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	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein Structure
	pLDDT scores
	Ramachandran Plot of Fusion Protein Structure
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:SRPK2-PRKAR2B

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: SRPK2-PRKAR2B
	FusionPDB ID: 86510
	FusionGDB2.0 ID: 86510
		Hgene	Tgene
	Gene symbol	SRPK2	PRKAR2B
	Gene ID	6733	5577
	Gene name	SRSF protein kinase 2	protein kinase cAMP-dependent type II regulatory subunit beta
	Synonyms	SFRSK2	PRKAR2\|RII-BETA
	Cytomap	7q22.3	7q22.3
	Type of gene	protein-coding	protein-coding
	Description	SRSF protein kinase 2SFRS protein kinase 2SR protein kinase 2SR-protein-specific kinase 2serine kinase SRPK2serine/arginine-rich protein-specific kinase 2serine/arginine-rich splicing factor kinase 2serine/threonine-protein kinase SRPK2	cAMP-dependent protein kinase type II-beta regulatory subunitH_RG363E19.2WUGSC:H_RG363E19.2cAMP-dependent protein kinase type II-beta regulatory chainprotein kinase, cAMP-dependent, regulatory subunit type II betaprotein kinase, cAMP-dependent, regul
	Modification date	20200313	20200329
	UniProtAcc	.	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000357311, ENST00000393651, ENST00000489828, ENST00000493638,	ENST00000393613, ENST00000265717,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	18 X 14 X 10=2520	7 X 6 X 5=210
	# samples	20	8
	** MAII score	log2(20/2520*10)=-3.65535182861255 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(8/210*10)=-1.39231742277876 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: SRPK2 [Title/Abstract] AND PRKAR2B [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	SRPK2(104800954)-PRKAR2B(106791367), # samples:3
Anticipated loss of major functional domain due to fusion event.	SRPK2-PRKAR2B 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. SRPK2-PRKAR2B 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. SRPK2-PRKAR2B seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. SRPK2-PRKAR2B seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. SRPK2-PRKAR2B seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF. SRPK2-PRKAR2B seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF. SRPK2-PRKAR2B seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF. SRPK2-PRKAR2B seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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	SRPK2	GO:0000245	spliceosomal complex assembly	9472028
Hgene	SRPK2	GO:0006468	protein phosphorylation	9472028
Hgene	SRPK2	GO:0008284	positive regulation of cell proliferation	18559500
Hgene	SRPK2	GO:0008380	RNA splicing	9472028
Hgene	SRPK2	GO:0035556	intracellular signal transduction	9472028
Hgene	SRPK2	GO:0045070	positive regulation of viral genome replication	20498328
Hgene	SRPK2	GO:0045071	negative regulation of viral genome replication	12417631
Tgene	PRKAR2B	GO:2000480	negative regulation of cAMP-dependent protein kinase activity	21812984

Fusion gene breakpoints across SRPK2 (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 PRKAR2B (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 Gene Sample Information

Fusion gene information from FusionGDB2.0.

Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* 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	Disease	Sample	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
ChimerDB4	KIRP	TCGA-5P-A9JZ-01A	SRPK2	chr7	104800954	-	PRKAR2B	chr7	106791367	+
ChimerDB4	KIRP	TCGA-5P-A9JZ	SRPK2	chr7	104800953	-	PRKAR2B	chr7	106791366	+
ChimerDB4	KIRP	TCGA-5P-A9JZ	SRPK2	chr7	104800954	-	PRKAR2B	chr7	106791367	+

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Fusion ORF Analysis

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)
ENST00000393651	SRPK2	chr7	104800954	-	ENST00000265717	PRKAR2B	chr7	106791367	+	3454	709	88	1224	378
ENST00000357311	SRPK2	chr7	104800954	-	ENST00000265717	PRKAR2B	chr7	106791367	+	3505	760	94	1275	393
ENST00000393651	SRPK2	chr7	104800953	-	ENST00000265717	PRKAR2B	chr7	106791366	+	3454	709	88	1224	378
ENST00000357311	SRPK2	chr7	104800953	-	ENST00000265717	PRKAR2B	chr7	106791366	+	3505	760	94	1275	393

