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Fusion Protein:TMPRSS2-GUCA2A |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: TMPRSS2-GUCA2A | FusionPDB ID: 92383 | FusionGDB2.0 ID: 92383 | Hgene | Tgene | Gene symbol | TMPRSS2 | GUCA2A | Gene ID | 7113 | 2980 |
| Gene name | transmembrane serine protease 2 | guanylate cyclase activator 2A | |
| Synonyms | PP9284|PRSS10 | GCAP-I|GUCA2|STARA | |
| Cytomap | 21q22.3 | 1p34.2 | |
| Type of gene | protein-coding | protein-coding | |
| Description | transmembrane protease serine 2epitheliasinserine protease 10transmembrane protease, serine 2 | guanylinguanylate cyclase activator 2A (guanylin 2, intestinal, heat-stable)guanylate cyclase-activating protein 1guanylate cyclase-activating protein Iprepro-guanylin | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | O15393 | Q02747 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000332149, ENST00000458356, ENST00000497881, ENST00000398585, | ENST00000357001, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 40 X 73 X 10=29200 | 3 X 1 X 3=9 |
| # samples | 130 | 4 | |
| ** MAII score | log2(130/29200*10)=-4.48938484073892 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(4/9*10)=2.15200309344505 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: TMPRSS2 [Title/Abstract] AND GUCA2A [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | TMPRSS2(42880008)-GUCA2A(42629281), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | TMPRSS2-GUCA2A 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. TMPRSS2-GUCA2A 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) |
| Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Hgene | TMPRSS2 | GO:0006508 | proteolysis | 21068237|24227843 |
| Hgene | TMPRSS2 | GO:0046598 | positive regulation of viral entry into host cell | 21068237|24227843 |
| Fusion gene breakpoints across TMPRSS2 (5'-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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| Fusion gene breakpoints across GUCA2A (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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Fusion Gene Sample Information |
| Fusion gene information from FusionGDB2.0. |
| 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. |
| Source | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| ChimerDB4 | PRAD | TCGA-KC-A4BR-01A | TMPRSS2 | chr21 | 42880008 | - | GUCA2A | chr1 | 42629281 | - |
| ChimerDB4 | PRAD | TCGA-KC-A4BR | TMPRSS2 | chr21 | 42879876 | - | GUCA2A | chr1 | 42629281 | - |
| ChimerDB4 | PRAD | TCGA-KC-A4BR | TMPRSS2 | chr21 | 42880007 | - | GUCA2A | chr1 | 42629281 | - |
| ChimerDB4 | PRAD | TCGA-KC-A4BR | TMPRSS2 | chr21 | 42880008 | - | GUCA2A | chr1 | 42629281 | - |
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Fusion ORF Analysis |
| Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
| ENST00000398585 | TMPRSS2 | chr21 | 42879876 | - | ENST00000357001 | GUCA2A | chr1 | 42629281 | - | 604 | 116 | 574 | 143 | 143 |
| DeepORF 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. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
| ENST00000398585 | ENST00000357001 | TMPRSS2 | chr21 | 42879876 | - | GUCA2A | chr1 | 42629281 | - | 0.49672526 | 0.50327474 |
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Fusion Amino Acid Sequences |
| 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 >92383_92383_1_TMPRSS2-GUCA2A_TMPRSS2_chr21_42879876_ENST00000398585_GUCA2A_chr1_42629281_ENST00000357001_length(amino acids)=143AA_BP= MKWQGRTVLGRGLQSPSSSPGCSSRLDQGRLSCWEWSIMGGPFCRRKELPCCGGEAGSGQAPLASGTGSVGTDFTCARVLSDFLQPLKYL -------------------------------------------------------------- |
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Fusion Protein Functional Features |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr21:42880008/chr1:42629281) - 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. |
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| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| TMPRSS2 | GUCA2A |
