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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:ZIC1_AKT2

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: ZIC1_AKT2
KinaseFusionDB ID: KFG7255
FusionGDB2.0 ID: KFG7255
HgeneTgene
Gene symbol

ZIC1

AKT2

Gene ID

7545

208

Gene nameZic family member 1AKT serine/threonine kinase 2
SynonymsBAIDCS|CRS6|ZIC|ZNF201HIHGHH|PKBB|PKBBETA|PRKBB|RAC-BETA
Cytomap

3q24

19q13.2

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein ZIC 1Zic family member 1 (odd-paired homolog, Drosophila)Zinc finger protein of the cerebellum 1zinc finger protein 201RAC-beta serine/threonine-protein kinasePKB betaRAC-PK-betamurine thymoma viral (v-akt) homolog-2protein kinase Akt-2protein kinase B betaputative v-akt murine thymoma viral oncoprotein 2rac protein kinase betav-akt murine thymoma viral oncogene h
Modification date2024030520240413
UniProtAcc

Q15915

P31751

Ensembl transtripts involved in fusion geneENST idsENST00000282928, ENST00000474034, 
ENST00000392038, ENST00000311278, 
ENST00000424901, ENST00000579047, 
ENST00000581582, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: ZIC1 [Title/Abstract] AND AKT2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZIC1(147132326)-AKT2(40771260), # 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
HgeneZIC1

GO:0007420

brain development

8542595

TgeneAKT2

GO:0030335

positive regulation of cell migration

25428377


check buttonKinase Fusion gene breakpoints across ZIC1 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonKinase Fusion gene breakpoints across AKT2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.


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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
ChiTaRS5.0DA742787ZIC1chr3

147132326

AKT2chr19

40771260



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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/:147132326/:40771260)
- 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
ZIC1

Q15915

AKT2

P31751

FUNCTION: Acts as a transcriptional activator. Involved in neurogenesis. Plays important roles in the early stage of organogenesis of the CNS, as well as during dorsal spinal cord development and maturation of the cerebellum. Involved in the spatial distribution of mossy fiber (MF) neurons within the pontine gray nucleus (PGN). Plays a role in the regulation of MF axon pathway choice. Promotes MF migration towards ipsilaterally-located cerebellar territories. May have a role in shear flow mechanotransduction in osteocytes. Retains nuclear GLI1 and GLI3 in the cytoplasm. Binds to the minimal GLI-consensus sequence 5'-TGGGTGGTC-3' (By similarity). {ECO:0000250|UniProtKB:P46684}.FUNCTION: AKT2 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. Involved in the inhibition of ciliogenesis associated with RAB8-dependent cilia growth (PubMed:31204173). {ECO:0000269|PubMed:31204173}.; FUNCTION: One of the few specific substrates of AKT2 identified recently is PITX2. Phosphorylation of PITX2 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1. AKT2 seems also to be the principal isoform responsible of the regulation of glucose uptake. Phosphorylates C2CD5 on 'Ser-197' during insulin-stimulated adipocytes. AKT2 is also specifically involved in skeletal muscle differentiation, one of its substrates in this process being ANKRD2. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. Phosphorylates CLK2 on 'Thr-343'.

