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Kinase Fusion Gene:HSPB1_CAMKK2 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: HSPB1_CAMKK2 | KinaseFusionDB ID: KFG2764 | FusionGDB2.0 ID: KFG2764 | Hgene | Tgene | Gene symbol | HSPB1 | CAMKK2 | Gene ID | 3315 | 10645 | |
| Gene name | heat shock protein family B (small) member 1 | calcium/calmodulin dependent protein kinase kinase 2 | ||||||||||
| Synonyms | CMT2F|HEL-S-102|HMN2B|HMND3|HS.76067|HSP27|HSP28|Hsp25|SRP27 | CAMKK|CAMKKB | ||||||||||
| Cytomap | 7q11.23 | 12q24.31 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | heat shock protein beta-128 kDa heat shock proteinepididymis secretory protein Li 102estrogen-regulated 24 kDa proteinheat shock 27 kDa proteinheat shock 27kD protein 1heat shock 27kDa protein 1stress-responsive protein 27 | calcium/calmodulin-dependent protein kinase kinase 2CAMKK beta proteincaM-KK 2caM-KK betacaM-kinase kinase 2caM-kinase kinase betacalcium/calmodulin-dependent protein kinase betacalcium/calmodulin-dependent protein kinase kinase 2, beta | ||||||||||
| Modification date | 20240416 | 20240403 | ||||||||||
| UniProtAcc | Q9Y547 | Q96RR4 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000248553, ENST00000429938, | ENST00000324774, ENST00000337174, ENST00000347034, ENST00000392473, ENST00000402834, ENST00000404169, ENST00000412367, ENST00000446440, ENST00000535524, ENST00000538733, ENST00000545538, ENST00000392474, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: HSPB1 [Title/Abstract] AND CAMKK2 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | HSPB1(75933612)-CAMKK2(121682418), # samples:1 | |||||||||||
| 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 |
| Tgene | CAMKK2 | GO:0006468 | protein phosphorylation | 11395482 |
| Tgene | CAMKK2 | GO:0046777 | protein autophosphorylation | 11395482 |
| Kinase Fusion gene breakpoints across HSPB1 (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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| Kinase Fusion gene breakpoints across CAMKK2 (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 |
| Kinase Fusion gene information. |
| 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. |
| Source | Sample | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp |
| ChimerDB4 | TCGA-XA-A8JR-01A | HSPB1 | chr7 | 75933612 | CAMKK2 | chr12 | 121682418 |
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Kinase Fusion ORF Analysis |
| Kinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Seq length (transcript) | Seq length (amino acids) |
| ENST00000248553 | ENST00000392474 | HSPB1 | chr7 | 75933612 | CAMKK2 | chr12 | 121682418 | 3801 | 231 |
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Kinase Fusion Amino Acid Sequences |
| 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 >ENST00000248553_ENST00000392474_HSPB1_chr7_75933612_CAMKK2_chr12_121682418_length(amino acids)=231 MEEHKSAAEPSAPHFSEQTSRAESASMTERRVPFSLLRGPSWDPFRDWYPHSRLFDQAFGLPRLPEEWSQWLGGSSWPGYVRPLPPAAIE SPAVAAPAYSRALSRQLSSGVSEIRHTADRWRVSLDVNHFAPDELTVKTKDGVVEITGKHEERQDEHGYISRCFTRKYTLPPGVDPTQVS -------------------------------------------------------------- |
Multiple Sequence Alignment of All Fusion Protein Isoforms |
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Kinase 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/chr7:75933612/chr12:121682418) - 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 |
| HSPB1 | CAMKK2 |
| FUNCTION: Component of the IFT complex B required for sonic hedgehog/SHH signaling. May mediate transport of SHH components: required for the export of SMO and PTCH1 receptors out of the cilium and the accumulation of GLI2 at the ciliary tip in response to activation of the SHH pathway, suggesting it is involved in the dynamic transport of SHH signaling molecules within the cilium. Not required for ciliary assembly. Its role in intraflagellar transport is mainly seen in tissues rich in ciliated cells such as kidney and testis. Essential for male fertility, spermiogenesis and sperm flagella formation. Plays a role in the early development of the kidney. May be involved in the regulation of ureteric bud initiation (By similarity). {ECO:0000250|UniProtKB:Q9D6H2}. | FUNCTION: Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5 and isoform 6 lacking part of the calmodulin-binding domain are inactive. Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca(2+) signals (By similarity). Seems to be involved in hippocampal activation of CREB1 (By similarity). May play a role in neurite growth. Isoform 3 may promote neurite elongation, while isoform 1 may promoter neurite branching. {ECO:0000250, ECO:0000269|PubMed:11395482, ECO:0000269|PubMed:12935886, ECO:0000269|PubMed:21957496, ECO:0000269|PubMed:9662074}. |
