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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:APPL2_CIT

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: APPL2_CIT
	KinaseFusionDB ID: KFG394
	FusionGDB2.0 ID: KFG394
		Hgene	Tgene
	Gene symbol	APPL2	CIT
	Gene ID	55198	79947
	Gene name	adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2
	Synonyms	DIP13B
	Cytomap	12q23.3
	Type of gene	protein-coding
	Description	DCC-interacting protein 13-betaDIP13 betaadapter protein containing PH domain, PTB domain and leucine zipper motif 2adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 2
	Modification date	20240403
	UniProtAcc	Q8NEU8	Q96RK1
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000258530, ENST00000551662, ENST00000539978, ENST00000546731, ENST00000549573,	ENST00000537607, ENST00000261833, ENST00000392521,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: APPL2 [Title/Abstract] AND CIT [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	APPL2(105629737)-CIT(120198859), # samples:3

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	APPL2	GO:0006606	protein import into nucleus	26583432
Hgene	APPL2	GO:0051289	protein homotetramerization	23055524
Hgene	APPL2	GO:2000045	regulation of G1/S transition of mitotic cell cycle	15016378

Kinase Fusion gene breakpoints across APPL2 (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 CIT (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
ChimerDB4	TCGA-34-5232-01A	APPL2	chr12	105629737	CIT	chr12	120198859
ChimerDB4	TCGA-34-5232	APPL2	chr12	105629736	CIT	chr12	120198859

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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)
ENST00000258530	ENST00000392521	APPL2	chr12	105629737	CIT	chr12	120198859	6628	1368
ENST00000258530	ENST00000392521	APPL2	chr12	105629736	CIT	chr12	120198859	6628	1368

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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

>ENST00000258530_ENST00000392521_APPL2_chr12_105629737_CIT_chr12_120198859_length(amino acids)=1368
MARRGRARGRRGHGVAAASPEPRAGECSRPPRLLPSVLPTQPSAEPRRTMPAVDKLLLEEALQDSPQVLDNQIKKDLADKETLENMMQRH
EEEAHEKGKILSEQKAMINAMDSKIRSLEQRIVELSEANKLAANSSLFTQRNMKAQEEMISELRQQKFYLETQAGKLEAQNRKLEEQLEK
ISHQDHSDKNRLLELETRLREVSLEHEEQKLELKRQLTELQLSLQERESQLTALQAARAALESQLRQAKTELEETTAEAEEEIQALTAHR
DEIQRKFDALRNSCTVITDLEEQLNQLTEDNAELNNQNFYLSKQLDEASGANDEIVQLRSEVDHLRREITEREMQLTSQKQTMEALKTTC
TMLEEQVMDLEALNDELLEKERQWEAWRSVLGDEKSQFECRVRELQRMLDTEKQSRARADQRITESRQVVELAVKEHKAEILALQQALKE
QKLKAESLSDKLNDLEKKHAMLEMNARSLQQKLETERELKQRLLEEQAKLQQQMDLQKNHIFRLTQGLQEALDRADLLKTERSDLEYQLE
NIQVLYSHEKVKMEGTISQQTKLIDFLQAKMDQPAKKKKGLFSRRKEDPALPTQVPLQYNELKLALEKEKARCAELEEALQKTRIELRSA
REEAAHRKATDHPHPSTPATARQQIAMSAIVRSPEHQPSAMSLLAPPSSRRKESSTPEEFSRRLKERMHHNIPHRFNVGLNMRATKCAVC
LDTVHFGRQASKCLECQVMCHPKCSTCLPATCGLPAEYATHFTEAFCRDKMNSPGLQTKEPSSSLHLEGWMKVPRNNKRGQQGWDRKYIV
LEGSKVLIYDNEAREAGQRPVEEFELCLPDGDVSIHGAVGASELANTAKADVPYILKMESHPHTTCWPGRTLYLLAPSFPDKQRWVTALE
SVVAGGRVSREKAEADAKLLGNSLLKLEGDDRLDMNCTLPFSDQVVLVGTEEGLYALNVLKNSLTHVPGIGAVFQIYIIKDLEKLLMIAG
EERALCLVDVKKVKQSLAQSHLPAQPDISPNIFEAVKGCHLFGAGKIENGLCICAAMPSKVVILRYNENLSKYCIRKEIETSEPCSCIHF
TNYSILIGTNKFYEIDMKQYTLEEFLDKNDHSLAPAVFAASSNSFPVSIVQVNSAGQREEYLLCFHEFGVFVDSYGRRSRTDDLKWSRLP
LAFAYREPYLFVTHFNSLEVIEIQARSSAGTPARAYLDIPNPRYLGPAISSGAIYLASSYQDKLRVICCKGNLVKESGTEHHRGPSTSRS
SPNKRGPPTYNEHITKRVASSPAPPEGPSHPREPSTPHRYREGRTELRRDKSPGRPLEREKSPGRMLSTRRERSPGRLFEDSSRGRLPAG

