaling pathway	10925297
Hgene	PTK2	GO:0090303	positive regulation of wound healing	26763945
Tgene	RNF139	GO:0008285	negative regulation of cell proliferation	17016439
Tgene	RNF139	GO:0016567	protein ubiquitination	10500182\|17016439
Tgene	RNF139	GO:0017148	negative regulation of translation	20068067
Tgene	RNF139	GO:0060628	regulation of ER to Golgi vesicle-mediated transport	19706601
Tgene	RNF139	GO:0070613	regulation of protein processing	19706601

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr8:141696731/chr8:125498072)
- 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.

Retention analysis results 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, are available here.

Fusion gene breakpoints across PTK2 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Fusion gene breakpoints across RNF139 (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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Fusion Amino Acid Sequences

Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	Seq length (transcript)	BP loci (transcript)	Predicted start (transcript)	Predicted stop (transcript)	Seq length (amino acids)
ENST00000535192	PTK2	chr8	141696731	-	ENST00000303545	RNF139	chr8	125498072	+	4539	2455	31	2481	816
ENST00000519465	PTK2	chr8	141696731	-	ENST00000303545	RNF139	chr8	125498072	+	3702	1618	1641	3431	596
ENST00000517887	PTK2	chr8	141696731	-	ENST00000303545	RNF139	chr8	125498072	+	5084	3000	264	3026	920
ENST00000521059	PTK2	chr8	141696731	-	ENST00000303545	RNF139	chr8	125498072	+	4828	2744	101	2770	889
ENST00000538769	PTK2	chr8	141696731	-	ENST00000303545	RNF139	chr8	125498072	+	3662	1578	1601	3391	596
ENST00000535192	PTK2	chr8	141710990	-	ENST00000303545	RNF139	chr8	125498072	+	4476	2392	31	2418	795
ENST00000519465	PTK2	chr8	141710990	-	ENST00000303545	RNF139	chr8	125498072	+	3639	1555	1527	3368	613
ENST00000517887	PTK2	chr8	141710990	-	ENST00000303545	RNF139	chr8	125498072	+	5021	2937	264	2963	899
ENST00000521059	PTK2	chr8	141710990	-	ENST00000303545	RNF139	chr8	125498072	+	4765	2681	101	2707	868
ENST00000538769	PTK2	chr8	141710990	-	ENST00000303545	RNF139	chr8	125498072	+	3599	1515	1487	3328	613

DeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	No-coding score	Coding score
ENST00000535192	ENST00000303545	PTK2	chr8	141696731	-	RNF139	chr8	125498072	+	0.000330115	0.9996699
ENST00000519465	ENST00000303545	PTK2	chr8	141696731	-	RNF139	chr8	125498072	+	0.00033535	0.99966466
ENST00000517887	ENST00000303545	PTK2	chr8	141696731	-	RNF139	chr8	125498072	+	0.00021956	0.9997805
ENST00000521059	ENST00000303545	PTK2	chr8	141696731	-	RNF139	chr8	125498072	+	0.000288109	0.9997118
ENST00000538769	ENST00000303545	PTK2	chr8	141696731	-	RNF139	chr8	125498072	+	0.000420806	0.99957925
ENST00000535192	ENST00000303545	PTK2	chr8	141710990	-	RNF139	chr8	125498072	+	0.000333698	0.99966633
ENST00000519465	ENST00000303545	PTK2	chr8	141710990	-	RNF139	chr8	125498072	+	0.000332411	0.99966764
ENST00000517887	ENST00000303545	PTK2	chr8	141710990	-	RNF139	chr8	125498072	+	0.000263115	0.99973685
ENST00000521059	ENST00000303545	PTK2	chr8	141710990	-	RNF139	chr8	125498072	+	0.000317348	0.99968266
ENST00000538769	ENST00000303545	PTK2	chr8	141710990	-	RNF139	chr8	125498072	+	0.000420642	0.99957937

Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for PTK2-RNF139

+/-13 AA sequence from the breakpoints of the fusion protein sequences.

