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Kinase Fusion Gene:MAP4K4_OGT |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: MAP4K4_OGT | KinaseFusionDB ID: KFG3486 | FusionGDB2.0 ID: KFG3486 | Hgene | Tgene | Gene symbol | MAP4K4 | OGT | Gene ID | 9448 | 8473 | |
Gene name | mitogen-activated protein kinase kinase kinase kinase 4 | O-linked N-acetylglucosamine (GlcNAc) transferase | ||||||||||
Synonyms | FLH21957|HEL-S-31|HGK|MEKKK4|NIK | HINCUT-1|HRNT1|MRX106|O-GLCNAC|OGT1|XLID106 | ||||||||||
Cytomap | 2q11.2 | Xq13.1 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | mitogen-activated protein kinase kinase kinase kinase 4HPK/GCK-like kinase HGKMAPK/ERK kinase kinase kinase 4MEK kinase kinase 4Ste20 group protein kinase HGKepididymis secretory protein Li 31hepatocyte progenitor kinase-like/germinal center kinase- | UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunitO-GlcNAc transferase p110 subunitO-GlcNAc transferase subunit p110O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminy | ||||||||||
Modification date | 20240407 | 20240407 | ||||||||||
UniProtAcc | O95819 | O15294 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000302217, ENST00000324219, ENST00000347699, ENST00000350198, ENST00000413150, ENST00000425019, ENST00000456652, ENST00000350878, ENST00000498066, | ENST00000498566, ENST00000373701, ENST00000373719, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: MAP4K4 [Title/Abstract] AND OGT [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | MAP4K4(102315000)-OGT(70764416), # 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 | MAP4K4 | GO:0006468 | protein phosphorylation | 9890973 |
Hgene | MAP4K4 | GO:0035556 | intracellular signal transduction | 9890973 |
Hgene | MAP4K4 | GO:0046328 | regulation of JNK cascade | 14966141 |
Tgene | OGT | GO:0006110 | regulation of glycolytic process | 22923583 |
Tgene | OGT | GO:0006493 | protein O-linked glycosylation | 21240259|21285374|22923583|23222540|23352454|24474760|30699359 |
Tgene | OGT | GO:0006915 | apoptotic process | 20824293 |
Tgene | OGT | GO:0032868 | response to insulin | 18288188 |
Tgene | OGT | GO:0035020 | regulation of Rac protein signal transduction | 18288188 |
Tgene | OGT | GO:0045727 | positive regulation of translation | 34074792 |
Tgene | OGT | GO:0045862 | positive regulation of proteolysis | 21285374 |
Tgene | OGT | GO:0045944 | positive regulation of transcription by RNA polymerase II | 23222540|23353889 |
Tgene | OGT | GO:0046626 | regulation of insulin receptor signaling pathway | 18288188 |
Tgene | OGT | GO:0071333 | cellular response to glucose stimulus | 37541260 |
Tgene | OGT | GO:1904263 | positive regulation of TORC1 signaling | 37541260 |
Kinase Fusion gene breakpoints across MAP4K4 (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 OGT (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-L5-A8NU | MAP4K4 | chr2 | 102315000 | OGT | chrX | 70764416 |
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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/chr2:102315000/chrX:70764416) - 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 |
MAP4K4 | OGT |
FUNCTION: Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322. {ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:9890973}. | FUNCTION: Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc) (PubMed:12150998, PubMed:19451179, PubMed:20018868, PubMed:26678539, PubMed:26369908, PubMed:23103939, PubMed:21240259, PubMed:21285374, PubMed:27713473, PubMed:15361863, PubMed:37541260). Glycosylates a large and diverse number of proteins including histone H2B, AKT1, AMPK, ATG4B, CAPRIN1, EZH2, FNIP1, RPTOR, HOXA1, PFKL, KMT2E/MLL5, MAPT/TAU, TET2, NOD2 and HCFC1 (PubMed:19451179, PubMed:20200153, PubMed:21285374, PubMed:22923583, PubMed:23353889, PubMed:24474760, PubMed:26678539, PubMed:26369908, PubMed:27527864, PubMed:30699359, PubMed:34074792, PubMed:34667079, PubMed:37541260). Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing (PubMed:21285374). Involved in insulin resistance in muscle and adipocyte cells via glycosylating insulin signaling components and inhibiting the 'Thr-308' phosphorylation of AKT1, enhancing IRS1 phosphorylation and attenuating insulin signaling (By similarity). Involved in glycolysis regulation by mediating glycosylation of 6-phosphofructokinase PFKL, inhibiting its activity (PubMed:22923583). Plays a key role in chromatin structure by mediating O-GlcNAcylation of 'Ser-112' of histone H2B: recruited to CpG-rich transcription start sites of active genes via its interaction with TET proteins (TET1, TET2 or TET3) (PubMed:22121020, PubMed:23353889). As part of the NSL complex indirectly involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). O-GlcNAcylation of 'Ser-75' of EZH2 increases its stability, and facilitating the formation of H3K27me3 by the PRC2/EED-EZH2 complex (PubMed:24474760). Stabilizes KMT2E/MLL5 by mediating its glycosylation, thereby preventing KMT2E/MLL5 ubiquitination (PubMed:26678539). Regulates circadian oscillation of the clock genes and glucose homeostasis in the liver (By similarity). Stabilizes clock proteins BMAL1 and CLOCK through O-glycosylation, which prevents their ubiquitination and subsequent degradation (By similarity). Promotes the CLOCK-BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2 and CRY1/2. O-glycosylates HCFC1 and regulates its proteolytic processing and transcriptional activity (PubMed:21285374, PubMed:28584052, PubMed:28302723). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). Regulates mitochondrial motility in neurons by mediating glycosylation of TRAK1 (By similarity). Promotes autophagy by mediating O-glycosylation of ATG4B (PubMed:27527864). Acts as a regulator of mTORC1 signaling by mediating O-glycosylation of RPTOR and FNIP1: O-GlcNAcylation of RPTOR in response to glucose sufficiency promotes activation of the mTORC1 complex (PubMed:30699359, PubMed:37541260). {ECO:0000250|UniProtKB:P56558, ECO:0000250|UniProtKB:Q8CGY8, ECO:0000269|PubMed:12150998, ECO:0000269|PubMed:15361863, ECO:0000269|PubMed:19451179, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:20018868, ECO:0000269|PubMed:20200153, ECO:0000269|PubMed:21240259, ECO:0000269|PubMed:21285374, ECO:0000269|PubMed:22121020, ECO:0000269|PubMed:22923583, ECO:0000269|PubMed:23103939, ECO:0000269|PubMed:23353889, ECO:0000269|PubMed:24474760, ECO:0000269|PubMed:24563466, ECO:0000269|PubMed:26369908, ECO:0000269|PubMed:26678539, ECO:0000269|PubMed:27527864, ECO:0000269|PubMed:28302723, ECO:0000269|PubMed:28584052, ECO:0000269|PubMed:30699359, ECO:0000269|PubMed:34074792, ECO:0000269|PubMed:34667079, ECO:0000269|PubMed:37541260}.; FUNCTION: [Isoform 2]: The mitochondrial isoform (mOGT) is cytotoxic and triggers apoptosis in several cell types including INS1, an insulinoma cell line. {ECO:0000269|PubMed:20824293}.; FUNCTION: [Isoform 4]: Has N-acetylglucosaminyltransferase activity: glycosylates proteins, such as HNRNPU, NEUROD1, NUP62 and PDCD6IP (PubMed:31527085). Displays specific substrate selectivity compared to other isoforms (PubMed:31527085). {ECO:0000269|PubMed:31527085}. |
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 MAP4K4_OGT |
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 |
MAP4K4 | O95819 | human | RDX | P35241 | T564 | AGRDKyKtLRQIRQG | ERM_C |
MAP4K4 | O95819 | human | EZR | P15311 | T567 | QGRDkyKtLRQIRQG | ERM_C |
MAP4K4 | O95819 | human | SMAD1 | Q15797 | T322 | sNVNRNStIENTRRH | MH2 |
MAP4K4 | O95819 | human | NR3C1 | P04150 | T562 | StWRIMTtLNMLGGR | Hormone_recep |
MAP4K4 | O95819 | human | LATS1 | O95835 | T1079 | EHAFyEFtFRRFFDD | |
MAP4K4 | O95819 | human | HTT | P42858 | S13 | kLMkAFEsLksFQQQ | |
MAP4K4 | O95819 | human | MAP3K11 | Q16584 | T738 | EEEPRGGtVsPPPGT | |
MAP4K4 | O95819 | human | ADAM10 | O14672 | S436 | NNKFSLCsIRNISQV | Reprolysin_2 |
MAP4K4 | O95819 | human | NR3C1 | P04150 | T519 | SENPGNKtIVPAtLP | |
MAP4K4 | O95819 | human | MSN | P26038 | T558 | LGRDKyKtLRQIRQG | ERM_C |
