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Center for Computational Systems Medicine
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Kinase Fusion Gene Summary

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Kinase Fusion Gene Sample Information

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Kinase Fusion ORF Analysis

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Kinase Fusion Amino Acid Sequences

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Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase Fusion Protein Functional Features

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Kinase Fusion Protein Structures

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Comparison of Fusion Protein Isoforms

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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

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pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.

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Ramachandran Plot of Kinase Fusion Protein Structure

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Potential Active Site Information

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Virtual Screening Results

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Kinase-Substrate Information

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Related Drugs with This Kinase Fusion Protein

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Related Disease with This Kinase Fusion Protein

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Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:CD74_ROS1

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: CD74_ROS1
KinaseFusionDB ID: KFG991
FusionGDB2.0 ID: KFG991
HgeneTgene
Gene symbol

CD74

ROS1

Gene ID

972

6098

Gene nameCD74 moleculeROS proto-oncogene 1, receptor tyrosine kinase
SynonymsCLIP|DHLAG|HLADG|II|Ia-GAMMA|p33MCF3|ROS|c-ros-1
Cytomap

5q33.1

6q22.1

Type of geneprotein-codingprotein-coding
DescriptionHLA class II histocompatibility antigen gamma chainCD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated)CD74 molecule, major histocompatibility complex, class II invariant chainHLA-DR antigens-associated proto-oncogene tyrosine-protein kinase ROSROS proto-oncogene 1 , receptor tyrosine kinasec-ros oncogene 1 , receptor tyrosine kinaseproto-oncogene c-Ros-1transmembrane tyrosine-specific protein kinasev-ros avian UR2 sarcoma virus oncogene homolog 1
Modification date2024031720240411
UniProtAcc

P04233

P08922

Ensembl transtripts involved in fusion geneENST idsENST00000009530, ENST00000353334, 
ENST00000377795, ENST00000524315, 
ENST00000368507, ENST00000368508, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: CD74 [Title/Abstract] AND ROS1 [Title/Abstract] AND fusion [Title/Abstract]

CD74-ROS1 fusion transcripts in resected non-small cell lung carcinoma (pmid: 23877438)
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CD74(149784243)-ROS1(117645578), # samples:6
CD74(149784243)-ROS1(117645580), # samples:6
ROS1(117700222)-CD74(149782188), # samples:2
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneCD74

GO:0001516

prostaglandin biosynthetic process

12782713

HgeneCD74

GO:0001934

positive regulation of protein phosphorylation

24942581

HgeneCD74

GO:0002792

negative regulation of peptide secretion

19849849

HgeneCD74

GO:0033674

positive regulation of kinase activity

24942581

HgeneCD74

GO:0034341

response to type II interferon

32855215

HgeneCD74

GO:0043066

negative regulation of apoptotic process

12782713

HgeneCD74

GO:0043123

positive regulation of canonical NF-kappaB signal transduction

24942581

HgeneCD74

GO:0043410

positive regulation of MAPK cascade

24942581

HgeneCD74

GO:0043518

negative regulation of DNA damage response, signal transduction by p53 class mediator

17045821

HgeneCD74

GO:0045657

positive regulation of monocyte differentiation

24942581

HgeneCD74

GO:0045893

positive regulation of DNA-templated transcription

24942581

HgeneCD74

GO:0046598

positive regulation of viral entry into host cell

24942581

HgeneCD74

GO:0050731

positive regulation of peptidyl-tyrosine phosphorylation

17045821

HgeneCD74

GO:0070374

positive regulation of ERK1 and ERK2 cascade

17045821|24942581

TgeneROS1

GO:0001558

regulation of cell growth

16885344

TgeneROS1

GO:0006468

protein phosphorylation

16885344

TgeneROS1

GO:0032006

regulation of TOR signaling

16885344


check buttonKinase Fusion gene breakpoints across CD74 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonKinase Fusion gene breakpoints across ROS1 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Kinase Fusion Gene Sample Information

check buttonKinase Fusion gene information.
check button 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.
SourceSampleHgeneHchrHbpTgeneTchrTbp
ChimerDB4TCGA-64-1680-01ACD74chr5

