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Fusion Protein:HSPA8-VSTM5 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: HSPA8-VSTM5 | FusionPDB ID: 37901 | FusionGDB2.0 ID: 37901 | Hgene | Tgene | Gene symbol | HSPA8 | VSTM5 | Gene ID | 3312 | 387804 |
| Gene name | heat shock protein family A (Hsp70) member 8 | V-set and transmembrane domain containing 5 | |
| Synonyms | HEL-33|HEL-S-72p|HSC54|HSC70|HSC71|HSP71|HSP73|HSPA10|LAP-1|LAP1|NIP71 | C11orf90 | |
| Cytomap | 11q24.1 | 11q21 | |
| Type of gene | protein-coding | protein-coding | |
| Description | heat shock cognate 71 kDa proteinLPS-associated protein 1N-myristoyltransferase inhibitor protein 71constitutive heat shock protein 70epididymis luminal protein 33epididymis secretory sperm binding protein Li 72pheat shock 70kDa protein 8heat shock | V-set and transmembrane domain-containing protein 5 | |
| Modification date | 20200327 | 20200313 | |
| UniProtAcc | P11142 | . | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000227378, ENST00000526110, ENST00000532636, ENST00000453788, ENST00000534624, ENST00000526862, ENST00000533540, ENST00000534319, | ENST00000409977, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 15 X 15 X 7=1575 | 1 X 1 X 1=1 |
| # samples | 17 | 1 | |
| ** MAII score | log2(17/1575*10)=-3.21174517713694 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(1/1*10)=3.32192809488736 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: HSPA8 [Title/Abstract] AND VSTM5 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | HSPA8(122931301)-VSTM5(93554489), # samples:2 | ||
| Anticipated loss of major functional domain due to fusion event. | HSPA8-VSTM5 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. HSPA8-VSTM5 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. HSPA8-VSTM5 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. HSPA8-VSTM5 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. HSPA8-VSTM5 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF. HSPA8-VSTM5 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. HSPA8-VSTM5 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target 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 | HSPA8 | GO:0042026 | protein refolding | 21231916|25719862 |
| Hgene | HSPA8 | GO:0045892 | negative regulation of transcription, DNA-templated | 10722728 |
| Hgene | HSPA8 | GO:0046034 | ATP metabolic process | 23921388 |
| Hgene | HSPA8 | GO:1902904 | negative regulation of supramolecular fiber organization | 23921388 |
| Fusion gene breakpoints across HSPA8 (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 VSTM5 (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 | HNSC | TCGA-KU-A6H7-01A | HSPA8 | chr11 | 122931301 | - | VSTM5 | chr11 | 93554489 | - |
| ChimerDB4 | HNSC | TCGA-KU-A6H7 | HSPA8 | chr11 | 122931301 | - | VSTM5 | chr11 | 93554489 | - |
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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) |
| ENST00000453788 | HSPA8 | chr11 | 122931301 | - | ENST00000409977 | VSTM5 | chr11 | 93554489 | - | 3537 | 688 | 277 | 933 | 218 |
| ENST00000534624 | HSPA8 | chr11 | 122931301 | - | ENST00000409977 | VSTM5 | chr11 | 93554489 | - | 3537 | 688 | 277 | 933 | 218 |
| 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 |
| ENST00000453788 | ENST00000409977 | HSPA8 | chr11 | 122931301 | - | VSTM5 | chr11 | 93554489 | - | 0.005544942 | 0.99445504 |
| ENST00000534624 | ENST00000409977 | HSPA8 | chr11 | 122931301 | - | VSTM5 | chr11 | 93554489 | - | 0.005544942 | 0.99445504 |
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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 >37901_37901_1_HSPA8-VSTM5_HSPA8_chr11_122931301_ENST00000453788_VSTM5_chr11_93554489_ENST00000409977_length(amino acids)=218AA_BP=137 MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKHW PFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEAYLGKVRVCPYTFLRPPSMPLSKKTSCSQLSTPVMECPPSNGHIHPIG -------------------------------------------------------------- >37901_37901_2_HSPA8-VSTM5_HSPA8_chr11_122931301_ENST00000534624_VSTM5_chr11_93554489_ENST00000409977_length(amino acids)=218AA_BP=137 MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKHW PFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEAYLGKVRVCPYTFLRPPSMPLSKKTSCSQLSTPVMECPPSNGHIHPIG -------------------------------------------------------------- |
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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/chr11:122931301/chr11:93554489) - 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 |
| HSPA8 | . |
| FUNCTION: Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488, PubMed:12526792). The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488, PubMed:12526792). The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24318877, PubMed:27474739, PubMed:24121476, PubMed:26865365). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:10722728, PubMed:11276205). Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1 (PubMed:23990462). Interacts with VGF-derived peptide TLQP-21 (PubMed:28934328). {ECO:0000269|PubMed:10722728, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:21148293, ECO:0000269|PubMed:21150129, ECO:0000269|PubMed:23018488, ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24732912, ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:27916661, ECO:0000269|PubMed:28934328, ECO:0000303|PubMed:24121476, ECO:0000303|PubMed:26865365}. | FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes. |
