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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:CYBA_TAOK2

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: CYBA_TAOK2
	KinaseFusionDB ID: KFG1578
	FusionGDB2.0 ID: KFG1578
		Hgene	Tgene
	Gene symbol	CYBA	TAOK2
	Gene ID	1535	9344
	Gene name	cytochrome b-245 alpha chain	TAO kinase 2
	Synonyms	CGD4\|p22-PHOX	MAP3K17\|PSK\|PSK1\|PSK1-BETA\|TAO1\|TAO2\|Tao2beta
	Cytomap	16q24.2	16p11.2
	Type of gene	protein-coding	protein-coding
	Description	cytochrome b-245 light chaincytochrome b light chaincytochrome b(558) alpha chaincytochrome b(558) alpha-subunitcytochrome b, alpha polypeptidecytochrome b-245, alpha polypeptidecytochrome b558 subunit alphaflavocytochrome b-558 alpha polypeptiden	serine/threonine-protein kinase TAO2PSK-1hKFC-Ckinase from chicken homolog Cprostate derived STE20-like kinase PSKprostate-derived STE20-like kinase 1prostate-derived sterile 20-like kinase 1thousand and one amino acid protein kinase 2
	Modification date	20240411	20240403
	UniProtAcc	P13498	Q9UL54
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000261623, ENST00000567174, ENST00000569359, ENST00000561972,	ENST00000308893, ENST00000543033, ENST00000279394, ENST00000416441,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: CYBA [Title/Abstract] AND TAOK2 [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	CYBA	GO:0017004	cytochrome complex assembly	7938008
Hgene	CYBA	GO:0032755	positive regulation of interleukin-6 production	22423966
Hgene	CYBA	GO:0032760	positive regulation of tumor necrosis factor production	22423966
Hgene	CYBA	GO:0034137	positive regulation of toll-like receptor 2 signaling pathway	22423966
Hgene	CYBA	GO:0050766	positive regulation of phagocytosis	22423966
Hgene	CYBA	GO:1900426	positive regulation of defense response to bacterium	22423966
Hgene	CYBA	GO:1903428	positive regulation of reactive oxygen species biosynthetic process	22423966
Tgene	TAOK2	GO:0006974	DNA damage response	17396146
Tgene	TAOK2	GO:0008360	regulation of cell shape	10660600
Tgene	TAOK2	GO:0030036	actin cytoskeleton organization	10660600
Tgene	TAOK2	GO:0043410	positive regulation of MAPK cascade	10660600
Tgene	TAOK2	GO:0046330	positive regulation of JNK cascade	10660600
Tgene	TAOK2	GO:0048041	focal adhesion assembly	10660600
Tgene	TAOK2	GO:0051403	stress-activated MAPK cascade	11279118

Kinase Fusion gene breakpoints across CYBA (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 TAOK2 (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
CCLE	VMRC-RCW	CYBA	chr16	88709877	TAOK2	chr16	29994932

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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)

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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

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/:/:)
- 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
CYBA P13498	TAOK2 Q9UL54
FUNCTION: Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. Associates with NOX3 to form a functional NADPH oxidase constitutively generating superoxide. {ECO:0000269\|PubMed:15824103, ECO:0000269\|PubMed:17140397}.	FUNCTION: Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Isoform 1, but not isoform 2, plays a role in apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation. This function, which requires the activation of MAPK8/JNK and nuclear localization of C-terminally truncated isoform 1, may be linked to the mitochondrial CASP9-associated death pathway. Isoform 1 binds to microtubules and affects their organization and stability independently of its kinase activity. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation, but not that of MAPK8/JNK. May play a role in the osmotic stress-MAPK8 pathway. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms are involved in MAPK14 phosphorylation. {ECO:0000269\|PubMed:10660600, ECO:0000269\|PubMed:11279118, ECO:0000269\|PubMed:12639963, ECO:0000269\|PubMed:12665513, ECO:0000269\|PubMed:13679851, ECO:0000269\|PubMed:16893890, ECO:0000269\|PubMed:17158878, ECO:0000269\|PubMed:17396146}.

