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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:JAK2_UHRF2

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: JAK2_UHRF2
	KinaseFusionDB ID: KFG2957
	FusionGDB2.0 ID: KFG2957
		Hgene	Tgene
	Gene symbol	JAK2	UHRF2
	Gene ID	3717	115426
	Gene name	Janus kinase 2	ubiquitin like with PHD and ring finger domains 2
	Synonyms	JTK10	NIRF\|RNF107\|TDRD23\|URF2
	Cytomap	9p24.1	9p24.1
	Type of gene	protein-coding	protein-coding
	Description	tyrosine-protein kinase JAK2JAK-2Janus kinase 2 (a protein tyrosine kinase)	E3 ubiquitin-protein ligase UHRF2Np95-like ring finger proteinRING finger protein 107RING-type E3 ubiquitin transferase UHRF2np95/ICBP90-like RING finger proteinnuclear protein 97nuclear zinc finger protein NP97ubiquitin-like PHD and RING finger do
	Modification date	20240411	20240411
	UniProtAcc	O60674	Q96PU4
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000539801, ENST00000381652, ENST00000544510, ENST00000487310,	ENST00000276893, ENST00000381373, ENST00000485617,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: JAK2 [Title/Abstract] AND UHRF2 [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	JAK2	GO:0007259	cell surface receptor signaling pathway via JAK-STAT	18692472\|31145836
Hgene	JAK2	GO:0010572	positive regulation of platelet activation	31145836
Hgene	JAK2	GO:0010811	positive regulation of cell-substrate adhesion	10925297
Hgene	JAK2	GO:0019221	cytokine-mediated signaling pathway	8609418
Hgene	JAK2	GO:0032729	positive regulation of type II interferon production	12023369\|19088061
Hgene	JAK2	GO:0032819	positive regulation of natural killer cell proliferation	19088061
Hgene	JAK2	GO:0033209	tumor necrosis factor-mediated signaling pathway	8609418
Hgene	JAK2	GO:0034612	response to tumor necrosis factor	8609418
Hgene	JAK2	GO:0035722	interleukin-12-mediated signaling pathway	7528775
Hgene	JAK2	GO:0038043	interleukin-5-mediated signaling pathway	7613138
Hgene	JAK2	GO:0038156	interleukin-3-mediated signaling pathway	8007942
Hgene	JAK2	GO:0038157	granulocyte-macrophage colony-stimulating factor signaling pathway	18692472
Hgene	JAK2	GO:0042102	positive regulation of T cell proliferation	11114383
Hgene	JAK2	GO:0043687	post-translational protein modification	19783980
Hgene	JAK2	GO:0046427	positive regulation of receptor signaling pathway via JAK-STAT	7638186\|12023369
Hgene	JAK2	GO:0046677	response to antibiotic	16280321
Hgene	JAK2	GO:0050727	regulation of inflammatory response	10925297
Hgene	JAK2	GO:0051142	positive regulation of NK T cell proliferation	19088061
Hgene	JAK2	GO:0060396	growth hormone receptor signaling pathway	10925297
Hgene	JAK2	GO:0070665	positive regulation of leukocyte proliferation	18692472
Hgene	JAK2	GO:0070671	response to interleukin-12	7528775
Hgene	JAK2	GO:1901731	positive regulation of platelet aggregation	31145836
Tgene	UHRF2	GO:0016567	protein ubiquitination	14741369
Tgene	UHRF2	GO:0051726	regulation of cell cycle	15178429
Tgene	UHRF2	GO:0051865	protein autoubiquitination	14741369

Kinase Fusion gene breakpoints across JAK2 (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 UHRF2 (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	SUM-229PE	JAK2	chr9	5090911	UHRF2	chr9	6475391

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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)
ENST00000539801	ENST00000276893	JAK2	chr9	5090911	UHRF2	chr9	6475391	5593	1534

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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

