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Fusion Protein:IDE-CAMK1D |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: IDE-CAMK1D | FusionPDB ID: 38230 | FusionGDB2.0 ID: 38230 | Hgene | Tgene | Gene symbol | IDE | CAMK1D | Gene ID | 3416 | 57118 |
| Gene name | insulin degrading enzyme | calcium/calmodulin dependent protein kinase ID | |
| Synonyms | INSULYSIN | CKLiK|CaM-K1|CaMKID | |
| Cytomap | 10q23.33 | 10p13 | |
| Type of gene | protein-coding | protein-coding | |
| Description | insulin-degrading enzymeAbeta-degrading proteaseinsulin proteaseinsulinase | calcium/calmodulin-dependent protein kinase type 1DCAMK1D/ANAPC5 fusionCaM kinase IDCamKI-like protein kinasecaM kinase I deltacaM-KI deltacaMKI delta | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | P14735 | Q8IU85 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000265986, ENST00000371581, ENST00000496903, | ENST00000378845, ENST00000487696, ENST00000378847, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 5 X 5 X 3=75 | 16 X 18 X 6=1728 |
| # samples | 5 | 19 | |
| ** MAII score | log2(5/75*10)=-0.584962500721156 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(19/1728*10)=-3.18503189383252 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: IDE [Title/Abstract] AND CAMK1D [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | IDE(94243012)-CAMK1D(12802947), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | IDE-CAMK1D 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. IDE-CAMK1D 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. IDE-CAMK1D 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. IDE-CAMK1D 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. IDE-CAMK1D seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. IDE-CAMK1D seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF. IDE-CAMK1D seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. IDE-CAMK1D seems lost the major protein functional domain in Tgene partner, which is a kinase due to the frame-shifted 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 | IDE | GO:0006508 | proteolysis | 18602473|20082125|21185309 |
| Hgene | IDE | GO:0008340 | determination of adult lifespan | 18448515 |
| Hgene | IDE | GO:0010815 | bradykinin catabolic process | 17613531|21185309 |
| Hgene | IDE | GO:0010992 | ubiquitin recycling | 21185309 |
| Hgene | IDE | GO:0032092 | positive regulation of protein binding | 9830016 |
| Hgene | IDE | GO:0042447 | hormone catabolic process | 19321446 |
| Hgene | IDE | GO:0043171 | peptide catabolic process | 20364150 |
| Hgene | IDE | GO:0050435 | amyloid-beta metabolic process | 9830016|17613531|26968463 |
| Hgene | IDE | GO:0051603 | proteolysis involved in cellular protein catabolic process | 9830016 |
| Hgene | IDE | GO:1901142 | insulin metabolic process | 18448515 |
| Hgene | IDE | GO:1901143 | insulin catabolic process | 9231799|9830016|19321446 |
| Tgene | CAMK1D | GO:0032793 | positive regulation of CREB transcription factor activity | 16324104 |
| Fusion gene breakpoints across IDE (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 CAMK1D (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-EJ-7314-01A | IDE | chr10 | 94243012 | - | CAMK1D | chr10 | 12802947 | + |
