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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:MARK1_RHOU

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: MARK1_RHOU
KinaseFusionDB ID: KFG3621
FusionGDB2.0 ID: KFG3621
HgeneTgene
Gene symbol

MARK1

RHOU

Gene ID

4139

58480

Gene namemicrotubule affinity regulating kinase 1ras homolog family member U
SynonymsMARK|Par-1c|Par1cARHU|CDC42L1|G28K|WRCH1|hG28K
Cytomap

1q41

1q42.13

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase MARK1MAP/microtubule affinity-regulating kinase 1PAR1 homolog crho-related GTP-binding protein RhoU2310026M05RikCDC42-like GTPase 1GTP-binding protein SB128GTP-binding protein like 1Ryu GTPaseras homolog gene family, member Uras-like gene family member Urho GTPase-like protein ARHUwnt-1 responsive Cdc42 homo
Modification date2024040320240407
UniProtAcc

Q9P0L2

Q7L0Q8

Ensembl transtripts involved in fusion geneENST idsENST00000366917, ENST00000366918, 
ENST00000402574, ENST00000485104, 
ENST00000493528, ENST00000366691, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: MARK1 [Title/Abstract] AND RHOU [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MARK1(220826694)-RHOU(228873420), # samples:2
MARK1(220831176)-RHOU(228873420), # samples:2
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneMARK1

GO:0006468

protein phosphorylation

14976552

HgeneMARK1

GO:0010628

positive regulation of gene expression

31281935

HgeneMARK1

GO:0010629

negative regulation of gene expression

31281935

HgeneMARK1

GO:0010719

negative regulation of epithelial to mesenchymal transition

31281935

HgeneMARK1

GO:0035556

intracellular signal transduction

14976552


check buttonKinase Fusion gene breakpoints across MARK1 (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 RHOU (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-EE-A29D-06AMARK1chr1

220826694

RHOUchr1

228873420

ChimerDB4TCGA-EE-A29D-06AMARK1chr1

220826694

RHOUchr1

228879032

ChimerDB4TCGA-EE-A29D-06AMARK1chr1

220831176

RHOUchr1

228873420



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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)
ENST00000402574ENST00000366691MARK1chr1220826694RHOUchr12288790325970745

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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

>ENST00000402574_ENST00000366691_MARK1_chr1_220826694_RHOU_chr1_228879032_length(amino acids)=745
MSAYPGGAAAGSGSPSSSSASSSLFPPPGPLVAPPRGLREPLAPALCSRPHPFPVAPRGPHHSPAGETPARPRCPHKMSARTPLPTVNER
DTENHTSVDGYTEPHIQPTKSSSRQNIPRCRNSITSATDEQPHIGNYRLQKTIGKGNFAKVKLARHVLTGREVAVKIIDKTQLNPTSLQK
LFREVRIMKILNHPNIVKLFEVIETEKTLYLVMEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKYIVHRDLKAENLLLDGD
MNIKIADFGFSNEFTVGNKLDTFCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTD
CENLLKKLLVLNPIKRGSLEQIMKDRWMNVGHEEEELKPYTEPDPDFNDTKRIDIMVTMGFARDEINDALINQKYDEVMATYILLGRKPP
EFEGGESLSSGNLCQRSRPSSDLNNSTLQSPAHLKVQRSISANQKQRRFSDHAGPSIPPAVSYTKRPQANSVESEQKEEWDKDVARKLGS
TTVGSKSEMTASPLVGPERKKSSTIPSNNVYSGGSMARRNTYVCERTTDRYVALQNGKDSSLTEMSVSSISSAGSSVASAVPSARPRHQK
SMSTSGHPIKVTLPTIKDGSEAYRPGTTQRVPAASPSAHSISTATPDRTRFPRGSSSRSTFHGEQLRERRSVAYNGPPASPSHETGAFAH

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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/chr1:220826694/chr1:228873420)
- 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
MARK1

Q9P0L2

RHOU

Q7L0Q8

FUNCTION: Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:17573348, ECO:0000269|PubMed:23666762}.FUNCTION: Acts upstream of PAK1 to regulate the actin cytoskeleton, adhesion turnover and increase cell migration. Stimulates quiescent cells to reenter the cell cycle. Has no detectable GTPase activity but its high intrinsic guanine nucleotide exchange activity suggests it is constitutively GTP-bound. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape. {ECO:0000269|PubMed:11459829, ECO:0000269|PubMed:16472646, ECO:0000269|PubMed:17620058, ECO:0000269|PubMed:18086875, ECO:0000269|PubMed:21834987}.