| 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 domain in the 5'-partner of fusion protein (protein functional feature from UniProt). |
| Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
| - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt). |
| Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
| Tgene | HSPB1 | 75933612 | CAMKK2 | 121682418 | ENST00000248553 | 0 | 15 | 165_446 | 0 | 499 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Tgene | HSPB1 | 75933612 | CAMKK2 | 121682418 | ENST00000248553 | 0 | 16 | 165_446 | 0 | 542 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
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Kinase Fusion Protein Structures |
| CIF files of the predicted kinase 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. |
| Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB) | Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | AA seq | Len(AA seq) |
| PDB file >>>TKFP_422_HSPB1_CAMKK2 | ENST00000248553 | ENST00000392474 | HSPB1 | chr7 | 75933612 | CAMKK2 | chr12 | 121682418 | MEEHKSAAEPSAPHFSEQTSRAESASMTERRVPFSLLRGPSWDPFRDWYPHSRLFDQAFGLPRLPEEWSQWLGGSSWPGYVRPLPPAAIE SPAVAAPAYSRALSRQLSSGVSEIRHTADRWRVSLDVNHFAPDELTVKTKDGVVEITGKHEERQDEHGYISRCFTRKYTLPPGVDPTQVS | 231_HSPB1_CAMKK2 |
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Comparison of Fusion Protein Isoforms |
| Superimpose the 3D Structures Among All Fusion Protein Isoforms * Download the pdb file and open it from the molstar online viewer. |
| Comparison of the Secondary Structures 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 score distribution |
| pLDDT score distribution of the predicted fusion protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. * The blue color at the bottom marks the best active site residues. |
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Potential Active Site Information |
| The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite. |
| Kinase Fusion AA seq ID in KinaseFusionDB | Site score | Size | Dscore | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
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Ramachandran Plot of Kinase 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. |
| 239_HSPB1_CAMKK2_ramachandran.png |
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Virtual Screening Results |
| Distribution of the average docking score across all approved kinase inhibitors. Distribution of the number of occurrence across all approved kinase inhibitors. |
| 5'-kinase fusion protein case |
| 3'-kinase fusion protein case |
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| Drug information from DrugBank of the top 20 interacting small molecules. * The detailed information of individual kinase inhibitors are available in the download page. |
| Fusion gene name info | Drug | Docking score | Glide g score | Glide energy |
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Kinase-Substrate Information of HSPB1_CAMKK2 |
| Phosphorylation target of the kinase (phosphosite, 03-17-2024) |
| Kinase | Kinase UniProt Acc | Kinase species | Substrate | Substrate UniProt Acc | Substrate phosphorylated residues | Substrate phosphorylated sites (+/-7AA) | Domain |
| CAMKK2 | Q96RR4 | human | SIRT1 | Q96EB6 | S47 | DGPGLERsPGEPGGA | |
| CAMKK2 | Q96RR4 | human | PRKAA1 | Q13131 | T183 | sDGEFLRtsCGsPNy | Pkinase |
| CAMKK2 | Q96RR4 | human | SIRT1 | Q96EB6 | S27 | ADREAAssPAGEPLR | |
| CAMKK2 | Q96RR4 | human | CAMKK2 | Q96RR4 | T85 | GQEVPLDtSGSQARP | |
| CAMKK2 | Q96RR4 | human | PRKAA2 | P54646 | T172 | sDGEFLRtsCGsPNy | Pkinase |
| CAMKK2 | Q96RR4 | human | AKT1 | P31749 | T308 | kDGAtMKtFCGtPEy | Pkinase |
| Biological Network Integration of This Kinase and Substrates (GeneMANIA website) |
| Enriched GO biological processes of the phosphorylation target genes of the kinase |
| Kinase | GOID | GO term | P.adjust |
| CAMKK2 | ID | Description | 0.00e+00 |
| CAMKK2 | GO:0034599 | cellular response to oxidative stress | 3.92e-07 |
| CAMKK2 | GO:0062197 | cellular response to chemical stress | 4.74e-07 |