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

>ENST00000258530_ENST00000392521_APPL2_chr12_105629736_CIT_chr12_120198859_length(amino acids)=1368
MARRGRARGRRGHGVAAASPEPRAGECSRPPRLLPSVLPTQPSAEPRRTMPAVDKLLLEEALQDSPQVLDNQIKKDLADKETLENMMQRH
EEEAHEKGKILSEQKAMINAMDSKIRSLEQRIVELSEANKLAANSSLFTQRNMKAQEEMISELRQQKFYLETQAGKLEAQNRKLEEQLEK
ISHQDHSDKNRLLELETRLREVSLEHEEQKLELKRQLTELQLSLQERESQLTALQAARAALESQLRQAKTELEETTAEAEEEIQALTAHR
DEIQRKFDALRNSCTVITDLEEQLNQLTEDNAELNNQNFYLSKQLDEASGANDEIVQLRSEVDHLRREITEREMQLTSQKQTMEALKTTC
TMLEEQVMDLEALNDELLEKERQWEAWRSVLGDEKSQFECRVRELQRMLDTEKQSRARADQRITESRQVVELAVKEHKAEILALQQALKE
QKLKAESLSDKLNDLEKKHAMLEMNARSLQQKLETERELKQRLLEEQAKLQQQMDLQKNHIFRLTQGLQEALDRADLLKTERSDLEYQLE
NIQVLYSHEKVKMEGTISQQTKLIDFLQAKMDQPAKKKKGLFSRRKEDPALPTQVPLQYNELKLALEKEKARCAELEEALQKTRIELRSA
REEAAHRKATDHPHPSTPATARQQIAMSAIVRSPEHQPSAMSLLAPPSSRRKESSTPEEFSRRLKERMHHNIPHRFNVGLNMRATKCAVC
LDTVHFGRQASKCLECQVMCHPKCSTCLPATCGLPAEYATHFTEAFCRDKMNSPGLQTKEPSSSLHLEGWMKVPRNNKRGQQGWDRKYIV
LEGSKVLIYDNEAREAGQRPVEEFELCLPDGDVSIHGAVGASELANTAKADVPYILKMESHPHTTCWPGRTLYLLAPSFPDKQRWVTALE
SVVAGGRVSREKAEADAKLLGNSLLKLEGDDRLDMNCTLPFSDQVVLVGTEEGLYALNVLKNSLTHVPGIGAVFQIYIIKDLEKLLMIAG
EERALCLVDVKKVKQSLAQSHLPAQPDISPNIFEAVKGCHLFGAGKIENGLCICAAMPSKVVILRYNENLSKYCIRKEIETSEPCSCIHF
TNYSILIGTNKFYEIDMKQYTLEEFLDKNDHSLAPAVFAASSNSFPVSIVQVNSAGQREEYLLCFHEFGVFVDSYGRRSRTDDLKWSRLP
LAFAYREPYLFVTHFNSLEVIEIQARSSAGTPARAYLDIPNPRYLGPAISSGAIYLASSYQDKLRVICCKGNLVKESGTEHHRGPSTSRS
SPNKRGPPTYNEHITKRVASSPAPPEGPSHPREPSTPHRYREGRTELRRDKSPGRPLEREKSPGRMLSTRRERSPGRLFEDSSRGRLPAG