>ENST00000539801_ENST00000276893_JAK2_chr9_5090911_UHRF2_chr9_6475391_length(amino acids)=1534
MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKSEADYLTFPSGEYVAEEICIAASKACGITPVYHNMFALMSE
TERIWYPPNHVFHIDESTRHNVLYRIRFYFPRWYCSGSNRAYRHGISRGAEAPLLDDFVMSYLFAQWRHDFVHGWIKVPVTHETQEECLG
MAVLDMMRIAKENDQTPLAIYNSISYKTFLPKCIRAKIQDYHILTRKRIRYRFRRFIQQFSQCKATARNLKLKYLINLETLQSAFYTEKF
EVKEPGSGPSGEEIFATIIITGNGGIQWSRGKHKESETLTEQDLQLYCDFPNIIDVSIKQANQEGSNESRVVTIHKQDGKNLEIELSSLR
EALSFVSLIDGYYRLTADAHHYLCKEVAPPAVLENIQSNCHGPISMDFAISKLKKAGNQTGLYVLRCSPKDFNKYFLTFAVERENVIEYK
HCLITKNENEEYNLSGTKKNFSSLKDLLNCYQMETVRSDNIIFQFTKCCPPKPKDKSNLLVFRTNGVSDVPTSPTLQRPTHMNQMVFHKI
RNEDLIFNESLGQGTFTKIFKGVRREVGDYGQLHETEVLLKVLDKAHRNYSESFFEAASMMSKLSHKHLVLNYGVCVCGDENILVQEFVK
FGSLDTYLKKNKNCINILWKLEVAKQLAWAMHFLEENTLIHGNVCAKNILLIREEDRKTGNPPFIKLSDPGISITVLPKDILQERIPWVP
PECIENPKNLNLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPKWAELANLINNCMDYEPDFRPSFRAIIRDLNSLFT
PDYELLTENDMLPNMRIGALGFSGAFEDRDPTQFEERHLKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHLRDFEREIE
ILKSLQHDNIVKYKGVCYSAGRRNLKLIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRV
KIGDFGLTKVLPQDKEYYKVKEPGESPIFWGSEGTLNDCKIISVDEIFKIERPGAHPLSFADGKFLRRNDPECDLCGGDPEKKCHSCSCR
VCGGKHEPNMQLLCDECNVAYHIYCLNPPLDKVPEEEYWYCPSCKTDSSEVVKAGERLKMSKKKAKMPSASTESRRDWGRGMACVGRTRE
CTIVPSNHYGPIPGIPVGSTWRFRVQVSEAGVHRPHVGGIHGRSNDGAYSLVLAGGFADEVDRGDEFTYTGSGGKNLAGNKRIGAPSADQ
TLTNMNRALALNCDAPLDDKIGAESRNWRAGKPVRVIRSFKGRKISKYAPEEGNRYDGIYKVVKYWPEISSSHGFLVWRYLLRRDDVEPA
PWTSEGIERSRRLCLRLQYPAGYPSDKEGKKPKGQSKKQPSGTTKRPISDDDCPSASKVYKASDSAEAIEAFQLTPQQQHLIREDCQNQK
LWDEVLSHLVEGPNFLKKLEQSFMCVCCQELVYQPVTTECFHNVCKDCLQRSFKAQVFSCPACRHDLGQNYIMIPNEILQTLLDLFFPGY

