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Kinase Fusion Gene:RIPK2_YWHAE |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: RIPK2_YWHAE | KinaseFusionDB ID: KFG5391 | FusionGDB2.0 ID: KFG5391 | Hgene | Tgene | Gene symbol | RIPK2 | YWHAE | Gene ID | 8767 | 7531 | |
| Gene name | receptor interacting serine/threonine kinase 2 | tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon | ||||||||||
| Synonyms | CARD3|CARDIAK|CCK|GIG30|RICK|RIP2 | 14-3-3E|HEL2|KCIP-1|MDCR|MDS | ||||||||||
| Cytomap | 8q21.3 | 17p13.3 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | receptor-interacting serine/threonine-protein kinase 2CARD-carrying kinaseCARD-containing IL-1 beta ICE-kinaseCARD-containing interleukin-1 beta-converting enzyme (ICE)-associated kinaseRIP-2growth-inhibiting gene 30receptor-interacting protein (RIP | 14-3-3 protein epsilon14-3-3 epsilonepididymis luminal protein 2mitochondrial import stimulation factor L subunitprotein kinase C inhibitor protein-1tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptidetyrosine | ||||||||||
| Modification date | 20240411 | 20240413 | ||||||||||
| UniProtAcc | O43353 | P62258 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000220751, ENST00000540020, | ENST00000264335, ENST00000571732, ENST00000573026, ENST00000575977, ENST00000498643, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: RIPK2 [Title/Abstract] AND YWHAE [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | ||||||||||||
| 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 | RIPK2 | GO:0006915 | apoptotic process | 16920334 |
| Hgene | RIPK2 | GO:0010800 | positive regulation of peptidyl-threonine phosphorylation | 21887730 |
| Hgene | RIPK2 | GO:0032731 | positive regulation of interleukin-1 beta production | 11432859 |
| Hgene | RIPK2 | GO:0033138 | positive regulation of peptidyl-serine phosphorylation | 21887730 |
| Hgene | RIPK2 | GO:0034134 | toll-like receptor 2 signaling pathway | 11894098 |
| Hgene | RIPK2 | GO:0042742 | defense response to bacterium | 16824733|29452636 |
| Hgene | RIPK2 | GO:0043123 | positive regulation of canonical NF-kappaB signal transduction | 10329646 |
| Hgene | RIPK2 | GO:0045087 | innate immune response | 23806334 |
| Hgene | RIPK2 | GO:0050731 | positive regulation of peptidyl-tyrosine phosphorylation | 21887730 |
| Hgene | RIPK2 | GO:0051092 | positive regulation of NF-kappaB transcription factor activity | 11821383|29452636|30026309|30279485|30478312 |
| Hgene | RIPK2 | GO:0051260 | protein homooligomerization | 30279485|30478312 |
| Hgene | RIPK2 | GO:0070427 | nucleotide-binding oligomerization domain containing 1 signaling pathway | 29452636|30279485 |
| Hgene | RIPK2 | GO:0070431 | nucleotide-binding oligomerization domain containing 2 signaling pathway | 16824733|17355968|17562858|23806334|28545134|29452636|30026309|30279485|30478312 |
| Hgene | RIPK2 | GO:0071225 | cellular response to muramyl dipeptide | 21887730 |
| Hgene | RIPK2 | GO:0097202 | activation of cysteine-type endopeptidase activity | 11821383 |
| Hgene | RIPK2 | GO:1902523 | positive regulation of protein K63-linked ubiquitination | 17562858 |
| Tgene | YWHAE | GO:0000165 | MAPK cascade | 12917326 |
| Tgene | YWHAE | GO:0002753 | cytoplasmic pattern recognition receptor signaling pathway | 22607805 |
| Tgene | YWHAE | GO:0034122 | negative regulation of toll-like receptor signaling pathway | 35343654 |
| Tgene | YWHAE | GO:0034605 | cellular response to heat | 12917326 |
| Tgene | YWHAE | GO:0046827 | positive regulation of protein export from nucleus | 12917326 |
| Tgene | YWHAE | GO:0051480 | regulation of cytosolic calcium ion concentration | 18029012 |
| Tgene | YWHAE | GO:0060306 | regulation of membrane repolarization | 11953308 |
| Tgene | YWHAE | GO:0070972 | protein localization to endoplasmic reticulum | 35343654 |
| Tgene | YWHAE | GO:1901016 | regulation of potassium ion transmembrane transporter activity | 11953308 |
| Tgene | YWHAE | GO:1901020 | negative regulation of calcium ion transmembrane transporter activity | 18029012 |
| Tgene | YWHAE | GO:1902309 | negative regulation of peptidyl-serine dephosphorylation | 11953308 |
| Tgene | YWHAE | GO:1905913 | negative regulation of calcium ion export across plasma membrane | 18029012 |
