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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:MARK2-BATF2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MARK2-BATF2
FusionPDB ID: 51741
FusionGDB2.0 ID: 51741
HgeneTgene
Gene symbol

MARK2

BATF2

Gene ID

2011

116071

Gene namemicrotubule affinity regulating kinase 2basic leucine zipper ATF-like transcription factor 2
SynonymsEMK-1|EMK1|PAR-1|Par-1b|Par1bSARI
Cytomap

11q13.1

11q13.1

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase MARK2ELKL motif kinase 1MAP/microtubule affinity-regulating kinase 2PAR1 homolog bSer/Thr protein kinase PAR-1Bserine/threonine protein kinase EMKtesticular tissue protein Li 117basic leucine zipper transcriptional factor ATF-like 2B-ATF-2basic leucine zipper transcription factor, ATF-like 2suppressor of AP-1 regulated by IFN
Modification date2020032920200313
UniProtAcc

Q7KZI7

Main function of 5'-partner protein: FUNCTION: Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:12429843, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15158914, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:15365179, ECO:0000269|PubMed:16775013, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:18626018, ECO:0000269|PubMed:20194617, ECO:0000269|PubMed:23666762}.

Q8N1L9

Main function of 5'-partner protein: FUNCTION: AP-1 family transcription factor that controls the differentiation of lineage-specific cells in the immune system. Following infection, participates in the differentiation of CD8(+) thymic conventional dendritic cells in the immune system. Acts via the formation of a heterodimer with JUN family proteins that recognizes and binds DNA sequence 5'-TGA[CG]TCA-3' and regulates expression of target genes (By similarity). Selectively suppresses CCN1 transcription and hence blocks the downstream cell proliferation signals produced by CCN1 and inhibits CCN1-induced anchorage-independent growth and invasion in several cancer types, such as breast cancer, malignant glioma and metastatic melanoma. Possibly acts by interfering with AP-1 binding to CCN1 promoter. {ECO:0000250, ECO:0000269|PubMed:20531301}.
Ensembl transtripts involved in fusion geneENST idsENST00000315032, ENST00000350490, 
ENST00000361128, ENST00000377809, 
ENST00000402010, ENST00000413835, 
ENST00000502399, ENST00000508192, 
ENST00000377810, ENST00000408948, 
ENST00000425897, ENST00000509502, 
ENST00000513765, 
ENST00000435842, 
ENST00000527716, ENST00000301887, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 9 X 11=12873 X 2 X 4=24
# samples 214
** MAII scorelog2(21/1287*10)=-2.61555082055458
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/24*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: MARK2 [Title/Abstract] AND BATF2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MARK2 [Title/Abstract] AND BATF2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MARK2(63607032)-BATF2(64762021), # samples:3
Anticipated loss of major functional domain due to fusion event.MARK2-BATF2 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
MARK2-BATF2 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
MARK2-BATF2 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
MARK2-BATF2 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneMARK2

GO:0006468

protein phosphorylation

14976552

HgeneMARK2

GO:0010976

positive regulation of neuron projection development

12429843

HgeneMARK2

GO:0018105

peptidyl-serine phosphorylation

10542369|16717194

HgeneMARK2

GO:0030010

establishment of cell polarity

12429843

HgeneMARK2

GO:0035556

intracellular signal transduction

14976552

HgeneMARK2

GO:0045197

establishment or maintenance of epithelial cell apical/basal polarity

15324659

HgeneMARK2

GO:0070507

regulation of microtubule cytoskeleton organization

10542369



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/chr11:63607032/chr11:64762021)
- 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 buttonRetention analysis results 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, are available here.

check buttonFusion gene breakpoints across MARK2 (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 buttonFusion gene breakpoints across BATF2 (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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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000377809MARK2chr1163607032+ENST00000301887BATF2chr1164762021-2605633100855317
ENST00000402010MARK2chr1163607032+ENST00000301887BATF2chr1164762021-2605633100855317
ENST00000413835MARK2chr1163607032+ENST00000301887BATF2chr1164762021-2605633100855317
ENST00000315032MARK2chr1163607032+ENST00000301887BATF2chr1164762021-2605633100855317
ENST00000508192MARK2chr1163607032+ENST00000301887BATF2chr1164762021-25285569312310
ENST00000361128MARK2chr1163607032+ENST00000301887BATF2chr1164762021-25285569312310
ENST00000350490MARK2chr1163607032+ENST00000301887BATF2chr1164762021-24404688431281
ENST00000502399MARK2chr1163607032+ENST00000301887BATF2chr1164762021-22382662121051279