149784242

ROS1chr6

117645577

ChimerDB4TCGA-64-1680-01ACD74chr5

149784243

ROS1chr6

117645578

ChimerDB4TCGA-86-8278CD74chr5

149784242

ROS1chr6

117645578

ChimerKB3.CD74chr5

149784242

ROS1chr6

117645578

ChimerKB3.CD74chr5

149784242

ROS1chr6

117650609

ChimerKB4.CD74chr5

149784242

ROS1chr6

117650609

ChiTaRS5.0AB795244CD74chr5

149784243

ROS1chr6

117650613

ChiTaRS5.0AB795245CD74chr5

149784243

ROS1chr6

117645580

ChimerDB4AB795245CD74chr5

149792317

ROS1chr6

117609626

COSMIC1612628CD74chr5

149784243

ROS1chr6

117650609

COSMIC1653126CD74chr5

149784243

ROS1chr6

117650609

COSMIC2266986CD74chr5

149784243

ROS1chr6

117650609



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Kinase Fusion ORF Analysis


check buttonKinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)		Seq length
(amino acids)
ENST00000353334ENST00000368508CD74chr5149784243ROS1chr61176506092793806
ENST00000353334ENST00000368508CD74chr5149784243ROS1chr61176455782484703
ENST00000353334ENST00000368508CD74chr5149784242ROS1chr61176455782484703
ENST00000353334ENST00000368508CD74chr5149784242ROS1chr61176455772484703
ENST00000353334ENST00000368508CD74chr5149784243ROS1chr61176506132793806
ENST00000353334ENST00000368508CD74chr5149784243ROS1chr61176455802484703
ENST00000353334ENST00000368508CD74chr5149784242ROS1chr61176506092793806

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Kinase Fusion Amino Acid Sequences


check button 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

>ENST00000353334_ENST00000368508_CD74_chr5_149784243_ROS1_chr6_117650609_length(amino acids)=806
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKAGVPNKPGIPKLLEGSKNSIQWEKAEDNGCRITYYILEIRKSTSNNLQNQNLRWKMTFNGSC
SSVCTWKSKNLKGIFQFRVVAANNLGFGEYSGISENIILVGDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLIN
EDKELAELRGLAAGVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEK
IEFLKEAHLMSKFNHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLA
ARNCLVSVKDYTSPRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVL
NYVQTGGRLEPPRNCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPV

--------------------------------------------------------------

>ENST00000353334_ENST00000368508_CD74_chr5_149784243_ROS1_chr6_117645578_length(amino acids)=703
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLINEDKELAELRGLAA
GVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEKIEFLKEAHLMSKF
NHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLAARNCLVSVKDYTS
PRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVLNYVQTGGRLEPPR
NCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPVALMETKNREGLNY

--------------------------------------------------------------

>ENST00000353334_ENST00000368508_CD74_chr5_149784242_ROS1_chr6_117645578_length(amino acids)=703
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLINEDKELAELRGLAA
GVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEKIEFLKEAHLMSKF
NHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLAARNCLVSVKDYTS
PRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVLNYVQTGGRLEPPR
NCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPVALMETKNREGLNY

--------------------------------------------------------------

>ENST00000353334_ENST00000368508_CD74_chr5_149784242_ROS1_chr6_117645577_length(amino acids)=703
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLINEDKELAELRGLAA
GVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEKIEFLKEAHLMSKF
NHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLAARNCLVSVKDYTS
PRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVLNYVQTGGRLEPPR
NCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPVALMETKNREGLNY

--------------------------------------------------------------

>ENST00000353334_ENST00000368508_CD74_chr5_149784243_ROS1_chr6_117650613_length(amino acids)=806
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKAGVPNKPGIPKLLEGSKNSIQWEKAEDNGCRITYYILEIRKSTSNNLQNQNLRWKMTFNGSC
SSVCTWKSKNLKGIFQFRVVAANNLGFGEYSGISENIILVGDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLIN
EDKELAELRGLAAGVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEK
IEFLKEAHLMSKFNHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLA
ARNCLVSVKDYTSPRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVL
NYVQTGGRLEPPRNCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPV

--------------------------------------------------------------

>ENST00000353334_ENST00000368508_CD74_chr5_149784243_ROS1_chr6_117645580_length(amino acids)=703
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLINEDKELAELRGLAA
GVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEKIEFLKEAHLMSKF
NHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLAARNCLVSVKDYTS
PRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVLNYVQTGGRLEPPR
NCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPVALMETKNREGLNY

--------------------------------------------------------------

>ENST00000353334_ENST00000368508_CD74_chr5_149784242_ROS1_chr6_117650609_length(amino acids)=806
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKAGVPNKPGIPKLLEGSKNSIQWEKAEDNGCRITYYILEIRKSTSNNLQNQNLRWKMTFNGSC
SSVCTWKSKNLKGIFQFRVVAANNLGFGEYSGISENIILVGDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLIN
EDKELAELRGLAAGVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEK
IEFLKEAHLMSKFNHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLA
ARNCLVSVKDYTSPRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVL
NYVQTGGRLEPPRNCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPV

--------------------------------------------------------------

Multiple Sequence Alignment of All Fusion Protein Isoforms



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Kinase Fusion Protein Functional Features


check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr5:149784243/chr6:117645578)
- 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.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
CD74