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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/chr12:105629737/chr12:120198859)
- 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
APPL2 Q8NEU8	CIT Q96RK1
FUNCTION: Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism (PubMed:26583432, PubMed:15016378, PubMed:24879834). Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex (PubMed:15016378). Plays a role in immune response by modulating phagocytosis, inflammatory and innate immune responses. In macrophages, enhances Fc-gamma receptor-mediated phagocytosis through interaction with RAB31 leading to activation of PI3K/Akt signaling. In response to LPS, modulates inflammatory responses by playing a key role on the regulation of TLR4 signaling and in the nuclear translocation of RELA/NF-kappa-B p65 and the secretion of pro- and anti-inflammatory cytokines. Also functions as a negative regulator of innate immune response via inhibition of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1 (By similarity). Plays a role in endosomal trafficking of TGFBR1 from the endosomes to the nucleus (PubMed:26583432). Plays a role in cell metabolism by regulating adiponecting ans insulin signaling pathways and adaptative thermogenesis (PubMed:24879834) (By similarity). In muscle, negatively regulates adiponectin-simulated glucose uptake and fatty acid oxidation by inhibiting adiponectin signaling pathway through APPL1 sequestration thereby antagonizing APPL1 action (By similarity). In muscles, negativeliy regulates insulin-induced plasma membrane recruitment of GLUT4 and glucose uptake through interaction with TBC1D1 (PubMed:24879834). Plays a role in cold and diet-induced adaptive thermogenesis by activating ventromedial hypothalamus (VMH) neurons throught AMPK inhibition which enhances sympathetic outflow to subcutaneous white adipose tissue (sWAT), sWAT beiging and cold tolerance (By similarity). Also plays a role in other signaling pathways namely Wnt/beta-catenin, HGF and glucocorticoid receptor signaling (PubMed:19433865) (By similarity). Positive regulator of beta-catenin/TCF-dependent transcription through direct interaction with RUVBL2/reptin resulting in the relief of RUVBL2-mediated repression of beta-catenin/TCF target genes by modulating the interactions within the beta-catenin-reptin-HDAC complex (PubMed:19433865). May affect adult neurogenesis in hippocampus and olfactory system via regulating the sensitivity of glucocorticoid receptor. Required for fibroblast migration through HGF cell signaling (By similarity). {ECO:0000250\|UniProtKB:Q8K3G9, ECO:0000269\|PubMed:15016378, ECO:0000269\|PubMed:19433865, ECO:0000269\|PubMed:24879834, ECO:0000269\|PubMed:26583432}.	FUNCTION: Acts as a transcriptional coactivator for TFAP2/AP-2. Enhances estrogen-dependent transactivation mediated by estrogen receptors. May function as an inhibitor of transactivation by HIF1A by disrupting HIF1A interaction with CREBBP. May be involved in regulation of gene expression during development and differentiation of blood cells, endothelial cells and mammary epithelial cells. {ECO:0000269\|PubMed:11744733, ECO:0000269\|PubMed:15342390}.

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	APPL2	105629736	CIT	120198859	ENST00000258530	17	47	1591_1881	726	2028	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	APPL2	105629736	CIT	120198859	ENST00000258530	18	48	1591_1881	768	2070	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	APPL2	105629737	CIT	120198859	ENST00000258530	17	47	1591_1881	726	2028	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	APPL2	105629737	CIT	120198859	ENST00000258530	18	48	1591_1881	768	2070	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	APPL2	105629736	CIT	120198859	ENST00000258530	17	47	1443_1563	726	2028	Domain	Note=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00145
Tgene	APPL2	105629736	CIT	120198859	ENST00000258530	18	48	1443_1563	768	2070	Domain	Note=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00145
Tgene	APPL2	105629737	CIT	120198859	ENST00000258530	17	47	1443_1563	726	2028	Domain	Note=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00145
Tgene	APPL2	105629737	CIT	120198859	ENST00000258530	18	48	1443_1563	768	2070	Domain	Note=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00145