| ChimerDB4 | PRAD | TCGA-EJ-7314 | IDE | chr10 | 94243012 | - | CAMK1D | chr10 | 12802947 | + |
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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) |
| ENST00000265986 | IDE | chr10 | 94243012 | - | ENST00000378847 | CAMK1D | chr10 | 12802947 | + | 9314 | 1796 | 45 | 2654 | 869 |
| 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 |
| ENST00000265986 | ENST00000378847 | IDE | chr10 | 94243012 | - | CAMK1D | chr10 | 12802947 | + | 0.000448767 | 0.99955124 |
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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 >38230_38230_1_IDE-CAMK1D_IDE_chr10_94243012_ENST00000265986_CAMK1D_chr10_12802947_ENST00000378847_length(amino acids)=869AA_BP=579 MRWLMRYRLAWLLHPALPSTFRSVLGARLPPPERLCGFQKKTYSKMNNPAIKRIGNHITKSPEDKREYRGLELANGIKVLLISDPTTDKS SAALDVHIGSLSDPPNIAGLSHFCEHMLFLGTKKYPKENEYSQFLSEHAGSSNAFTSGEHTNYYFDVSHEHLEGALDRFAQFFLCPLFDE SCKDREVNAVDSEHEKNVMNDAWRLFQLEKATGNPKHPFSKFGTGNKYTLETRPNQEGIDVRQELLKFHSAYYSSNLMAVCVLGRESLDD LTNLVVKLFSEVENKNVPLPEFPEHPFQEEHLKQLYKIVPIKDIRNLYVTFPIPDLQKYYKSNPGHYLGHLIGHEGPGSLLSELKSKGWV NTLVGGQKEGARGFMFFIINVDLTEEGLLHVEDIILHMFQYIQKLRAEGPQEWVFQECKDLNAVAFRFKDKERPRGYTSKIAGILHYYPL EEVLTAEYLLEEFRPDLIEMVLDKLRPENVRVAIVSKSFEGKTDRTEEWYGTQYKQEAIPDEVIKKWQNADLNGKFKLPTKNEFIPTNFE ILPLEKEATPYPALIKDTAMSKLWFKQDDKFFLPKACLNFEFFRVSGGELFDRIVEKGFYTEKDASTLIRQVLDAVYYLHRMGIVHRDLK PENLLYYSQDEESKIMISDFGLSKMEGKGDVMSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDSKLFEQILKA EYEFDSPYWDDISDSAKDFIRNLMEKDPNKRYTCEQAARHPWIAGDTALNKNIHESVSAQIRKNFAKSKWRQAFNATAVVRHMRKLHLGS -------------------------------------------------------------- |
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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/chr10:94243012/chr10:12802947) - 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 |
| IDE | CAMK1D |
| FUNCTION: Plays a role in the cellular breakdown of insulin, APP peptides, IAPP peptides, natriuretic peptides, glucagon, bradykinin, kallidin, and other peptides, and thereby plays a role in intercellular peptide signaling (PubMed:2293021, PubMed:10684867, PubMed:26968463, PubMed:17051221, PubMed:17613531, PubMed:18986166, PubMed:19321446, PubMed:23922390, PubMed:24847884, PubMed:26394692, PubMed:29596046, PubMed:21098034). Substrate binding induces important conformation changes, making it possible to bind and degrade larger substrates, such as insulin (PubMed:23922390, PubMed:26394692, PubMed:29596046). Contributes to the regulation of peptide hormone signaling cascades and regulation of blood glucose homeostasis via its role in the degradation of insulin, glucagon and IAPP (By similarity). Plays a role in the degradation and clearance of APP-derived amyloidogenic peptides that are secreted by neurons and microglia (PubMed:9830016, PubMed:26394692) (Probable). Degrades the natriuretic peptides ANP, BNP and CNP, inactivating their ability to raise intracellular cGMP (PubMed:21098034). Also degrades an aberrant frameshifted 40-residue form of NPPA (fsNPPA) which is associated with familial atrial fibrillation in heterozygous patients (PubMed:21098034). Involved in antigen processing. Produces both the N terminus and the C terminus of MAGEA3-derived antigenic peptide (EVDPIGHLY) that is presented