Hgene

Hchr

Hbp

Tgene

Tchr

Tbp

Length(fusion protein)

BP in fusion protein

Peptide

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Potential FusionNeoAntigen Information of PTK2-RNF139 in HLA I

Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)

Fusion gene

Hchr

Hbp

Tgene

Tchr

Tbp

HLA I

FusionNeoAntigen peptide

Binding score

Immunogenic score

Neoantigen start (at BP 13)

Neoantigen end (at BP 13)

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Potential FusionNeoAntigen Information of PTK2-RNF139 in HLA II

Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).

Fusion gene

Hchr

Hbp

Tgene

Tchr

Tbp

HLA II

FusionNeoAntigen peptide

Neoantigen start (at BP 13)

Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of PTK2-RNF139

3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PTK2-RNF139

Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.

HLA allele

PDB ID

File name

BPseq

Docking score

Glide score

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Vaccine Design for the FusionNeoAntigens of PTK2-RNF139

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.

Fusion gene

Hchr

Hbp

Tchr

Tbp

Start in +/-13AA

End in +/-13AA

FusionNeoAntigen peptide sequence

FusionNeoAntigen RNA sequence

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.

Fusion gene

Hchr

Hbp

Tchr

Tbp

Start in +/-13AA

End in +/-13AA

FusionNeoAntigen peptide

FusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of PTK2-RNF139

These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.

Cancer type

Fusion gene

Hchr

Hbp

Henst

Tchr

Tbp

Tenst

Sample

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Potential target of CAR-T therapy development for PTK2-RNF139

Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features

* Minus value of BPloci means that the break point is located before the CDS.

- In-frame and retained 'Transmembrane'.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Tgene

RNF139

chr8:141696731

chr8:125498072

ENST00000303545

125_145

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141696731

chr8:125498072

ENST00000303545

154_174

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141696731

chr8:125498072

ENST00000303545

178_198

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141696731

chr8:125498072

ENST00000303545

293_313

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141696731

chr8:125498072

ENST00000303545

323_343

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141696731

chr8:125498072

ENST00000303545

356_376

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141696731

chr8:125498072

ENST00000303545

390_410

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141696731

chr8:125498072

ENST00000303545

420_440

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141696731

chr8:125498072

ENST00000303545

469_489

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141696731

chr8:125498072

ENST00000303545

495_512

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141696731

chr8:125498072

ENST00000303545

85_105

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141710990

chr8:125498072

ENST00000303545

125_145

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141710990

chr8:125498072

ENST00000303545

154_174

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141710990

chr8:125498072

ENST00000303545

178_198

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141710990

chr8:125498072

ENST00000303545

293_313

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141710990

chr8:125498072

ENST00000303545

323_343

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141710990

chr8:125498072

ENST00000303545

356_376

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141710990

chr8:125498072

ENST00000303545

390_410

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141710990

chr8:125498072

ENST00000303545

420_440

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141710990

chr8:125498072

ENST00000303545

469_489

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141710990

chr8:125498072

ENST00000303545

495_512

665.0

Transmembrane

Helical

Tgene

RNF139

chr8:141710990

chr8:125498072

ENST00000303545

85_105

665.0

Transmembrane

Helical

Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.

Hgene

Hchr

Hbp

Henst

Tgene

Tchr

Tbp

Tenst

DeepLoc result

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Related Drugs to PTK2-RNF139

Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Drug

Source

PMID

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Related Diseases to PTK2-RNF139

Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Disease

Source

PMID

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source

	Fusion Gene and Fusion Protein Summary
	Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)
	Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)
	Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)
	Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)
	Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)
	Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)
	Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)
	Potential target of CAR-T therapy development
	Information on the samples that have these potential fusion neoantigens
	Fusion Protein Targeting Drugs - (Manual Curation)
	Fusion Protein Related diseases - (Manual Curation)