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Kinase Fusion Gene:MELK_CAMK2D |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: MELK_CAMK2D | KinaseFusionDB ID: KFG3769 | FusionGDB2.0 ID: KFG3769 | Hgene | Tgene | Gene symbol | MELK | CAMK2D | Gene ID | 9833 | 817 | |
Gene name | maternal embryonic leucine zipper kinase | calcium/calmodulin dependent protein kinase II delta | ||||||||||
Synonyms | HPK38 | CAMKD | ||||||||||
Cytomap | 9p13.2 | 4q26 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | maternal embryonic leucine zipper kinasepEg3 kinaseprotein kinase Eg3protein kinase PK38tyrosine-protein kinase MELK | calcium/calmodulin-dependent protein kinase type II subunit deltaCaM kinase II delta subunitCaM-kinase II delta chainCaMK-II delta subunitcalcium/calmodulin-dependent protein kinase (CaM kinase) II deltacalcium/calmodulin-dependent protein kinase typ | ||||||||||
Modification date | 20240403 | 20240407 | ||||||||||
UniProtAcc | Q14680 | Q13557 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000298048, ENST00000487398, ENST00000536329, ENST00000536860, ENST00000536987, ENST00000538311, ENST00000541717, ENST00000543751, ENST00000545008, | ENST00000296402, ENST00000394524, ENST00000394526, ENST00000418639, ENST00000429180, ENST00000454265, ENST00000342666, ENST00000379773, ENST00000394522, ENST00000505990, ENST00000508738, ENST00000509907, ENST00000511664, ENST00000514328, ENST00000515496, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: MELK [Title/Abstract] AND CAMK2D [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | MELK(36616841)-CAMK2D(114373574), # 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 |
Hgene | MELK | GO:0006915 | apoptotic process | 17280616 |
Hgene | MELK | GO:0008283 | cell population proliferation | 17280616 |
Hgene | MELK | GO:0046777 | protein autophosphorylation | 16216881 |
Tgene | CAMK2D | GO:0003254 | regulation of membrane depolarization | 22514276 |
Tgene | CAMK2D | GO:0006468 | protein phosphorylation | 17179159|23283722 |
Tgene | CAMK2D | GO:0018105 | peptidyl-serine phosphorylation | 22514276|23283722 |
Tgene | CAMK2D | GO:0018107 | peptidyl-threonine phosphorylation | 22514276|23283722 |
Tgene | CAMK2D | GO:0046777 | protein autophosphorylation | 22514276 |
Tgene | CAMK2D | GO:1901897 | regulation of relaxation of cardiac muscle | 23283722 |
Tgene | CAMK2D | GO:1902306 | negative regulation of sodium ion transmembrane transport | 22514276 |
Tgene | CAMK2D | GO:2000650 | negative regulation of sodium ion transmembrane transporter activity | 22514276 |
Kinase Fusion gene breakpoints across MELK (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
Kinase Fusion gene breakpoints across CAMK2D (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 |
ChiTaRS5.0 | BI492715 | MELK | chr9 | 36616841 | CAMK2D | chr4 | 114373574 |
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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) |
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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 |
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/:36616841/:114373574) - 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. |
Main function of each fusion partner protein. (from UniProt) |
Hgene | Tgene |
MELK | CAMK2D |
FUNCTION: Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis. {ECO:0000269|PubMed:11802789, ECO:0000269|PubMed:12400006, ECO:0000269|PubMed:14699119, ECO:0000269|PubMed:15908796, ECO:0000269|PubMed:16216881, ECO:0000269|PubMed:17280616}. | FUNCTION: Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and K(+) channel transport. Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure. Contributes to cardiac decompensation and heart failure by regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+) channel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2 repressor HDAC4, promoting its nuclear export and binding to 14-3-3 protein, and expression of MEF2 and genes involved in the hypertrophic program (PubMed:17179159). Is essential for left ventricular remodeling responses to myocardial infarction. In pathological myocardial remodeling acts downstream of the beta adrenergic receptor signaling cascade to regulate key proteins involved in ECC. Regulates Ca(2+) influx to myocytes by binding and phosphorylating the L-type Ca(2+) channel subunit beta-2 CACNB2. In addition to Ca(2+) channels, can target and regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca(2+) uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis (PubMed:16690701). May participate in the modulation of skeletal muscle function in response to exercise, by regulating SR Ca(2+) transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q6PHZ2, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:17179159}. |
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 |
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Kinase-Substrate Information of MELK_CAMK2D |
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 |
CAMK2D | Q13557 | human | HDAC4 | P56524 | S210 | YGKTQHSsLDQSsPP | |
CAMK2D | Q13557 | human | SCN5A | Q14524 | T594 | LHGkKNStVDCNGVV | Na_trans_cytopl |
CAMK2D | Q13557 | human | KCNQ1 | P51787 | T482 | sMPHFMRtNsFAEDL | |
CAMK2D | Q13557 | human | KCNJ11 | Q14654 | T224 | MQVVRKTtSPEGEVV | IRK_C |
CAMK2D | Q13557 | human | ANKRD28 | O15084 | S1011 | TNTskTVsFEALPIM | |
CAMK2D | Q13557 | human | RNF8 | O76064 | S157 | LRTKRkFsLDELAGP | |
CAMK2D | Q13557 | human | TTN | Q8WZ42 | T11922 | EVEVPTVtKRERKIP | |
CAMK2D | Q13557 | human | CACNB2 | Q08289-2 | T499 | RGLSRQEtFDSETQE | |
CAMK2D | Q13557 | human | KCNQ1 | P51787 | S484 | PHFMRtNsFAEDLDL | KCNQ_channel |
CAMK2D | Q13557 | human | CEACAM1 | P13688-8 | S459 | LHFGKtGsSGPLQ__ | |
CAMK2D | Q13557 | human | TTN | Q8WZ42 | S12022 | RRKLRPGsGGEKPPD | |
CAMK2D | Q13557 | human | SCN5A | Q14524 | S516 | LsLTrGLsRTsMKPR | Na_trans_cytopl |
CAMK2D | Q13557 | human | TTN | Q8WZ42 | T11932 | ERKIPEPtKVPEIKP | |
CAMK2D | Q13557 | human | TTN | Q8WZ42 | T11969 | PPVEPEPtPIAAPVT | |
CAMK2D | Q13557 | human | CAMK2D | Q13557 | T287 | sMMHRQEtVDCLKKF | |
CAMK2D | Q13557 | human | OCLN | Q16625 | S471 | LDDyREEsEEyMAAA | Occludin_ELL |
CAMK2D | Q13557 | human | CAMK2B | Q13554 | T287 | sMMHRQEtVECLKKF | |
CAMK2D | Q13557 | human | CEACAM1 | P13688-8 | T457 | CFLHFGKtGsSGPLQ | |
CAMK2D | Q13557 | human | TTN | Q8WZ42 | S11878 | KEEVVLKsVLRKRPE | |
CAMK2D | Q13557-8 | human | TPD52 | P55327 | S176 | kNsPtFksFEEkVEN | TPD52 |
MELK | Q14680 | human | CDC25B | P30305 | S169 | VLRNItNsQAPDGRR | M-inducer_phosp |
MELK | Q14680 | human | MELK | Q14680 | T539 | RGLDkVItVLtRsKR | |
MELK | Q14680 | human | MELK | Q14680 | T387 | DLSTGAAtPRTsQFT | |
MELK | Q14680 | human | MELK | Q14680 | T494 | TGtDkLMtGVIsPER | |
MELK | Q14680 | human | MELK | Q14680 | S431 | ENVytPKsAVkNEEy | |
MELK | Q14680 | human | MELK | Q14680 | T398 | sQFTkYWtEsNGVEs | |
MELK | Q14680 | human | MELK | Q14680 | T167 | NkDyHLQtCCGsLAY | Pkinase |
MELK | Q14680 | human | MELK | Q14680 | S171 | HLQtCCGsLAYAAPE | Pkinase |
MELK | Q14680 | human | CDC25B | P30305 | S323 | QRLFRsPsMPCsVIR | M-inducer_phosp |
MELK | Q14680 | human | MELK | Q14680 | S405 | tEsNGVEsksLtPAL | |
MELK | Q14680 | human | MELK | Q14680 | T409 | GVEsksLtPALCRtP | |
MELK | Q14680 | human | MELK | Q14680 | S356 | DIKSNNWsLEDVTAs | |
MELK | Q14680 | human | MELK | Q14680 | Y438 | sAVkNEEyFMFPEPK | |
MELK | Q14680 | human | MELK | Q14680 | S529 | KGAkVFGsLERGLDk | |
MELK | Q14680 | human | MELK | Q14680 | Y367 | VTAsDKNyVAGLIDY | |
MELK | Q14680 | human | EIF4B | P23588 | S406 | RPRERHPsWRsEEtQ | |
MELK | Q14680 | human | EZH2 | Q15910 | S220 | RPPRKFPsDKIFEAI | PRC2_HTH_1 |
MELK | Q14680 | human | MELK | Q14680 | S505 | sPERRCRsVELDLNQ | |
MELK | Q14680 | human | MELK | Q14680 | S407 | sNGVEsksLtPALCR | |
MELK | Q14680 | human | MELK | Q14680 | S336 | PVRLRLssFsCGQAs | |
MELK | Q14680 | human | MELK | Q14680 | S343 | sFsCGQAsAtPFtDI | |
MELK | Q14680 | human | MELK | Q14680 | S391 | GAAtPRTsQFTkYWt | |
MELK | Q14680 | human | EIF4B | P23588 | S422 | RERsRtGsEssQtGt | |
MELK | Q14680 | human | MELK | Q14680 | Y163 | kPKGNkDyHLQtCCG | Pkinase |
