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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:MAPKAPK2_SRGAP2

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: MAPKAPK2_SRGAP2
KinaseFusionDB ID: KFG3594
FusionGDB2.0 ID: KFG3594
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 date2024030520240403
UniProtAcc

P49137

O75044

Ensembl transtripts involved in fusion geneENST idsENST00000294981, ENST00000367103, 
ENST00000479009, 		ENST00000419187, 
ENST00000471256, ENST00000414007, 
Context (manual curation of fusion genes in KinaseFusionDB)

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
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|27373832

TgeneSRGAP2

GO:0046847

filopodium assembly

22559944

TgeneSRGAP2

GO:0051014

actin filament severing

21148482

TgeneSRGAP2

GO:0060996

dendritic spine development

22559944

TgeneSRGAP2

GO:1904861

excitatory synapse assembly

27373832

TgeneSRGAP2

GO:1904862

inhibitory synapse assembly

27373832

TgeneSRGAP2

GO:2001223

negative regulation of neuron migration

22559944


check buttonKinase Fusion 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 buttonKinase Fusion 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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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-CV-5435MAPKAPK2chr1

206858853

SRGAP2chr1

206589249



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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)

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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

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/chr1:206858853/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

SRGAP2

O75044

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: Postsynaptic RAC1 GTPase activating protein (GAP) that plays a key role in neuronal morphogenesis and migration mainly during development of the cerebral cortex (PubMed:20810653, PubMed:27373832, PubMed:28333212). Regulates excitatory and inhibitory synapse maturation and density in cortical pyramidal neurons (PubMed:22559944, PubMed:27373832). SRGAP2/SRGAP2A limits excitatory and inhibitory synapse density through its RAC1-specific GTPase activating activity, while it promotes maturation of both excitatory and inhibitory synapses through its ability to bind to the postsynaptic scaffolding protein HOMER1 at excitatory synapses, and the postsynaptic protein GPHN at inhibitory synapses (By similarity). Mechanistically, acts by binding and deforming membranes, thereby regulating actin dynamics to regulate cell migration and differentiation (PubMed:27373832). Promotes cell repulsion and contact inhibition of locomotion: localizes to protrusions with curved edges and controls the duration of RAC1 activity in contact protrusions (By similarity). In non-neuronal cells, may also play a role in cell migration by regulating the formation of lamellipodia and filopodia (PubMed:20810653, PubMed:21148482). {ECO:0000250|UniProtKB:Q91Z67, ECO:0000269|PubMed:20810653, ECO:0000269|PubMed:21148482, ECO:0000269|PubMed:22559944, ECO:0000269|PubMed:27373832, ECO:0000269|PubMed:28333212}.

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


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Kinase-Substrate Information of MAPKAPK2_SRGAP2