MAP4K4 | O95819 | human | HTT | P42858 | T3 | _____MAtLEkLMkA |
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 |
MAP4K4 | ID | Description | 0.00e+00 |
MAP4K4 | GO:1902946 | protein localization to early endosome | 4.12e-06 |
MAP4K4 | GO:1905668 | positive regulation of protein localization to endosome | 4.12e-06 |
MAP4K4 | GO:1905666 | regulation of protein localization to endosome | 4.12e-06 |
MAP4K4 | GO:1903651 | positive regulation of cytoplasmic transport | 4.91e-06 |
MAP4K4 | GO:2000641 | regulation of early endosome to late endosome transport | 8.36e-06 |
MAP4K4 | GO:0036010 | protein localization to endosome | 2.10e-05 |
MAP4K4 | GO:1903649 | regulation of cytoplasmic transport | 3.05e-05 |
MAP4K4 | GO:0045022 | early endosome to late endosome transport | 7.10e-05 |
MAP4K4 | GO:0061028 | establishment of endothelial barrier | 7.89e-05 |
MAP4K4 | GO:0098927 | vesicle-mediated transport between endosomal compartments | 7.89e-05 |
MAP4K4 | GO:1902115 | regulation of organelle assembly | 1.09e-04 |
MAP4K4 | GO:0001885 | endothelial cell development | 1.48e-04 |
MAP4K4 | GO:0032535 | regulation of cellular component size | 7.52e-04 |
MAP4K4 | GO:0045446 | endothelial cell differentiation | 9.32e-04 |
MAP4K4 | GO:0008360 | regulation of cell shape | 1.25e-03 |
MAP4K4 | GO:0003158 | endothelium development | 1.25e-03 |
MAP4K4 | GO:0016482 | cytosolic transport | 2.41e-03 |
MAP4K4 | GO:0032388 | positive regulation of intracellular transport | 3.06e-03 |
MAP4K4 | GO:0045732 | positive regulation of protein catabolic process | 3.30e-03 |
MAP4K4 | GO:0002064 | epithelial cell development | 3.31e-03 |
MAP4K4 | GO:0010737 | protein kinase A signaling | 3.87e-03 |
MAP4K4 | GO:0022604 | regulation of cell morphogenesis | 4.60e-03 |
MAP4K4 | GO:0044843 | cell cycle G1/S phase transition | 6.06e-03 |
MAP4K4 | GO:1902895 | positive regulation of miRNA transcription | 6.06e-03 |
MAP4K4 | GO:0071900 | regulation of protein serine/threonine kinase activity | 6.06e-03 |
MAP4K4 | GO:0071560 | cellular response to transforming growth factor beta stimulus | 6.06e-03 |
MAP4K4 | GO:0071559 | response to transforming growth factor beta | 6.21e-03 |
MAP4K4 | GO:0043525 | positive regulation of neuron apoptotic process | 6.33e-03 |
MAP4K4 | GO:0034332 | adherens junction organization | 6.33e-03 |
MAP4K4 | GO:2000630 | positive regulation of miRNA metabolic process | 7.72e-03 |
MAP4K4 | GO:0061180 | mammary gland epithelium development | 7.83e-03 |
MAP4K4 | GO:0032386 | regulation of intracellular transport | 7.83e-03 |
MAP4K4 | GO:2000401 | regulation of lymphocyte migration | 8.04e-03 |
MAP4K4 | GO:1902893 | regulation of miRNA transcription | 8.04e-03 |
MAP4K4 | GO:0061614 | miRNA transcription | 8.04e-03 |
MAP4K4 | GO:1990778 | protein localization to cell periphery | 8.04e-03 |
MAP4K4 | GO:0072678 | T cell migration | 8.14e-03 |
MAP4K4 | GO:0042176 | regulation of protein catabolic process | 8.33e-03 |
MAP4K4 | GO:1902117 | positive regulation of organelle assembly | 9.98e-03 |
MAP4K4 | GO:2000628 | regulation of miRNA metabolic process | 1.04e-02 |
MAP4K4 | GO:0043254 | regulation of protein-containing complex assembly | 1.11e-02 |
MAP4K4 | GO:0022406 | membrane docking | 1.11e-02 |
MAP4K4 | GO:0140747 | regulation of ncRNA transcription | 1.11e-02 |
MAP4K4 | GO:0048732 | gland development | 1.27e-02 |
MAP4K4 | GO:1901655 | cellular response to ketone | 1.33e-02 |
MAP4K4 | GO:0010586 | miRNA metabolic process | 1.35e-02 |
MAP4K4 | GO:0007015 | actin filament organization | 1.36e-02 |
MAP4K4 | GO:1903829 | positive regulation of protein localization | 1.44e-02 |
MAP4K4 | GO:0022411 | cellular component disassembly | 1.60e-02 |
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Related Drugs to MAP4K4_OGT |
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 MAP4K4-OGT 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 MAP4K4_OGT |
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 |