P04233

ROS1

P08922

FUNCTION: Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to the endosomal/lysosomal system where the antigen processing and binding of antigenic peptides to MHC class II takes place. Serves as cell surface receptor for the cytokine MIF.; FUNCTION: [Class-II-associated invariant chain peptide]: Binds to the peptide-binding site of MHC class II alpha/beta heterodimers forming an alpha-beta-CLIP complex, thereby preventing the loading of antigenic peptides to the MHC class II complex until its release by HLA-DM in the endosome. {ECO:0000269|PubMed:1448172}.; FUNCTION: [Isoform p41]: Stabilizes the conformation of mature CTSL by binding to its active site and serving as a chaperone to help maintain a pool of mature enzyme in endocytic compartments and extracellular space of antigen-presenting cells (APCs). Has antiviral activity by stymieing the endosomal entry of Ebola virus and coronaviruses, including SARS-CoV-2 (PubMed:32855215). Disrupts cathepsin-mediated Ebola virus glycoprotein processing, which prevents viral fusion and entry. This antiviral activity is specific to p41 isoform (PubMed:32855215). {ECO:0000250|UniProtKB:P04441, ECO:0000269|PubMed:32855215}.FUNCTION: Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. NELL2 is an endogenous ligand for ROS1. Upon endogenous stimulation by NELL2, ROS1 activates the intracellular signaling pathway and triggers epididymal epithelial differentiation and subsequent sperm maturation (By similarity). May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and PLCG2. {ECO:0000250|UniProtKB:Q78DX7, ECO:0000269|PubMed:11094073, ECO:0000269|PubMed:16885344}.

check buttonRetention 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

download page

* Minus value of BPloci means that the break pointn is located before the CDS.

check button - Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


check button - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote
TgeneCD74149784242ROS1117650609ENST0000035333430431752_185417492348DomainNote=Fibronectin type-III 9;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316
TgeneCD74149784243ROS1117650609ENST0000035333430431752_185417492348DomainNote=Fibronectin type-III 9;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316
TgeneCD74149784243ROS1117650613ENST0000035333430431752_185417492348DomainNote=Fibronectin type-III 9;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316
TgeneCD74149784242ROS1117645577ENST0000035333432431945_222218522348DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgeneCD74149784242ROS1117645578ENST0000035333432431945_222218522348DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgeneCD74149784242ROS1117650609ENST0000035333430431945_222217492348DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgeneCD74149784243ROS1117645578ENST0000035333432431945_222218522348DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgeneCD74149784243ROS1117645580ENST0000035333432431945_222218522348DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgeneCD74149784243ROS1117650609ENST0000035333430431945_222217492348DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgeneCD74149784243ROS1117650613ENST0000035333430431945_222217492348DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159


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Kinase Fusion Protein Structures

check button CIF files of the predicted kinase fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB)HenstTenstHgeneHchrHbpTgeneTchrTbpAA seqLen(AA seq)
PDB file >>>91_CD74_ROS1ENST00000353334ENST00000368508CD74chr5149784242ROS1chr6117650609
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKAGVPNKPGIPKLLEGSKNSIQWEKAEDNGCRITYYILEIRKSTSNNLQNQNLRWKMTFNGSC
SSVCTWKSKNLKGIFQFRVVAANNLGFGEYSGISENIILVGDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLIN
EDKELAELRGLAAGVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEK
IEFLKEAHLMSKFNHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLA
ARNCLVSVKDYTSPRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVL
NYVQTGGRLEPPRNCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPV
806
3D view using mol* of 91_CD74_ROS1
PDB file >>>TKFP_154_CD74_ROS1ENST00000353334ENST00000368508CD74chr5149784243ROS1chr6117650609
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKAGVPNKPGIPKLLEGSKNSIQWEKAEDNGCRITYYILEIRKSTSNNLQNQNLRWKMTFNGSC
SSVCTWKSKNLKGIFQFRVVAANNLGFGEYSGISENIILVGDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLIN
EDKELAELRGLAAGVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEK
IEFLKEAHLMSKFNHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLA
ARNCLVSVKDYTSPRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVL
NYVQTGGRLEPPRNCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPV
806_CD74_ROS1
PDB file >>>TKFP_155_CD74_ROS1ENST00000353334ENST00000368508CD74chr5149784243ROS1chr6117645578
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLINEDKELAELRGLAA
GVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEKIEFLKEAHLMSKF
NHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLAARNCLVSVKDYTS
PRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVLNYVQTGGRLEPPR
NCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPVALMETKNREGLNY
703_CD74_ROS1
3D view using mol* of TKFP_155_CD74_ROS1
PDB file >>>TKFP_156_CD74_ROS1ENST00000353334ENST00000368508CD74chr5149784242ROS1chr6117645578
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLINEDKELAELRGLAA
GVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEKIEFLKEAHLMSKF
NHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLAARNCLVSVKDYTS
PRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVLNYVQTGGRLEPPR
NCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPVALMETKNREGLNY
703_CD74_ROS1
PDB file >>>TKFP_157_CD74_ROS1ENST00000353334ENST00000368508CD74chr5149784242ROS1chr6117645577
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLINEDKELAELRGLAA
GVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEKIEFLKEAHLMSKF
NHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLAARNCLVSVKDYTS
PRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVLNYVQTGGRLEPPR
NCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPVALMETKNREGLNY
703_CD74_ROS1
PDB file >>>TKFP_158_CD74_ROS1ENST00000353334ENST00000368508CD74chr5149784243ROS1chr6117650613
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKAGVPNKPGIPKLLEGSKNSIQWEKAEDNGCRITYYILEIRKSTSNNLQNQNLRWKMTFNGSC
SSVCTWKSKNLKGIFQFRVVAANNLGFGEYSGISENIILVGDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLIN
EDKELAELRGLAAGVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEK
IEFLKEAHLMSKFNHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLA
ARNCLVSVKDYTSPRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVL
NYVQTGGRLEPPRNCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPV
806_CD74_ROS1
PDB file >>>TKFP_159_CD74_ROS1ENST00000353334ENST00000368508CD74chr5149784243ROS1chr6117645580
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLINEDKELAELRGLAA
GVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEKIEFLKEAHLMSKF
NHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLAARNCLVSVKDYTS
PRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVLNYVQTGGRLEPPR
NCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPVALMETKNREGLNY
703_CD74_ROS1
PDB file >>>TKFP_160_CD74_ROS1ENST00000353334ENST00000368508CD74chr5149784242ROS1chr6117650609
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLLLAGQATTAYFLYQQQGRLDKLTVTSQNLQL
ENLRMKLPKPPKPVSKMRMATPLLMQALPMGALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKAGVPNKPGIPKLLEGSKNSIQWEKAEDNGCRITYYILEIRKSTSNNLQNQNLRWKMTFNGSC
SSVCTWKSKNLKGIFQFRVVAANNLGFGEYSGISENIILVGDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLIN
EDKELAELRGLAAGVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLKKGSTDQEK
IEFLKEAHLMSKFNHPNILKQLGVCLLNEPQYIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLA
ARNCLVSVKDYTSPRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIFTTQSDVWSFGILIWEILTLGHQPYPAHSNLDVL
NYVQTGGRLEPPRNCPDDLWNLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLNSDDIMPV
806_CD74_ROS1


