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	Fusion Gene Summary
	Fusion Gene ORF analysis
	Fusion Genomic Features
	Fusion Protein Features
	Fusion Gene Sequence
	Fusion Gene PPI analysis
	Related Drugs
	Related Diseases

Fusion gene:TYK2-ARRB2 (FusionGDB2 ID:95648)

Fusion Gene Summary for TYK2-ARRB2

Fusion gene summary

Fusion gene information	Fusion gene name: TYK2-ARRB2
	Fusion gene ID: 95648
		Hgene	Tgene
	Gene symbol	TYK2	ARRB2
	Gene ID	7297	409
	Gene name	tyrosine kinase 2	arrestin beta 2
	Synonyms	IMD35\|JTK1	ARB2\|ARR2\|BARR2
	Cytomap	19p13.2	17p13.2
	Type of gene	protein-coding	protein-coding
	Description	non-receptor tyrosine-protein kinase TYK2	beta-arrestin-2arrestin 3non-visual arrestin-3
	Modification date	20200329	20200313
	UniProtAcc	.	P32121
	Ensembl transtripts involved in fusion gene	ENST00000264818, ENST00000524462, ENST00000525621, ENST00000529370, ENST00000529422,	ENST00000269260, ENST00000381488, ENST00000412477, ENST00000571206, ENST00000572457, ENST00000574954, ENST00000575877, ENST00000346341, ENST00000570718,
Fusion gene scores	* DoF score	13 X 11 X 8=1144	3 X 4 X 2=24
	# samples	15	4
	** MAII score	log2(15/1144*10)=-2.93105264628251 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(4/24*10)=0.736965594166206 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0
Context	PubMed: TYK2 [Title/Abstract] AND ARRB2 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	TYK2(10472807)-ARRB2(4620996), # samples:1
Anticipated loss of major functional domain due to fusion event.

* 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
Tgene	ARRB2	GO:0002031	G protein-coupled receptor internalization	10644702
Tgene	ARRB2	GO:0006366	transcription by RNA polymerase II	16820410
Tgene	ARRB2	GO:0007179	transforming growth factor beta receptor signaling pathway	12958365
Tgene	ARRB2	GO:0031397	negative regulation of protein ubiquitination	16378096
Tgene	ARRB2	GO:0031623	receptor internalization	12958365
Tgene	ARRB2	GO:0032088	negative regulation of NF-kappaB transcription factor activity	15125834\|16378096
Tgene	ARRB2	GO:0060765	regulation of androgen receptor signaling pathway	19372219
Tgene	ARRB2	GO:0070374	positive regulation of ERK1 and ERK2 cascade	10644702

Fusion gene breakpoints across TYK2 (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 ARRB2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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
ChiTaRS5.0	N/A	BI024982	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+

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Fusion Gene ORF analysis for TYK2-ARRB2

Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.

ORF	Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
intron-3CDS	ENST00000264818	ENST00000269260	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-3CDS	ENST00000524462	ENST00000269260	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-3CDS	ENST00000525621	ENST00000269260	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-3CDS	ENST00000529370	ENST00000269260	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-3CDS	ENST00000529422	ENST00000269260	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000264818	ENST00000381488	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000264818	ENST00000412477	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000264818	ENST00000571206	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000264818	ENST00000572457	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000264818	ENST00000574954	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000264818	ENST00000575877	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000524462	ENST00000381488	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000524462	ENST00000412477	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000524462	ENST00000571206	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000524462	ENST00000572457	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000524462	ENST00000574954	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000524462	ENST00000575877	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000525621	ENST00000381488	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000525621	ENST00000412477	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000525621	ENST00000571206	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000525621	ENST00000572457	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000525621	ENST00000574954	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000525621	ENST00000575877	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000529370	ENST00000381488	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000529370	ENST00000412477	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000529370	ENST00000571206	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000529370	ENST00000572457	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000529370	ENST00000574954	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000529370	ENST00000575877	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000529422	ENST00000381488	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000529422	ENST00000412477	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000529422	ENST00000571206	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000529422	ENST00000572457	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000529422	ENST00000574954	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-5UTR	ENST00000529422	ENST00000575877	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-intron	ENST00000264818	ENST00000346341	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-intron	ENST00000264818	ENST00000570718	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-intron	ENST00000524462	ENST00000346341	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-intron	ENST00000524462	ENST00000570718	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-intron	ENST00000525621	ENST00000346341	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-intron	ENST00000525621	ENST00000570718	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-intron	ENST00000529370	ENST00000346341	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-intron	ENST00000529370	ENST00000570718	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-intron	ENST00000529422	ENST00000346341	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+
intron-intron	ENST00000529422	ENST00000570718	TYK2	chr19	10472807	+	ARRB2	chr17	4620996	+

ORFfinder result based on the fusion transcript sequence of in-frame fusion genes.

