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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:ACAP2_TTBK1

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: ACAP2_TTBK1
	KinaseFusionDB ID: KFG108
	FusionGDB2.0 ID: KFG108
		Hgene	Tgene
	Gene symbol	ACAP2	TTBK1
	Gene ID	23527	84630
	Gene name	ArfGAP with coiled-coil, ankyrin repeat and PH domains 2	tau tubulin kinase 1
	Synonyms	CENTB2\|CNT-B2	BDTK
	Cytomap	3q29	6p21.1
	Type of gene	protein-coding	protein-coding
	Description	arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2Arf GAP with coiled coil, ANK repeat and PH domains 2centaurin-beta-2	tau-tubulin kinase 1brain-derived tau kinase
	Modification date	20240407	20240403
	UniProtAcc	Q15057	Q5TCY1
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000326793, ENST00000472860,	ENST00000259750, ENST00000304139,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: ACAP2 [Title/Abstract] AND TTBK1 [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	ACAP2	GO:0030029	actin filament-based process	11062263
Tgene	TTBK1	GO:0018105	peptidyl-serine phosphorylation	16923168
Tgene	TTBK1	GO:0018107	peptidyl-threonine phosphorylation	16923168
Tgene	TTBK1	GO:0018108	peptidyl-tyrosine phosphorylation	16923168
Tgene	TTBK1	GO:0032273	positive regulation of protein polymerization	16923168

Kinase Fusion gene breakpoints across ACAP2 (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 TTBK1 (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	NCI-H1385	ACAP2	chr3	195163524	TTBK1	chr6	43214345
CCLE	NCI-H1385	ACAP2	chr3	195163524	TTBK1	chr6	43220477

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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)
ENST00000326793	ENST00000259750	ACAP2	chr3	195163524	TTBK1	chr6	43220477	7025	1326

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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

>ENST00000326793_ENST00000259750_ACAP2_chr3_195163524_TTBK1_chr6_43220477_length(amino acids)=1326
MRPSAAAPAAPSALPAPPARRRQDEDDCGFRGVSEGLAPLQLKKIGGGGFGEIYEAMDLLTRENVALKVESAQQPKQVLKMEVAVLKKLQ
GKDHVCRFIGCGRNEKFNYVVMQLQGRNLADLRRSQPRGTFTLSTTLRLGKQILESIEAIHSVGFLHRDIKPSNFAMGRLPSTYRKCYML
DFGLARQYTNTTGDVRPPRNVAGFRGTVRYASVNAHKNREMGRHDDLWSLFYMLVEFAVGQLPWRKIKDKEQVGMIKEKYEHRMLLKHMP
SEFHLFLDHIASLDYFTKPDYQLIMSVFENSMKERGIAENEAFDWEKAGTDALLSTSTSTPPQQNTRQTAAMFGVVNVTPVPGDLLRENT
EDVLQGEHLSDQENAPPILPGRPSEGLGPSPHLVPHPGGPEAEVWEETDVNRNKLRINIGKSPCVEEEQSRGMGVPSSPVRAPPDSPTTP
VRSLRYRRVNSPESERLSTADGRVELPERRSRMDLPGSPSRQACSSQPAQMLSVDTGHADRQASGRMDVSASVEQEALSNAFRSVPLAEE
EDFDSKEWVIIDKETELKDFPPGAEPSTSGTTDEEPEELRPLPEEGEERRRLGAEPTVRPRGRSMQALAEEDLQHLPPQPLPPQLSQGDG
RSETSQPPTPGSPSHSPLHSGPRPRRRESDPTGPQRQVFSVAPPFEVNGLPRAVPLSLPYQDFKRDLSDYRERARLLNRVRRVGFSHMLL
TTPQVPLAPVQPQANGKEEEEEEEEDEEEEEEDEEEEEEEEEEEEEEEEEEEEEEEAAAAVALGEVLGPRSGSSSEGSERSTDRSQEGAP
STLLADDQKESRGRASMADGDLEPEEGSKTLVLVSPGDMKKSPVTAELAPDPDLGTLAALTPQHERPQPTGSQLDVSEPGTLSSVLKSEP
KPPGPGAGLGAGTVTTGVGGVAVTSSPFTKVERTFVHIAEKTHLNVMSSGGQALRSEEFSAGGELGLELASDGGAVEEGARAPLENGLAL
SGLNGAEIEGSALSGAPRETPSEMATNSLPNGPALADGPAPVSPLEPSPEKVATISPRRHAMPGSRPRSRIPVLLSEEDTGSEPSGSLSA
KERWSKRARPQQDLARLVMEKRQGRLLLRLASGASSSSSEEQRRASETLSGTGSEEDTPASEPAAALPRKSGRAAATRSRIPRPIGLRMP
MPVAAQQPASRSHGAAPALDTAITSRLQLQTPPGSATAADLRPKQPPGRGLGPGRAQAGARPPAPRSPRLPASTSAARNASASPRSQSLS

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

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/chr3:/chr6:)
- 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
ACAP2 Q15057	TTBK1 Q5TCY1
FUNCTION: GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6). {ECO:0000269\|PubMed:11062263}.	FUNCTION: Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU. {ECO:0000269\|PubMed:16923168}.