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Comparison of Fusion Protein Isoforms

check button Superimpose the 3D Structures Among All Fusion Protein Isoforms
* Download the pdb file and open it from the molstar online viewer.
3D view using mol* of viewer/superimpose_isoforms/TKFP_154_CD74_ROS1_vs_TKFP_155_CD74_ROS1_superimposed.pdb.html

check button Comparison of the Secondary Structures of Fusion Protein Isoforms
./secondary_str/TKFP_154_CD74_ROS1_vs_TKFP_155_CD74_ROS1.png
secondary structure of ./secondary_str/TKFP_154_CD74_ROS1_vs_TKFP_155_CD74_ROS1.png

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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

check button Abstract of the Multiple Sequence Alignment of the Longest Fusion Protein Sequence and Known Sequence from PDB Search Using Fusion Gene Names
check button Multiple Sequence Alignment of the Longest Fusion Protein Sequence and Known Sequence from PDB Search Using Fusion Gene Names

check button Superimpose the 3D Structures Between the Longest Fusion Protein and the Longest Known PDB
3D view using mol* of viewer/superimpose_pdbs/CD74_ROS1_3ZBF_superimposed.pdb.html
3D view using mol* of viewer/superimpose_pdbs/CD74_ROS1_4UXL_superimposed.pdb.html


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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/91_CD74_ROS1.pngall_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/TKFP_155_CD74_ROS1_updated_violin_plot.png
check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
* The blue color at the bottom marks the best active site residues.
91_CD74_ROS1.png
all structure sitemap plddt3 91_CD74_ROS1.png
91_CD74_ROS1.png
all structure sitemap plddt4 91_CD74_ROS1.png
TKFP_155_CD74_ROS1.png
all structure sitemap plddt3 TKFP_155_CD74_ROS1.png


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Potential Active Site Information


check button The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.
Kinase Fusion AA seq ID in KinaseFusionDBSite scoreSizeDscoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues
TKFP_155_CD74_ROS11.1151011.179268.2260.5470.7640.9972.0040.6732.9771.105Chain A: 307,308,315,334,335,336,382,384,385,386,3
87,388,389,392,393,396,439,442,446,448,459,461,462
,465,466

