UTHEALTH HOME    ABOUT SBMI    A-Z    WEBMAIL    INSIDE THE UNIVERSITY
FusionGDB Logo

Home

Download

Statistics

Examples

Help

Contact

Terms of Use
Center for Computational Systems Medicine
leaf

Kinase Fusion Gene Summary

leaf

Kinase Fusion Gene Sample Information

leaf

Kinase Fusion ORF Analysis

leaf

Kinase Fusion Amino Acid Sequences

leaf

Multiple Sequence Alignment of All Fusion Protein Isoforms

leaf

Kinase Fusion Protein Functional Features

leaf

Kinase Fusion Protein Structures

leaf

Comparison of Fusion Protein Isoforms

leaf

Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

leaf

pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.

leaf

Ramachandran Plot of Kinase Fusion Protein Structure

leaf

Potential Active Site Information

leaf

Virtual Screening Results

leaf

Kinase-Substrate Information

leaf

Related Drugs with This Kinase Fusion Protein

leaf

Related Disease with This Kinase Fusion Protein

leaf

Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:NEDD4L_TLK2

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: NEDD4L_TLK2
KinaseFusionDB ID: KFG4104
FusionGDB2.0 ID: KFG4104
HgeneTgene
Gene symbol

NEDD4L

TLK2

Gene ID

23327

11011

Gene nameNEDD4 like E3 ubiquitin protein ligasetousled like kinase 2
SynonymsNEDD4-2|NEDD4.2|PVNH7|RSP5|hNEDD4-2HsHPK|MRD57|PKU-ALPHA
Cytomap

18q21.31

17q23.2

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase NEDD4-likeHECT-type E3 ubiquitin transferase NED4Lneural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligaseubiquitin-protein ligase Rsp5serine/threonine-protein kinase tousled-like 2
Modification date2024041620240403
UniProtAcc

Q96PU5

Q86UE8

Ensembl transtripts involved in fusion geneENST idsENST00000256830, ENST00000256832, 
ENST00000356462, ENST00000357895, 
ENST00000382850, ENST00000400345, 
ENST00000431212, ENST00000435432, 
ENST00000456173, ENST00000456986, 
ENST00000586263, ENST00000588516, 
ENST00000589054, 		ENST00000326270, 
ENST00000343388, ENST00000346027, 
ENST00000542523, ENST00000577616, 
ENST00000582809, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: NEDD4L [Title/Abstract] AND TLK2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NEDD4L(55830140)-TLK2(60570256), # samples:1
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneNEDD4L

GO:0003254

regulation of membrane depolarization

15217910

HgeneNEDD4L

GO:0006511

ubiquitin-dependent protein catabolic process

21463633

HgeneNEDD4L

GO:0016567

protein ubiquitination

15217910|18577513|25631046

HgeneNEDD4L

GO:0034765

regulation of monoatomic ion transmembrane transport

17289006

HgeneNEDD4L

GO:0042391

regulation of membrane potential

17289006

HgeneNEDD4L

GO:0043161

proteasome-mediated ubiquitin-dependent protein catabolic process

21463633

HgeneNEDD4L

GO:0060306

regulation of membrane repolarization

21463633

HgeneNEDD4L

GO:0070936

protein K48-linked ubiquitination

21463633

HgeneNEDD4L

GO:1901016

regulation of potassium ion transmembrane transporter activity

17289006

HgeneNEDD4L

GO:1901017

negative regulation of potassium ion transmembrane transporter activity

21463633

HgeneNEDD4L

GO:1901380

negative regulation of potassium ion transmembrane transport

21463633

HgeneNEDD4L

GO:1902305

regulation of sodium ion transmembrane transport

11244092

HgeneNEDD4L

GO:1902306

negative regulation of sodium ion transmembrane transport

15217910

HgeneNEDD4L

GO:1903861

positive regulation of dendrite extension

23999003

HgeneNEDD4L

GO:2000009

negative regulation of protein localization to cell surface

21463633

HgeneNEDD4L

GO:2000650

negative regulation of sodium ion transmembrane transporter activity

15217910

TgeneTLK2

GO:0006468

protein phosphorylation

12660173

TgeneTLK2

GO:0006974

DNA damage response

12660173

TgeneTLK2

GO:0018105

peptidyl-serine phosphorylation

20016786

TgeneTLK2

GO:0035556

intracellular signal transduction

12660173

TgeneTLK2

GO:0071480

cellular response to gamma radiation

12660173

TgeneTLK2

GO:1902275

regulation of chromatin organization

12660173


check buttonKinase Fusion gene breakpoints across NEDD4L (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonKinase Fusion gene breakpoints across TLK2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.