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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 >>>31_APPL2_CIT	ENST00000258530	ENST00000392521	APPL2	chr12	105629736	CIT	chr12	120198859	MARRGRARGRRGHGVAAASPEPRAGECSRPPRLLPSVLPTQPSAEPRRTMPAVDKLLLEEALQDSPQVLDNQIKKDLADKETLENMMQRH EEEAHEKGKILSEQKAMINAMDSKIRSLEQRIVELSEANKLAANSSLFTQRNMKAQEEMISELRQQKFYLETQAGKLEAQNRKLEEQLEK ISHQDHSDKNRLLELETRLREVSLEHEEQKLELKRQLTELQLSLQERESQLTALQAARAALESQLRQAKTELEETTAEAEEEIQALTAHR DEIQRKFDALRNSCTVITDLEEQLNQLTEDNAELNNQNFYLSKQLDEASGANDEIVQLRSEVDHLRREITEREMQLTSQKQTMEALKTTC TMLEEQVMDLEALNDELLEKERQWEAWRSVLGDEKSQFECRVRELQRMLDTEKQSRARADQRITESRQVVELAVKEHKAEILALQQALKE QKLKAESLSDKLNDLEKKHAMLEMNARSLQQKLETERELKQRLLEEQAKLQQQMDLQKNHIFRLTQGLQEALDRADLLKTERSDLEYQLE NIQVLYSHEKVKMEGTISQQTKLIDFLQAKMDQPAKKKKGLFSRRKEDPALPTQVPLQYNELKLALEKEKARCAELEEALQKTRIELRSA REEAAHRKATDHPHPSTPATARQQIAMSAIVRSPEHQPSAMSLLAPPSSRRKESSTPEEFSRRLKERMHHNIPHRFNVGLNMRATKCAVC LDTVHFGRQASKCLECQVMCHPKCSTCLPATCGLPAEYATHFTEAFCRDKMNSPGLQTKEPSSSLHLEGWMKVPRNNKRGQQGWDRKYIV LEGSKVLIYDNEAREAGQRPVEEFELCLPDGDVSIHGAVGASELANTAKADVPYILKMESHPHTTCWPGRTLYLLAPSFPDKQRWVTALE SVVAGGRVSREKAEADAKLLGNSLLKLEGDDRLDMNCTLPFSDQVVLVGTEEGLYALNVLKNSLTHVPGIGAVFQIYIIKDLEKLLMIAG EERALCLVDVKKVKQSLAQSHLPAQPDISPNIFEAVKGCHLFGAGKIENGLCICAAMPSKVVILRYNENLSKYCIRKEIETSEPCSCIHF TNYSILIGTNKFYEIDMKQYTLEEFLDKNDHSLAPAVFAASSNSFPVSIVQVNSAGQREEYLLCFHEFGVFVDSYGRRSRTDDLKWSRLP LAFAYREPYLFVTHFNSLEVIEIQARSSAGTPARAYLDIPNPRYLGPAISSGAIYLASSYQDKLRVICCKGNLVKESGTEHHRGPSTSRS SPNKRGPPTYNEHITKRVASSPAPPEGPSHPREPSTPHRYREGRTELRRDKSPGRPLEREKSPGRMLSTRRERSPGRLFEDSSRGRLPAG	1368
3D view using mol* of 31_APPL2_CIT