check button Binding site residues of the found PDBs.
PDB accessionAA sequenceResidue position
3ZBFILE1934
3ZBFGLU1935
3ZBFASN1936
3ZBFLEU1937
3ZBFPRO1938
3ZBFALA1939
3ZBFPHE1940
3ZBFPRO1941
3ZBFARG1942
3ZBFGLU1943
3ZBFLYS1944
3ZBFLEU1945
3ZBFTHR1946
3ZBFLEU1947
3ZBFARG1948
3ZBFLEU1949
3ZBFLEU1950
3ZBFLEU1951
3ZBFGLY1952
3ZBFSER1953
3ZBFGLY1957
3ZBFGLU1958
3ZBFVAL1959
3ZBFTYR1960
3ZBFGLU1961
3ZBFGLY1962
3ZBFTHR1963
3ZBFALA1964
3ZBFVAL1965
3ZBFASP1966
3ZBFILE1967
3ZBFLEU1968
3ZBFGLY1969
3ZBFVAL1970
3ZBFGLY1971
3ZBFSER1972
3ZBFGLY1973
3ZBFGLU1974
3ZBFILE1975
3ZBFLYS1976
3ZBFVAL1977
3ZBFALA1978
3ZBFVAL1979
3ZBFLYS1980
3ZBFTHR1981
3ZBFLEU1982
3ZBFLYS1983
3ZBFLYS1984
3ZBFGLY1985
3ZBFSER1986
3ZBFTHR1987
3ZBFASP1988
3ZBFGLN1989
3ZBFGLU1990
3ZBFLYS1991
3ZBFILE1992
3ZBFGLU1993
3ZBFPHE1994
3ZBFLEU1995
3ZBFLYS1996
3ZBFGLU1997
3ZBFALA1998
3ZBFHIS1999
3ZBFLEU2000
3ZBFMET2001
3ZBFSER2002
3ZBFLYS2003
3ZBFPHE2004
3ZBFASN2005
3ZBFHIS2006
3ZBFPRO2007
3ZBFASN2008
3ZBFILE2009
3ZBFLEU2010
3ZBFLYS2011
3ZBFGLN2012
3ZBFLEU2013
3ZBFGLY2014
3ZBFVAL2015
3ZBFCYS2016
3ZBFLEU2017
3ZBFLEU2018
3ZBFASN2019
3ZBFGLU2020
3ZBFPRO2021
3ZBFGLN2022
3ZBFTYR2023
3ZBFILE2024
3ZBFILE2025
3ZBFLEU2026
3ZBFGLU2027
3ZBFLEU2028
3ZBFMET2029
3ZBFGLU2030
3ZBFGLY2031
3ZBFGLY2032
3ZBFASP2033
3ZBFLEU2034
3ZBFLEU2035
3ZBFTHR2036
3ZBFTYR2037
3ZBFLEU2038
3ZBFARG2039
3ZBFLYS2040
3ZBFALA2041
3ZBFARG2042
3ZBFMET2043
3ZBFALA2044
3ZBFTHR2045
3ZBFPHE2046
3ZBFTYR2047
3ZBFGLY2048
3ZBFPRO2049
3ZBFLEU2050
3ZBFLEU2051
3ZBFTHR2052
3ZBFLEU2053
3ZBFVAL2054
3ZBFASP2055
3ZBFLEU2056
3ZBFVAL2057
3ZBFASP2058
3ZBFLEU2059
3ZBFCYS2060
3ZBFVAL2061
3ZBFASP2062
3ZBFILE2063
3ZBFSER2064
3ZBFLYS2065
3ZBFGLY2066
3ZBFCYS2067
3ZBFVAL2068
3ZBFTYR2069
3ZBFLEU2070
3ZBFGLU2071
3ZBFARG2072
3ZBFMET2073
3ZBFHIS2074
3ZBFPHE2075
3ZBFILE2076
3ZBFHIS2077
3ZBFARG2078
3ZBFASP2079
3ZBFLEU2080
3ZBFALA2081
3ZBFALA2082
3ZBFARG2083
3ZBFASN2084
3ZBFCYS2085
3ZBFLEU2086
3ZBFVAL2087
3ZBFSER2088
3ZBFVAL2089
3ZBFLYS2090
3ZBFASP2091
3ZBFTYR2092
3ZBFTHR2093
3ZBFSER2094
3ZBFPRO2095
3ZBFARG2096
3ZBFILE2097
3ZBFVAL2098
3ZBFLYS2099
3ZBFILE2100
3ZBFGLY2101
3ZBFASP2102
3ZBFPHE2103
3ZBFGLY2104
3ZBFLEU2105
3ZBFALA2106
3ZBFARG2107
3ZBFASP2108
3ZBFILE2109
3ZBFTYR2110
3ZBFLEU2123
3ZBFPRO2124
3ZBFVAL2125
3ZBFARG2126
3ZBFTRP2127
3ZBFMET2128
3ZBFALA2129
3ZBFPRO2130
3ZBFGLU2131
3ZBFSER2132
3ZBFLEU2133