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)

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

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Fusion Genomic Features for TYK2-ARRB2

FusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

1-p

p (fusion gene breakpoint)

Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.

Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for TYK2-ARRB2

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:10472807/:4620996)
- 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
.	ARRB2 P32121
FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.	FUNCTION: Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Mediates endocytosis of CCR7 following ligation of CCL19 but not CCL21. Involved in internalization of P2RY1, P2RY4, P2RY6 and P2RY11 and ATP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 and subsequent recycling or degradation. Involved in ubiquitination of IGF1R. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Acts as signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2) and MAPK10 (JNK3). ERK1/2 and JNK3 activated by the beta-arrestin scaffold are largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Acts as signaling scaffold for the AKT1 pathway. GPCRs for which the beta-arrestin-mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Increases ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Involved in CCR7-mediated ERK1/2 signaling involving ligand CCL19. Is involved in type-1A angiotensin II receptor/AGTR1-mediated ERK activity. Is involved in type-1A angiotensin II receptor/AGTR1-mediated MAPK10 activity. Is involved in dopamine-stimulated AKT1 activity in the striatum by disrupting the association of AKT1 with its negative regulator PP2A. Involved in AGTR1-mediated chemotaxis. Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. Suppresses UV-induced NF-kappa-B-dependent activation by interacting with CHUK. The function is promoted by stimulation of ADRB2 and dephosphorylation of ARRB2. Involved in p53/TP53-mediated apoptosis by regulating MDM2 and reducing the MDM2-mediated degradation of p53/TP53. May serve as nuclear messenger for GPCRs. Upon stimulation of OR1D2, may be involved in regulation of gene expression during the early processes of fertilization. Also involved in regulation of receptors other than GPCRs. Involved in endocytosis of TGFBR2 and TGFBR3 and down-regulates TGF-beta signaling such as NF-kappa-B activation. Involved in endocytosis of low-density lipoprotein receptor/LDLR. Involved in endocytosis of smoothened homolog/Smo, which also requires GRK2. Involved in endocytosis of SLC9A5. Involved in endocytosis of ENG and subsequent TGF-beta-mediated ERK activation and migration of epithelial cells. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN. Involved in insulin resistance by acting as insulin-induced signaling scaffold for SRC, AKT1 and INSR. Involved in regulation of inhibitory signaling of natural killer cells by recruiting PTPN6 and PTPN11 to KIR2DL1. Involved in IL8-mediated granule release in neutrophils. Involved in the internalization of the atypical chemokine receptor ACKR3. Acts as an adapter protein coupling FFAR4 receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis (PubMed:22282525, PubMed:23809162). During the activation step of NLRP3 inflammasome, directly associates with NLRP3 leading to inhibition of proinflammatory cytokine release and inhibition of inflammation (PubMed:23809162). {ECO:0000269\|PubMed:10644702, ECO:0000269\|PubMed:11877451, ECO:0000269\|PubMed:12488444, ECO:0000269\|PubMed:12582207, ECO:0000269\|PubMed:12949261, ECO:0000269\|PubMed:12958365, ECO:0000269\|PubMed:14711824, ECO:0000269\|PubMed:15054093, ECO:0000269\|PubMed:15125834, ECO:0000269\|PubMed:15205453, ECO:0000269\|PubMed:15475570, ECO:0000269\|PubMed:15618519, ECO:0000269\|PubMed:15635042, ECO:0000269\|PubMed:15671180, ECO:0000269\|PubMed:15699339, ECO:0000269\|PubMed:15878855, ECO:0000269\|PubMed:16144840, ECO:0000269\|PubMed:16280323, ECO:0000269\|PubMed:16378096, ECO:0000269\|PubMed:16492667, ECO:0000269\|PubMed:16820410, ECO:0000269\|PubMed:17540773, ECO:0000269\|PubMed:18419762, ECO:0000269\|PubMed:18604210, ECO:0000269\|PubMed:19325136, ECO:0000269\|PubMed:19620252, ECO:0000269\|PubMed:19643177, ECO:0000269\|PubMed:20048153, ECO:0000269\|PubMed:22282525, ECO:0000269\|PubMed:22457824, ECO:0000269\|PubMed:23809162}.

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.

- In-frame and 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

- In-frame and 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

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Fusion Gene Sequence for TYK2-ARRB2

For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for TYK2-ARRB2

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 (BIOGRID-3.4.160)

Hgene

Hgene's interactors

Tgene

Tgene's interactors

- Retained PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

- Retained PPIs, but lost function due to frame-shift fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

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Related Drugs for TYK2-ARRB2

Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)

Partner

Gene

UniProtAcc

DrugBank ID

Drug name

Drug activity

Drug type

Drug status

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Related Diseases for TYK2-ARRB2

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source