PDB file >>>TKFP_47_APPL2_CIT	ENST00000258530	ENST00000392521	APPL2	chr12	105629737	CIT	chr12	120198859	MARRGRARGRRGHGVAAASPEPRAGECSRPPRLLPSVLPTQPSAEPRRTMPAVDKLLLEEALQDSPQVLDNQIKKDLADKETLENMMQRH EEEAHEKGKILSEQKAMINAMDSKIRSLEQRIVELSEANKLAANSSLFTQRNMKAQEEMISELRQQKFYLETQAGKLEAQNRKLEEQLEK ISHQDHSDKNRLLELETRLREVSLEHEEQKLELKRQLTELQLSLQERESQLTALQAARAALESQLRQAKTELEETTAEAEEEIQALTAHR DEIQRKFDALRNSCTVITDLEEQLNQLTEDNAELNNQNFYLSKQLDEASGANDEIVQLRSEVDHLRREITEREMQLTSQKQTMEALKTTC TMLEEQVMDLEALNDELLEKERQWEAWRSVLGDEKSQFECRVRELQRMLDTEKQSRARADQRITESRQVVELAVKEHKAEILALQQALKE QKLKAESLSDKLNDLEKKHAMLEMNARSLQQKLETERELKQRLLEEQAKLQQQMDLQKNHIFRLTQGLQEALDRADLLKTERSDLEYQLE NIQVLYSHEKVKMEGTISQQTKLIDFLQAKMDQPAKKKKGLFSRRKEDPALPTQVPLQYNELKLALEKEKARCAELEEALQKTRIELRSA REEAAHRKATDHPHPSTPATARQQIAMSAIVRSPEHQPSAMSLLAPPSSRRKESSTPEEFSRRLKERMHHNIPHRFNVGLNMRATKCAVC LDTVHFGRQASKCLECQVMCHPKCSTCLPATCGLPAEYATHFTEAFCRDKMNSPGLQTKEPSSSLHLEGWMKVPRNNKRGQQGWDRKYIV LEGSKVLIYDNEAREAGQRPVEEFELCLPDGDVSIHGAVGASELANTAKADVPYILKMESHPHTTCWPGRTLYLLAPSFPDKQRWVTALE SVVAGGRVSREKAEADAKLLGNSLLKLEGDDRLDMNCTLPFSDQVVLVGTEEGLYALNVLKNSLTHVPGIGAVFQIYIIKDLEKLLMIAG EERALCLVDVKKVKQSLAQSHLPAQPDISPNIFEAVKGCHLFGAGKIENGLCICAAMPSKVVILRYNENLSKYCIRKEIETSEPCSCIHF TNYSILIGTNKFYEIDMKQYTLEEFLDKNDHSLAPAVFAASSNSFPVSIVQVNSAGQREEYLLCFHEFGVFVDSYGRRSRTDDLKWSRLP LAFAYREPYLFVTHFNSLEVIEIQARSSAGTPARAYLDIPNPRYLGPAISSGAIYLASSYQDKLRVICCKGNLVKESGTEHHRGPSTSRS SPNKRGPPTYNEHITKRVASSPAPPEGPSHPREPSTPHRYREGRTELRRDKSPGRPLEREKSPGRMLSTRRERSPGRLFEDSSRGRLPAG	1368_APPL2_CIT
PDB file >>>TKFP_48_APPL2_CIT	ENST00000258530	ENST00000392521	APPL2	chr12	105629736	CIT	chr12	120198859	MARRGRARGRRGHGVAAASPEPRAGECSRPPRLLPSVLPTQPSAEPRRTMPAVDKLLLEEALQDSPQVLDNQIKKDLADKETLENMMQRH EEEAHEKGKILSEQKAMINAMDSKIRSLEQRIVELSEANKLAANSSLFTQRNMKAQEEMISELRQQKFYLETQAGKLEAQNRKLEEQLEK ISHQDHSDKNRLLELETRLREVSLEHEEQKLELKRQLTELQLSLQERESQLTALQAARAALESQLRQAKTELEETTAEAEEEIQALTAHR DEIQRKFDALRNSCTVITDLEEQLNQLTEDNAELNNQNFYLSKQLDEASGANDEIVQLRSEVDHLRREITEREMQLTSQKQTMEALKTTC TMLEEQVMDLEALNDELLEKERQWEAWRSVLGDEKSQFECRVRELQRMLDTEKQSRARADQRITESRQVVELAVKEHKAEILALQQALKE QKLKAESLSDKLNDLEKKHAMLEMNARSLQQKLETERELKQRLLEEQAKLQQQMDLQKNHIFRLTQGLQEALDRADLLKTERSDLEYQLE NIQVLYSHEKVKMEGTISQQTKLIDFLQAKMDQPAKKKKGLFSRRKEDPALPTQVPLQYNELKLALEKEKARCAELEEALQKTRIELRSA REEAAHRKATDHPHPSTPATARQQIAMSAIVRSPEHQPSAMSLLAPPSSRRKESSTPEEFSRRLKERMHHNIPHRFNVGLNMRATKCAVC LDTVHFGRQASKCLECQVMCHPKCSTCLPATCGLPAEYATHFTEAFCRDKMNSPGLQTKEPSSSLHLEGWMKVPRNNKRGQQGWDRKYIV LEGSKVLIYDNEAREAGQRPVEEFELCLPDGDVSIHGAVGASELANTAKADVPYILKMESHPHTTCWPGRTLYLLAPSFPDKQRWVTALE SVVAGGRVSREKAEADAKLLGNSLLKLEGDDRLDMNCTLPFSDQVVLVGTEEGLYALNVLKNSLTHVPGIGAVFQIYIIKDLEKLLMIAG EERALCLVDVKKVKQSLAQSHLPAQPDISPNIFEAVKGCHLFGAGKIENGLCICAAMPSKVVILRYNENLSKYCIRKEIETSEPCSCIHF TNYSILIGTNKFYEIDMKQYTLEEFLDKNDHSLAPAVFAASSNSFPVSIVQVNSAGQREEYLLCFHEFGVFVDSYGRRSRTDDLKWSRLP LAFAYREPYLFVTHFNSLEVIEIQARSSAGTPARAYLDIPNPRYLGPAISSGAIYLASSYQDKLRVICCKGNLVKESGTEHHRGPSTSRS SPNKRGPPTYNEHITKRVASSPAPPEGPSHPREPSTPHRYREGRTELRRDKSPGRPLEREKSPGRMLSTRRERSPGRLFEDSSRGRLPAG	1368_APPL2_CIT

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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

APPL2_CIT does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/31_APPL2_CIT.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.