3ZBFMET2134
3ZBFASP2135
3ZBFGLY2136
3ZBFILE2137
3ZBFPHE2138
3ZBFTHR2139
3ZBFTHR2140
3ZBFGLN2141
3ZBFSER2142
3ZBFASP2143
3ZBFVAL2144
3ZBFTRP2145
3ZBFSER2146
3ZBFPHE2147
3ZBFGLY2148
3ZBFILE2149
3ZBFLEU2150
3ZBFILE2151
3ZBFTRP2152
3ZBFGLU2153
3ZBFILE2154
3ZBFLEU2155
3ZBFTHR2156
3ZBFLEU2157
3ZBFGLY2158
3ZBFHIS2159
3ZBFGLN2160
3ZBFPRO2161
3ZBFTYR2162
3ZBFPRO2163
3ZBFALA2164
3ZBFHIS2165
3ZBFSER2166
3ZBFASN2167
3ZBFLEU2168
3ZBFASP2169
3ZBFVAL2170
3ZBFLEU2171
3ZBFASN2172
3ZBFTYR2173
3ZBFVAL2174
3ZBFGLN2175
3ZBFTHR2176
3ZBFGLY2177
3ZBFGLY2178
3ZBFARG2179
3ZBFLEU2180
3ZBFGLU2181
3ZBFPRO2182
3ZBFPRO2183
3ZBFARG2184
3ZBFASN2185
3ZBFCYS2186
3ZBFPRO2187
3ZBFASP2188
3ZBFASP2189
3ZBFLEU2190
3ZBFTRP2191
3ZBFASN2192
3ZBFLEU2193
3ZBFMET2194
3ZBFTHR2195
3ZBFGLN2196
3ZBFCYS2197
3ZBFTRP2198
3ZBFALA2199
3ZBFGLN2200
3ZBFGLU2201
3ZBFPRO2202
3ZBFASP2203
3ZBFGLN2204
3ZBFARG2205
3ZBFPRO2206
3ZBFTHR2207
3ZBFPHE2208
3ZBFHIS2209
3ZBFARG2210
3ZBFILE2211
3ZBFGLN2212
3ZBFASP2213
3ZBFGLN2214
3ZBFLEU2215
3ZBFGLN2216
3ZBFLEU2217
3ZBFPHE2218
3ZBFARG2219
3ZBFASN2220
3ZBFPHE2221
3ZBFPHE2222
3ZBFLEU2223
3ZBFASN2224
3ZBFSER2225
3ZBFILE2226
3ZBFTYR2227
3ZBFLYS2228
3ZBFSER2229
3ZBFARG2230
4UXLILE1934
4UXLGLU1935
4UXLASN1936
4UXLLEU1937
4UXLPRO1938
4UXLALA1939
4UXLPHE1940
4UXLPRO1941
4UXLARG1942
4UXLGLU1943
4UXLLYS1944
4UXLLEU1945
4UXLTHR1946
4UXLLEU1947
4UXLARG1948
4UXLLEU1949
4UXLLEU1950
4UXLLEU1951
4UXLGLY1952
4UXLSER1953
4UXLGLY1954
4UXLALA1955
4UXLPHE1956
4UXLGLY1957
4UXLGLU1958
4UXLVAL1959
4UXLTYR1960
4UXLGLU1961
4UXLGLY1962
4UXLTHR1963
4UXLALA1964
4UXLVAL1965
4UXLASP1966
4UXLILE1967
4UXLLEU1968
4UXLGLY1969
4UXLVAL1970
4UXLGLY1971
4UXLSER1972
4UXLGLY1973
4UXLGLU1974
4UXLILE1975
4UXLLYS1976
4UXLVAL1977
4UXLALA1978
4UXLVAL1979
4UXLLYS1980
4UXLTHR1981
4UXLLEU1982
4UXLLYS1983
4UXLLYS1984
4UXLGLY1985
4UXLSER1986
4UXLTHR1987
4UXLASP1988
4UXLGLN1989
4UXLGLU1990
4UXLLYS1991
4UXLILE1992
4UXLGLU1993
4UXLPHE1994
4UXLLEU1995
4UXLLYS1996
4UXLGLU1997
4UXLALA1998
4UXLHIS1999
4UXLLEU2000
4UXLMET2001
4UXLSER2002
4UXLLYS2003
4UXLPHE2004
4UXLASN2005
4UXLHIS2006
4UXLPRO2007
4UXLASN2008
4UXLILE2009
4UXLLEU2010
4UXLLYS2011
4UXLGLN2012
4UXLLEU2013
4UXLGLY2014
4UXLVAL2015
4UXLCYS2016
4UXLLEU2017
4UXLLEU2018
4UXLASN2019
4UXLGLU2020
4UXLPRO2021
4UXLGLN2022
4UXLTYR2023
4UXLILE2024
4UXLILE2025
4UXLLEU2026
4UXLGLU2027
4UXLLEU2028
4UXLMET2029