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).
640527662640527662
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote
HgeneMARK1220826694RHOU228879032ENST00000402574151660_3111759DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
HgeneMARK1220826694RHOU228879032ENST00000402574161760_3111646DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
HgeneMARK1220826694RHOU228879032ENST00000402574161860_3111796DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
HgeneMARK1220826694RHOU228879032ENST000004025741516325_3701759DomainNote=UBA;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00212
HgeneMARK1220826694RHOU228879032ENST000004025741617325_3701646DomainNote=UBA;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00212
HgeneMARK1220826694RHOU228879032ENST000004025741618325_3701796DomainNote=UBA;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00212


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


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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 >>>163_MARK1_RHOUENST00000402574ENST00000366691MARK1chr1220826694RHOUchr1228879032
MSAYPGGAAAGSGSPSSSSASSSLFPPPGPLVAPPRGLREPLAPALCSRPHPFPVAPRGPHHSPAGETPARPRCPHKMSARTPLPTVNER
DTENHTSVDGYTEPHIQPTKSSSRQNIPRCRNSITSATDEQPHIGNYRLQKTIGKGNFAKVKLARHVLTGREVAVKIIDKTQLNPTSLQK
LFREVRIMKILNHPNIVKLFEVIETEKTLYLVMEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKYIVHRDLKAENLLLDGD
MNIKIADFGFSNEFTVGNKLDTFCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTD
CENLLKKLLVLNPIKRGSLEQIMKDRWMNVGHEEEELKPYTEPDPDFNDTKRIDIMVTMGFARDEINDALINQKYDEVMATYILLGRKPP
EFEGGESLSSGNLCQRSRPSSDLNNSTLQSPAHLKVQRSISANQKQRRFSDHAGPSIPPAVSYTKRPQANSVESEQKEEWDKDVARKLGS
TTVGSKSEMTASPLVGPERKKSSTIPSNNVYSGGSMARRNTYVCERTTDRYVALQNGKDSSLTEMSVSSISSAGSSVASAVPSARPRHQK
SMSTSGHPIKVTLPTIKDGSEAYRPGTTQRVPAASPSAHSISTATPDRTRFPRGSSSRSTFHGEQLRERRSVAYNGPPASPSHETGAFAH
745
3D view using mol* of 163_MARK1_RHOU
PDB file >>>HKFP_237_MARK1_RHOUENST00000402574ENST00000366691MARK1chr1220826694RHOUchr1228879032
MSAYPGGAAAGSGSPSSSSASSSLFPPPGPLVAPPRGLREPLAPALCSRPHPFPVAPRGPHHSPAGETPARPRCPHKMSARTPLPTVNER
DTENHTSVDGYTEPHIQPTKSSSRQNIPRCRNSITSATDEQPHIGNYRLQKTIGKGNFAKVKLARHVLTGREVAVKIIDKTQLNPTSLQK
LFREVRIMKILNHPNIVKLFEVIETEKTLYLVMEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKYIVHRDLKAENLLLDGD
MNIKIADFGFSNEFTVGNKLDTFCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTD
CENLLKKLLVLNPIKRGSLEQIMKDRWMNVGHEEEELKPYTEPDPDFNDTKRIDIMVTMGFARDEINDALINQKYDEVMATYILLGRKPP
EFEGGESLSSGNLCQRSRPSSDLNNSTLQSPAHLKVQRSISANQKQRRFSDHAGPSIPPAVSYTKRPQANSVESEQKEEWDKDVARKLGS
TTVGSKSEMTASPLVGPERKKSSTIPSNNVYSGGSMARRNTYVCERTTDRYVALQNGKDSSLTEMSVSSISSAGSSVASAVPSARPRHQK
SMSTSGHPIKVTLPTIKDGSEAYRPGTTQRVPAASPSAHSISTATPDRTRFPRGSSSRSTFHGEQLRERRSVAYNGPPASPSHETGAFAH
745_MARK1_RHOU


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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

MARK1_RHOU 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.

