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Kinase Fusion Gene:LMTK2_CUL4A |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: LMTK2_CUL4A | KinaseFusionDB ID: KFG3181 | FusionGDB2.0 ID: KFG3181 | Hgene | Tgene | Gene symbol | LMTK2 | CUL4A | Gene ID | 22853 | 8451 | |
Gene name | lemur tyrosine kinase 2 | cullin 4A | ||||||||||
Synonyms | AATYK2|BREK|KPI-2|KPI2|LMR2|PPP1R100|cprk|hBREK | - | ||||||||||
Cytomap | 7q21.3 | 13q34 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | serine/threonine-protein kinase LMTK2CDK5/p35-regulated kinaseapoptosis-associated tyrosine kinase 2brain-enriched kinasecyclin-dependent kinase 5/p35-regulated kinasekinase/phosphatase/inhibitor 2protein phosphatase 1, regulatory subunit 100serine | cullin-4ACUL-4A | ||||||||||
Modification date | 20240411 | 20240407 | ||||||||||
UniProtAcc | Q8IWU2 | Q13619 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000297293, ENST00000493372, | ENST00000463426, ENST00000326335, ENST00000375440, ENST00000375441, ENST00000451881, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: LMTK2 [Title/Abstract] AND CUL4A [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | LMTK2(97788737)-CUL4A(113873259), # 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 | LMTK2 | GO:0006468 | protein phosphorylation | 12393858 |
Hgene | LMTK2 | GO:0018105 | peptidyl-serine phosphorylation | 16887929 |
Hgene | LMTK2 | GO:0018107 | peptidyl-threonine phosphorylation | 16887929 |
Hgene | LMTK2 | GO:0046777 | protein autophosphorylation | 12393858 |
Tgene | CUL4A | GO:0007283 | spermatogenesis | 34065512 |
Tgene | CUL4A | GO:0016567 | protein ubiquitination | 26431207 |
Tgene | CUL4A | GO:0042110 | T cell activation | 34065512 |
Tgene | CUL4A | GO:0045732 | positive regulation of protein catabolic process | 11027288|20870715 |
Tgene | CUL4A | GO:0140627 | ubiquitin-dependent protein catabolic process via the C-end degron rule pathway | 34065512 |
Kinase Fusion gene breakpoints across LMTK2 (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 CUL4A (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 | ERR315425 | LMTK2 | chr7 | 97788737 | CUL4A | chr13 | 113873259 |
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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/:97788737/:113873259) - 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 |
LMTK2 | CUL4A |
FUNCTION: Phosphorylates PPP1C, phosphorylase b and CFTR. | FUNCTION: Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination of target proteins (PubMed:14578910, PubMed:15811626, PubMed:15548678, PubMed:15448697, PubMed:14739464, PubMed:16678110, PubMed:17041588, PubMed:24209620, PubMed:30166453, PubMed:33854232, PubMed:33854239). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (PubMed:14578910, PubMed:15811626, PubMed:15548678, PubMed:15448697, PubMed:14739464, PubMed:16678110, PubMed:17041588, PubMed:24209620). The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (PubMed:14578910, PubMed:15811626, PubMed:15548678, PubMed:15448697, PubMed:14739464, PubMed:16678110, PubMed:17041588, PubMed:24209620). The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component (PubMed:14578910, PubMed:15811626, PubMed:15548678, PubMed:15448697, PubMed:14739464, PubMed:16678110, PubMed:17041588, PubMed:24209620). DCX(DET1-COP1) directs ubiquitination of JUN (PubMed:14739464). DCX(DDB2) directs ubiquitination of XPC (PubMed:15811626). DCX(DDB2) ubiquitinates histones H3-H4 and is required for efficient histone deposition during replication-coupled (H3.1) and replication-independent (H3.3) nucleosome assembly, probably by facilitating the transfer of H3 from ASF1A/ASF1B to other chaperones involved in histone deposition (PubMed:16678110, PubMed:17041588, PubMed:24209620). DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of p53/TP53 in response to radiation-induced DNA damage and during DNA replication (PubMed:14578910, PubMed:15548678, PubMed:15448697). DCX(DTL) directs autoubiquitination of DTL (PubMed:23478445). In association with DDB1 and SKP2 probably is involved in ubiquitination of CDKN1B/p27kip (PubMed:16537899). Is involved in ubiquitination of HOXA9 (PubMed:14609952). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207). A number of DCX complexes (containing either TRPC4AP or DCAF12 as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:29779948). The DCX(AMBRA1) complex is a master regulator of the transition from G1 to S cell phase by mediating ubiquitination of phosphorylated cyclin-D (CCND1, CCND2 and CCND3) (PubMed:33854232, PubMed:33854239). The DCX(AMBRA1) complex also acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (ELOC) component of CRL5 complexes (PubMed:30166453). With CUL4B, contributes to ribosome biogenesis (PubMed:26711351). {ECO:0000269|PubMed:14578910, ECO:0000269|PubMed:14609952, ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:15448697, ECO:0000269|PubMed:15548678, ECO:0000269|PubMed:15811626, ECO:0000269|PubMed:16537899, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:17041588, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:24209620, ECO:0000269|PubMed:26431207, ECO:0000269|PubMed:26711351, ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:30166453, ECO:0000269|PubMed:33854232, ECO:0000269|PubMed:33854239}. |