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 ZIC1_AKT2


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
AKT2P31751humanATP7AQ04656S1424SYELPARsQIGQKsP
AKT2P31751humanPKP1Q13835S63ssQsstLsHsNRGsM
AKT2P31751humanIRF3Q14653T180sPsLDNPtPFPNLGP
AKT2P31751humanEGFRP00533S229rCrGKSPsDCCHNQCFurin-like
AKT2P31751humanPKP1Q13835T179LGsKGQKttQNRysF
AKT2P31751humanEZRP15311T567QGRDkyKtLRQIRQGERM_C
AKT2P31751humanCBY1Q9Y3M2S20TPPRKsAsLSNLHsLChibby
AKT2P31751humanHSF1Q00613S230PkYSRQFsLEHVHGS
AKT2P31751humanBMI1P35226S316ANRPRKssVNGSSAT
AKT2P31751humanADARP55265T1033RLGERLRtMSCSDKIA_deamin
AKT2P31751humanPKP1Q13835S191ysFystCsGQKAIKK
AKT2P31751humanFLNCQ14315S2233LGRERLGsFGsItRQFilamin
AKT2P31751humanPKP1Q13835T180GsKGQKttQNRysFy
AKT2P31751humanIRS2Q9Y4H2S365sCRVRtAsEGDGGAA
AKT2P31751humanH3C1P68431S10tkQtArkstGGkAPrHistone
AKT2P31751humanWIPF1O43516T398TSRALPAtPQLPSrS
AKT2P31751humanPKP1Q13835S127ysQMENWsRHYPRGS
AKT2P31751humanEDC3Q96F86S161sFRRRHNsWssssRHEdc3_linker
AKT2P31751humanATP7AQ04656S1466ysRAsINsLLsDkRs
AKT2P31751humanPKP1Q13835S118EPDNRRFssysQMEN
AKT2P31751humanPHB2Q99623S91RARPRkIssPTGSkDBand_7
AKT2P31751humanCHUKO15111T23EMRERLGtGGFGNVCPkinase
AKT2P31751humanPHB2Q99623S176TERAKDFsLILDDVABand_7
AKT2P31751humanH3C1P68431S28ATkAArksAPATGGVHistone
AKT2P31751humanADARB1P78563T553LQGERLLtMSCSDKIA_deamin
AKT2P31751humanPKP1Q13835S65QsstLsHsNRGsMyD
AKT2P31751humanLMNAP02545S390EEErLRLsPsPtsQR
AKT2P31751humanATP7AQ04656S1463IVNysRAsINsLLsD
AKT2P31751humanPKP1Q13835T171RGtLRKGtLGsKGQK
AKT2P31751humanPKP1Q13835T82ADNyNyGttsRssYy
AKT2P31751humanIRF3Q14653S175PQPLRsPsLDNPtPF
AKT2P31751humanPPIFP30405S31LPAARACsKGsGDPS
AKT2P31751humanPKP1Q13835T61sKssQsstLsHsNRG
AKT2P31751humanGAPDHP04406T237GMAFrVPtANVsVVDGp_dh_C
AKT2P31751humanPKP1Q13835S69LsHsNRGsMyDGLAD
AKT2P31751humanPKP1Q13835S174LRKGtLGsKGQKttQ
AKT2P31751humanLMNAP02545S404RsRGRAssHssQtQG
AKT2P31751humanPKP1Q13835S54MTVKRQKsKssQsst
AKT2P31751humanMAP3K5Q99683S83ATRGRGssVGGGSrR
AKT2P31751humanHTRA2O43464S212RVRVRLLsGDTYEAVTrypsin_2; Peptidase_M50
AKT2P31751humanPKP1Q13835S185KttQNRysFystCsG
AKT2P31751humanXIAPP98170S87VGRHRKVsPNCRFINBIR
AKT2P31751humanPKP1Q13835S57KRQKsKssQsstLsH
AKT2P31751humanIRF3Q14653S14RILPWLVsQLDLGQLIRF
AKT2P31751humanCYCSP99999Y47ktGQAPGysytAANkCytochrom_C
AKT2P31751humanIRS2Q9Y4H2S1149GGRRRHssEtFSsTt
AKT2P31751humanUPF1Q92900T151FCNGRGNtSGSHIVNUPF1_Zn_bind
AKT2P31751humanGATA6Q92908-2S290KPQKRVPsSRRLGLS
AKT2P31751humanESR1P03372S167GGRERLAsTNDkGSMOest_recep
AKT2P31751humanPKP1Q13835T166LyCDPRGtLRKGtLG
AKT2P31751humanPKP1Q13835T189NRysFystCsGQKAI
AKT2P31751humanFSCN1Q16658T403GCRkVTGtLDANRSSFascin
AKT2P31751humanRACGAP1Q9H0H5T249WTRSRRktGtLQPWN
AKT2P31751humanIRS2Q9Y4H2S306EFRPRsksQssGssA
AKT2P31751humanRPS6KA3P51812T115KVRDRVRtKMERDIL
AKT2P31751humanNF2P35240S10GAIASRMsFSsLkRK
AKT2P31751humanPKP1Q13835S188QNRysFystCsGQKA
AKT2P31751humanPKP1Q13835S84NyNyGttsRssYySK
AKT2P31751humanPKP1Q13835S60KsKssQsstLsHsNR
AKT2P31751humanPKP1Q13835S121NRRFssysQMENWsR
AKT2P31751humanKHSRPQ92945S193GLPERsVsLtGAPEsKH_1
AKT2P31751humanPIP5K1CO60331S555RYRRRtQssGQDGRP
AKT2P31751humanMAT1AQ00266T202VIPVRIHtIVISVQHS-AdoMet_synt_M
AKT2P31751humanHSF1Q00613S326ssVDtLLsPTALIDsVert_HS_TF
AKT2P31751humanCTNNB1P35222S552QDtQRRtsMGGtQQQ
AKT2P31751humanANKRD2Q9GZV1S99QERVRKTsLDLRREI
AKT2P31751humanIRS2Q9Y4H2S577GLRKRtysLttPARQ
AKT2P31751humanIRF3Q14653T207EEWEFEVtAFYRGRQIRF-3
AKT2P31751humanC2CD5Q86YS7S197EARQRLIsLMsGELQ
AKT2P31751humanSH3RF1Q7Z6J0S304KNTKKRHsFtsLtMA
AKT2P31751humanPDK1Q15118T346APRPRVEtsRAVPLAHATPase_c
AKT2P31751humanPKP1Q13835S59QKsKssQsstLsHsN
AKT2P31751humanH3C1P68431T45PHryrPGtVALrEIRHistone
AKT2P31751humanPKP1Q13835S119PDNRRFssysQMENW
AKT2P31751humanEPRS1P07814S999NQGGGLsssGAGEGQ
AKT2P31751humanWIPF1O43516S154PGrFPVPsPGHRSGP
AKT2P31751humanPKP1Q13835S56VKRQKsKssQsstLs
AKT2P31751humanMAT1AQ00266S180LPWLRPDsKTQVTVQS-AdoMet_synt_M