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000377809ENST00000301887MARK2chr1163607032+BATF2chr1164762021-0.307248030.692752
ENST00000402010ENST00000301887MARK2chr1163607032+BATF2chr1164762021-0.307248030.692752
ENST00000413835ENST00000301887MARK2chr1163607032+BATF2chr1164762021-0.307248030.692752
ENST00000315032ENST00000301887MARK2chr1163607032+BATF2chr1164762021-0.307248030.692752
ENST00000508192ENST00000301887MARK2chr1163607032+BATF2chr1164762021-0.257766070.742234
ENST00000361128ENST00000301887MARK2chr1163607032+BATF2chr1164762021-0.257766070.742234
ENST00000350490ENST00000301887MARK2chr1163607032+BATF2chr1164762021-0.270917860.7290821
ENST00000502399ENST00000301887MARK2chr1163607032+BATF2chr1164762021-0.3683830.631617

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for MARK2-BATF2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MARK2chr1163607032BATF2chr116476202126617RTPLPTLNERDTEQDPKEQQRQLKKQ
MARK2chr1163607032BATF2chr1164762021468161GGGNREAWRKGGKGRRGARPGGASHS
MARK2chr1163607032BATF2chr1164762021556161GGGNREAWRKGGKGRRGARPGGASHS
MARK2chr1163607032BATF2chr1164762021633161GGGNREAWRKGGKGRRGARPGGASHS

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Potential FusionNeoAntigen Information of MARK2-BATF2 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
MARK2-BATF2_63607032_64762021.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
MARK2-BATF2chr1163607032chr1164762021266HLA-B45:01NERDTEQDP0.91120.5041716
MARK2-BATF2chr1163607032chr1164762021266HLA-B39:11EQDPKEQQRQL0.99470.72671223

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Potential FusionNeoAntigen Information of MARK2-BATF2 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of MARK2-BATF2

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
5322LNERDTEQDPKEQQMARK2BATF2chr1163607032chr1164762021266

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MARK2-BATF2

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN5322LNERDTEQDPKEQQ-8.85616-8.96956
HLA-B14:023BVN5322LNERDTEQDPKEQQ-5.66423-6.69953
HLA-B52:013W395322LNERDTEQDPKEQQ-6.49489-6.60829
HLA-B52:013W395322LNERDTEQDPKEQQ-3.99785-5.03315
HLA-A11:014UQ25322LNERDTEQDPKEQQ-4.90759-5.94289
HLA-A24:025HGA5322LNERDTEQDPKEQQ-7.27887-7.39227
HLA-A24:025HGA5322LNERDTEQDPKEQQ-7.11524-8.15054
HLA-B27:056PYJ5322LNERDTEQDPKEQQ-6.11615-6.22955
HLA-B27:056PYJ5322LNERDTEQDPKEQQ-4.78818-5.82348
HLA-B44:053DX85322LNERDTEQDPKEQQ-7.22602-7.33942
HLA-B44:053DX85322LNERDTEQDPKEQQ-4.86671-5.90201

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Vaccine Design for the FusionNeoAntigens of MARK2-BATF2

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
MARK2-BATF2chr1163607032chr11647620211223EQDPKEQQRQLCAGGACCCCAAGGAGCAACAAAGGCAGCTGAAG
MARK2-BATF2chr1163607032chr1164762021716NERDTEQDPGAGAGGGACACGGAGCAGGACCCCAAG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of MARK2-BATF2

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
SKCMMARK2-BATF2chr1163607032ENST00000502399chr1164762021ENST00000301887TCGA-GN-A26D-06A

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Potential target of CAR-T therapy development for MARK2-BATF2

check button Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to MARK2-BATF2

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

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Related Diseases to MARK2-BATF2

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

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