MELK | Q14680 | human | MELK | Q14680 | S253 | VDPKKRIsMkNLLNH | Pkinase |
MELK | Q14680 | human | MELK | Q14680 | T56 | sDLPRIktEIEALkN | 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 |
CAMK2D | ID | Description | 0.00e+00 |
CAMK2D | GO:0003012 | muscle system process | 2.29e-06 |
CAMK2D | GO:0086091 | regulation of heart rate by cardiac conduction | 2.54e-06 |
CAMK2D | GO:0060048 | cardiac muscle contraction | 3.64e-06 |
CAMK2D | GO:0001508 | action potential | 3.64e-06 |
CAMK2D | GO:0086065 | cell communication involved in cardiac conduction | 5.79e-06 |
CAMK2D | GO:0006941 | striated muscle contraction | 8.17e-06 |
CAMK2D | GO:0086001 | cardiac muscle cell action potential | 1.09e-05 |
CAMK2D | GO:0086003 | cardiac muscle cell contraction | 1.09e-05 |
CAMK2D | GO:0086014 | atrial cardiac muscle cell action potential | 1.28e-05 |
CAMK2D | GO:0086026 | atrial cardiac muscle cell to AV node cell signaling | 1.28e-05 |
CAMK2D | GO:0086066 | atrial cardiac muscle cell to AV node cell communication | 1.28e-05 |
CAMK2D | GO:0060047 | heart contraction | 1.44e-05 |
CAMK2D | GO:0043502 | regulation of muscle adaptation | 1.44e-05 |
CAMK2D | GO:0090257 | regulation of muscle system process | 1.44e-05 |
CAMK2D | GO:0061337 | cardiac conduction | 1.47e-05 |
CAMK2D | GO:0003015 | heart process | 1.47e-05 |
CAMK2D | GO:0002027 | regulation of heart rate | 1.68e-05 |
CAMK2D | GO:0070252 | actin-mediated cell contraction | 1.78e-05 |
CAMK2D | GO:0043500 | muscle adaptation | 2.70e-05 |
CAMK2D | GO:0030048 | actin filament-based movement | 4.11e-05 |
CAMK2D | GO:0086019 | cell-cell signaling involved in cardiac conduction | 4.11e-05 |
CAMK2D | GO:0006936 | muscle contraction | 5.19e-05 |
CAMK2D | GO:0010959 | regulation of metal ion transport | 9.21e-05 |
CAMK2D | GO:0086002 | cardiac muscle cell action potential involved in contraction | 1.38e-04 |
CAMK2D | GO:0042391 | regulation of membrane potential | 1.38e-04 |
CAMK2D | GO:0034765 | regulation of monoatomic ion transmembrane transport | 1.55e-04 |
CAMK2D | GO:0008016 | regulation of heart contraction | 1.82e-04 |
CAMK2D | GO:0055117 | regulation of cardiac muscle contraction | 3.86e-04 |
CAMK2D | GO:1903522 | regulation of blood circulation | 3.88e-04 |
CAMK2D | GO:0051899 | membrane depolarization | 3.88e-04 |
CAMK2D | GO:0086016 | AV node cell action potential | 4.57e-04 |
CAMK2D | GO:0086027 | AV node cell to bundle of His cell signaling | 4.57e-04 |
CAMK2D | GO:0099624 | atrial cardiac muscle cell membrane repolarization | 4.57e-04 |
CAMK2D | GO:0014854 | response to inactivity | 5.17e-04 |
CAMK2D | GO:0086067 | AV node cell to bundle of His cell communication | 5.17e-04 |
CAMK2D | GO:0014874 | response to stimulus involved in regulation of muscle adaptation | 5.81e-04 |
CAMK2D | GO:0003300 | cardiac muscle hypertrophy | 5.81e-04 |
CAMK2D | GO:0006942 | regulation of striated muscle contraction | 5.81e-04 |
CAMK2D | GO:0014897 | striated muscle hypertrophy | 6.19e-04 |
CAMK2D | GO:1904062 | regulation of monoatomic cation transmembrane transport | 6.25e-04 |
CAMK2D | GO:0014896 | muscle hypertrophy | 6.25e-04 |
CAMK2D | GO:1902514 | regulation of calcium ion transmembrane transport via high voltage-gated calcium channel | 8.86e-04 |
CAMK2D | GO:1902074 | response to salt | 1.05e-03 |
CAMK2D | GO:0061577 | calcium ion transmembrane transport via high voltage-gated calcium channel | 1.06e-03 |
CAMK2D | GO:0098659 | inorganic cation import across plasma membrane | 1.27e-03 |
CAMK2D | GO:0099587 | inorganic ion import across plasma membrane | 1.27e-03 |
CAMK2D | GO:0086012 | membrane depolarization during cardiac muscle cell action potential | 1.34e-03 |
CAMK2D | GO:0051592 | response to calcium ion | 1.41e-03 |
CAMK2D | GO:0060307 | regulation of ventricular cardiac muscle cell membrane repolarization | 1.41e-03 |
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Related Drugs to MELK_CAMK2D |
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 MELK-CAMK2D 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 MELK_CAMK2D |
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 |