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
AKT2IDDescription0.00e+00
AKT2GO:0034599cellular response to oxidative stress9.95e-05
AKT2GO:0062197cellular response to chemical stress2.64e-04
AKT2GO:0034614cellular response to reactive oxygen species4.30e-04
AKT2GO:0071276cellular response to cadmium ion4.30e-04
AKT2GO:0043281regulation of cysteine-type endopeptidase activity involved in apoptotic process4.30e-04
AKT2GO:0006979response to oxidative stress5.07e-04
AKT2GO:0052548regulation of endopeptidase activity5.85e-04
AKT2GO:2000116regulation of cysteine-type endopeptidase activity7.62e-04
AKT2GO:0052547regulation of peptidase activity7.73e-04
AKT2GO:0000302response to reactive oxygen species8.13e-04
AKT2GO:0046686response to cadmium ion1.24e-03
AKT2GO:0008631intrinsic apoptotic signaling pathway in response to oxidative stress1.40e-03
AKT2GO:0002221pattern recognition receptor signaling pathway1.40e-03
AKT2GO:2001234negative regulation of apoptotic signaling pathway1.54e-03
AKT2GO:0071456cellular response to hypoxia1.77e-03
AKT2GO:0002758innate immune response-activating signaling pathway1.77e-03
AKT2GO:0032481positive regulation of type I interferon production1.78e-03
AKT2GO:0043122regulation of canonical NF-kappaB signal transduction1.95e-03
AKT2GO:0036294cellular response to decreased oxygen levels1.99e-03
AKT2GO:0002218activation of innate immune response2.19e-03
AKT2GO:0051402neuron apoptotic process2.19e-03
AKT2GO:0045088regulation of innate immune response2.35e-03
AKT2GO:0071453cellular response to oxygen levels2.61e-03
AKT2GO:0048732gland development2.61e-03
AKT2GO:0001666response to hypoxia2.61e-03
AKT2GO:0048145regulation of fibroblast proliferation2.61e-03
AKT2GO:0007249canonical NF-kappaB signal transduction2.61e-03
AKT2GO:0010464regulation of mesenchymal cell proliferation2.82e-03
AKT2GO:0032872regulation of stress-activated MAPK cascade2.85e-03
AKT2GO:0070302regulation of stress-activated protein kinase signaling cascade2.98e-03
AKT2GO:0036293response to decreased oxygen levels2.99e-03
AKT2GO:0097193intrinsic apoptotic signaling pathway3.10e-03
AKT2GO:0002757immune response-activating signaling pathway3.10e-03
AKT2GO:0043123positive regulation of canonical NF-kappaB signal transduction3.12e-03
AKT2GO:0043086negative regulation of catalytic activity3.20e-03
AKT2GO:0071248cellular response to metal ion3.24e-03
AKT2GO:0010863positive regulation of phospholipase C activity3.32e-03
AKT2GO:0071392cellular response to estradiol stimulus3.37e-03
AKT2GO:0010586miRNA metabolic process3.37e-03
AKT2GO:0048144fibroblast proliferation3.37e-03
AKT2GO:1900274regulation of phospholipase C activity3.37e-03
AKT2GO:0002764immune response-regulating signaling pathway3.37e-03
AKT2GO:0045089positive regulation of innate immune response3.37e-03
AKT2GO:0070482response to oxygen levels3.37e-03
AKT2GO:0045216cell-cell junction organization3.57e-03
AKT2GO:0032355response to estradiol3.87e-03
AKT2GO:0010463mesenchymal cell proliferation4.42e-03
AKT2GO:0071241cellular response to inorganic substance4.51e-03
AKT2GO:0002833positive regulation of response to biotic stimulus4.51e-03

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Related Drugs to ZIC1_AKT2


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 ZIC1-AKT2 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 ZIC1_AKT2


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