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Center for Computational Systems Medicine
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FusionGeneSummary

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FusionProtFeature

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FusionGeneSequence

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FusionGenePPI

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RelatedDrugs

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RelatedDiseases

Fusion gene ID: 17793

FusionGeneSummary for ITCH_SRC

check button Fusion gene summary
Fusion gene informationFusion gene name: ITCH_SRC
Fusion gene ID: 17793
HgeneTgene
Gene symbol

ITCH

SRC

Gene ID

83737

6714

Gene nameitchy E3 ubiquitin protein ligaseSRC proto-oncogene, non-receptor tyrosine kinase
SynonymsADMFD|AIF4|AIP4|NAPP1ASV|SRC1|THC6|c-SRC|p60-Src
Cytomap

20q11.22

20q11.23

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase Itchy homologHECT-type E3 ubiquitin transferase Itchy homologNFE2-associated polypeptide 1atrophin-1 interacting protein 4itchy E3 ubiquitin protein ligase homologproto-oncogene tyrosine-protein kinase Srcproto-oncogene c-Srcprotooncogene SRC, Rous sarcomatyrosine kinase pp60c-srctyrosine-protein kinase SRC-1v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog
Modification date2018052320180527
UniProtAcc

Q96J02

P12931

Ensembl transtripts involved in fusion geneENST00000374864, ENST00000535650, 
ENST00000262650, ENST00000483727, 
ENST00000445403, ENST00000373578, 
ENST00000360723, ENST00000358208, 
ENST00000373567, ENST00000373558, 
ENST00000477066, 
Fusion gene scores* DoF score18 X 13 X 12=28085 X 4 X 3=60
# samples 224
** MAII scorelog2(22/2808*10)=-3.6739675067799
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/60*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: ITCH [Title/Abstract] AND SRC [Title/Abstract] AND fusion [Title/Abstract]

Functional or gene categories assigned by FusionGDB annotation
* 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
HgeneITCH

GO:0006511

ubiquitin-dependent protein catabolic process

15678106

HgeneITCH

GO:0016567

protein ubiquitination

17592138|25631046

HgeneITCH

GO:0035519

protein K29-linked ubiquitination

17028573|18628966

HgeneITCH

GO:0070534

protein K63-linked ubiquitination

18718448|19592251

HgeneITCH

GO:0070936

protein K48-linked ubiquitination

19881509

TgeneSRC

GO:0018108

peptidyl-tyrosine phosphorylation

12051764|22732588

TgeneSRC

GO:0035556

intracellular signal transduction

15248232

TgeneSRC

GO:0046777

protein autophosphorylation

16441665

TgeneSRC

GO:0071902

positive regulation of protein serine/threonine kinase activity

19059439


check button Fusion gene information from three resources
(ChiTars (NAR, 2018), tumorfusions (NAR, 2018), Gao et al. (Cell, 2018))
* 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.
Data typeSourceCancer typeSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
TCGARVCOADTCGA-NH-A50V-01AITCHchr20

32957276

+SRCchr20

35993607

+
* LD: Li Ding group's fusion gene list
  RV: Roel Verhaak group's fusion gene list
  ChiTaRs fusion database

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
5UTR-intronENST00000374864ENST00000445403ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-5UTRENST00000374864ENST00000373578ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000374864ENST00000360723ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000374864ENST00000358208ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000374864ENST00000373567ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000374864ENST00000373558ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000374864ENST00000477066ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000535650ENST00000445403ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-5UTRENST00000535650ENST00000373578ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000535650ENST00000360723ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000535650ENST00000358208ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000535650ENST00000373567ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000535650ENST00000373558ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000535650ENST00000477066ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000262650ENST00000445403ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-5UTRENST00000262650ENST00000373578ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000262650ENST00000360723ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000262650ENST00000358208ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000262650ENST00000373567ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000262650ENST00000373558ITCHchr20