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

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/chr9:/chr9:)
- 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
JAK2 O60674	UHRF2 Q96PU4
FUNCTION: Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins (PubMed:7615558). Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:9618263). Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin (PubMed:19783980). {ECO:0000269\|PubMed:12023369, ECO:0000269\|PubMed:19783980, ECO:0000269\|PubMed:20098430, ECO:0000269\|PubMed:21368206, ECO:0000269\|PubMed:21423214, ECO:0000269\|PubMed:7615558, ECO:0000269\|PubMed:9618263}.	FUNCTION: E3 ubiquitin ligase that plays important roles in DNA methylation, histone modifications, cell cycle and DNA repair (PubMed:15178429, PubMed:29506131, PubMed:27743347, PubMed:23404503). Acts as a specific reader for 5-hydroxymethylcytosine (5hmC) and thereby recruits various substrates to these sites to ubiquitinate them (PubMed:27129234, PubMed:24813944). This activity also allows the maintenance of 5mC levels at specific genomic loci and regulates neuron-related gene expression (By similarity). Participates in cell cycle regulation by ubiquitinating cyclins CCND1 and CCNE1 and thereby inducing G1 arrest (PubMed:15178429, PubMed:15361834, PubMed:21952639). Ubiquitinates also PCNP leading to its degradation by the proteasome (PubMed:14741369, PubMed:12176013). Plays an active role in DNA damage repair by ubiquitinating p21/CDKN1A leading to its proteasomal degradation (PubMed:29923055). Promotes also DNA repair by acting as an interstrand cross-links (ICLs) sensor. Mechanistically, cooperates with UHRF1 to ensure recruitment of FANCD2 to ICLs, leading to FANCD2 monoubiquitination and subsequent activation (PubMed:30335751). Contributes to UV-induced DNA damage response by physically interacting with ATR in response to irradiation, thereby promoting ATR activation (PubMed:33848395). {ECO:0000250\|UniProtKB:Q7TMI3, ECO:0000269\|PubMed:12176013, ECO:0000269\|PubMed:14741369, ECO:0000269\|PubMed:15178429, ECO:0000269\|PubMed:15361834, ECO:0000269\|PubMed:21952639, ECO:0000269\|PubMed:23404503, ECO:0000269\|PubMed:24813944, ECO:0000269\|PubMed:27129234, ECO:0000269\|PubMed:27743347, ECO:0000269\|PubMed:29506131, ECO:0000269\|PubMed:29923055, ECO:0000269\|PubMed:30335751, ECO:0000269\|PubMed:33848395}.

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).

101910191019101910191019

Partner

Hgeneene

Hbp

Tgeneene

Tbp

ENST

BPexon

TotalExon

Protein feature loci

BPloci

TotalLen

Feature

Note

Hgene

JAK2

5090911

UHRF2

6475391

ENST00000539801

37_380

1133

Domain

Note=FERM;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00084

Hgene

JAK2

5090911

UHRF2

6475391

ENST00000539801

37_380

1133

Domain

Note=FERM;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00084

Hgene

JAK2

5090911

UHRF2

6475391

ENST00000539801

545_809

1133

Domain

Note=Protein kinase 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159

Hgene

JAK2

5090911

UHRF2

6475391

ENST00000539801

545_809

1133

Domain

Note=Protein kinase 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159

Hgene

JAK2

5090911

UHRF2

6475391

ENST00000539801

401_482

1133

Domain

Note=SH2%3B atypical;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00191

Hgene

JAK2

5090911

UHRF2

6475391

ENST00000539801

401_482

1133

Domain

Note=SH2%3B atypical;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00191

- 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 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 >>>141_JAK2_UHRF2	ENST00000539801	ENST00000276893	JAK2	chr9	5090911	UHRF2	chr9	6475391	MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKSEADYLTFPSGEYVAEEICIAASKACGITPVYHNMFALMSE TERIWYPPNHVFHIDESTRHNVLYRIRFYFPRWYCSGSNRAYRHGISRGAEAPLLDDFVMSYLFAQWRHDFVHGWIKVPVTHETQEECLG MAVLDMMRIAKENDQTPLAIYNSISYKTFLPKCIRAKIQDYHILTRKRIRYRFRRFIQQFSQCKATARNLKLKYLINLETLQSAFYTEKF EVKEPGSGPSGEEIFATIIITGNGGIQWSRGKHKESETLTEQDLQLYCDFPNIIDVSIKQANQEGSNESRVVTIHKQDGKNLEIELSSLR EALSFVSLIDGYYRLTADAHHYLCKEVAPPAVLENIQSNCHGPISMDFAISKLKKAGNQTGLYVLRCSPKDFNKYFLTFAVERENVIEYK HCLITKNENEEYNLSGTKKNFSSLKDLLNCYQMETVRSDNIIFQFTKCCPPKPKDKSNLLVFRTNGVSDVPTSPTLQRPTHMNQMVFHKI RNEDLIFNESLGQGTFTKIFKGVRREVGDYGQLHETEVLLKVLDKAHRNYSESFFEAASMMSKLSHKHLVLNYGVCVCGDENILVQEFVK FGSLDTYLKKNKNCINILWKLEVAKQLAWAMHFLEENTLIHGNVCAKNILLIREEDRKTGNPPFIKLSDPGISITVLPKDILQERIPWVP PECIENPKNLNLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPKWAELANLINNCMDYEPDFRPSFRAIIRDLNSLFT PDYELLTENDMLPNMRIGALGFSGAFEDRDPTQFEERHLKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHLRDFEREIE ILKSLQHDNIVKYKGVCYSAGRRNLKLIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRV KIGDFGLTKVLPQDKEYYKVKEPGESPIFWGSEGTLNDCKIISVDEIFKIERPGAHPLSFADGKFLRRNDPECDLCGGDPEKKCHSCSCR VCGGKHEPNMQLLCDECNVAYHIYCLNPPLDKVPEEEYWYCPSCKTDSSEVVKAGERLKMSKKKAKMPSASTESRRDWGRGMACVGRTRE CTIVPSNHYGPIPGIPVGSTWRFRVQVSEAGVHRPHVGGIHGRSNDGAYSLVLAGGFADEVDRGDEFTYTGSGGKNLAGNKRIGAPSADQ TLTNMNRALALNCDAPLDDKIGAESRNWRAGKPVRVIRSFKGRKISKYAPEEGNRYDGIYKVVKYWPEISSSHGFLVWRYLLRRDDVEPA PWTSEGIERSRRLCLRLQYPAGYPSDKEGKKPKGQSKKQPSGTTKRPISDDDCPSASKVYKASDSAEAIEAFQLTPQQQHLIREDCQNQK LWDEVLSHLVEGPNFLKKLEQSFMCVCCQELVYQPVTTECFHNVCKDCLQRSFKAQVFSCPACRHDLGQNYIMIPNEILQTLLDLFFPGY	1534
3D view using mol* of 141_JAK2_UHRF2