| CAMKK2 | GO:0045913 | positive regulation of carbohydrate metabolic process | 4.74e-07 |
| CAMKK2 | GO:0010506 | regulation of autophagy | 5.19e-07 |
| CAMKK2 | GO:1901655 | cellular response to ketone | 6.30e-07 |
| CAMKK2 | GO:0006979 | response to oxidative stress | 6.30e-07 |
| CAMKK2 | GO:0071380 | cellular response to prostaglandin E stimulus | 6.46e-07 |
| CAMKK2 | GO:0055089 | fatty acid homeostasis | 6.86e-07 |
| CAMKK2 | GO:0071379 | cellular response to prostaglandin stimulus | 1.19e-06 |
| CAMKK2 | GO:0032006 | regulation of TOR signaling | 1.33e-06 |
| CAMKK2 | GO:0062013 | positive regulation of small molecule metabolic process | 1.33e-06 |
| CAMKK2 | GO:0034695 | response to prostaglandin E | 1.33e-06 |
| CAMKK2 | GO:0010508 | positive regulation of autophagy | 1.33e-06 |
| CAMKK2 | GO:0034614 | cellular response to reactive oxygen species | 1.37e-06 |
| CAMKK2 | GO:2000756 | regulation of peptidyl-lysine acetylation | 1.66e-06 |
| CAMKK2 | GO:0031929 | TOR signaling | 1.66e-06 |
| CAMKK2 | GO:0034694 | response to prostaglandin | 2.35e-06 |
| CAMKK2 | GO:0006109 | regulation of carbohydrate metabolic process | 2.38e-06 |
| CAMKK2 | GO:0090311 | regulation of protein deacetylation | 2.78e-06 |
| CAMKK2 | GO:0000302 | response to reactive oxygen species | 3.03e-06 |
| CAMKK2 | GO:1901654 | response to ketone | 3.06e-06 |
| CAMKK2 | GO:1901983 | regulation of protein acetylation | 4.20e-06 |
| CAMKK2 | GO:0042593 | glucose homeostasis | 5.80e-06 |
| CAMKK2 | GO:0033500 | carbohydrate homeostasis | 5.80e-06 |
| CAMKK2 | GO:0042149 | cellular response to glucose starvation | 6.31e-06 |
| CAMKK2 | GO:0006476 | protein deacetylation | 9.55e-06 |
| CAMKK2 | GO:0035601 | protein deacylation | 1.43e-05 |
| CAMKK2 | GO:0018394 | peptidyl-lysine acetylation | 1.44e-05 |
| CAMKK2 | GO:0098732 | macromolecule deacylation | 1.49e-05 |
| CAMKK2 | GO:0062012 | regulation of small molecule metabolic process | 1.49e-05 |
| CAMKK2 | GO:0032007 | negative regulation of TOR signaling | 1.68e-05 |
| CAMKK2 | GO:0097009 | energy homeostasis | 1.91e-05 |
| CAMKK2 | GO:0031331 | positive regulation of cellular catabolic process | 2.58e-05 |
| CAMKK2 | GO:0006631 | fatty acid metabolic process | 2.63e-05 |
| CAMKK2 | GO:1903432 | regulation of TORC1 signaling | 2.98e-05 |
| CAMKK2 | GO:0038202 | TORC1 signaling | 3.41e-05 |
| CAMKK2 | GO:0031400 | negative regulation of protein modification process | 3.41e-05 |
| CAMKK2 | GO:0097306 | cellular response to alcohol | 3.73e-05 |
| CAMKK2 | GO:0006473 | protein acetylation | 3.97e-05 |
| CAMKK2 | GO:0045833 | negative regulation of lipid metabolic process | 4.57e-05 |
| CAMKK2 | GO:0031667 | response to nutrient levels | 5.06e-05 |
| CAMKK2 | GO:0032070 | regulation of deoxyribonuclease activity | 5.19e-05 |
| CAMKK2 | GO:1903943 | regulation of hepatocyte apoptotic process | 5.19e-05 |
| CAMKK2 | GO:1904179 | positive regulation of adipose tissue development | 5.19e-05 |
| CAMKK2 | GO:0008286 | insulin receptor signaling pathway | 5.65e-05 |
| CAMKK2 | GO:0099004 | calmodulin dependent kinase signaling pathway | 6.07e-05 |
| CAMKK2 | GO:0043467 | regulation of generation of precursor metabolites and energy | 7.45e-05 |
| CAMKK2 | GO:1903008 | organelle disassembly | 8.46e-05 |
| CAMKK2 | GO:0043543 | protein acylation | 8.46e-05 |
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Related Drugs to HSPB1_CAMKK2 |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
| Distribution of the number of studies mentioning HSPB1-CAMKK2 and kinase inhibitors the PubMed Abstract (04-01-2024) |
| Fusion gene - drug pair 1 | Fusion gene - drug pair 2 | PMID | Publication date | DOI | Study title |
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Related Diseases to HSPB1_CAMKK2 |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Related diseases from the literature mentioned this fusion gene and drug. (PubMed, 04-01-2024) |
| MeSH ID | MeSH term |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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Clinical Trials of the Found Drugs/Small Molecules |
| Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024) |
| Clinical Trials from clinicaltrials.gov (06-17-2024) |
| Fusion Gene | Kinase Inhibitor | NCT ID | Study Status | Phases | Disease | # Enrolment | Date |
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