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

ACAP2

195163524

TTBK1

43220477

ENST00000326793

34_297

1322

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 >>>TKFP_7_ACAP2_TTBK1	ENST00000326793	ENST00000259750	ACAP2	chr3	195163524	TTBK1	chr6	43220477	MRPSAAAPAAPSALPAPPARRRQDEDDCGFRGVSEGLAPLQLKKIGGGGFGEIYEAMDLLTRENVALKVESAQQPKQVLKMEVAVLKKLQ GKDHVCRFIGCGRNEKFNYVVMQLQGRNLADLRRSQPRGTFTLSTTLRLGKQILESIEAIHSVGFLHRDIKPSNFAMGRLPSTYRKCYML DFGLARQYTNTTGDVRPPRNVAGFRGTVRYASVNAHKNREMGRHDDLWSLFYMLVEFAVGQLPWRKIKDKEQVGMIKEKYEHRMLLKHMP SEFHLFLDHIASLDYFTKPDYQLIMSVFENSMKERGIAENEAFDWEKAGTDALLSTSTSTPPQQNTRQTAAMFGVVNVTPVPGDLLRENT EDVLQGEHLSDQENAPPILPGRPSEGLGPSPHLVPHPGGPEAEVWEETDVNRNKLRINIGKSPCVEEEQSRGMGVPSSPVRAPPDSPTTP VRSLRYRRVNSPESERLSTADGRVELPERRSRMDLPGSPSRQACSSQPAQMLSVDTGHADRQASGRMDVSASVEQEALSNAFRSVPLAEE EDFDSKEWVIIDKETELKDFPPGAEPSTSGTTDEEPEELRPLPEEGEERRRLGAEPTVRPRGRSMQALAEEDLQHLPPQPLPPQLSQGDG RSETSQPPTPGSPSHSPLHSGPRPRRRESDPTGPQRQVFSVAPPFEVNGLPRAVPLSLPYQDFKRDLSDYRERARLLNRVRRVGFSHMLL TTPQVPLAPVQPQANGKEEEEEEEEDEEEEEEDEEEEEEEEEEEEEEEEEEEEEEEAAAAVALGEVLGPRSGSSSEGSERSTDRSQEGAP STLLADDQKESRGRASMADGDLEPEEGSKTLVLVSPGDMKKSPVTAELAPDPDLGTLAALTPQHERPQPTGSQLDVSEPGTLSSVLKSEP KPPGPGAGLGAGTVTTGVGGVAVTSSPFTKVERTFVHIAEKTHLNVMSSGGQALRSEEFSAGGELGLELASDGGAVEEGARAPLENGLAL SGLNGAEIEGSALSGAPRETPSEMATNSLPNGPALADGPAPVSPLEPSPEKVATISPRRHAMPGSRPRSRIPVLLSEEDTGSEPSGSLSA KERWSKRARPQQDLARLVMEKRQGRLLLRLASGASSSSSEEQRRASETLSGTGSEEDTPASEPAAALPRKSGRAAATRSRIPRPIGLRMP MPVAAQQPASRSHGAAPALDTAITSRLQLQTPPGSATAADLRPKQPPGRGLGPGRAQAGARPPAPRSPRLPASTSAARNASASPRSQSLS	1326_ACAP2_TTBK1
3D view using mol* of TKFP_7_ACAP2_TTBK1

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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

ACAP2_TTBK1 does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/TKFP_7_ACAP2_TTBK1_updated_violin_plot.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.

TKFP_7_ACAP2_TTBK1.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
TKFP_7_ACAP2_TTBK1	1.042	115	1.036	348.145	0.521	0.761	1.049	0.961	1.106	0.869	0.977	Chain A: 45,46,47,48,49,50,51,53,66,68,82,96,112,1 13,114,115,116,117,118,121,161,163,164,166,169,179 ,180,181,182,183,184

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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.