PDB file >>>HKFP_211_JAK2_UHRF2	ENST00000539801	ENST00000276893	JAK2	chr9	5090911	UHRF2	chr9	6475391	MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKSEADYLTFPSGEYVAEEICIAASKACGITPVYHNMFALMSE TERIWYPPNHVFHIDESTRHNVLYRIRFYFPRWYCSGSNRAYRHGISRGAEAPLLDDFVMSYLFAQWRHDFVHGWIKVPVTHETQEECLG MAVLDMMRIAKENDQTPLAIYNSISYKTFLPKCIRAKIQDYHILTRKRIRYRFRRFIQQFSQCKATARNLKLKYLINLETLQSAFYTEKF EVKEPGSGPSGEEIFATIIITGNGGIQWSRGKHKESETLTEQDLQLYCDFPNIIDVSIKQANQEGSNESRVVTIHKQDGKNLEIELSSLR EALSFVSLIDGYYRLTADAHHYLCKEVAPPAVLENIQSNCHGPISMDFAISKLKKAGNQTGLYVLRCSPKDFNKYFLTFAVERENVIEYK HCLITKNENEEYNLSGTKKNFSSLKDLLNCYQMETVRSDNIIFQFTKCCPPKPKDKSNLLVFRTNGVSDVPTSPTLQRPTHMNQMVFHKI RNEDLIFNESLGQGTFTKIFKGVRREVGDYGQLHETEVLLKVLDKAHRNYSESFFEAASMMSKLSHKHLVLNYGVCVCGDENILVQEFVK FGSLDTYLKKNKNCINILWKLEVAKQLAWAMHFLEENTLIHGNVCAKNILLIREEDRKTGNPPFIKLSDPGISITVLPKDILQERIPWVP PECIENPKNLNLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPKWAELANLINNCMDYEPDFRPSFRAIIRDLNSLFT PDYELLTENDMLPNMRIGALGFSGAFEDRDPTQFEERHLKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHLRDFEREIE ILKSLQHDNIVKYKGVCYSAGRRNLKLIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRV KIGDFGLTKVLPQDKEYYKVKEPGESPIFWGSEGTLNDCKIISVDEIFKIERPGAHPLSFADGKFLRRNDPECDLCGGDPEKKCHSCSCR VCGGKHEPNMQLLCDECNVAYHIYCLNPPLDKVPEEEYWYCPSCKTDSSEVVKAGERLKMSKKKAKMPSASTESRRDWGRGMACVGRTRE CTIVPSNHYGPIPGIPVGSTWRFRVQVSEAGVHRPHVGGIHGRSNDGAYSLVLAGGFADEVDRGDEFTYTGSGGKNLAGNKRIGAPSADQ TLTNMNRALALNCDAPLDDKIGAESRNWRAGKPVRVIRSFKGRKISKYAPEEGNRYDGIYKVVKYWPEISSSHGFLVWRYLLRRDDVEPA PWTSEGIERSRRLCLRLQYPAGYPSDKEGKKPKGQSKKQPSGTTKRPISDDDCPSASKVYKASDSAEAIEAFQLTPQQQHLIREDCQNQK LWDEVLSHLVEGPNFLKKLEQSFMCVCCQELVYQPVTTECFHNVCKDCLQRSFKAQVFSCPACRHDLGQNYIMIPNEILQTLLDLFFPGY	1534_JAK2_UHRF2