| FUNCTION: Plasma membrane-anchored serine protease that participates in proteolytic cascades of relevance for the normal physiologic function of the prostate (PubMed:25122198). Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix disruption and metastasis of prostate cancer cells (PubMed:15537383, PubMed:26018085, PubMed:25122198). In addition, activates trigeminal neurons and contribute to both spontaneous pain and mechanical allodynia (By similarity). {ECO:0000250|UniProtKB:Q9JIQ8, ECO:0000269|PubMed:15537383, ECO:0000269|PubMed:25122198, ECO:0000269|PubMed:26018085}.; FUNCTION: (Microbial infection) Facilitates human coronaviruses SARS-CoV and SARS-CoV-2 infections via two independent mechanisms, proteolytic cleavage of ACE2 receptor which promotes viral uptake, and cleavage of coronavirus spike glycoproteins which activates the glycoprotein for host cell entry (PubMed:24227843, PubMed:32142651, PubMed:32404436, PubMed:34159616, PubMed:33051876). Upon SARS-CoV-2 infection, increases syncytia formation by accelerating the fusion process (PubMed:34159616, PubMed:33051876). Proteolytically cleaves and activates the spike glycoproteins of human coronavirus 229E (HCoV-229E) and human coronavirus EMC (HCoV-EMC) and the fusion glycoproteins F0 of Sendai virus (SeV), human metapneumovirus (HMPV), human parainfluenza 1, 2, 3, 4a and 4b viruses (HPIV). Essential for spread and pathogenesis of influenza A virus (strains H1N1, H3N2 and H7N9); involved in proteolytic cleavage and activation of hemagglutinin (HA) protein which is essential for viral infectivity. {ECO:0000269|PubMed:21068237, ECO:0000269|PubMed:21325420, ECO:0000269|PubMed:23536651, ECO:0000269|PubMed:23966399, ECO:0000269|PubMed:24027332, ECO:0000269|PubMed:24227843, ECO:0000269|PubMed:32142651, ECO:0000269|PubMed:32404436, ECO:0000269|PubMed:33051876, ECO:0000269|PubMed:34159616}. | FUNCTION: Endogenous activator of intestinal guanylate cyclase. It stimulates this enzyme through the same receptor binding region as the heat-stable enterotoxins. |
| Retention 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 * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| - Not-retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000332149 | - | 1 | 14 | 112_149 | 0 | 493.0 | Domain | LDL-receptor class A |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000332149 | - | 1 | 14 | 150_242 | 0 | 493.0 | Domain | SRCR |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000332149 | - | 1 | 14 | 256_489 | 0 | 493.0 | Domain | Peptidase S1 |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000398585 | - | 1 | 14 | 112_149 | 18.333333333333332 | 530.0 | Domain | LDL-receptor class A |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000398585 | - | 1 | 14 | 150_242 | 18.333333333333332 | 530.0 | Domain | SRCR |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000398585 | - | 1 | 14 | 256_489 | 18.333333333333332 | 530.0 | Domain | Peptidase S1 |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000458356 | - | 1 | 14 | 112_149 | 0 | 493.0 | Domain | LDL-receptor class A |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000458356 | - | 1 | 14 | 150_242 | 0 | 493.0 | Domain | SRCR |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000458356 | - | 1 | 14 | 256_489 | 0 | 493.0 | Domain | Peptidase S1 |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000332149 | - | 1 | 14 | 106_492 | 0 | 493.0 | Topological domain | Extracellular |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000332149 | - | 1 | 14 | 1_84 | 0 | 493.0 | Topological domain | Cytoplasmic |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000398585 | - | 1 | 14 | 106_492 | 18.333333333333332 | 530.0 | Topological domain | Extracellular |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000398585 | - | 1 | 14 | 1_84 | 18.333333333333332 | 530.0 | Topological domain | Cytoplasmic |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000458356 | - | 1 | 14 | 106_492 | 0 | 493.0 | Topological domain | Extracellular |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000458356 | - | 1 | 14 | 1_84 | 0 | 493.0 | Topological domain | Cytoplasmic |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000332149 | - | 1 | 14 | 85_105 | 0 | 493.0 | Transmembrane | Helical%3B Signal-anchor for type II membrane protein |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000398585 | - | 1 | 14 | 85_105 | 18.333333333333332 | 530.0 | Transmembrane | Helical%3B Signal-anchor for type II membrane protein |