32957276

+SRCchr20

35993607

+
5UTR-intronENST00000262650ENST00000477066ITCHchr20

32957276

+SRCchr20

35993607

+
intron-intronENST00000483727ENST00000445403ITCHchr20

32957276

+SRCchr20

35993607

+
intron-5UTRENST00000483727ENST00000373578ITCHchr20

32957276

+SRCchr20

35993607

+
intron-intronENST00000483727ENST00000360723ITCHchr20

32957276

+SRCchr20

35993607

+
intron-intronENST00000483727ENST00000358208ITCHchr20

32957276

+SRCchr20

35993607

+
intron-intronENST00000483727ENST00000373567ITCHchr20

32957276

+SRCchr20

35993607

+
intron-intronENST00000483727ENST00000373558ITCHchr20

32957276

+SRCchr20

35993607

+
intron-intronENST00000483727ENST00000477066ITCHchr20

32957276

+SRCchr20

35993607

+

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FusionProtFeatures for ITCH_SRC


check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
ITCH

Q96J02

SRC

P12931

Non-receptor protein tyrosine kinase which is activatedfollowing engagement of many different classes of cellularreceptors including immune response receptors, integrins and otheradhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates insignaling pathways that control a diverse spectrum of biologicalactivities including gene transcription, immune response, celladhesion, cell cycle progression, apoptosis, migration, andtransformation. Due to functional redundancy between members ofthe SRC kinase family, identification of the specific role of eachSRC kinase is very difficult. SRC appears to be one of the primarykinases activated following engagement of receptors and plays arole in the activation of other protein tyrosine kinase (PTK)families. Receptor clustering or dimerization leads to recruitmentof SRC to the receptor complexes where it phosphorylates thetyrosine residues within the receptor cytoplasmic domains. Playsan important role in the regulation of cytoskeletal organizationthrough phosphorylation of specific substrates such as AFAP1.Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1and to localize to actin filaments. Cytoskeletal reorganization isalso controlled through the phosphorylation of cortactin (CTTN)(Probable). When cells adhere via focal adhesions to theextracellular matrix, signals are transmitted by integrins intothe cell resulting in tyrosine phosphorylation of a number offocal adhesion proteins, including PTK2/FAK1 and paxillin (PXN)(PubMed:21411625). In addition to phosphorylating focal adhesionproteins, SRC is also active at the sites of cell-cell contactadherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP).Another type of cell-cell junction, the gap junction, is also atarget for SRC, which phosphorylates connexin-43 (GJA1). SRC isimplicated in regulation of pre-mRNA-processing and phosphorylatesRNA-binding proteins such as KHDRBS1 (Probable). Also plays a rolein PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3,leading to increased DNA binding activity of these transcriptionfactors (By similarity). Involved in the RAS pathway throughphosphorylation of RASA1 and RASGRF1 (PubMed:11389730). Plays arole in EGF-mediated calcium-activated chloride channel activation(PubMed:18586953). Required for epidermal growth factor receptor(EGFR) internalization through phosphorylation of clathrin heavychain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin(ARRB1 and ARRB2) desensitization through phosphorylation andactivation of GRK2, leading to beta-arrestin phosphorylation andinternalization. Has a critical role in the stimulation of theCDK20/MAPK3 mitogen-activated protein kinase cascade by epidermalgrowth factor (Probable). Might be involved not only in mediatingthe transduction of mitogenic signals at the level of the plasmamembrane but also in controlling progression through the cellcycle via interaction with regulatory proteins in the nucleus(PubMed:7853507). Plays an important role in osteoclastic boneresorption in conjunction with PTK2B/PYK2. Both the formation of aSRC-PTK2B/PYK2 complex and SRC kinase activity are necessary forthis function. Recruited to activated integrins by PTK2B/PYK2,thereby phosphorylating CBL, which in turn induces the activationand recruitment of phosphatidylinositol 3-kinase to the cellmembrane in a signaling pathway that is critical for osteoclastfunction (PubMed:8755529, PubMed:14585963). Promotes energyproduction in osteoclasts by activating mitochondrial cytochrome Coxidase (PubMed:12615910). Phosphorylates DDR2 on tyrosineresidues, thereby promoting its subsequent autophosphorylation(PubMed:16186108). Phosphorylates RUNX3 and COX2 on tyrosineresidues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731' (PubMed:20100835,PubMed:21309750). Enhances DDX58/RIG-I-elicited antiviralsignaling (PubMed:19419966). Phosphorylates PDPK1 at 'Tyr-9','Tyr-373' and 'Tyr-376' (PubMed:14585963). Phosphorylates BCAR1 at'Tyr-128' (PubMed:22710723). Phosphorylates CBLC at multipletyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3activity (PubMed:20525694). Involved in anchorage-independent cellgrowth (PubMed:19307596). Required for podosome formation (Bysimilarity). {ECO:0000250|UniProtKB:P05480,ECO:0000269|PubMed:11389730, ECO:0000269|PubMed:12615910,ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:16186108,ECO:0000269|PubMed:18586953, ECO:0000269|PubMed:19307596,ECO:0000269|PubMed:19419966, ECO:0000269|PubMed:20100835,ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:21309750,ECO:0000269|PubMed:21411625, ECO:0000269|PubMed:22710723,ECO:0000269|PubMed:7853507, ECO:0000269|PubMed:8755529,ECO:0000269|PubMed:8759729, ECO:0000305|PubMed:11964124,ECO:0000305|PubMed:8672527, ECO:0000305|PubMed:9442882}.