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
MAPKAPK2P49137humanTAB3Q8N5C8S506HKYQRsSsSGSDDyA
MAPKAPK2P49137humanCDC25BP30305S169VLRNItNsQAPDGRRM-inducer_phosp
MAPKAPK2P49137humanPOU5F1Q01860S93PQGGLEtsQPEGEAG
MAPKAPK2P49137humanHNRNPA0Q13151S84VELkRAVsREDsARP
MAPKAPK2P49137humanGJA1P17302S255HAtsGALsPAkDCGs
MAPKAPK2P49137humanHSPB1P04792S78PAysRALsRQLssGV
MAPKAPK2P49137humanLIMK1P53667S323KDLGrSEsLRVVCRP
MAPKAPK2P49137humanWNK4Q96J92S575PFLFRHAsYSSTTSD
MAPKAPK2P49137humanCREB1P16220S119EILsRRPsyRkILNDpKID
MAPKAPK2P49137humanRCSD1Q6JBY9S179RRFRRsQsDCGELGDCAP-ZIP_m
MAPKAPK2P49137humanMRTFAQ969V6S333CGLARQNstsLtGKP
MAPKAPK2P49137humanYWHAZP63104S58VVGARRssWRVVssI14-3-3
MAPKAPK2P49137humanAGO2Q9UKV8S387SkLMRsAsFNtDPyVArgoL2
MAPKAPK2P49137humanBAG2O95816S20GRFCRSSsMADRSSR
MAPKAPK2P49137humanPOU5F1Q01860S111EsNsDGAsPEPCtVt
MAPKAPK2P49137humanMDM2Q00987S157SHLVSRPstSsRRRA
MAPKAPK2P49137humanRBM7Q9Y580S204QrkVrMNsyPYLADr
MAPKAPK2P49137humanMDM2Q00987S166SsRRRAIsEtEENsD
MAPKAPK2P49137humanEEF2KO00418S377PPLLRPLsENsGDEN
MAPKAPK2P49137humanTHP07101-4S44RFIGRRQsLIEDARKTOH_N
MAPKAPK2P49137humanKRT18P05783S53IsVsrstsFrGGMGs
MAPKAPK2P49137humanNELFEP18615S51GGVkRsLsEQPVMDt
MAPKAPK2P49137humanRBM7Q9Y580S136QIIQRsFssPENFQr
MAPKAPK2P49137humanMAPKAPK2P49137T338VPQtPLHtsRVLKED
MAPKAPK2P49137humanZFP36L1Q07352S92RFRDRsFsEGGERLLTis11B_N
MAPKAPK2P49137humanRTN4Q9NQC3-2S107VAPERQPsWDPSPVS
MAPKAPK2P49137humanPLK1P53350S326LTIPPRFsIAPssLD
MAPKAPK2P49137humanCEP131Q9UPN4S47kPIVRsVsVVTGsEQ
MAPKAPK2P49137humanRCSD1Q6JBY9S244PPLRRsPsRTEKQEERCSD
MAPKAPK2P49137humanAKT1P31749S473RPHFPQFsysAsGtAPkinase_C
MAPKAPK2P49137humanARPC5O15511S77AVKDrAGsIVLKVLIP16-Arc
MAPKAPK2P49137humanTP53P04637S20PLsQEtFsDLWkLLPP53_TAD
MAPKAPK2P49137humanTRIM29Q14134S550GyPsLMRsQsPkAQP
MAPKAPK2P49137humanHSPA1LP34931S241DFDNRLVsHFVEEFKHSP70
MAPKAPK2P49137humanRPS6KA3P51812S386HQLFRGFsFVAItsDPkinase_C
MAPKAPK2P49137humanCDC25BP30305S323QRLFRsPsMPCsVIRM-inducer_phosp
MAPKAPK2P49137humanZFP36L1Q07352S203PRLQHsFsFAGFPSA
MAPKAPK2P49137humanTHP07101-3S19KGFRRAVsELDAKQATOH_N
MAPKAPK2P49137humanPLK1P53350S383DMLQQLHsVNAskPS
MAPKAPK2P49137humanPARNO95453S557NHyYRNNsFTAPsTV
MAPKAPK2P49137humanDDX5P17844S198CRACRLkstCIyGGADEAD
MAPKAPK2P49137humanTHP07101-2S19KGFRRAVsELDAKQATOH_N
MAPKAPK2P49137humanTHP07101-2S67RFIGRRQsLIEDARKTOH_N
MAPKAPK2P49137humanRPS6KA1Q15418S380HQLFRGFsFVAtGLMPkinase_C
MAPKAPK2P49137humanGJA1P17302S279sSPtAPLsPMsPPGy
MAPKAPK2P49137humanCEP131Q9UPN4S78NNLRRsNsttQVSQP
MAPKAPK2P49137humanDAZLQ92904S65SFFARYGsVkEVKIIRRM_1
MAPKAPK2P49137humanRIPK1Q13546S320AVVkRMQsLQLdCVA
MAPKAPK2P49137humanZFP36L1Q07352S54GGFPRRHsVtLPSSkTis11B_N
MAPKAPK2P49137humanNELFEP18615S251GPFRRsDsFPERRAP
MAPKAPK2P49137humanCOPS5Q92905S177IDPTRTIsAGkVNLG
MAPKAPK2P49137humanTHP07101-4S19KGFRRAVsELDAKQATOH_N
MAPKAPK2P49137humanSRFP11831S103RGLKRsLsEMEIGMV
MAPKAPK2P49137humanTRIM28Q13263S473sGVkRsRsGEGEVsG
MAPKAPK2P49137humanGJA1P17302S282tAPLsPMsPPGykLV
MAPKAPK2P49137humanTHP07101S71RFIGRRQsLIEDARKTOH_N
MAPKAPK2P49137humanNELFEP18615S115QPFQRsIsADDDLQE
MAPKAPK2P49137humanLSP1P33241S252PKLARQAsIELPsMACaldesmon
MAPKAPK2P49137humanPDE4DQ08499-6S133sFLYRSDsDYDLSPk
MAPKAPK2P49137humanPIAS1O75925S522DTSYINTsLIQDYRH
MAPKAPK2P49137humanTHP07101-3S404GELLHCLsEEPEIRABiopterin_H
MAPKAPK2P49137humanALOX5P09917S272CsLERQLsLEQEVQQLipoxygenase
MAPKAPK2P49137humanMRTFAQ969V6S312tPPVRsLstTNSsSS
MAPKAPK2P49137humanAATFQ9NY61T366FTVYRNRtLQkWHDKAATF-Che1
MAPKAPK2P49137humanHSPB1P04792S15FsLLrGPsWDPFrDW
MAPKAPK2P49137humanCDC25BP30305S375ARVLRsksLCHDEIEM-inducer_phosp
MAPKAPK2P49137humanTRIM29Q14134S552PsLMRsQsPkAQPQT
MAPKAPK2P49137humanHSF1Q00613S121NIkRkVtsVSTLksE
MAPKAPK2P49137humanBCL2L1Q07817S62PSWHLADsPAVNGAT
MAPKAPK2P49137humanPFKFB3Q16875S461NPLMRRNsVtPLAsP
MAPKAPK2P49137humanTSC2P49815S1254TALyksLsVPAASTA
MAPKAPK2P49137humanTHP07101S19KGFRRAVsELDAKQATOH_N
MAPKAPK2P49137humanCDC25CP30307S216sGLyRsPsMPENLNRM-inducer_phosp
MAPKAPK2P49137humanTHP07101-3S40RFIGRRQsLIEDARKTOH_N
MAPKAPK2P49137humanBECN1Q14457S90IPPARMMstEsANsF
MAPKAPK2P49137humanKRT20P35900S13RSFHRsLsSSLQAPV
MAPKAPK2P49137humanHSPB1P04792S82RALsRQLssGVsEIr
MAPKAPK2P49137humanCDC25BP30305S353VQNkRRRsVtPPEEQM-inducer_phosp