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
ENST00000393651	ENST00000265717	SRPK2	chr7	104800954	-	PRKAR2B	chr7	106791367	+	0.0002605	0.99973947
ENST00000357311	ENST00000265717	SRPK2	chr7	104800954	-	PRKAR2B	chr7	106791367	+	0.000229339	0.9997707
ENST00000393651	ENST00000265717	SRPK2	chr7	104800953	-	PRKAR2B	chr7	106791366	+	0.0002605	0.99973947
ENST00000357311	ENST00000265717	SRPK2	chr7	104800953	-	PRKAR2B	chr7	106791366	+	0.000229339	0.9997707

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Fusion Amino Acid Sequences

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

>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>86510_86510_1_SRPK2-PRKAR2B_SRPK2_chr7_104800953_ENST00000357311_PRKAR2B_chr7_106791366_ENST00000265717_length(amino acids)=393AA_BP=222
MKARAGNLGCEYFLIFPEIKQKIELLMSVNSEKSSSSERPEPQQKAPLVPPPPPPPPPPPPPLPDPTPPEPEEEILGSDDEEQEDPADYC
KGGYHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQLIDDFKI
SGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQDRVTFRRIIVKNNAKKRKMYESFIESLPFLKSLEFSERLKVVDVIGTK
VYNDGEQIIAQGDSADSFFIVESGEVKITMKRKGKSEVEENGAVEIARCSRGQYFGELALVTNKPRAASAHAIGTVKCLAMDVQAFERLL

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

>86510_86510_2_SRPK2-PRKAR2B_SRPK2_chr7_104800953_ENST00000393651_PRKAR2B_chr7_106791366_ENST00000265717_length(amino acids)=378AA_BP=207
MSSRKVLAIQARKRRPKREKHPKKPEPQQKAPLVPPPPPPPPPPPPPLPDPTPPEPEEEILGSDDEEQEDPADYCKGGYHPVKIGDLFNG
RYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQLIDDFKISGMNGIHVCMVFEVL
GHHLLKWIIKSNYQGLPVRCVKSIIRQDRVTFRRIIVKNNAKKRKMYESFIESLPFLKSLEFSERLKVVDVIGTKVYNDGEQIIAQGDSA
DSFFIVESGEVKITMKRKGKSEVEENGAVEIARCSRGQYFGELALVTNKPRAASAHAIGTVKCLAMDVQAFERLLGPCMEIMKRNIATYE

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

>86510_86510_3_SRPK2-PRKAR2B_SRPK2_chr7_104800954_ENST00000357311_PRKAR2B_chr7_106791367_ENST00000265717_length(amino acids)=393AA_BP=222
MKARAGNLGCEYFLIFPEIKQKIELLMSVNSEKSSSSERPEPQQKAPLVPPPPPPPPPPPPPLPDPTPPEPEEEILGSDDEEQEDPADYC
KGGYHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQLIDDFKI
SGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQDRVTFRRIIVKNNAKKRKMYESFIESLPFLKSLEFSERLKVVDVIGTK
VYNDGEQIIAQGDSADSFFIVESGEVKITMKRKGKSEVEENGAVEIARCSRGQYFGELALVTNKPRAASAHAIGTVKCLAMDVQAFERLL

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

>86510_86510_4_SRPK2-PRKAR2B_SRPK2_chr7_104800954_ENST00000393651_PRKAR2B_chr7_106791367_ENST00000265717_length(amino acids)=378AA_BP=207
MSSRKVLAIQARKRRPKREKHPKKPEPQQKAPLVPPPPPPPPPPPPPLPDPTPPEPEEEILGSDDEEQEDPADYCKGGYHPVKIGDLFNG
RYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQLIDDFKISGMNGIHVCMVFEVL
GHHLLKWIIKSNYQGLPVRCVKSIIRQDRVTFRRIIVKNNAKKRKMYESFIESLPFLKSLEFSERLKVVDVIGTKVYNDGEQIIAQGDSA
DSFFIVESGEVKITMKRKGKSEVEENGAVEIARCSRGQYFGELALVTNKPRAASAHAIGTVKCLAMDVQAFERLLGPCMEIMKRNIATYE

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

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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/chr7:104800954/chr7:106791367)
- 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
.	.
FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.	FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.