TKFP_7_ACAP2_TTBK1_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

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Kinase-Substrate Information of ACAP2_TTBK1

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
TTBK1	Q5TCY1	human	MAPT	P10636-8	S199	GDRsGyssPGsPGtP
TTBK1	Q5TCY1	human	MAPT	P10636-8	S202	sGyssPGsPGtPGsR
TTBK1	Q5TCY1	human	MAPT	P10636-8	S198	sGDRsGyssPGsPGt
TTBK1	Q5TCY1	human	MAPT	P10636-8	T427	VDsPQLAtLADEVsA
TTBK1	Q5TCY1	human	MAPT	P10636-8	Y197	KsGDRsGyssPGsPG
TTBK1	Q5TCY1	human	MAPT	P10636-8	S422	GsIDMVDsPQLAtLA
TTBK1	Q5TCY1	human	MAPT	P10636-8	S416	sNVsstGsIDMVDsP

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
TTBK1	ID	Description	0.00e+00
TTBK1	GO:0010917	negative regulation of mitochondrial membrane potential	1.18e-02
TTBK1	GO:0045837	negative regulation of membrane potential	1.18e-02
TTBK1	GO:1900452	regulation of long-term synaptic depression	1.18e-02
TTBK1	GO:0032930	positive regulation of superoxide anion generation	1.18e-02
TTBK1	GO:1900034	regulation of cellular response to heat	1.18e-02
TTBK1	GO:0048311	mitochondrion distribution	1.18e-02
TTBK1	GO:0019896	axonal transport of mitochondrion	1.18e-02
TTBK1	GO:0032928	regulation of superoxide anion generation	1.18e-02
TTBK1	GO:0010288	response to lead ion	1.18e-02
TTBK1	GO:0090043	regulation of tubulin deacetylation	1.18e-02
TTBK1	GO:1902473	regulation of protein localization to synapse	1.18e-02
TTBK1	GO:0090042	tubulin deacetylation	1.18e-02
TTBK1	GO:0070841	inclusion body assembly	1.18e-02
TTBK1	GO:0048143	astrocyte activation	1.18e-02
TTBK1	GO:0034643	establishment of mitochondrion localizatio	1.38e-03
TTBK1	GO:0090218	positive regulation of lipid kinase activity	1.18e-02
TTBK1	GO:0051654	establishment of mitochondrion localization	1.18e-02
TTBK1	GO:0090140	regulation of mitochondrial fission	1.18e-02
TTBK1	GO:0034063	stress granule assembly	1.18e-02
TTBK1	GO:0090322	regulation of superoxide metabolic process	1.18e-02
TTBK1	GO:0031116	positive regulation of microtubule polymerization	1.18e-02
TTBK1	GO:0060292	long-term synaptic depression	1.18e-02
TTBK1	GO:0090311	regulation of protein deacetylation	1.18e-02
TTBK1	GO:0031112	positive regulation of microtubule polymerization or depolymerization	1.18e-02
TTBK1	GO:0045773	positive regulation of axon extension	1.18e-02
TTBK1	GO:0043550	regulation of lipid kinase activity	1.18e-02
TTBK1	GO:0000266	mitochondrial fission	1.18e-02
TTBK1	GO:0042554	superoxide anion generation	1.18e-02
TTBK1	GO:1990000	amyloid fibril formation	1.18e-02
TTBK1	GO:0014002	astrocyte development	1.18e-02
TTBK1	GO:1990090	cellular response to nerve growth factor stimulus	1.18e-02
TTBK1	GO:1990089	response to nerve growth factor	1.18e-02
TTBK1	GO:0001774	microglial cell activation	1.18e-02
TTBK1	GO:0051646	mitochondrion localization	1.18e-02
TTBK1	GO:1903747	regulation of establishment of protein localization to mitochondrion	1.18e-02
TTBK1	GO:0002269	leukocyte activation involved in inflammatory response	1.18e-02
TTBK1	GO:0010823	negative regulation of mitochondrion organization	1.18e-02
TTBK1	GO:0050805	negative regulation of synaptic transmission	1.19e-02
TTBK1	GO:0061900	glial cell activation	1.19e-02
TTBK1	GO:0006475	internal protein amino acid acetylation	1.19e-02
TTBK1	GO:0006476	protein deacetylation	1.19e-02
TTBK1	GO:0031122	cytoplasmic microtubule organization	1.19e-02
TTBK1	GO:0031113	regulation of microtubule polymerization	1.20e-02
TTBK1	GO:0098930	axonal transport	1.20e-02
TTBK1	GO:0034605	cellular response to heat	1.20e-02
TTBK1	GO:0035601	protein deacylation	1.20e-02
TTBK1	GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process	1.20e-02
TTBK1	GO:2000379	positive regulation of reactive oxygen species metabolic process	1.20e-02
TTBK1	GO:0098732	macromolecule deacylation	1.21e-02

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Related Drugs to ACAP2_TTBK1

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 ACAP2-TTBK1 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 ACAP2_TTBK1

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