| 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 | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000227378 | - | 2 | 8 | 12_15 | 137.0 | 647.0 | Nucleotide binding | Note=ATP |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000453788 | - | 3 | 8 | 12_15 | 137.0 | 494.0 | Nucleotide binding | Note=ATP |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000532636 | - | 3 | 9 | 12_15 | 137.0 | 647.0 | Nucleotide binding | Note=ATP |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000534624 | - | 3 | 9 | 12_15 | 137.0 | 647.0 | Nucleotide binding | Note=ATP |
| Tgene | VSTM5 | chr11:122931301 | chr11:93554489 | ENST00000409977 | 0 | 4 | 37_139 | 30.333333333333332 | 201.0 | Domain | Note=Ig-like C2-type | |
| Tgene | VSTM5 | chr11:122931301 | chr11:93554489 | ENST00000409977 | 0 | 4 | 170_186 | 30.333333333333332 | 201.0 | Region | Important for CDC42-dependent filopodia induction | |
| Tgene | VSTM5 | chr11:122931301 | chr11:93554489 | ENST00000409977 | 0 | 4 | 169_200 | 30.333333333333332 | 201.0 | Topological domain | Cytoplasmic | |
| Tgene | VSTM5 | chr11:122931301 | chr11:93554489 | ENST00000409977 | 0 | 4 | 29_147 | 30.333333333333332 | 201.0 | Topological domain | Extracellular | |
| Tgene | VSTM5 | chr11:122931301 | chr11:93554489 | ENST00000409977 | 0 | 4 | 148_168 | 30.333333333333332 | 201.0 | Transmembrane | Helical |
| - 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 | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000227378 | - | 2 | 8 | 202_204 | 137.0 | 647.0 | Nucleotide binding | Note=ATP |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000227378 | - | 2 | 8 | 268_275 | 137.0 | 647.0 | Nucleotide binding | Note=ATP |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000453788 | - | 3 | 8 | 202_204 | 137.0 | 494.0 | Nucleotide binding | Note=ATP |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000453788 | - | 3 | 8 | 268_275 | 137.0 | 494.0 | Nucleotide binding | Note=ATP |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000532636 | - | 3 | 9 | 202_204 | 137.0 | 647.0 | Nucleotide binding | Note=ATP |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000532636 | - | 3 | 9 | 268_275 | 137.0 | 647.0 | Nucleotide binding | Note=ATP |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000534624 | - | 3 | 9 | 202_204 | 137.0 | 647.0 | Nucleotide binding | Note=ATP |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000534624 | - | 3 | 9 | 268_275 | 137.0 | 647.0 | Nucleotide binding | Note=ATP |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000227378 | - | 2 | 8 | 2_386 | 137.0 | 647.0 | Region | Nucleotide-binding domain (NBD) |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000227378 | - | 2 | 8 | 394_509 | 137.0 | 647.0 | Region | Substrate-binding domain (SBD) |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000453788 | - | 3 | 8 | 2_386 | 137.0 | 494.0 | Region | Nucleotide-binding domain (NBD) |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000453788 | - | 3 | 8 | 394_509 | 137.0 | 494.0 | Region | Substrate-binding domain (SBD) |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000532636 | - | 3 | 9 | 2_386 | 137.0 | 647.0 | Region | Nucleotide-binding domain (NBD) |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000532636 | - | 3 | 9 | 394_509 | 137.0 | 647.0 | Region | Substrate-binding domain (SBD) |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000534624 | - | 3 | 9 | 2_386 | 137.0 | 647.0 | Region | Nucleotide-binding domain (NBD) |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000534624 | - | 3 | 9 | 394_509 | 137.0 | 647.0 | Region | Substrate-binding domain (SBD) |
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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 >>>320_HSPA8_122931301_VSTM5_93554489_ranked_0.pdb | HSPA8 | 122931301 | 122931301 | ENST00000409977 | VSTM5 | chr11 | 93554489 | - | MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKHW PFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEAYLGKVRVCPYTFLRPPSMPLSKKTSCSQLSTPVMECPPSNGHIHPIG | 218 |
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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. |
HSPA8_pLDDT.png  |
VSTM5_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 |
| HSPA8 | |
| VSTM5 |
| - 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 |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000227378 | - | 2 | 8 | 186_377 | 137.0 | 647.0 | BAG1 |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000453788 | - | 3 | 8 | 186_377 | 137.0 | 494.0 | BAG1 |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000532636 | - | 3 | 9 | 186_377 | 137.0 | 647.0 | BAG1 |
| Hgene | HSPA8 | chr11:122931301 | chr11:93554489 | ENST00000534624 | - | 3 | 9 | 186_377 | 137.0 | 647.0 | BAG1 |
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Related Drugs to HSPA8-VSTM5 |
| 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 HSPA8-VSTM5 |
| 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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