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

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Kinase-Substrate Information of CYBA_TAOK2

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
TAOK2	Q9UL54	human	RND3	P61587	S210	KNVKRNKsQRATKRI
TAOK2	Q9UL54	human	RND3	P61587	S218	QRATKRIsHMPsRPE
TAOK2	Q9UL54	human	TAOK2	Q9UL54	S181	SIMAPANsFVGtPYW	Pkinase
TAOK2	Q9UL54	human	RND3	P61587	S240	LRKDKAKsCTVM___
TAOK2	Q9UL54	human	SEPTIN7	Q16181	T426	EQQNssrtLEKNKKK

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
TAOK2	ID	Description	0.00e+00
TAOK2	GO:0008360	regulation of cell shape	1.26e-02
TAOK2	GO:0022604	regulation of cell morphogenesis	1.95e-02
TAOK2	GO:0140059	dendrite arborization	3.36e-02
TAOK2	GO:1902855	regulation of non-motile cilium assembly	3.36e-02
TAOK2	GO:0031954	positive regulation of protein autophosphorylation	4.79e-02
TAOK2	GO:0045724	positive regulation of cilium assembly	4.79e-02
TAOK2	GO:0140058	neuron projection arborization	4.79e-02
TAOK2	GO:0007095	mitotic G2 DNA damage checkpoint signaling	4.79e-02
TAOK2	GO:0031952	regulation of protein autophosphorylation	4.79e-02
TAOK2	GO:0044818	mitotic G2/M transition checkpoint	4.79e-02
TAOK2	GO:1905515	non-motile cilium assembly	4.79e-02
TAOK2	GO:0010972	negative regulation of G2/M transition of mitotic cell cycle	4.79e-02
TAOK2	GO:1902750	negative regulation of cell cycle G2/M phase transition	4.79e-02
TAOK2	GO:1902017	regulation of cilium assembly	4.79e-02
TAOK2	GO:0044773	mitotic DNA damage checkpoint signaling	4.79e-02
TAOK2	GO:1902117	positive regulation of organelle assembly	4.79e-02
TAOK2	GO:0048041	focal adhesion assembly	4.79e-02
TAOK2	GO:0044774	mitotic DNA integrity checkpoint signaling	4.79e-02
TAOK2	GO:0032147	activation of protein kinase activity	4.79e-02
TAOK2	GO:0046330	positive regulation of JNK cascade	4.79e-02
TAOK2	GO:0045995	regulation of embryonic development	4.79e-02
TAOK2	GO:0007044	cell-substrate junction assembly	4.79e-02
TAOK2	GO:0150115	cell-substrate junction organization	4.79e-02
TAOK2	GO:0010389	regulation of G2/M transition of mitotic cell cycle	4.79e-02
TAOK2	GO:0120034	positive regulation of plasma membrane bounded cell projection assembly	4.79e-02
TAOK2	GO:1902749	regulation of cell cycle G2/M phase transition	4.79e-02
TAOK2	GO:0061640	cytoskeleton-dependent cytokinesis	4.79e-02
TAOK2	GO:0032874	positive regulation of stress-activated MAPK cascade	4.79e-02
TAOK2	GO:0070304	positive regulation of stress-activated protein kinase signaling cascade	4.79e-02
TAOK2	GO:0000077	DNA damage checkpoint signaling	4.79e-02
TAOK2	GO:0046328	regulation of JNK cascade	4.79e-02
TAOK2	GO:0006612	protein targeting to membrane	4.79e-02
TAOK2	GO:0031570	DNA integrity checkpoint signaling	4.79e-02
TAOK2	GO:0048813	dendrite morphogenesis	4.79e-02
TAOK2	GO:0000086	G2/M transition of mitotic cell cycle	4.79e-02
TAOK2	GO:0007093	mitotic cell cycle checkpoint signaling	4.79e-02
TAOK2	GO:0044839	cell cycle G2/M phase transition	5.09e-02
TAOK2	GO:0007254	JNK cascade	5.21e-02
TAOK2	GO:0032872	regulation of stress-activated MAPK cascade	5.28e-02
TAOK2	GO:0000910	cytokinesis	5.28e-02
TAOK2	GO:0042770	signal transduction in response to DNA damage	5.28e-02
TAOK2	GO:0070302	regulation of stress-activated protein kinase signaling cascade	5.28e-02
TAOK2	GO:0000075	cell cycle checkpoint signaling	5.28e-02
TAOK2	GO:1901991	negative regulation of mitotic cell cycle phase transition	5.28e-02
TAOK2	GO:0046777	protein autophosphorylation	5.28e-02
TAOK2	GO:0120032	regulation of plasma membrane bounded cell projection assembly	5.28e-02
TAOK2	GO:0060491	regulation of cell projection assembly	5.28e-02
TAOK2	GO:1902115	regulation of organelle assembly	5.50e-02
TAOK2	GO:0051403	stress-activated MAPK cascade	5.56e-02

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Related Drugs to CYBA_TAOK2

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 CYBA-TAOK2 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 CYBA_TAOK2

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