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 protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

SRPK2

chr7:104800953

chr7:106791366

ENST00000357311

87_95

196.0

689.0

Nucleotide binding

ATP

Hgene

SRPK2

chr7:104800953

chr7:106791366

ENST00000393651

87_95

207.0

700.0

Nucleotide binding

ATP

Hgene

SRPK2

chr7:104800953

chr7:106791366

ENST00000489828

87_95

196.0

689.0

Nucleotide binding

ATP

Hgene

SRPK2

chr7:104800954

chr7:106791367

ENST00000357311

87_95

196.0

689.0

Nucleotide binding

ATP

Hgene

SRPK2

chr7:104800954

chr7:106791367

ENST00000393651

87_95

207.0

700.0

Nucleotide binding

ATP

Hgene

SRPK2

chr7:104800954

chr7:106791367

ENST00000489828

87_95

196.0

689.0

Nucleotide binding

ATP

Tgene

PRKAR2B

chr7:104800953

chr7:106791366

ENST00000265717

276_418

247.0

419.0

Nucleotide binding

Note=cAMP 2

Tgene

PRKAR2B

chr7:104800954

chr7:106791367

ENST00000265717

276_418

247.0

419.0

Nucleotide binding

Note=cAMP 2

- Not-retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

SRPK2

chr7:104800953

chr7:106791366

ENST00000357311

81_684

196.0

689.0

Domain

Protein kinase

Hgene

SRPK2

chr7:104800953

chr7:106791366

ENST00000393651

81_684

207.0

700.0

Domain

Protein kinase

Hgene

SRPK2

chr7:104800953

chr7:106791366

ENST00000489828

81_684

196.0

689.0

Domain

Protein kinase

Hgene

SRPK2

chr7:104800954

chr7:106791367

ENST00000357311

81_684

196.0

689.0

Domain

Protein kinase

Hgene

SRPK2

chr7:104800954

chr7:106791367

ENST00000393651

81_684

207.0

700.0

Domain

Protein kinase

Hgene

SRPK2

chr7:104800954

chr7:106791367

ENST00000489828

81_684

196.0

689.0

Domain

Protein kinase

Tgene

PRKAR2B

chr7:104800953

chr7:106791366

ENST00000265717

154_275

247.0

419.0

Nucleotide binding

Note=cAMP 1

Tgene

PRKAR2B

chr7:104800954

chr7:106791367

ENST00000265717

154_275

247.0

419.0

Nucleotide binding

Note=cAMP 1

Tgene

PRKAR2B

chr7:104800953

chr7:106791366

ENST00000265717

2_153

247.0

419.0

Region

Note=Dimerization and phosphorylation

Tgene

PRKAR2B

chr7:104800954

chr7:106791367

ENST00000265717

2_153

247.0

419.0

Region

Note=Dimerization and phosphorylation

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Fusion Protein Structures

PDB and CIF files of the predicted 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.

Fusion protein PDB link (fusion AA seq ID in FusionPDB)	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	AA seq	Len(AA seq)
PDB file >>>788_SRPK2_104800954_PRKAR2B_106791367_ranked_0.pdb	SRPK2	104800953	104800954	ENST00000265717	PRKAR2B	chr7	106791367	+	MKARAGNLGCEYFLIFPEIKQKIELLMSVNSEKSSSSERPEPQQKAPLVPPPPPPPPPPPPPLPDPTPPEPEEEILGSDDEEQEDPADYC KGGYHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQLIDDFKI SGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQDRVTFRRIIVKNNAKKRKMYESFIESLPFLKSLEFSERLKVVDVIGTK VYNDGEQIIAQGDSADSFFIVESGEVKITMKRKGKSEVEENGAVEIARCSRGQYFGELALVTNKPRAASAHAIGTVKCLAMDVQAFERLL	393

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pLDDT score distribution

pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

SRPK2_pLDDT.png

PRKAR2B_pLDDT.png

pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

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Ramachandran Plot of 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.

Fusion AA seq ID in FusionPDB and their Ramachandran plots

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Fusion Protein-Protein Interaction

Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in
ChiPPI page.

Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)

Gene

PPI interactors

Protein-protein interactors based on sequence similarity (STRING)

Gene	STRING network
SRPK2
PRKAR2B

- Retained interactions in fusion protein (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost interactions due to fusion (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

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Related Drugs to SRPK2-PRKAR2B

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 SRPK2-PRKAR2B

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