4UXLGLU2030
4UXLGLY2031
4UXLGLY2032
4UXLASP2033
4UXLLEU2034
4UXLLEU2035
4UXLTHR2036
4UXLTYR2037
4UXLLEU2038
4UXLARG2039
4UXLLYS2040
4UXLALA2041
4UXLARG2042
4UXLMET2043
4UXLALA2044
4UXLTHR2045
4UXLPHE2046
4UXLTYR2047
4UXLGLY2048
4UXLPRO2049
4UXLLEU2050
4UXLLEU2051
4UXLTHR2052
4UXLLEU2053
4UXLVAL2054
4UXLASP2055
4UXLLEU2056
4UXLVAL2057
4UXLASP2058
4UXLLEU2059
4UXLCYS2060
4UXLVAL2061
4UXLASP2062
4UXLILE2063
4UXLSER2064
4UXLLYS2065
4UXLGLY2066
4UXLCYS2067
4UXLVAL2068
4UXLTYR2069
4UXLLEU2070
4UXLGLU2071
4UXLARG2072
4UXLMET2073
4UXLHIS2074
4UXLPHE2075
4UXLILE2076
4UXLHIS2077
4UXLARG2078
4UXLASP2079
4UXLLEU2080
4UXLALA2081
4UXLALA2082
4UXLARG2083
4UXLASN2084
4UXLCYS2085
4UXLLEU2086
4UXLVAL2087
4UXLSER2088
4UXLVAL2089
4UXLLYS2090
4UXLASP2091
4UXLTYR2092
4UXLTHR2093
4UXLSER2094
4UXLPRO2095
4UXLARG2096
4UXLILE2097
4UXLVAL2098
4UXLLYS2099
4UXLILE2100
4UXLGLY2101
4UXLASP2102
4UXLPHE2103
4UXLGLY2104
4UXLLEU2105
4UXLALA2106
4UXLARG2107
4UXLASP2108
4UXLILE2109
4UXLTYR2110
4UXLLYS2111
4UXLGLU2120
4UXLGLY2121
4UXLLEU2122
4UXLLEU2123
4UXLPRO2124
4UXLVAL2125
4UXLARG2126
4UXLTRP2127
4UXLMET2128
4UXLALA2129
4UXLPRO2130
4UXLGLU2131
4UXLSER2132
4UXLLEU2133
4UXLMET2134
4UXLASP2135
4UXLGLY2136
4UXLILE2137
4UXLPHE2138
4UXLTHR2139
4UXLTHR2140
4UXLGLN2141
4UXLSER2142
4UXLASP2143
4UXLVAL2144
4UXLTRP2145
4UXLSER2146
4UXLPHE2147
4UXLGLY2148
4UXLILE2149
4UXLLEU2150
4UXLILE2151
4UXLTRP2152
4UXLGLU2153
4UXLILE2154
4UXLLEU2155
4UXLTHR2156
4UXLLEU2157
4UXLGLY2158
4UXLHIS2159
4UXLGLN2160
4UXLPRO2161
4UXLTYR2162
4UXLPRO2163
4UXLALA2164
4UXLHIS2165
4UXLSER2166
4UXLASN2167
4UXLLEU2168
4UXLASP2169
4UXLVAL2170
4UXLLEU2171
4UXLASN2172
4UXLTYR2173
4UXLVAL2174
4UXLGLN2175
4UXLTHR2176
4UXLGLY2177
4UXLGLY2178
4UXLARG2179
4UXLLEU2180
4UXLGLU2181
4UXLPRO2182
4UXLPRO2183
4UXLARG2184
4UXLASN2185
4UXLCYS2186
4UXLPRO2187
4UXLASP2188
4UXLASP2189
4UXLLEU2190
4UXLTRP2191
4UXLASN2192
4UXLLEU2193
4UXLMET2194
4UXLTHR2195
4UXLGLN2196
4UXLCYS2197
4UXLTRP2198
4UXLALA2199
4UXLGLN2200
4UXLGLU2201
4UXLPRO2202
4UXLASP2203
4UXLGLN2204
4UXLARG2205
4UXLPRO2206
4UXLTHR2207
4UXLPHE2208
4UXLHIS2209
4UXLARG2210
4UXLILE2211
4UXLGLN2212
4UXLASP2213
4UXLGLN2214
4UXLLEU2215
4UXLGLN2216
4UXLLEU2217
4UXLPHE2218
4UXLARG2219
4UXLASN2220
4UXLPHE2221
4UXLPHE2222
4UXLLEU2223
4UXLASN2224
4UXLSER2225
4UXLILE2226
4UXLTYR2227
4UXLLYS2228
4UXLSER2229
4UXLARG2230