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.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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FusionGeneSequence for ITCH_SRC


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences.
(nt: nucleotides, aa: amino acids)

* Fusion amino acid sequences.

* Fusion transcript sequences (only coding sequence (CDS) region).

* Fusion transcript sequences (Full-length transcript).

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FusionGenePPI for ITCH_SRC


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 (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors
ITCHNEDD9, SFN, NUMB, SCNN1A, SCNN1B, ATN1, RIPK1, RNF11, CXCR4, ARRB2, ARRB1, ITCH, NFE2, DTX1, CFLAR, TP53, ERBB4, N4BP1, TP73, UBE2L3, USP13, YAP1, USP9X, JUN, FYN, SMAD7, MLANA, SMAD3, POLR2A, CPSF6, NUDT21, UBAP2L, SH3GL2, HGS, CBLC, TP63, OCLN, SNX9, SNX18, BID, NDFIP2, SPG20, MAP2K4, TRPV4, CYLD, CBL, SH3GLB1, GLI1, TNFRSF10B, LATS1, LAPTM5, TOLLIP, ARRDC1, SMAD2, TGFBR1, AMOT, ELAVL1, TAX1BP1, TRAF6, STAM, STAM2, CAV1, MAVS, PCBP2, ARHGEF7, PRKACA, CSNK2A1, SGK3, TXNIP, MAPK8, DVL1, DVL2, DVL3, USP12, WDR48, BECN1, KLF10, LITAF, CUL3, UBC, MDM2, GNAI2, UBE2E1, UBE2G1, UBE2D2, UBE2E3, UBE2J2, CDC34, UBE2K, POU5F1, GBA, MGRN1, ARRDC3, ARRDC4, ADRB2, FBXL15, RASSF5, UBE2D3, NOTCH1, ARID1A, URI1, EWSR1, POLR2B, POLR2C, POLR2E, SMARCC1, SMARCC2, SMARCE1, DAZAP1, RPAP2, HNRNPL, HNRNPUL1, CPSF7, PABPC1, SF1, RPAP3, UBAP2, WBP2, WWOX, DTX3L, SMAD6, EGFR, HTT, ATXN3, PTCH1, GSN, GGA3, KPNB1, FAM189B, TMEM51, TMEM171, PLEKHB2, GRAP2, FAM189A2, WBP1, TMEM255A, TMEM92, LDLRAD4, TP53BP2, GRB2, NCOA1, NDFIP1, MAP3K7, TAB1, UBE2D1, GLIS3, LDLRAD3, IKBKB, BIN1, PACSIN1, ITSN1, PDCD6IP, COL18A1, HDAC6, KPNA2, LRRK2, PCNA, SCAMP3, SLC1A5, SLC3A2, UBA1, UBA6, USP5, WWP1, SMN1, GEMIN8, DDX20, RASSF1, WWP2, SARAF, ILDR1, UBE2M, JUNB, MARVELD2SRCEPHB2, ND2, TRIP6, CDH1, PIK3R1, ESR2, BCAR1, ESR1, AR, PELP1, NCOA6, TRPC6, GRIN2A, PLSCR1, PLD2, PLD1, CTNND1, ADRBK1, PDE6G, GRB2, CRK, DOCK1, PTK2, KHDRBS1, PLCG1, WAS, KIFAP3, ADRB2, ADRB3, GRB10, MAPK8IP3, TNFSF11, TRAF1, TRAF3, TRAF6, PTPN21, SLC9A2, AXL, DOK1, MAP2, LRP1, RET, FYN, LYN, EGFR, STAT1, TYRO3, PTK2B, RASA1, EFNB1, SYK, ASAP1, GAB3, ERBB2, RPS6KB1, RPS6KB2, DAG1, CDC37, RAF1, SKAP1, ARHGAP17, EVL, PECAM1, ASAP2, PXN, CSF1R, GSN, ARHGAP32, ITK, MUC1, SH3BP1, MET, RPL10, ARHGAP1, CD44, GNB2L1, PRKCZ, PTPRA, STAT3, BMX, DAB2, CSK, CAV1, MPZL1, EPS8, DDR2, GAB2, MATK, MYLK, SHB, TRPV4, CAV2, MICAL1, SYN1, HSP90AA1, CD46, EPHA3, EPHA4, RARA, ABL1, FLNA, PDGFRB, HDAC3, VDR, PRDM2, FGFR1, RXRA, THRB, CBL, HCK, EFNA5, PPARGC1B, CFL1, CBLL1, TNK2, NDFIP2, TLR4, TLR9, STUB1, CRMP1, EGLN1, SRC, NR3C1, CCNA1, PGR, PSMB9, SH3KBP1, TNFRSF1A, PDCD6IP, DNM2, DNM1, CBLC, SORBS1, KIT, LNX1, KDR, IQGAP1, CREBBP, FASLG, CHUK, IKBKB, KCNB1, KCND3, OSTF1, KCNA5, KCNA4, EFS, DDX58, MAVS, TBK1, PAK2, ADAM15, SKAP2, SH3BP2, CLTC, TOM1L1, IKBKG, PTPN2, SNCA, ENO1, WASL, SRCIN1, USP8, CDKN1B, PDE4D, HIF1A, MED28, DDX4, ZNF658B, KRT10, ERBB3, ARRB1, ARRB2, EDNRA, JAK2, EPOR, CSNK2A1, PTPN1, ANXA7, RGS16, PTGER4, SPRR2A, CA3, NEDD4, MAPT, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2L, POLR2J, POLR2K, CORO7, ALK, CCDC8, FBXO5, ABCE1, PHF19, SLC25A41, HOXB5, CEACAM21, FSD1, FYTTD1, NFKBIA, TMEM185A, CCNL2, TP53, MDM2, NTRK1, RASGRF1, YTHDC1, PIK3R3, SRPK2, AKT1, TRIM15, SH2D2A, PTGER2, TLN1, MAPK1, MAPK3, NR1I3, PBK, APP, HNRNPK, ERRFI1, CDC25A, EP300, CHEK1, S100B, RORC, ACTA1, P2RY2, PRUNE2, ACBD7, MED21, C1QL4, CYP2S1, RPS27, VDAC3, S1PR2, TNFAIP3, PCDHGC3, IL36RN, SLC29A1, S1PR1, ALOXE3, ISG20, PDIK1L, NCSTN, PRDM1, DHX57, FMO5, GLRX3, IFNGR1, COX6B1, TMEM220, PROM1, FAS, GRASP, GRM1, HSP90AB1, PTPN11, EMD, TMPO, PTPN6