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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

JAK2_UHRF2 does not have any known PDB structures.

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pLDDT score distribution

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.

141_JAK2_UHRF2.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.

141_JAK2_UHRF2_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
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Upadacitinib	-8.0127	-8.0137	-39.5488
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Afatinib	-7.8228100000000005	-8.00511	-55.1977
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Afatinib	-7.8228100000000005	-8.00511	-55.1977
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Afatinib	-7.82141	-8.00511	-55.1977
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Dasatinib	-7.38543	-7.88373	-55.5544
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Dasatinib	-7.38543	-7.88373	-55.5544
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Dasatinib	-7.38543	-7.88373	-55.5544
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Zanubrutinib	-7.25367	-7.25367	-37.085
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Axitinib	-7.1144	-7.1176	-48.6695
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Afatinib	-7.04506	-7.227360000000001	-39.2006
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Afatinib	-7.04506	-7.227360000000001	-39.2006
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Afatinib	-7.043660000000001	-7.227360000000001	-39.2006
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Fostamatinib	-6.9039600000000005	-6.967560000000001	-61.273999999999994
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Fostamatinib	-6.9039600000000005	-6.967560000000001	-61.273999999999994
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Infigratinib	-6.83126	-7.43076	-54.7712
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Infigratinib	-6.83126	-7.43076	-54.7712
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Infigratinib	-6.83126	-7.43076	-54.7712
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Netarsudil	-6.68544	-6.69654	-62.2634
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Netarsudil	-6.68544	-6.69654	-62.2634
141_JAK2_UHRF2_2-DOCK_HTVS_1-001	Afatinib	-6.68009	-7.582389999999999	-51.4828

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Kinase-Substrate Information of JAK2_UHRF2