| Hgene | TMPRSS2 | chr21:42879876 | chr1:42629281 | ENST00000458356 | - | 1 | 14 | 85_105 | 0 | 493.0 | Transmembrane | Helical%3B Signal-anchor for type II membrane protein |
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Fusion Protein-Protein Interaction |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in |
| Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160) |
| Gene | PPI interactors |
| TMPRSS2 | CLK1, HNRNPL, DCAF4, S, ACE2, STX7, SCD, PLP2, PLLP, MOSPD3, UPK2, SELK, C3orf52, IGFBP5, SEC22A, PLP1, CLN6, TMEM128, C14orf1, CFHR5, TMEM243, TMEM60, CXCL9, BNIP2, CNIH3, PGAP2, TMEM218, TMEM86A, CMTM7, ZFPL1, BMP10, TMEM79, SLC35A1, SFTPC, VAMP5, FAXDC2, STX8, NINJ2, CLEC7A, C2CD2L, CNIH2, BNIP3, DEFB103A, DEFB103B, TMEM11, C17orf62, TMEM86B, ADIPOQ, EDDM3B, BRICD5, PTTG1IP, PTCH1, ANKRD46, TMEM222, C1QL4, TMEM120B, FAM3C, TMEM229B, PLN, CTXN3, TNF, SMIM1, AQP1, TMPRSS2, DNASE2, MYO1C, PGRMC1, NDUFA4, ADAM10, CLGN, SEC16A, SPINT2, COCH, B4GAT1, XPOT, MYO1B, LANCL1, CALU, PLXNA2, GPC4, BANF1, CPD, CLPX, STC2, SLIT2, MYO1D, ERLIN2, BAG2, TFRC, HLA-A, TP53, RPN1, RPN2, GNAI2, APP, ITGB1, INSR, GLA, GPI, ITGAV, CTSD, APRT, IGF1R, MET, GNAI3, CLTA, CALM2, HLA-C, DLAT, HSPA5, LAMC1, LAMP1, IGF2R, PDIA4, P4HA1, HSP90B1, PVR, RPA2, ATP2A2, PFKL, CDH2, MSH3, RPA1, CALR, RPA3, LONP1, TGFBR1, DDOST, HADHA, ECE1, DNM2, FXR2, PLXNA3, ATP1B3, HADHB, SEC61A1, GNB1, NOMO3, PRKDC, TFAM, SLC7A5, PFKP, KIF23, FMR1, PTK7, ADAM15, CUL2, SCARB2, WRN, DSC3, ITIH4, GANAB, KARS, RCN1, SAFB, IMMT, HSD17B12, UBR4, QSOX2, RRM2B, MON2, YTHDF3, PABPN1, PLD3, PELP1, TTC13, CNNM3, IPO4, FAR1, GGH, ERLEC1, RBM33, DNAJA3, RBM14, PPP1R9B, SDF2, NEU1, GRWD1, AIF1L, NTPCR, FUCA2, EDEM3, RACGAP1, RAB18, TMEM106B, CHPF2, GNG12, DNAJB11, EGFL7, DDX20, ADAMTS1, LNPEP, ITM2B, MRPL11, HYOU1, AFG3L2, YTHDF2, SUPT16H, PDHX, IPO5, SAP18, HGS, SPTBN2, PLXNB2, ARPC3, ACTN4, TRIM13, PDCD6, MPDU1, SEC22B, ATP6AP2, STAM2, ARL6IP5, UFL1, SEC31A, STBD1, SMC2, SEC24A, SEC24B, ACSL3, CDK1, SRPR, SPTB, MTHFD1, ACTN1, ETFA, RAB6A, VDAC1, HMOX2, MYH10, DEK, ATP5C1, NAMPT, VDAC2, QARS, TUFM, SERPINH1, BCAP31, PSMD7, CLCN7, SLC25A1, YARS, EPPK1, RAB10, ABCE1, RHOA, CNBP, TPM4, SLC25A11, LMNB2, CKAP4, GOLGA3, TWF1, TRAP1, STX5, DDX39B, RAB3GAP1, PON2, PPA1, SEC23A, SEC23B, NDUFA9, ATP6V1F, INF2, ANO6, ACTBL2, MIA3, CDKAL1, KIAA0368, C19orf70, SLC25A24, HUWE1, MEGF8, KTN1, COMTD1, ANKLE2, VRK2, ZDHHC17, DNAH10, NUP93, MMGT1, TMEM199, ATPAF2, EMC1, PDZD8, NBEA, MOSPD2, PDCD6IP, SYNE2, UBXN4, CCDC47, LRRC59, C7orf55, DDRGK1, NGLY1, CDK5RAP3, CCDC115, CLCC1, OSBPL9, RBM15, CGRRF1, ESYT1, NDC1, EFHD1, OSBPL8, KIAA1715, LSG1, RAB1B, TMX1, GORASP2, SFXN1, XPO5, VEZT, JPH1, BIRC6, AAAS, TOMM22, DDX19A, SMPD4, TMOD3, EMC3, VAPA, CEP72, LARS, DPM3, DHCR7, UBA2, AASS, ATP6V1H, SLC25A13, STOML2, RAB21, MYO6, VDAC3, AUP1, SEC23IP, |
| Protein-protein interactors based on sequence similarity (STRING) |
| Gene | STRING network |
| TMPRSS2 |  |
| GUCA2A |
| - Retained interactions in fusion protein (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost interactions due to fusion (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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Related Drugs to TMPRSS2-GUCA2A |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to TMPRSS2-GUCA2A |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
| Hgene | TMPRSS2 | C0033578 | Prostatic Neoplasms | 4 | CTD_human |
| Hgene | TMPRSS2 | C0376358 | Malignant neoplasm of prostate | 4 | CTD_human |
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