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Center for Computational Systems Medicine
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Kinase Fusion Gene Summary

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Kinase Fusion Gene Sample Information

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Kinase Fusion ORF Analysis

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Kinase Fusion Amino Acid Sequences

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Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase Fusion Protein Functional Features

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Kinase Fusion Protein Structures

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Comparison of Fusion Protein Isoforms

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

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

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Ramachandran Plot of Kinase Fusion Protein Structure

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Potential Active Site Information

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Virtual Screening Results

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Kinase-Substrate Information

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Related Drugs with This Kinase Fusion Protein

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Related Disease with This Kinase Fusion Protein

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Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:PLAUR_MARK4

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: PLAUR_MARK4
KinaseFusionDB ID: KFG4724
FusionGDB2.0 ID: KFG4724
HgeneTgene
Gene symbol

PLAUR

MARK4

Gene ID

5329

57787

Gene nameplasminogen activator, urokinase receptormicrotubule affinity regulating kinase 4
SynonymsCD87|U-PAR|UPAR|URKRMARK4L|MARK4S|MARKL1|MARKL1L|PAR-1D
Cytomap

19q13.31

19q13.32

Type of geneprotein-codingprotein-coding
Descriptionurokinase plasminogen activator surface receptormonocyte activation antigen Mo3u-plasminogen activator receptor form 2urokinase-type plasminogen activator (uPA) receptorMAP/microtubule affinity-regulating kinase 4MAP/microtubule affinity-regulating kinase like 1MARK4 serine/threonine protein kinaseepididymis secretory sperm binding protein
Modification date2024040320240305
UniProtAcc

Q03405

Q96L34

Ensembl transtripts involved in fusion geneENST idsENST00000221264, ENST00000339082, 
ENST00000340093, ENST00000601723, 
ENST00000262891, ENST00000300843, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: PLAUR [Title/Abstract] AND MARK4 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PLAUR(44174218)-MARK4(45762247), # 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
HgenePLAUR

GO:0030155

regulation of cell adhesion

10722842

HgenePLAUR

GO:0043388

positive regulation of DNA binding

22984561

TgeneMARK4

GO:0007399

nervous system development

14594945

TgeneMARK4

GO:0045787

positive regulation of cell cycle

26882547

TgeneMARK4

GO:1900227

positive regulation of NLRP3 inflammasome complex assembly

28656979


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

check buttonKinase Fusion gene breakpoints across MARK4 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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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
ChimerDB4TCGA-AB-3007-03APLAURchr19

44174218

MARK4chr19

45762247



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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)
ENST00000339082ENST00000262891PLAURchr1944174218MARK4chr19457622473292732

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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

>ENST00000339082_ENST00000262891_PLAUR_chr19_44174218_MARK4_chr19_45762247_length(amino acids)=732
MGSGRSSDKGPSWSSRSLGARCRNSIASCPEEQPHVGNYRLLRTIGKGNFAKVKLARHILTGREVAIKIIDKTQLNPSSLQKLFREVRIM
KGLNHPNIVKLFEVIETEKTLYLVMEYASAGEVFDYLVSHGRMKEKEARAKFRQIVSAVHYCHQKNIVHRDLKAENLLLDAEANIKIADF
GFSNEFTLGSKLDTFCGSPPYAAPELFQGKKYDGPEVDIWSLGVILYTLVSGSLPFDGHNLKELRERVLRGKYRVPFYMSTDCESILRRF
LVLNPAKRCTLEQIMKDKWINIGYEGEELKPYTEPEEDFGDTKRIEVMVGMGYTREEIKESLTSQKYNEVTATYLLLGRKTEEGGDRGAP
GLALARVRAPSDTTNGTSSSKGTSHSKGQRSSSSTYHRQRRHSDFCGPSPAPLHPKRSPTSTGEAELKEERLPGRKASCSTAGSGSRGLP
PSSPMVSSAHNPNKAEIPERRKDSTSTPNNLPPSMMTRRNTYVCTERPGAERPSLLPNGKENSSGTPRVPPASPSSHSLAPPSGERSRLA
RGSTIRSTFHGGQVRDRRAGGGGGGGVQNGPPASPTLAHEAAPLPAGRPRPTTNLFTKLTSKLTRRVADEPERIGGPEVTSCHLPWDQTE
TAPRLLRFPWSVKLTSSRPPEALMAALRQATAAARCRCRQPQPFLLACLHGGAGGPEPLSHFEVEVCQLPRPGLRGVLFRRVAGTALAFR