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
JAK2	O60674	human	GTF2I	P78347-2	Y248	EESEDPDyyQyNIQG
JAK2	O60674	human	BECN1	Q14457	Y333	QRYRLVPyGNHsYLE	APG6
JAK2	O60674	human	PAK1	Q13153	Y285	QGASGTVyTAMDVAT	Pkinase
JAK2	O60674	human	PRMT5	O14744	Y307	FAKGyEDyLQsPLQP	PRMT5
JAK2	O60674	human	STAP2	Q9UGK3	Y250	PFLLDEDyEKVLGyV
JAK2	O60674	human	GRB2	P62993	Y209	TGMFPRNyVtPVNrN
JAK2	O60674	human	PRLR	P16471	S349	YLDPDTDsGRGSCDs
JAK2	O60674	human	EZH2	Q15910	Y641	kNEFISEyCGEIISQ	SET
JAK2	O60674	human	STAT5A	P42229	Y694	LAkAVDGyVkPQIkQ
JAK2	O60674	human	PPDPF	Q9H3Y8	Y17	LVATHDyyRRRLGst
JAK2	O60674	human	CCR2	P41597	Y139	ILLTIDRyLAIVHAV	7tm_1
JAK2	O60674	human	KDM3A	Q9Y4C1	Y1101	PDLGPKMyNAyGLIT
JAK2	O60674	human	BRD4	O60885	Y98	kLNLPDyykIIKtPM	Bromodomain
JAK2	O60674	human	JAK2	O60674	Y570	VRREVGDyGQLHETE	PK_Tyr_Ser-Thr
JAK2	O60674	human	PAK1	Q13153	Y153	tDksAEDyNssNALN
JAK2	O60674	human	GRB2	P62993	Y52	DGFIPkNyIEMkPHP
JAK2	O60674	human	SOCS3	O14543	Y221	IREFLDQyDAPL___
JAK2	O60674	human	STAT3	P40763	Y705	DPGsAAPyLktKFIC
JAK2	O60674	human	PRMT5	O14744	Y304	yELFAKGyEDyLQsP	PRMT5
JAK2	O60674	human	STAP2	Q9UGK3	Y22	GVLPSHYyESFLEKK	PH
JAK2	O60674	human	GAB2	Q9UQC2	Y643	tsDEKVDyVQVDKEK
JAK2	O60674	human	MAP3K5	Q99683	Y718	IPERDSRySQPLHEE	Pkinase
JAK2	O60674	human	ARHGEF1	Q92888	Y738	WDQEAQIyELVAQTV	PH_16
JAK2	O60674	human	H3C1	P68431	Y41	GVkkPHryrPGtVAL	Histone
JAK2	O60674	human	GRB2	P62993	Y37	EECDQNWykAELNGk	SH3_1
JAK2	O60674	human	GRB2	P62993	Y7	_MEAIAkyDFkATAD	SH3_1
JAK2	O60674	human	JAK2	O60674	S523	GVsDVPtsPTLQRPT
JAK2	O60674	human	PPDPF	Q9H3Y8	Y16	sLVATHDyyRRRLGs
JAK2	O60674	human	STAP2	Q9UGK3	Y322	GDGPAVDyENQDVAS
JAK2	O60674	human	TET2	Q6N021	Y1964	HETSEPTyLRFIKSL
JAK2	O60674	human	CHEK2	O96017	Y156	EVGPKNSyIAYIEDH	FHA
JAK2	O60674	human	PBK	Q96KB5	Y74	NPICNDHyRsVyQkR	Pkinase
JAK2	O60674	human	STAP2	Q9UGK3	Y310	LPNQEENyVTPIGDG
JAK2	O60674	human	PRMT5	O14744	Y297	NRPPPNAyELFAKGy	PRMT5
JAK2	O60674	human	MAPK1	P28482	Y187	HtGFLtEyVAtRWyr	Pkinase
JAK2	O60674	human	JAK2	O60674	Y119	VLYRIRFyFPRWYCS	FERM_F1
JAK2	O60674	human	PDHA1	P08559	Y301	MsDPGVsyRtREEIQ	E1_dh
JAK2	O60674	human	SOCS3	O14543	Y204	VNGHLDSyEkVTQLP
JAK2	O60674	human	PDK1	Q15118	Y243	ARRLCDLyyINSPEL
JAK2	O60674	human	BRD4	O60885	Y97	VkLNLPDyykIIKtP	Bromodomain
JAK2	O60674	human	MAPK3	P27361	Y204	HtGFLtEyVAtRWyr	Pkinase
JAK2	O60674	human	PAK1	Q13153	Y201	PEHtKsVyTRsVIEP
JAK2	O60674	human	TET2	Q6N021	Y1939	CEKYGPDyVPQKSHG
JAK2	O60674	human	STAT1	P42224	Y701	DGPkGtGyIktELIs

