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Fusion Protein:TYK2-KEAP1 |
Fusion Gene and Fusion Protein Summary |
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Fusion partner gene information | Fusion gene name: TYK2-KEAP1 | FusionPDB ID: 95651 | FusionGDB2.0 ID: 95651 | Hgene | Tgene | Gene symbol | TYK2 | KEAP1 | Gene ID | 7297 | 9817 |
Gene name | tyrosine kinase 2 | kelch like ECH associated protein 1 | |
Synonyms | IMD35|JTK1 | INrf2|KLHL19 | |
Cytomap | 19p13.2 | 19p13.2 | |
Type of gene | protein-coding | protein-coding | |
Description | non-receptor tyrosine-protein kinase TYK2 | kelch-like ECH-associated protein 1KEAP1 delta Ccytosolic inhibitor of Nrf2kelch-like family member 19kelch-like protein 19 | |
Modification date | 20200329 | 20200327 | |
UniProtAcc | . | Q14145 Main function of 5'-partner protein: FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination (PubMed:14585973, PubMed:15379550, PubMed:15572695, PubMed:15983046, PubMed:15601839). KEAP1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:15601839, PubMed:16006525). In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine residues in KEAP1, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes (PubMed:19489739, PubMed:16006525, PubMed:17127771, PubMed:18251510, PubMed:29590092). In response to selective autophagy, KEAP1 is sequestered in inclusion bodies following its interaction with SQSTM1/p62, leading to inactivation of the BCR(KEAP1) complex and activation of NFE2L2/NRF2 (PubMed:20452972). The BCR(KEAP1) complex also mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62 sequestering activity and degradation (PubMed:28380357). The BCR(KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradation by the proteasome (PubMed:15379550, PubMed:17046835). {ECO:0000269|PubMed:14585973, ECO:0000269|PubMed:15379550, ECO:0000269|PubMed:15572695, ECO:0000269|PubMed:15601839, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16006525, ECO:0000269|PubMed:17046835, ECO:0000269|PubMed:17127771, ECO:0000269|PubMed:18251510, ECO:0000269|PubMed:19489739, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:29590092}. | |
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000264818, ENST00000524462, ENST00000525621, ENST00000529370, ENST00000529422, | ENST00000588024, ENST00000171111, ENST00000393623, |
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 13 X 11 X 8=1144 | 6 X 5 X 5=150 |
# samples | 15 | 8 | |
** MAII score | log2(15/1144*10)=-2.93105264628251 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(8/150*10)=-0.906890595608519 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
Fusion gene context | PubMed: TYK2 [Title/Abstract] AND KEAP1 [Title/Abstract] AND fusion [Title/Abstract] | ||
Fusion neoantigen context | PubMed: TYK2 [Title/Abstract] AND KEAP1 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | TYK2(10490291)-KEAP1(10610756), # samples:2 | ||
Anticipated loss of major functional domain due to fusion event. | TYK2-KEAP1 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. TYK2-KEAP1 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. |
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types ** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10) |
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Partner | Gene | GO ID | GO term | PubMed ID |
Tgene | KEAP1 | GO:0006511 | ubiquitin-dependent protein catabolic process | 15601839 |
Tgene | KEAP1 | GO:0010506 | regulation of autophagy | 20452972 |
Tgene | KEAP1 | GO:0016567 | protein ubiquitination | 15601839|15983046 |
Tgene | KEAP1 | GO:0034599 | cellular response to oxidative stress | 15601839 |
![]() Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr19:10490291/chr19:10610756) - 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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![]() * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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![]() * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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Fusion Amino Acid Sequences |
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Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
ENST00000264818 | TYK2 | chr19 | 10476192 | - | ENST00000171111 | KEAP1 | chr19 | 10602938 | - | 2779 | 1011 | 0 | 2246 | 748 |
ENST00000264818 | TYK2 | chr19 | 10476192 | - | ENST00000393623 | KEAP1 | chr19 | 10602938 | - | 2773 | 1011 | 0 | 2246 | 748 |
ENST00000524462 | TYK2 | chr19 | 10476192 | - | ENST00000171111 | KEAP1 | chr19 | 10602938 | - | 2370 | 602 | 38 | 1837 | 599 |
ENST00000524462 | TYK2 | chr19 | 10476192 | - | ENST00000393623 | KEAP1 | chr19 | 10602938 | - | 2364 | 602 | 38 | 1837 | 599 |
ENST00000525621 | TYK2 | chr19 | 10476192 | - | ENST00000171111 | KEAP1 | chr19 | 10602938 | - | 3261 | 1493 | 482 | 2728 | 748 |