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Multiple Sequence Alignment of All Fusion Protein Isoforms



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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/chr19:44174218/chr19:45762247)
- 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
PLAUR

Q03405

MARK4

Q96L34

FUNCTION: Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.FUNCTION: Serine/threonine-protein kinase (PubMed:15009667, PubMed:14594945, PubMed:23666762, PubMed:23184942). Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:14594945, PubMed:23666762). Also phosphorylates the microtubule-associated proteins MAP2 and MAP4 (PubMed:14594945). Involved in regulation of the microtubule network, causing reorganization of microtubules into bundles (PubMed:14594945, PubMed:25123532). Required for the initiation of axoneme extension during cilium assembly (PubMed:23400999). Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in vitro (PubMed:23400999). Plays a role in cell cycle progression, specifically in the G1/S checkpoint (PubMed:25123532). Reduces neuronal cell survival (PubMed:15009667). Plays a role in energy homeostasis by regulating satiety and metabolic rate (By similarity). Promotes adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway (By similarity). Phosphorylates mTORC1 complex member RPTOR and acts as a negative regulator of the mTORC1 complex, probably due to disruption of the interaction between phosphorylated RPTOR and the RRAGA/RRAGC heterodimer which is required for mTORC1 activation (PubMed:23184942). Involved in NLRP3 positioning along microtubules by mediating NLRP3 recruitment to microtubule organizing center (MTOC) upon inflammasome activation (PubMed:28656979). {ECO:0000250|UniProtKB:Q8CIP4, ECO:0000269|PubMed:14594945, ECO:0000269|PubMed:15009667, ECO:0000269|PubMed:23184942, ECO:0000269|PubMed:23400999, ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:25123532, ECO:0000269|PubMed:28656979}.

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
TgenePLAUR44174218MARK445762247ENST00000339082017703_75217753DomainNote=KA1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00565
TgenePLAUR44174218MARK445762247ENST00000339082018703_75217689DomainNote=KA1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00565
TgenePLAUR44174218MARK445762247ENST0000033908201759_31017753DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgenePLAUR44174218MARK445762247ENST0000033908201859_31017689DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgenePLAUR44174218MARK445762247ENST00000339082017324_36817753DomainNote=UBA;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00212
TgenePLAUR44174218MARK445762247ENST00000339082018324_36817689DomainNote=UBA;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00212


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Kinase Fusion Protein Structures