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
JAK2	ID	Description	0.00e+00
JAK2	GO:0007259	receptor signaling pathway via JAK-STAT	3.87e-06
JAK2	GO:0097696	receptor signaling pathway via STAT	3.87e-06
JAK2	GO:0071375	cellular response to peptide hormone stimulus	3.87e-06
JAK2	GO:1901653	cellular response to peptide	1.25e-05
JAK2	GO:0043434	response to peptide hormone	2.93e-05
JAK2	GO:0060397	growth hormone receptor signaling pathway via JAK-STAT	7.35e-05
JAK2	GO:0000302	response to reactive oxygen species	7.56e-05
JAK2	GO:0034198	cellular response to amino acid starvation	1.40e-04
JAK2	GO:1990928	response to amino acid starvation	1.57e-04
JAK2	GO:0006979	response to oxidative stress	1.59e-04
JAK2	GO:0051347	positive regulation of transferase activity	1.82e-04
JAK2	GO:0048732	gland development	2.58e-04
JAK2	GO:0034614	cellular response to reactive oxygen species	2.58e-04
JAK2	GO:0070665	positive regulation of leukocyte proliferation	3.46e-04
JAK2	GO:0001659	temperature homeostasis	5.21e-04
JAK2	GO:0060396	growth hormone receptor signaling pathway	5.21e-04
JAK2	GO:0071378	cellular response to growth hormone stimulus	5.32e-04
JAK2	GO:0042063	gliogenesis	5.32e-04
JAK2	GO:0009755	hormone-mediated signaling pathway	5.32e-04
JAK2	GO:0046777	protein autophosphorylation	5.87e-04
JAK2	GO:0030522	intracellular receptor signaling pathway	5.88e-04
JAK2	GO:0032869	cellular response to insulin stimulus	6.31e-04
JAK2	GO:0042542	response to hydrogen peroxide	7.28e-04
JAK2	GO:0120162	positive regulation of cold-induced thermogenesis	7.28e-04
JAK2	GO:0071356	cellular response to tumor necrosis factor	1.12e-03
JAK2	GO:0060416	response to growth hormone	1.16e-03
JAK2	GO:0048863	stem cell differentiation	1.21e-03
JAK2	GO:0050727	regulation of inflammatory response	1.25e-03
JAK2	GO:0030518	intracellular steroid hormone receptor signaling pathway	1.25e-03
JAK2	GO:0030099	myeloid cell differentiation	1.25e-03
JAK2	GO:0034599	cellular response to oxidative stress	1.25e-03
JAK2	GO:0008286	insulin receptor signaling pathway	1.27e-03
JAK2	GO:0034612	response to tumor necrosis factor	1.27e-03
JAK2	GO:0045022	early endosome to late endosome transport	1.35e-03
JAK2	GO:0070663	regulation of leukocyte proliferation	1.35e-03
JAK2	GO:0032868	response to insulin	1.35e-03
JAK2	GO:1905521	regulation of macrophage migration	1.35e-03
JAK2	GO:0030879	mammary gland development	1.35e-03
JAK2	GO:0060711	labyrinthine layer development	1.35e-03
JAK2	GO:0070849	response to epidermal growth factor	1.35e-03
JAK2	GO:0072538	T-helper 17 type immune response	1.40e-03
JAK2	GO:0043401	steroid hormone mediated signaling pathway	1.42e-03
JAK2	GO:0045860	positive regulation of protein kinase activity	1.46e-03
JAK2	GO:0098927	vesicle-mediated transport between endosomal compartments	1.48e-03
JAK2	GO:0048009	insulin-like growth factor receptor signaling pathway	1.73e-03
JAK2	GO:0120161	regulation of cold-induced thermogenesis	1.80e-03
JAK2	GO:0106106	cold-induced thermogenesis	1.81e-03
JAK2	GO:0048872	homeostasis of number of cells	2.23e-03
JAK2	GO:0062197	cellular response to chemical stress	2.23e-03

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Related Drugs to JAK2_UHRF2

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 JAK2-UHRF2 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 JAK2_UHRF2

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
Hgene	JAK2	C0032463	Polycythemia Vera	12	CTD_human;ORPHANET;UNIPROT
Hgene	JAK2	C0040028	Thrombocythemia, Essential	10	CTD_human;ORPHANET
Hgene	JAK2	C0001815	Primary Myelofibrosis	9	CGI;CTD_human;GENOMICS_ENGLAND;ORPHANET
Hgene	JAK2	C3489628	Thrombocytosis, Autosomal Dominant	8	CTD_human
Hgene	JAK2	C0019154	Hepatic Vein Thrombosis	3	CTD_human;ORPHANET
Hgene	JAK2	C0856761	Budd-Chiari Syndrome	3	CTD_human;ORPHANET
Hgene	JAK2	C0009324	Ulcerative Colitis	2	CTD_human
Hgene	JAK2	C0027022	Myeloproliferative disease	2	CTD_human
Hgene	JAK2	C0151744	Myocardial Ischemia	2	CTD_human
Hgene	JAK2	C0836924	Thrombocytosis	2	CTD_human
Hgene	JAK2	C3281125	THROMBOCYTHEMIA 3	2	UNIPROT

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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