Top

Kinase Fusion Gene Sample Information

check buttonKinase Fusion gene information.
check button 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.
SourceSampleHgeneHchrHbpTgeneTchrTbp
ChiTaRS5.0EC526608NEDD4Lchr18

55830140

TLK2chr17

60570256



Top

Kinase Fusion ORF Analysis


check buttonKinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)		Seq length
(amino acids)

Top

Kinase Fusion Amino Acid Sequences


check button 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



Top

Kinase Fusion Protein Functional Features


check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:55830140/:60570256)
- 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.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
NEDD4L

Q96PU5

TLK2

Q86UE8

FUNCTION: E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins and is thereby implicated in the regulation of various signaling pathways including autophagy, innate immunity or DNA repair (PubMed:31959741, PubMed:33608556, PubMed:20064473). Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation (PubMed:15496141). Downregulates autophagy and cell growth by ubiquitinating and reducing cellular ULK1 or ASCT2 levels (PubMed:28820317, PubMed:31959741). Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5 (PubMed:26363003, PubMed:27445338). Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Involved in the regulation of TOR signaling (PubMed:27694961). Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (PubMed:27445338). Plays a role in antiviral innate immunity by catalyzing 'Lys-29'-linked cysteine ubiquitination of TRAF3, resulting in enhanced 'Lys-48' and 'Lys-63'-linked ubiquitination of TRAF3 (PubMed:33608556). {ECO:0000250|UniProtKB:Q8CFI0, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15489223, ECO:0000269|PubMed:15496141, ECO:0000269|PubMed:15576372, ECO:0000269|PubMed:19144635, ECO:0000269|PubMed:23999003, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:26363003, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27694961, ECO:0000269|PubMed:33608556}.FUNCTION: Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation (PubMed:9427565, PubMed:10523312, PubMed:11470414, PubMed:12660173, PubMed:12955071, PubMed:29955062, PubMed:33323470). Phosphorylates the chromatin assembly factors ASF1A and ASF1B (PubMed:11470414, PubMed:20016786, PubMed:29955062, PubMed:35136069). Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly (PubMed:20016786). Negative regulator of amino acid starvation-induced autophagy (PubMed:22354037). {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:20016786, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:29955062, ECO:0000269|PubMed:33323470, ECO:0000269|PubMed:35136069, ECO:0000269|PubMed:9427565}.

check buttonRetention 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.

check button - Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


check button - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


Top

Kinase-Substrate Information of NEDD4L_TLK2


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
TLK2Q86UE8humanASF1BQ9NVP2S198PGLLPENsMDCI___
TLK2Q86UE8humanASF1AQ9Y294S192GWSTSENsLNVMLES


check button Biological Network Integration of This Kinase and Substrates
(GeneMANIA website)

check button Enriched GO biological processes of the phosphorylation target genes of the kinase
KinaseGOIDGO termP.adjust
TLK2IDDescription0.00e+00
TLK2GO:0006334nucleosome assembly4.25e-04
TLK2GO:0034728nucleosome organization4.25e-04
TLK2GO:0065004protein-DNA complex assembly8.59e-04
TLK2GO:0140861DNA repair-dependent chromatin remodeling6.29e-03
TLK2GO:0001835blastocyst hatching6.29e-03
TLK2GO:0035188hatching6.29e-03
TLK2GO:0071684organism emergence from protective structure6.29e-03
TLK2GO:0031297replication fork processing1.04e-02
TLK2GO:0045005DNA-templated DNA replication maintenance of fidelity1.05e-02
TLK2GO:0001824blastocyst development1.96e-02
TLK2GO:0006261DNA-templated DNA replication2.47e-02
TLK2GO:0001649osteoblast differentiation3.60e-02
TLK2GO:0006260DNA replication3.60e-02
TLK2GO:0001701in utero embryonic development4.65e-02
TLK2GO:0042692muscle cell differentiation4.65e-02
TLK2GO:0001503ossification4.65e-02

Top

Related Drugs to NEDD4L_TLK2


check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

check button Distribution of the number of studies mentioning NEDD4L-TLK2 and kinase inhibitors the PubMed Abstract (04-01-2024)

Fusion gene - drug pair 1Fusion gene - drug pair 2PMIDPublication dateDOIStudy title

Top

Related Diseases to NEDD4L_TLK2


check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Related diseases from the literature mentioned this fusion gene and drug.
(PubMed, 04-01-2024)
MeSH IDMeSH term

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource


Top

Clinical Trials of the Found Drugs/Small Molecules


check button Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024)

check button Clinical Trials from clinicaltrials.gov (06-17-2024)

Fusion GeneKinase InhibitorNCT IDStudy StatusPhasesDisease# EnrolmentDate