| Kinase Fusion gene breakpoints across RIPK2 (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 YWHAE (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 |
| CCLE | OCI-P5x | RIPK2 | chr8 | 90785056 | YWHAE | chr17 | 1265302 |
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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/:/:) - 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 |
| RIPK2 | YWHAE |
| FUNCTION: Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses (PubMed:9575181, PubMed:9642260, PubMed:14638696, PubMed:21123652, PubMed:17054981, PubMed:28656966). Acts as a key effector of NOD1 and NOD2 signaling pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2 oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the formation of RIPK2 filaments (PubMed:17562858, PubMed:21123652, PubMed:17054981, PubMed:22607974, PubMed:28656966, PubMed:29452636, PubMed:30026309). Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3, as well as 'Met-1'-linked (linear) polyubiquitination by the LUBAC complex, becoming a scaffolding protein for downstream effectors (PubMed:22607974, PubMed:29452636, PubMed:28545134, PubMed:30279485, PubMed:30478312, PubMed:30026309). 'Met-1'-linked polyubiquitin chains attached to RIPK2 recruit IKBKG/NEMO, which undergoes 'Lys-63'-linked polyubiquitination in a RIPK2-dependent process (PubMed:22607974, PubMed:17562858, PubMed:29452636, PubMed:30026309). 'Lys-63'-linked polyubiquitin chains attached to RIPK2 serve as docking sites for TAB2 and TAB3 and mediate the recruitment of MAP3K7/TAK1 to IKBKG/NEMO, inducing subsequent activation of IKBKB/IKKB (PubMed:18079694). In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18079694). The protein kinase activity is dispensable for the NOD1 and NOD2 signaling pathways (PubMed:29452636, PubMed:30026309). Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappa-B activation by NOD2 (PubMed:21887730). Also involved in adaptive immunity: plays a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation (PubMed:14638696). Plays a role in the inactivation of RHOA in response to NGFR signaling (PubMed:26646181). {ECO:0000269|PubMed:14638696, ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:17562858, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:21123652, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:22607974, ECO:0000269|PubMed:26646181, ECO:0000269|PubMed:28545134, ECO:0000269|PubMed:28656966, ECO:0000269|PubMed:29452636, ECO:0000269|PubMed:30026309, ECO:0000269|PubMed:30279485, ECO:0000269|PubMed:30478312, ECO:0000269|PubMed:9575181, ECO:0000269|PubMed:9642260}. | FUNCTION: Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326). Plays a positive role in the antiviral signaling pathway upstream of TBK1 via interaction with RIGI (PubMed:37555661). Mechanistically, directs RIGI redistribution from the cytosol to mitochondrial associated membranes where it mediates MAVS-dependent innate immune signaling during viral infection (PubMed:22607805). Plays a role in proliferation inhibition and cell cycle arrest by exporting HNRNPC from the nucleus to the cytoplasm to be degraded by ubiquitination (PubMed:37599448). {ECO:0000250|UniProtKB:P62261, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:22607805, ECO:0000269|PubMed:37555661, ECO:0000269|PubMed:37599448}. |
| 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 RIPK2_YWHAE |
| 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 |
| RIPK2 | O43353 | human | RIPK2 | O43353 | S181 | sLsQsRsskSAPEGG | PK_Tyr_Ser-Thr |
| RIPK2 | O43353 | human | RIPK2 | O43353 | S180 | MsLsQsRsskSAPEG | PK_Tyr_Ser-Thr |
| RIPK2 | O43353 | human | RIPK2 | O43353 | S174 | LsKWRMMsLsQsRss | PK_Tyr_Ser-Thr |
| RIPK2 | O43353 | human | RIPK2 | O43353 | S176 | KWRMMsLsQsRsskS | PK_Tyr_Ser-Thr |
| RIPK2 | O43353 | human | RIPK2 | O43353 | S178 | RMMsLsQsRsskSAP | PK_Tyr_Ser-Thr |
| RIPK2 | O43353 | human | RIPK2 | O43353 | Y474 | DLIMKEDyELVSTkP | CARD |
| 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 |
| RIPK2 | ID | Description | 0.00e+00 |
| RIPK2 | GO:0070391 | response to lipoteichoic acid | 1.19e-02 |
| RIPK2 | GO:0071223 | cellular response to lipoteichoic acid | 1.19e-02 |
