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Center for Computational Systems Medicine level2
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein Structure

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pLDDT scores

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Ramachandran Plot of Fusion Protein Structure

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:MAPKAPK2-SRGAP2

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MAPKAPK2-SRGAP2
FusionPDB ID: 51612
FusionGDB2.0 ID: 51612
HgeneTgene
Gene symbol

MAPKAPK2

SRGAP2

Gene ID

9261

23380

Gene nameMAPK activated protein kinase 2SLIT-ROBO Rho GTPase activating protein 2
SynonymsMAPKAP-K2|MK-2|MK2ARHGAP34|FNBP2|SRGAP2A|SRGAP3
Cytomap

1q32.1

1q32.1

Type of geneprotein-codingprotein-coding
DescriptionMAP kinase-activated protein kinase 2MAPKAP kinase 2mitogen-activated protein kinase-activated protein kinase 2SLIT-ROBO Rho GTPase-activating protein 2SLIT-ROBO GAP2formin-binding protein 2rho GTPase-activating protein 34
Modification date2020032720200313
UniProtAcc

P49137

.
Ensembl transtripts involved in fusion geneENST idsENST00000294981, ENST00000367103, 
ENST00000479009, 
ENST00000419187, 
ENST00000471256, ENST00000414007, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 6 X 5=24015 X 15 X 7=1575
# samples 816
** MAII scorelog2(8/240*10)=-1.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/1575*10)=-3.29920801838728
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: MAPKAPK2 [Title/Abstract] AND SRGAP2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MAPKAPK2(206858853)-SRGAP2(206589249), # samples:2
SRGAP2(206135293)-MAPKAPK2(206904483), # samples:1
Anticipated loss of major functional domain due to fusion event.MAPKAPK2-SRGAP2 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.
MAPKAPK2-SRGAP2 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.
MAPKAPK2-SRGAP2 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.
MAPKAPK2-SRGAP2 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
HgeneMAPKAPK2

GO:0018105

peptidyl-serine phosphorylation

15850461

HgeneMAPKAPK2

GO:0032680

regulation of tumor necrosis factor production

15014438

HgeneMAPKAPK2

GO:0034097

response to cytokine

8774846

HgeneMAPKAPK2

GO:0070935

3'-UTR-mediated mRNA stabilization

14517288|15014438|20932473

TgeneSRGAP2

GO:0043547

positive regulation of GTPase activity

21148482

TgeneSRGAP2

GO:0046847

filopodium assembly

22559944

TgeneSRGAP2

GO:0051014

actin filament severing

21148482

TgeneSRGAP2

GO:0060996

dendritic spine development

22559944

TgeneSRGAP2

GO:2001223

negative regulation of neuron migration

22559944


check buttonFusion gene breakpoints across MAPKAPK2 (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 SRGAP2 (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 Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4HNSCTCGA-CV-5435-01AMAPKAPK2chr1

206858853

-SRGAP2chr1

206589249

+
ChimerDB4HNSCTCGA-CV-5435MAPKAPK2chr1

206858853

+SRGAP2chr1

206589249

+


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Fusion ORF Analysis


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)
ENST00000294981MAPKAPK2chr1206858853+ENST00000414007SRGAP2chr1206589249+54435651422424760
ENST00000367103MAPKAPK2chr1206858853+ENST00000414007SRGAP2chr1206589249+5350472492331760

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
ENST00000294981ENST00000414007MAPKAPK2chr1206858853+SRGAP2chr1206589249+0.0014282170.99857175
ENST00000367103ENST00000414007MAPKAPK2chr1206858853+SRGAP2chr1206589249+0.0014585170.9985415