ENST00000525621 | TYK2 | chr19 | 10476192 | - | ENST00000393623 | KEAP1 | chr19 | 10602938 | - | 3255 | 1493 | 482 | 2728 | 748 |
ENST00000529370 | TYK2 | chr19 | 10476192 | - | ENST00000171111 | KEAP1 | chr19 | 10602938 | - | 3110 | 1342 | 331 | 2577 | 748 |
ENST00000529370 | TYK2 | chr19 | 10476192 | - | ENST00000393623 | KEAP1 | chr19 | 10602938 | - | 3104 | 1342 | 331 | 2577 | 748 |
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Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
ENST00000264818 | ENST00000171111 | TYK2 | chr19 | 10476192 | - | KEAP1 | chr19 | 10602938 | - | 0.007327702 | 0.9926723 |
ENST00000264818 | ENST00000393623 | TYK2 | chr19 | 10476192 | - | KEAP1 | chr19 | 10602938 | - | 0.00734379 | 0.99265623 |
ENST00000524462 | ENST00000171111 | TYK2 | chr19 | 10476192 | - | KEAP1 | chr19 | 10602938 | - | 0.005444741 | 0.99455523 |
ENST00000524462 | ENST00000393623 | TYK2 | chr19 | 10476192 | - | KEAP1 | chr19 | 10602938 | - | 0.005435188 | 0.9945648 |
ENST00000525621 | ENST00000171111 | TYK2 | chr19 | 10476192 | - | KEAP1 | chr19 | 10602938 | - | 0.008322332 | 0.99167764 |
ENST00000525621 | ENST00000393623 | TYK2 | chr19 | 10476192 | - | KEAP1 | chr19 | 10602938 | - | 0.008357569 | 0.9916425 |
ENST00000529370 | ENST00000171111 | TYK2 | chr19 | 10476192 | - | KEAP1 | chr19 | 10602938 | - | 0.007759729 | 0.9922403 |
ENST00000529370 | ENST00000393623 | TYK2 | chr19 | 10476192 | - | KEAP1 | chr19 | 10602938 | - | 0.007793255 | 0.99220675 |
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Get the fusion protein sequences from here. |
Fusion protein sequence information is available in the fasta format. >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP |
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Fusion Protein Breakpoint Sequences for TYK2-KEAP1 |
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Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Length(fusion protein) | BP in fusion protein | Peptide |
TYK2 | chr19 | 10476192 | KEAP1 | chr19 | 10602938 | 1011 | 337 | QWWPVEEEVNKEEVAKQEEFFNLSHC |
TYK2 | chr19 | 10476192 | KEAP1 | chr19 | 10602938 | 1342 | 337 | QWWPVEEEVNKEEVAKQEEFFNLSHC |
TYK2 | chr19 | 10476192 | KEAP1 | chr19 | 10602938 | 1493 | 337 | QWWPVEEEVNKEEVAKQEEFFNLSHC |
TYK2 | chr19 | 10476192 | KEAP1 | chr19 | 10602938 | 602 | 188 | QWWPVEEEVNKEEVAKQEEFFNLSHC |
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Potential FusionNeoAntigen Information of TYK2-KEAP1 in HLA I |
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TYK2-KEAP1_10476192_10602938.msa |
![]() * We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5) |
Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA I | FusionNeoAntigen peptide | Binding score | Immunogenic score | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B44:03 | EEVAKQEEF | 0.9991 | 0.9558 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B45:01 | EEEVNKEEV | 0.9968 | 0.9428 | 5 | 14 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B18:01 | EEVAKQEEF | 0.9959 | 0.8307 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B45:01 | EEVNKEEVA | 0.9951 | 0.9331 | 6 | 15 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B50:02 | EEVNKEEVA | 0.992 | 0.7216 | 6 | 15 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B41:01 | EEVNKEEVA | 0.6144 | 0.9487 | 6 | 15 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B44:03 | EEVAKQEEFF | 0.9975 | 0.9616 | 11 | 21 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B44:03 | KEEVAKQEEF | 0.9955 | 0.9671 | 10 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B45:01 | EEEVNKEEVA | 0.9787 | 0.9511 | 5 | 15 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B41:01 | VEEEVNKEEVA | 0.9985 | 0.9446 | 4 | 15 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B44:07 | EEVAKQEEF | 0.9991 | 0.9558 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B44:13 | EEVAKQEEF | 0.9991 | 0.9558 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B44:26 | EEVAKQEEF | 0.9991 | 0.9558 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-A25:01 | EVAKQEEFF | 0.9985 | 0.8505 | 12 | 21 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B18:04 | EEVAKQEEF | 0.9967 | 0.8492 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B18:11 | EEVAKQEEF | 0.9965 | 0.7244 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B18:08 | EEVAKQEEF | 0.9964 | 0.8226 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B18:07 | EEVAKQEEF | 0.9963 | 0.8045 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B18:05 | EEVAKQEEF | 0.9959 | 0.8307 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B18:06 | EEVAKQEEF | 0.995 | 0.839 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B18:03 | EEVAKQEEF | 0.9917 | 0.8235 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B40:04 | EEVAKQEEF | 0.9787 | 0.6616 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B35:20 | EEVAKQEEF | 0.7803 | 0.8233 