| RIPK2 | GO:2000563 | positive regulation of CD4-positiv | 5.30e-04 |
| RIPK2 | GO:0070673 | response to interleukin-18 | 1.19e-02 |
| RIPK2 | GO:0033083 | regulation of immature T cell proliferation | 1.19e-02 |
| RIPK2 | GO:0033084 | regulation of immature T cell proliferation in thymus | 1.19e-02 |
| RIPK2 | GO:0070671 | response to interleukin-12 | 1.19e-02 |
| RIPK2 | GO:0032494 | response to peptidoglycan | 1.19e-02 |
| RIPK2 | GO:0033079 | immature T cell proliferation | 1.19e-02 |
| RIPK2 | GO:0033080 | immature T cell proliferation in thymus | 1.19e-02 |
| RIPK2 | GO:0097202 | activation of cysteine-type endopeptidase activity | 1.19e-02 |
| RIPK2 | GO:0098792 | xenophagy | 1.19e-02 |
| RIPK2 | GO:1900044 | regulation of protein K63-linked ubiquitination | 1.19e-02 |
| RIPK2 | GO:0034134 | toll-like receptor 2 signaling pathway | 1.19e-02 |
| RIPK2 | GO:1902916 | positive regulation of protein polyubiquitination | 1.19e-02 |
| RIPK2 | GO:0002827 | positive regulation of T-helper 1 type immune response | 1.19e-02 |
| RIPK2 | GO:0070431 | nucleotide-binding oligomerization domain containing 2 signaling pathway | 1.19e-02 |
| RIPK2 | GO:0032495 | response to muramyl dipeptide | 1.19e-02 |
| RIPK2 | GO:0035739 | CD4-positiv | 1.17e-03 |
| RIPK2 | GO:2000561 | regulation of CD4-positiv | 1.17e-03 |
| RIPK2 | GO:0032727 | positive regulation of interferon-alpha production | 1.19e-02 |
| RIPK2 | GO:0060907 | positive regulation of macrophage cytokine production | 1.19e-02 |
| RIPK2 | GO:0046641 | positive regulation of alpha-beta T cell proliferation | 1.19e-02 |
| RIPK2 | GO:0070423 | nucleotide-binding oligomerization domain containing signaling pathway | 1.19e-02 |
| RIPK2 | GO:1902914 | regulation of protein polyubiquitination | 1.19e-02 |
| RIPK2 | GO:0010800 | positive regulation of peptidyl-threonine phosphorylation | 1.19e-02 |
| RIPK2 | GO:0035872 | nucleotide-binding domai | 1.54e-03 |
| RIPK2 | GO:0032647 | regulation of interferon-alpha production | 1.19e-02 |
| RIPK2 | GO:0002825 | regulation of T-helper 1 type immune response | 1.19e-02 |
| RIPK2 | GO:0032743 | positive regulation of interleukin-2 production | 1.24e-02 |
| RIPK2 | GO:0043372 | positive regulation of CD4-positiv | 1.80e-03 |
| RIPK2 | GO:0010934 | macrophage cytokine production | 1.24e-02 |
| RIPK2 | GO:0010935 | regulation of macrophage cytokine production | 1.24e-02 |
| RIPK2 | GO:0032728 | positive regulation of interferon-beta production | 1.25e-02 |
| RIPK2 | GO:0032735 | positive regulation of interleukin-12 production | 1.25e-02 |
| RIPK2 | GO:0045622 | regulation of T-helper cell differentiation | 1.25e-02 |
| RIPK2 | GO:0046640 | regulation of alpha-beta T cell proliferation | 1.25e-02 |
| RIPK2 | GO:2000516 | positive regulation of CD4-positiv | 2.33e-03 |
| RIPK2 | GO:0046633 | alpha-beta T cell proliferation | 1.25e-02 |
| RIPK2 | GO:0042088 | T-helper 1 type immune response | 1.25e-02 |
| RIPK2 | GO:0043330 | response to exogenous dsRNA | 1.25e-02 |
| RIPK2 | GO:0061082 | myeloid leukocyte cytokine production | 1.25e-02 |
| RIPK2 | GO:0046638 | positive regulation of alpha-beta T cell differentiation | 1.25e-02 |
| RIPK2 | GO:0034142 | toll-like receptor 4 signaling pathway | 1.25e-02 |
| RIPK2 | GO:0043370 | regulation of CD4-positiv | 2.97e-03 |
| RIPK2 | GO:0031663 | lipopolysaccharide-mediated signaling pathway | 1.25e-02 |
| RIPK2 | GO:0070534 | protein K63-linked ubiquitination | 1.25e-02 |
| RIPK2 | GO:0031638 | zymogen activation | 1.25e-02 |
| RIPK2 | GO:0032608 | interferon-beta production | 1.25e-02 |
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Related Drugs to RIPK2_YWHAE |
| 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 RIPK2-YWHAE 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 RIPK2_YWHAE |
| 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 |
| Tgene | YWHAE | C0036341 | Schizophrenia | 4 | PSYGENET |
| Tgene | YWHAE | C0005586 | Bipolar Disorder | 2 | PSYGENET |
| Tgene | YWHAE | C0206630 | Endometrial Stromal Sarcoma | 2 | ORPHANET |
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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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