31_APPL2_CIT.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

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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.

31_APPL2_CIT_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 APPL2_CIT

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
CIT	O14578	human	GLI2	P10070	S149	IsAArGLsPADVAQE
CIT	O14578	human	MYL9	P24844	T19	KKRPQRAtsNVFAMF
CIT	O14578	human	MYL9	P24844	S20	KRPQRAtsNVFAMFD

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
CIT	ID	Description	0.00e+00
CIT	GO:0033089	positive regulation of T cell differentiation in thymus	2.55e-02
CIT	GO:0033504	floor plate development	2.55e-02
CIT	GO:0060579	ventral spinal cord interneuron fate commitment	2.55e-02
CIT	GO:0060581	cell fate commitment involved in pattern specification	2.55e-02
CIT	GO:0021514	ventral spinal cord interneuron differentiation	2.55e-02
CIT	GO:0002076	osteoblast development	2.55e-02
CIT	GO:0021513	spinal cord dorsal/ventral patterning	2.55e-02
CIT	GO:0021511	spinal cord patterning	2.55e-02
CIT	GO:0033081	regulation of T cell differentiation in thymus	2.55e-02
CIT	GO:0021952	central nervous system projection neuron axonogenesis	2.55e-02
CIT	GO:0031069	hair follicle morphogenesis	2.55e-02
CIT	GO:0048566	embryonic digestive tract development	2.55e-02
CIT	GO:0009954	proximal/distal pattern formation	2.55e-02
CIT	GO:0048665	neuron fate specification	2.55e-02
CIT	GO:0021696	cerebellar cortex morphogenesis	2.55e-02
CIT	GO:0048730	epidermis morphogenesis	2.55e-02
CIT	GO:0045740	positive regulation of DNA replication	2.55e-02
CIT	GO:0021955	central nervous system neuron axonogenesis	2.55e-02
CIT	GO:0021983	pituitary gland development	2.55e-02
CIT	GO:0021587	cerebellum morphogenesis	2.55e-02
CIT	GO:0021517	ventral spinal cord development	2.55e-02
CIT	GO:0021575	hindbrain morphogenesis	2.55e-02
CIT	GO:0048546	digestive tract morphogenesis	2.55e-02
CIT	GO:0021515	cell differentiation in spinal cord	2.55e-02
CIT	GO:0021695	cerebellar cortex development	2.55e-02
CIT	GO:0030239	myofibril assembly	3.14e-02
CIT	GO:0070527	platelet aggregation	3.14e-02
CIT	GO:0048663	neuron fate commitment	3.14e-02
CIT	GO:0055002	striated muscle cell development	3.14e-02
CIT	GO:0021536	diencephalon development	3.15e-02
CIT	GO:0033077	T cell differentiation in thymus	3.15e-02
CIT	GO:0021954	central nervous system neuron development	3.15e-02
CIT	GO:0001942	hair follicle development	3.15e-02
CIT	GO:0042475	odontogenesis of dentin-containing tooth	3.15e-02
CIT	GO:0022404	molting cycle process	3.15e-02
CIT	GO:0022405	hair cycle process	3.15e-02
CIT	GO:0034109	homotypic cell-cell adhesion	3.15e-02
CIT	GO:0009953	dorsal/ventral pattern formation	3.15e-02
CIT	GO:0021510	spinal cord development	3.15e-02
CIT	GO:0021549	cerebellum development	3.15e-02
CIT	GO:0001708	cell fate specification	3.15e-02
CIT	GO:0022037	metencephalon development	3.15e-02
CIT	GO:0045582	positive regulation of T cell differentiation	3.15e-02
CIT	GO:0042303	molting cycle	3.15e-02
CIT	GO:0042633	hair cycle	3.15e-02
CIT	GO:0006275	regulation of DNA replication	3.15e-02
CIT	GO:0010927	cellular component assembly involved in morphogenesis	3.15e-02
CIT	GO:0098773	skin epidermis development	3.15e-02
CIT	GO:0045621	positive regulation of lymphocyte differentiation	3.15e-02

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Related Drugs to APPL2_CIT

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 APPL2-CIT 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 APPL2_CIT

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