check button 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)HenstTenstHgeneHchrHbpTgeneTchrTbpAA seqLen(AA seq)
PDB file >>>376_PLAUR_MARK4ENST00000339082ENST00000262891PLAURchr1944174218MARK4chr1945762247
MGSGRSSDKGPSWSSRSLGARCRNSIASCPEEQPHVGNYRLLRTIGKGNFAKVKLARHILTGREVAIKIIDKTQLNPSSLQKLFREVRIM
KGLNHPNIVKLFEVIETEKTLYLVMEYASAGEVFDYLVSHGRMKEKEARAKFRQIVSAVHYCHQKNIVHRDLKAENLLLDAEANIKIADF
GFSNEFTLGSKLDTFCGSPPYAAPELFQGKKYDGPEVDIWSLGVILYTLVSGSLPFDGHNLKELRERVLRGKYRVPFYMSTDCESILRRF
LVLNPAKRCTLEQIMKDKWINIGYEGEELKPYTEPEEDFGDTKRIEVMVGMGYTREEIKESLTSQKYNEVTATYLLLGRKTEEGGDRGAP
GLALARVRAPSDTTNGTSSSKGTSHSKGQRSSSSTYHRQRRHSDFCGPSPAPLHPKRSPTSTGEAELKEERLPGRKASCSTAGSGSRGLP
PSSPMVSSAHNPNKAEIPERRKDSTSTPNNLPPSMMTRRNTYVCTERPGAERPSLLPNGKENSSGTPRVPPASPSSHSLAPPSGERSRLA
RGSTIRSTFHGGQVRDRRAGGGGGGGVQNGPPASPTLAHEAAPLPAGRPRPTTNLFTKLTSKLTRRVADEPERIGGPEVTSCHLPWDQTE
TAPRLLRFPWSVKLTSSRPPEALMAALRQATAAARCRCRQPQPFLLACLHGGAGGPEPLSHFEVEVCQLPRPGLRGVLFRRVAGTALAFR
732
3D view using mol* of 376_PLAUR_MARK4
PDB file >>>TKFP_648_PLAUR_MARK4ENST00000339082ENST00000262891PLAURchr1944174218MARK4chr1945762247
MGSGRSSDKGPSWSSRSLGARCRNSIASCPEEQPHVGNYRLLRTIGKGNFAKVKLARHILTGREVAIKIIDKTQLNPSSLQKLFREVRIM
KGLNHPNIVKLFEVIETEKTLYLVMEYASAGEVFDYLVSHGRMKEKEARAKFRQIVSAVHYCHQKNIVHRDLKAENLLLDAEANIKIADF
GFSNEFTLGSKLDTFCGSPPYAAPELFQGKKYDGPEVDIWSLGVILYTLVSGSLPFDGHNLKELRERVLRGKYRVPFYMSTDCESILRRF
LVLNPAKRCTLEQIMKDKWINIGYEGEELKPYTEPEEDFGDTKRIEVMVGMGYTREEIKESLTSQKYNEVTATYLLLGRKTEEGGDRGAP
GLALARVRAPSDTTNGTSSSKGTSHSKGQRSSSSTYHRQRRHSDFCGPSPAPLHPKRSPTSTGEAELKEERLPGRKASCSTAGSGSRGLP
PSSPMVSSAHNPNKAEIPERRKDSTSTPNNLPPSMMTRRNTYVCTERPGAERPSLLPNGKENSSGTPRVPPASPSSHSLAPPSGERSRLA
RGSTIRSTFHGGQVRDRRAGGGGGGGVQNGPPASPTLAHEAAPLPAGRPRPTTNLFTKLTSKLTRRVADEPERIGGPEVTSCHLPWDQTE
TAPRLLRFPWSVKLTSSRPPEALMAALRQATAAARCRCRQPQPFLLACLHGGAGGPEPLSHFEVEVCQLPRPGLRGVLFRRVAGTALAFR
732_PLAUR_MARK4


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Comparison of Fusion Protein Isoforms

check button Superimpose the 3D Structures Among All Fusion Protein Isoforms
* Download the pdb file and open it from the molstar online viewer.

check button 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

PLAUR_MARK4 does not have any known PDB structures.

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pLDDT score distribution

check button 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.


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Potential Active Site Information


check button The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.
Kinase Fusion AA seq ID in KinaseFusionDBSite scoreSizeDscoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues

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Ramachandran Plot of Kinase Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.


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Virtual Screening Results


check button 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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check button 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 infoDrugDocking scoreGlide g scoreGlide energy

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Kinase-Substrate Information of PLAUR_MARK4


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
MARK4Q96L34humanTNK1Q13470S502RMKGIsRsLEsVLsL


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
MARK4IDDescription0.00e+00
MARK4GO:0046777protein autophosphorylation1.05e-02

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Related Drugs to PLAUR_MARK4


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 PLAUR-MARK4 and kinase inhibitors the PubMed Abstract (04-01-2024)

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

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Related Diseases to PLAUR_MARK4


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


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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