163_MARK1_RHOU_ramachandran.png
all structure MARK1-RHOU

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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 MARK1_RHOU


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
MARK1Q9P0L2humanMAPTP10636-8T231KKVAVVRtPPKsPss
MARK1Q9P0L2humanMAPTP10636-8S320VDLskVTskCGsLGNTubulin-binding
MARK1Q9P0L2humanMAPTP10636-8S396GAEIVyKsPVVsGDt
MARK1Q9P0L2humanMAPTP10636-8S262NVKskIGstENLkHQTubulin-binding
MARK1Q9P0L2humanMAPTP10636-8S324kVTskCGsLGNIHHkTubulin-binding
MARK1Q9P0L2humanMAPTP10636-8S293NVQskCGsKDNIkHVTubulin-binding
MARK1Q9P0L2humanTNK1Q13470S502RMKGIsRsLEsVLsL
MARK1Q9P0L2humanDIXDC1Q155Q3-2S381SKLPHSQsSPTVSST
MARK1Q9P0L2humanMAPTP10636-8S356rVQskIGsLDNItHVTubulin-binding
MARK1Q9P0L2humanFEZ1Q99689S58SEIISFKsMEDLVNEFEZ
MARK1Q9P0L2humanDIXDC1Q155Q3S592SKLPHsQssPTVSST
MARK1Q9P0L2humanMAPTP10636-8S422GsIDMVDsPQLAtLA
MARK1Q9P0L2humanMAPTP10636-8S305kHVPGGGsVQIVykPTubulin-binding


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
MARK1IDDescription0.00e+00
MARK1GO:0019896axonal transport of mitochondrion5.74e-04
MARK1GO:0032886regulation of microtubule-based process5.74e-04
MARK1GO:0034643establishment of mitochondrion localizatio1.09e-05
MARK1GO:0051654establishment of mitochondrion localization6.15e-04
MARK1GO:0051646mitochondrion localization1.44e-03
MARK1GO:0098930axonal transport2.09e-03
MARK1GO:0008088axo-dendritic transport2.57e-03
MARK1GO:0072384organelle transport along microtubule3.06e-03
MARK1GO:0070507regulation of microtubule cytoskeleton organization9.01e-03
MARK1GO:0010970transport along microtubule9.46e-03
MARK1GO:0021543pallium development1.06e-02
MARK1GO:0030705cytoskeleton-dependent intracellular transport1.13e-02
MARK1GO:0099111microtubule-based transport1.13e-02
MARK1GO:0021537telencephalon development1.76e-02
MARK1GO:0010506regulation of autophagy2.39e-02
MARK1GO:0031346positive regulation of cell projection organization2.39e-02
MARK1GO:1902513regulation of organelle transport along microtubule2.39e-02
MARK1GO:0010639negative regulation of organelle organization2.39e-02
MARK1GO:0010917negative regulation of mitochondrial membrane potential2.44e-02
MARK1GO:0045837negative regulation of membrane potential2.44e-02
MARK1GO:0030900forebrain development2.44e-02
MARK1GO:1902902negative regulation of autophagosome assembly2.44e-02
MARK1GO:0007018microtubule-based movement2.44e-02
MARK1GO:1900452regulation of long-term synaptic depression2.44e-02
MARK1GO:0007409axonogenesis2.44e-02
MARK1GO:0010975regulation of neuron projection development2.44e-02
MARK1GO:0032930positive regulation of superoxide anion generation2.44e-02
MARK1GO:1900034regulation of cellular response to heat2.44e-02
MARK1GO:0051656establishment of organelle localization2.44e-02
MARK1GO:0048311mitochondrion distribution2.44e-02
MARK1GO:0032928regulation of superoxide anion generation2.64e-02
MARK1GO:0010288response to lead ion2.67e-02
MARK1GO:0070584mitochondrion morphogenesis2.67e-02
MARK1GO:0090043regulation of tubulin deacetylation2.67e-02
MARK1GO:1902473regulation of protein localization to synapse2.72e-02
MARK1GO:0090042tubulin deacetylation2.76e-02
MARK1GO:0070841inclusion body assembly2.81e-02
MARK1GO:0048143astrocyte activation2.85e-02
MARK1GO:0090218positive regulation of lipid kinase activity2.89e-02
MARK1GO:0021846cell proliferation in forebrain2.93e-02
MARK1GO:0090140regulation of mitochondrial fission3.02e-02
MARK1GO:0034063stress granule assembly3.02e-02
MARK1GO:0090322regulation of superoxide metabolic process3.02e-02
MARK1GO:0016242negative regulation of macroautophagy3.02e-02
MARK1GO:0031116positive regulation of microtubule polymerization3.02e-02
MARK1GO:0060292long-term synaptic depression3.02e-02
MARK1GO:0090311regulation of protein deacetylation3.20e-02
MARK1GO:0021799cerebral cortex radially oriented cell migration3.20e-02
MARK1GO:0031112positive regulation of microtubule polymerization or depolymerization3.20e-02

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Related Drugs to MARK1_RHOU


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 MARK1-RHOU 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 MARK1_RHOU


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