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 LMTK2_CUL4A |
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 |
LMTK2 | Q8IWU2 | human | PPP1CA | P62136 | T320 | NPGGRPItPPRNsAK | |
LMTK2 | Q8IWU2 | human | CFTR | P13569 | S737 | EPLERRLsLVPDSEQ | CFTR_R |
LMTK2 | Q8IWU2 | human | PYGB | P11216 | S15 | sEkRKQIsVRGLAGL |
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 |
LMTK2 | ID | Description | 0.00e+00 |
LMTK2 | GO:0005980 | glycogen catabolic process | 2.26e-04 |
LMTK2 | GO:0009251 | glucan catabolic process | 2.26e-04 |
LMTK2 | GO:0000272 | polysaccharide catabolic process | 2.26e-04 |
LMTK2 | GO:0005977 | glycogen metabolic process | 1.94e-03 |
LMTK2 | GO:0044042 | glucan metabolic process | 1.94e-03 |
LMTK2 | GO:0006112 | energy reserve metabolic process | 2.11e-03 |
LMTK2 | GO:0005976 | polysaccharide metabolic process | 2.37e-03 |
LMTK2 | GO:0016052 | carbohydrate catabolic process | 5.31e-03 |
LMTK2 | GO:0015980 | energy derivation by oxidation of organic compounds | 2.01e-02 |
LMTK2 | GO:0042045 | epithelial fluid transport | 2.51e-02 |
LMTK2 | GO:0060081 | membrane hyperpolarization | 2.51e-02 |
LMTK2 | GO:2001241 | positive regulation of extrinsic apoptotic signaling pathway in absence of ligand | 2.51e-02 |
LMTK2 | GO:0070170 | regulation of tooth mineralization | 2.51e-02 |
LMTK2 | GO:0043558 | regulation of translational initiation in response to stress | 2.51e-02 |
LMTK2 | GO:0070262 | peptidyl-serine dephosphorylation | 2.51e-02 |
LMTK2 | GO:1904321 | response to forskolin | 2.51e-02 |
LMTK2 | GO:1904322 | cellular response to forskolin | 2.51e-02 |
LMTK2 | GO:0035970 | peptidyl-threonine dephosphorylation | 2.89e-02 |
LMTK2 | GO:0044070 | regulation of monoatomic anion transport | 2.89e-02 |
LMTK2 | GO:0010288 | response to lead ion | 2.91e-02 |
LMTK2 | GO:0043555 | regulation of translation in response to stress | 2.91e-02 |
LMTK2 | GO:0070166 | enamel mineralization | 2.91e-02 |
LMTK2 | GO:0043153 | entrainment of circadian clock by photoperiod | 2.95e-02 |
LMTK2 | GO:0097186 | amelogenesis | 2.95e-02 |
LMTK2 | GO:0009648 | photoperiodism | 2.95e-02 |
LMTK2 | GO:0006833 | water transport | 2.95e-02 |
LMTK2 | GO:0009649 | entrainment of circadian clock | 2.95e-02 |
LMTK2 | GO:0035774 | positive regulation of insulin secretion involved in cellular response to glucose stimulus | 2.95e-02 |
LMTK2 | GO:0005979 | regulation of glycogen biosynthetic process | 2.95e-02 |
LMTK2 | GO:0010962 | regulation of glucan biosynthetic process | 2.95e-02 |
LMTK2 | GO:0034505 | tooth mineralization | 2.95e-02 |
LMTK2 | GO:0048240 | sperm capacitation | 2.95e-02 |
LMTK2 | GO:0050891 | multicellular organismal-level water homeostasis | 3.05e-02 |
LMTK2 | GO:0015701 | bicarbonate transport | 3.05e-02 |
LMTK2 | GO:0070633 | transepithelial transport | 3.05e-02 |
LMTK2 | GO:0042044 | fluid transport | 3.13e-02 |
LMTK2 | GO:0070873 | regulation of glycogen metabolic process | 3.13e-02 |
LMTK2 | GO:0032885 | regulation of polysaccharide biosynthetic process | 3.13e-02 |
LMTK2 | GO:0006904 | vesicle docking involved in exocytosis | 3.26e-02 |
LMTK2 | GO:0005978 | glycogen biosynthetic process | 3.26e-02 |
LMTK2 | GO:0009250 | glucan biosynthetic process | 3.26e-02 |
LMTK2 | GO:0032881 | regulation of polysaccharide metabolic process | 3.26e-02 |
LMTK2 | GO:2001239 | regulation of extrinsic apoptotic signaling pathway in absence of ligand | 3.26e-02 |
LMTK2 | GO:0071320 | cellular response to cAMP | 3.46e-02 |
LMTK2 | GO:2001238 | positive regulation of extrinsic apoptotic signaling pathway | 3.50e-02 |
LMTK2 | GO:0061178 | regulation of insulin secretion involved in cellular response to glucose stimulus | 3.50e-02 |
LMTK2 | GO:0070169 | positive regulation of biomineral tissue development | 3.50e-02 |
LMTK2 | GO:0006695 | cholesterol biosynthetic process | 3.58e-02 |
LMTK2 | GO:1902653 | secondary alcohol biosynthetic process | 3.58e-02 |
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Related Drugs to LMTK2_CUL4A |
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 LMTK2-CUL4A 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 LMTK2_CUL4A |
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 |