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B41:03 | EEVAKQEEF | 0.6865 | 0.5189 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B15:53 | EEVAKQEEF | 0.4519 | 0.7876 | 11 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B44:13 | EEVAKQEEFF | 0.9975 | 0.9616 | 11 | 21 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B44:07 | EEVAKQEEFF | 0.9975 | 0.9616 | 11 | 21 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B44:26 | EEVAKQEEFF | 0.9975 | 0.9616 | 11 | 21 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B44:13 | KEEVAKQEEF | 0.9955 | 0.9671 | 10 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B44:26 | KEEVAKQEEF | 0.9955 | 0.9671 | 10 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B44:07 | KEEVAKQEEF | 0.9955 | 0.9671 | 10 | 20 |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 | HLA-B41:03 | KEEVAKQEEF | 0.8648 | 0.5503 | 10 | 20 |
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Potential FusionNeoAntigen Information of TYK2-KEAP1 in HLA II |
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![]() * We used NetMHCIIpan v4.1 (%rank<0.5). |
Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA II | FusionNeoAntigen peptide | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
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Fusion breakpoint peptide structures of TYK2-KEAP1 |
![]() * The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA. |
File name | BPseq | Hgene | Tgene | Hchr | Hbp | Tchr | Tbp | AAlen |
1706 | EEVNKEEVAKQEEF | TYK2 | KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 1011 |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TYK2-KEAP1 |
![]() * We used Glide to predict the interaction between HLAs and neoantigens. |
HLA allele | PDB ID | File name | BPseq | Docking score | Glide score |
HLA-B14:02 | 3BVN | 1706 | EEVNKEEVAKQEEF | -7.4838 | -7.5956 |
HLA-B14:02 | 3BVN | 1706 | EEVNKEEVAKQEEF | -3.16066 | -4.20376 |
HLA-B52:01 | 3W39 | 1706 | EEVNKEEVAKQEEF | -6.93679 | -7.04859 |
HLA-B52:01 | 3W39 | 1706 | EEVNKEEVAKQEEF | -6.10064 | -7.14374 |
HLA-A11:01 | 4UQ2 | 1706 | EEVNKEEVAKQEEF | -7.21307 | -7.32487 |
HLA-A24:02 | 5HGA | 1706 | EEVNKEEVAKQEEF | -6.56769 | -6.67949 |
HLA-A24:02 | 5HGA | 1706 | EEVNKEEVAKQEEF | -4.65311 | -5.69621 |
HLA-B44:05 | 3DX8 | 1706 | EEVNKEEVAKQEEF | -6.68002 | -6.79182 |
HLA-B44:05 | 3DX8 | 1706 | EEVNKEEVAKQEEF | -3.22493 | -4.26803 |
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Vaccine Design for the FusionNeoAntigens of TYK2-KEAP1 |
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Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide sequence | FusionNeoAntigen RNA sequence |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 10 | 20 | KEEVAKQEEF | AAGGAGGAGGTGGCCAAGCAAGAGGAGTTC |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 11 | 20 | EEVAKQEEF | GAGGAGGTGGCCAAGCAAGAGGAGTTC |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 11 | 21 | EEVAKQEEFF | GAGGAGGTGGCCAAGCAAGAGGAGTTCTTC |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 12 | 21 | EVAKQEEFF | GAGGTGGCCAAGCAAGAGGAGTTCTTC |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 4 | 15 | VEEEVNKEEVA | GTAGAGGAGGAGGTGAACAAGGAGGAGGTGGCC |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 5 | 14 | EEEVNKEEV | GAGGAGGAGGTGAACAAGGAGGAGGTG |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 5 | 15 | EEEVNKEEVA | GAGGAGGAGGTGAACAAGGAGGAGGTGGCC |
TYK2-KEAP1 | chr19 | 10476192 | chr19 | 10602938 | 6 | 15 | EEVNKEEVA | GAGGAGGTGAACAAGGAGGAGGTGGCC |
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Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide | FusionNEoAntigen RNA sequence |
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Information of the samples that have these potential fusion neoantigens of TYK2-KEAP1 |
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Cancer type | Fusion gene | Hchr | Hbp | Henst | Tchr | Tbp | Tenst | Sample |
LUSC | TYK2-KEAP1 | chr19 | 10476192 | ENST00000264818 | chr19 | 10602938 | ENST00000171111 | TCGA-77-A5GH |
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Potential target of CAR-T therapy development for TYK2-KEAP1 |
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![]() * Minus value of BPloci means that the break point is located before the CDS. |
- In-frame and retained 'Transmembrane'. |
Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
![]() * We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image. |
Hgene | Hchr | Hbp | Henst | Tgene | Tchr | Tbp | Tenst | DeepLoc result |
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Related Drugs to TYK2-KEAP1 |
![]() (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to TYK2-KEAP1 |
![]() (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Disease | Source | PMID |
![]() (DisGeNet 4.0) |
Partner | Gene | Disease ID | Disease name | # pubmeds | Source |