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Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>51612_51612_1_MAPKAPK2-SRGAP2_MAPKAPK2_chr1_206858853_ENST00000294981_SRGAP2_chr1_206589249_ENST00000414007_length(amino acids)=760AA_BP=139
MEPGRVGEAGSSPERTSQPVGGRRGGGPEPEEGAAAGTPACAPASPGTMLSNSQGQSPPVPFPAPAPPPQPPTPALPHPPAQPPPPPPQQ
FPQFHVKSGLQIKKNAIIDDYKVTSQVLGLGINGKVLQIFNKRTQEKFALKKMKEYLEGRNLITKLQAKHDLLQKTLGESQRTDCSLARR
SSTVRKQDSSQAIPLVVESCIRFISRHGLQHEGIFRVSGSQVEVNDIKNAFERGEDPLAGDQNDHDMDSIAGVLKLYFRGLEHPLFPKDI
FHDLMACVTMDNLQERALHIRKVLLVLPKTTLIIMRYLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSVPEGHDQVSCQAHVNELIKTI
IIQHENIFPSPRELEGPVYSRGGSMEDYCDSPHGETTSVEDSTQDVTAEHHTSDDECEPIEAIAKFDYVGRTARELSFKKGASLLLYQRA
SDDWWEGRHNGIDGLIPHQYIVVQDTEDGVVERSSPKSEIEVISEPPEEKVTARAGASCPSGGHVADIYLANINKQRKRPESGSIRKTFR
SDSHGLSSSLTDSSSPGVGASCRPSSQPIMSQSLPKEGPDKCSISGHGSLNSISRHSSLKNRLDSPQIRKTATAGRSKSFNNHRPMDPEV
IAQDIEATMNSALNELRELERQSSVKHTPDVVLDTLEPLKTSPVVAPTSEPSSPLHTQLLKDPEPAFQRSASTAGDIACAFRPVKSVKMA

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

>51612_51612_2_MAPKAPK2-SRGAP2_MAPKAPK2_chr1_206858853_ENST00000367103_SRGAP2_chr1_206589249_ENST00000414007_length(amino acids)=760AA_BP=139
MEPGRVGEAGSSPERTSQPVGGRRGGGPEPEEGAAAGTPACAPASPGTMLSNSQGQSPPVPFPAPAPPPQPPTPALPHPPAQPPPPPPQQ
FPQFHVKSGLQIKKNAIIDDYKVTSQVLGLGINGKVLQIFNKRTQEKFALKKMKEYLEGRNLITKLQAKHDLLQKTLGESQRTDCSLARR
SSTVRKQDSSQAIPLVVESCIRFISRHGLQHEGIFRVSGSQVEVNDIKNAFERGEDPLAGDQNDHDMDSIAGVLKLYFRGLEHPLFPKDI
FHDLMACVTMDNLQERALHIRKVLLVLPKTTLIIMRYLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSVPEGHDQVSCQAHVNELIKTI
IIQHENIFPSPRELEGPVYSRGGSMEDYCDSPHGETTSVEDSTQDVTAEHHTSDDECEPIEAIAKFDYVGRTARELSFKKGASLLLYQRA
SDDWWEGRHNGIDGLIPHQYIVVQDTEDGVVERSSPKSEIEVISEPPEEKVTARAGASCPSGGHVADIYLANINKQRKRPESGSIRKTFR
SDSHGLSSSLTDSSSPGVGASCRPSSQPIMSQSLPKEGPDKCSISGHGSLNSISRHSSLKNRLDSPQIRKTATAGRSKSFNNHRPMDPEV
IAQDIEATMNSALNELRELERQSSVKHTPDVVLDTLEPLKTSPVVAPTSEPSSPLHTQLLKDPEPAFQRSASTAGDIACAFRPVKSVKMA

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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/chr1:206858853/chr1:206589249)
- 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
MAPKAPK2

P49137

.
FUNCTION: Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:11844797, ECO:0000269|PubMed:12456657, ECO:0000269|PubMed:12565831, ECO:0000269|PubMed:14499342, ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15629715, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:16456544, ECO:0000269|PubMed:17481585, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:8093612, ECO:0000269|PubMed:8280084, ECO:0000269|PubMed:8774846}.FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.