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
MAPKAPK2IDDescription0.00e+00
MAPKAPK2GO:0031330negative regulation of cellular catabolic process9.29e-06
MAPKAPK2GO:0010586miRNA metabolic process1.44e-05
MAPKAPK2GO:0031667response to nutrient levels3.85e-05
MAPKAPK2GO:0034655nucleobase-containing compound catabolic process3.85e-05
MAPKAPK2GO:0036293response to decreased oxygen levels5.86e-05
MAPKAPK2GO:0062197cellular response to chemical stress5.86e-05
MAPKAPK2GO:0070482response to oxygen levels9.77e-05
MAPKAPK2GO:0009895negative regulation of catabolic process9.89e-05
MAPKAPK2GO:1903311regulation of mRNA metabolic process1.19e-04
MAPKAPK2GO:0006401RNA catabolic process1.21e-04
MAPKAPK2GO:0071480cellular response to gamma radiation1.63e-04
MAPKAPK2GO:0061614miRNA transcription2.51e-04
MAPKAPK2GO:0016242negative regulation of macroautophagy2.51e-04
MAPKAPK2GO:0006402mRNA catabolic process2.51e-04
MAPKAPK2GO:0034504protein localization to nucleus2.51e-04
MAPKAPK2GO:0051348negative regulation of transferase activity3.26e-04
MAPKAPK2GO:0043488regulation of mRNA stability4.10e-04
MAPKAPK2GO:0070918regulatory ncRNA processing4.37e-04
MAPKAPK2GO:0043487regulation of RNA stability4.80e-04
MAPKAPK2GO:0010507negative regulation of autophagy4.80e-04
MAPKAPK2GO:0031669cellular response to nutrient levels4.80e-04
MAPKAPK2GO:0043086negative regulation of catalytic activity4.80e-04
MAPKAPK2GO:0061013regulation of mRNA catabolic process4.80e-04
MAPKAPK2GO:0034599cellular response to oxidative stress4.97e-04
MAPKAPK2GO:1901653cellular response to peptide6.03e-04
MAPKAPK2GO:0035196miRNA processing6.72e-04
MAPKAPK2GO:0001701in utero embryonic development7.84e-04
MAPKAPK2GO:0031668cellular response to extracellular stimulus7.84e-04
MAPKAPK2GO:2001233regulation of apoptotic signaling pathway7.84e-04
MAPKAPK2GO:1901873regulation of post-translational protein modification7.84e-04
MAPKAPK2GO:0010332response to gamma radiation7.84e-04
MAPKAPK2GO:0010823negative regulation of mitochondrion organization8.14e-04
MAPKAPK2GO:2001242regulation of intrinsic apoptotic signaling pathway8.14e-04
MAPKAPK2GO:0018105peptidyl-serine phosphorylation9.06e-04
MAPKAPK2GO:0001666response to hypoxia9.24e-04
MAPKAPK2GO:0001558regulation of cell growth9.24e-04
MAPKAPK2GO:1901800positive regulation of proteasomal protein catabolic process9.46e-04
MAPKAPK2GO:0071248cellular response to metal ion9.46e-04
MAPKAPK2GO:0035821modulation of process of another organism1.01e-03
MAPKAPK2GO:0018209peptidyl-serine modification1.01e-03
MAPKAPK2GO:0043434response to peptide hormone1.01e-03
MAPKAPK2GO:0002763positive regulation of myeloid leukocyte differentiation1.11e-03
MAPKAPK2GO:0097193intrinsic apoptotic signaling pathway1.19e-03
MAPKAPK2GO:0045931positive regulation of mitotic cell cycle1.25e-03
MAPKAPK2GO:0070301cellular response to hydrogen peroxide1.56e-03
MAPKAPK2GO:0098781ncRNA transcription1.56e-03
MAPKAPK2GO:1904375regulation of protein localization to cell periphery1.56e-03
MAPKAPK2GO:0071241cellular response to inorganic substance1.56e-03
MAPKAPK2GO:0044772mitotic cell cycle phase transition1.56e-03

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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

check button Distribution of the number of studies mentioning MAPKAPK2-SRGAP2 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 MAPKAPK2_SRGAP2


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