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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RelatedDrugs for ITCH_SRC


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.0 2018-04-02)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status
TgeneSRCP12931DB06616BosutinibProto-oncogene tyrosine-protein kinase Srcsmall moleculeapproved
TgeneSRCP12931DB09079NintedanibProto-oncogene tyrosine-protein kinase Srcsmall moleculeapproved
TgeneSRCP12931DB01254DasatinibProto-oncogene tyrosine-protein kinase Srcsmall moleculeapproved|investigational
TgeneSRCP12931DB08901PonatinibProto-oncogene tyrosine-protein kinase Srcsmall moleculeapproved|investigational
TgeneSRCP12931DB04272Citric AcidProto-oncogene tyrosine-protein kinase Srcsmall moleculeapproved|nutraceutical|vet_approved

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RelatedDiseases for ITCH_SRC


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
TgeneSRCC0005695Bladder Neoplasm2CTD_human
TgeneSRCC0027626Neoplasm Invasiveness2CTD_human
TgeneSRCC0009319Colitis1CTD_human
TgeneSRCC0009375Colonic Neoplasms1CTD_human
TgeneSRCC0018800Cardiomegaly1CTD_human
TgeneSRCC0038220Status Epilepticus1CTD_human
TgeneSRCC0085548Autosomal Recessive Polycystic Kidney Disease1CTD_human
TgeneSRCC1458155Mammary Neoplasms1CTD_human