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.
- Retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000294981+11010_4093.0371.0Compositional biasNote=Pro-rich
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000294981+11035_4093.0371.0Compositional biasNote=Poly-Pro
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000367103+11010_4093.0401.0Compositional biasNote=Pro-rich
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000367103+11035_4093.0401.0Compositional biasNote=Poly-Pro
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000294981+11070_7893.0371.0Nucleotide bindingATP
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000367103+11070_7893.0401.0Nucleotide bindingATP

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000294981+11064_32593.0371.0DomainProtein kinase
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000367103+11064_32593.0401.0DomainProtein kinase
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000294981+110356_36593.0371.0MotifNote=Nuclear export signal (NES)
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000294981+110371_37493.0371.0MotifNote=Bipartite nuclear localization signal 1
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000294981+110385_38993.0371.0MotifNote=Bipartite nuclear localization signal 2
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000367103+110356_36593.0401.0MotifNote=Nuclear export signal (NES)
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000367103+110371_37493.0401.0MotifNote=Bipartite nuclear localization signal 1
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000367103+110385_38993.0401.0MotifNote=Bipartite nuclear localization signal 2
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000294981+110139_14193.0371.0RegionNote=Staurosporine binding
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000294981+110328_36493.0371.0RegionAutoinhibitory helix
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000294981+110366_39093.0371.0RegionNote=p38 MAPK-binding site
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000367103+110139_14193.0401.0RegionNote=Staurosporine binding
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000367103+110328_36493.0401.0RegionAutoinhibitory helix
HgeneMAPKAPK2chr1:206858853chr1:206589249ENST00000367103+110366_39093.0401.0RegionNote=p38 MAPK-binding site


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Fusion Protein Structures

check button PDB and CIF files of the predicted 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.
Fusion protein PDB link (fusion AA seq ID in FusionPDB)HgeneHchrHbpHstrandTgeneTchrTbpTstrandAA seqLen(AA seq)
PDB file >>>1531_MAPKAPK2_206858853_SRGAP2_206589249_ranked_0.pdbMAPKAPK2206858853206858853ENST00000414007SRGAP2chr1206589249+
MEPGRVGEAGSSPERTSQPVGGRRGGGPEPEEGAAAGTPACAPASPGTMLSNSQGQSPPVPFPAPAPPPQPPTPALPHPPAQPPPPPPQQ
FPQFHVKSGLQIKKNAIIDDYKVTSQVLGLGINGKVLQIFNKRTQEKFALKKMKEYLEGRNLITKLQAKHDLLQKTLGESQRTDCSLARR
SSTVRKQDSSQAIPLVVESCIRFISRHGLQHEGIFRVSGSQVEVNDIKNAFERGEDPLAGDQNDHDMDSIAGVLKLYFRGLEHPLFPKDI
FHDLMACVTMDNLQERALHIRKVLLVLPKTTLIIMRYLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSVPEGHDQVSCQAHVNELIKTI
IIQHENIFPSPRELEGPVYSRGGSMEDYCDSPHGETTSVEDSTQDVTAEHHTSDDECEPIEAIAKFDYVGRTARELSFKKGASLLLYQRA
SDDWWEGRHNGIDGLIPHQYIVVQDTEDGVVERSSPKSEIEVISEPPEEKVTARAGASCPSGGHVADIYLANINKQRKRPESGSIRKTFR
SDSHGLSSSLTDSSSPGVGASCRPSSQPIMSQSLPKEGPDKCSISGHGSLNSISRHSSLKNRLDSPQIRKTATAGRSKSFNNHRPMDPEV
IAQDIEATMNSALNELRELERQSSVKHTPDVVLDTLEPLKTSPVVAPTSEPSSPLHTQLLKDPEPAFQRSASTAGDIACAFRPVKSVKMA
760


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pLDDT score distribution

check button pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
MAPKAPK2_pLDDT.png
all structure
all structure
SRGAP2_pLDDT.png
all structure
all structure

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.
all structure


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Ramachandran Plot of 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.
Fusion AA seq ID in FusionPDB and their Ramachandran plots

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Fusion Protein-Protein Interaction


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)
GenePPI interactors


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
MAPKAPK2
SRGAP2


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs to MAPKAPK2-SRGAP2


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 MAPKAPK2-SRGAP2


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