to cytotoxic T lymphocytes by MHC class I. {ECO:0000250|UniProtKB:Q9JHR7, ECO:0000269|PubMed:10684867, ECO:0000269|PubMed:17051221, ECO:0000269|PubMed:17613531, ECO:0000269|PubMed:18986166, ECO:0000269|PubMed:19321446, ECO:0000269|PubMed:20364150, ECO:0000269|PubMed:21098034, ECO:0000269|PubMed:2293021, ECO:0000269|PubMed:23922390, ECO:0000269|PubMed:24847884, ECO:0000269|PubMed:26394692, ECO:0000269|PubMed:26968463, ECO:0000269|PubMed:29596046, ECO:0000269|PubMed:9830016, ECO:0000305|PubMed:23922390}.; FUNCTION: (Microbial infection) The membrane-associated isoform acts as an entry receptor for varicella-zoster virus (VZV). {ECO:0000269|PubMed:17055432, ECO:0000269|PubMed:17553876}. | FUNCTION: Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, activates CREB-dependent gene transcription, regulates calcium-mediated granulocyte function and respiratory burst and promotes basal dendritic growth of hippocampal neurons. In neutrophil cells, required for cytokine-induced proliferative responses and activation of the respiratory burst. Activates the transcription factor CREB1 in hippocampal neuron nuclei. May play a role in apoptosis of erythroleukemia cells. In vitro, phosphorylates transcription factor CREM isoform Beta. {ECO:0000269|PubMed:11050006, ECO:0000269|PubMed:15840691, ECO:0000269|PubMed:16324104, ECO:0000269|PubMed:17056143}. |
| 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 |
| Hgene | IDE | chr10:94243012 | chr10:12802947 | ENST00000265986 | - | 14 | 25 | 336_342 | 579.6666666666666 | 1020.0 | Region | Note=Substrate binding exosite |
| Hgene | IDE | chr10:94243012 | chr10:12802947 | ENST00000265986 | - | 14 | 25 | 359_363 | 579.6666666666666 | 1020.0 | Region | Substrate binding |
| Tgene | CAMK1D | chr10:94243012 | chr10:12802947 | ENST00000378845 | 2 | 10 | 326_364 | 99.66666666666667 | 358.0 | Compositional bias | Note=Ser-rich | |
| Tgene | CAMK1D | chr10:94243012 | chr10:12802947 | ENST00000378847 | 2 | 11 | 326_364 | 99.66666666666667 | 386.0 | Compositional bias | Note=Ser-rich | |
| Tgene | CAMK1D | chr10:94243012 | chr10:12802947 | ENST00000378845 | 2 | 10 | 318_324 | 99.66666666666667 | 358.0 | Motif | Nuclear export signal | |
| Tgene | CAMK1D | chr10:94243012 | chr10:12802947 | ENST00000378847 | 2 | 11 | 318_324 | 99.66666666666667 | 386.0 | Motif | Nuclear export signal | |
| Tgene | CAMK1D | chr10:94243012 | chr10:12802947 | ENST00000378845 | 2 | 10 | 279_319 | 99.66666666666667 | 358.0 | Region | Autoinhibitory domain | |
| Tgene | CAMK1D | chr10:94243012 | chr10:12802947 | ENST00000378845 | 2 | 10 | 299_320 | 99.66666666666667 | 358.0 | Region | Calmodulin-binding | |
| Tgene | CAMK1D | chr10:94243012 | chr10:12802947 | ENST00000378847 | 2 | 11 | 279_319 | 99.66666666666667 | 386.0 | Region | Autoinhibitory domain | |
| Tgene | CAMK1D | chr10:94243012 | chr10:12802947 | ENST00000378847 | 2 | 11 | 299_320 | 99.66666666666667 | 386.0 | Region | Calmodulin-binding |
| - 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 | IDE | chr10:94243012 | chr10:12802947 | ENST00000265986 | - | 14 | 25 | 853_858 | 579.6666666666666 | 1020.0 | Motif | SlyX motif |
| Hgene | IDE | chr10:94243012 | chr10:12802947 | ENST00000371581 | - | 4 | 15 | 853_858 | 24.666666666666668 | 465.0 | Motif | SlyX motif |
| Hgene | IDE | chr10:94243012 | chr10:12802947 | ENST00000265986 | - | 14 | 25 | 895_901 | 579.6666666666666 | 1020.0 | Nucleotide binding | ATP |
| Hgene | IDE | chr10:94243012 | chr10:12802947 | ENST00000371581 | - | 4 | 15 | 895_901 | 24.666666666666668 | 465.0 | Nucleotide binding | ATP |
| Hgene | IDE | chr10:94243012 | chr10:12802947 | ENST00000371581 | - | 4 | 15 | 336_342 | 24.666666666666668 | 465.0 | Region | Note=Substrate binding exosite |
| Hgene | IDE | chr10:94243012 | chr10:12802947 | ENST00000371581 | - | 4 | 15 | 359_363 | 24.666666666666668 | 465.0 | Region | Substrate binding |
| Tgene | CAMK1D | chr10:94243012 | chr10:12802947 | ENST00000378845 | 2 | 10 | 23_279 | 99.66666666666667 | 358.0 | Domain | Protein kinase | |
| Tgene | CAMK1D | chr10:94243012 | chr10:12802947 | ENST00000378847 | 2 | 11 | 23_279 | 99.66666666666667 | 386.0 | Domain | Protein kinase | |
| Tgene | CAMK1D | chr10:94243012 | chr10:12802947 | ENST00000378845 | 2 | 10 | 29_37 | 99.66666666666667 | 358.0 | Nucleotide binding | ATP | |
| Tgene | CAMK1D | chr10:94243012 | chr10:12802947 | ENST00000378847 | 2 | 11 | 29_37 | 99.66666666666667 | 386.0 | Nucleotide binding | ATP |
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Fusion Protein Structures |
| 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) | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | AA seq | Len(AA seq) |
| PDB file >>>1657_IDE_94243012_CAMK1D_12802947_ranked_0.pdb | IDE | 94243012 | 94243012 | ENST00000378847 | CAMK1D | chr10 | 12802947 | + | MRWLMRYRLAWLLHPALPSTFRSVLGARLPPPERLCGFQKKTYSKMNNPAIKRIGNHITKSPEDKREYRGLELANGIKVLLISDPTTDKS SAALDVHIGSLSDPPNIAGLSHFCEHMLFLGTKKYPKENEYSQFLSEHAGSSNAFTSGEHTNYYFDVSHEHLEGALDRFAQFFLCPLFDE SCKDREVNAVDSEHEKNVMNDAWRLFQLEKATGNPKHPFSKFGTGNKYTLETRPNQEGIDVRQELLKFHSAYYSSNLMAVCVLGRESLDD LTNLVVKLFSEVENKNVPLPEFPEHPFQEEHLKQLYKIVPIKDIRNLYVTFPIPDLQKYYKSNPGHYLGHLIGHEGPGSLLSELKSKGWV NTLVGGQKEGARGFMFFIINVDLTEEGLLHVEDIILHMFQYIQKLRAEGPQEWVFQECKDLNAVAFRFKDKERPRGYTSKIAGILHYYPL EEVLTAEYLLEEFRPDLIEMVLDKLRPENVRVAIVSKSFEGKTDRTEEWYGTQYKQEAIPDEVIKKWQNADLNGKFKLPTKNEFIPTNFE ILPLEKEATPYPALIKDTAMSKLWFKQDDKFFLPKACLNFEFFRVSGGELFDRIVEKGFYTEKDASTLIRQVLDAVYYLHRMGIVHRDLK PENLLYYSQDEESKIMISDFGLSKMEGKGDVMSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDSKLFEQILKA EYEFDSPYWDDISDSAKDFIRNLMEKDPNKRYTCEQAARHPWIAGDTALNKNIHESVSAQIRKNFAKSKWRQAFNATAVVRHMRKLHLGS | 869 |
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pLDDT score distribution |
| 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. |
IDE_pLDDT.png  |
CAMK1D_pLDDT.png  |
| pLDDT score distribution of the predicted fusion protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
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Ramachandran Plot of Fusion Protein Structure |
| 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 |
| 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 |
| Protein-protein interactors based on sequence similarity (STRING) |
| Gene | STRING network |
| IDE | |
| CAMK1D |
| - 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 IDE-CAMK1D |
| 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 IDE-CAMK1D |
| 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 |
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