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Ramachandran Plot of Kinase Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.

91_CD74_ROS1_ramachandran.png
all structure CD74-ROS1
TKFP_155_CD74_ROS1_ramachandran.png
all structure CD74-ROS1

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Virtual Screening Results


check button Distribution of the average docking score across all approved kinase inhibitors.
Distribution of the number of occurrence across all approved kinase inhibitors.
5'-kinase fusion protein case
3'-kinase fusion protein case
all structure CD74-ROS1

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check button Drug information from DrugBank of the top 20 interacting small molecules.
* The detailed information of individual kinase inhibitors are available in the download page.
Fusion gene name infoDrugDocking scoreGlide g scoreGlide energy
91_CD74_ROS1-DOCK_HTVS_1-001Pexidartinib-7.85887-8.55967-49.0534
91_CD74_ROS1-DOCK_HTVS_1-001Pexidartinib-7.85887-8.55967-49.0534
91_CD74_ROS1-DOCK_HTVS_1-001Pexidartinib-7.61065-7.82745-43.5955
91_CD74_ROS1-DOCK_HTVS_1-001Pexidartinib-7.61065-7.82745-43.5955
91_CD74_ROS1-DOCK_HTVS_1-001Selumetinib-7.50853-7.5172300000000005-43.1201
91_CD74_ROS1-DOCK_HTVS_1-001Selumetinib-7.50853-7.5172300000000005-43.1201
91_CD74_ROS1-DOCK_HTVS_1-001Upadacitinib-7.450080000000001-7.45108-38.5647
91_CD74_ROS1-DOCK_HTVS_1-001Belumosudil-7.38254-7.3902399999999995-52.6473
91_CD74_ROS1-DOCK_HTVS_1-001Netarsudil-7.326789999999999-7.33789-49.7949
91_CD74_ROS1-DOCK_HTVS_1-001Netarsudil-7.326789999999999-7.33789-49.7949
91_CD74_ROS1-DOCK_HTVS_1-001Binimetinib-7.300389999999999-7.309089999999999-40.2957
91_CD74_ROS1-DOCK_HTVS_1-001Binimetinib-7.300389999999999-7.309089999999999-40.2957
91_CD74_ROS1-DOCK_HTVS_1-001Tofacitinib-7.23287-7.24437-29.4946
91_CD74_ROS1-DOCK_HTVS_1-001Tofacitinib-7.23287-7.24437-29.4946
91_CD74_ROS1-DOCK_HTVS_1-001Belumosudil-7.2123-7.22-53.6384
91_CD74_ROS1-DOCK_HTVS_1-001Fostamatinib-7.076910000000001-7.140510000000001-48.1015
91_CD74_ROS1-DOCK_HTVS_1-001Fostamatinib-7.076910000000001-7.140510000000001-48.1015
91_CD74_ROS1-DOCK_HTVS_1-001Fedratinib-7.057980000000001-7.109380000000001-59.8553
91_CD74_ROS1-DOCK_HTVS_1-001Fedratinib-7.057980000000001-7.109380000000001-59.8553
91_CD74_ROS1-DOCK_HTVS_1-001Larotrectinib-7.02663-7.02663-48.2061

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Kinase-Substrate Information of CD74_ROS1


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain


check button Biological Network Integration of This Kinase and Substrates
(GeneMANIA website)

check button Enriched GO biological processes of the phosphorylation target genes of the kinase
KinaseGOIDGO termP.adjust

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Related Drugs to CD74_ROS1


check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID
CD74ROS1Crizotinib + EntrectinibPubMed34319660

check button Distribution of the number of studies mentioning CD74-ROS1 and kinase inhibitors the PubMed Abstract (04-01-2024)
all structure sitemap plddt CD74-ROS1

Fusion gene - drug pair 1Fusion gene - drug pair 2PMIDPublication dateDOIStudy title
CD74-ROS1 AND Crizotinib 383392782024-01-2610.3390/cancers16030528Real-World Outcomes of Crizotinib in ROS1-Rearranged Advanced Non-Small-Cell Lung Cancer.
CD74-ROS1 AND Crizotinib 373498672023-06-2210.1080/14756366.2023.2227779Discovery of novel 2-aminopyridine derivatives as ROS1 and ALK dual inhibitors to combat drug-resistant mutants including ROS1(G2032R) and ALK(G1202R).
CD74-ROS1 AND Crizotinib 352845602022-210.21037/atm-21-6754ROS1 fusion lung adenosquamous carcinoma patient with short-term clinical benefit after crizotinib treatment: a case report.
CD74-ROS1 AND Crizotinib 339459211905-07-1310.1016/j.ctarc.2021.100377Crizotinib resistance conferred by BRAF V600E mutation in non-small cell lung cancer harboring an oncogenic ROS1 fusion.
CD74-ROS1 AND Crizotinib 332041042020-1110.2147/ott.s278907A Novel ROS1-FBXL17 Fusion Co-Existing with CD74-ROS1 Fusion May Improve Sensitivity to Crizotinib and Prolong Progression-Free Survival of Patients with Lung Adenocarcinoma.
CD74-ROS1 AND Crizotinib 330004742020-10-2810.1002/onco.13545Acquired MET D1228N Mutations Mediate Crizotinib Resistance in Lung Adenocarcinoma with ROS1 Fusion: A Case Report.
CD74-ROS1 AND Crizotinib 328716262020-09-1410.1002/1878-0261.12789Molecular and clinicopathological characteristics of ROS1-rearranged non-small-cell lung cancers identified by next-generation sequencing.
CD74-ROS1 AND CrizotinibCD74-ROS1 AND Cabozantinib321039852020-210.2147/ott.s234733Effective Treatment with Cabozantinib in an Advanced Non-Small-Cell Lung Cancer Patient Harboring a CD74-ROS1 Fusion: A Case Report.
CD74-ROS1 AND Crizotinib 310277452019-510.1016/j.jtho.2019.01.005Next-Generation Sequencer Analysis of Pulmonary Pleomorphic Carcinoma With a CD74-ROS1 Fusion Successfully Treated With Crizotinib.
CD74-ROS1 AND Crizotinib 309785022019-710.1016/j.jtho.2019.03.020Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial.
CD74-ROS1 AND CrizotinibSLC34A2-ROS1 AND Crizotinib300533322018-09-1110.1111/cas.13752Combined effect of cabozantinib and gefitinib in crizotinib-resistant lung tumors harboring ROS1 fusions.
CD74-ROS1 AND Crizotinib 297046752018-710.1016/j.jtho.2018.04.016Efficacy of Crizotinib among Different Types of�ROS1 Fusion Partners in Patients with ROS1-Rearranged Non-Small Cell Lung Cancer.
CD74-ROS1 AND CrizotinibCD74-ROS1 AND Cabozantinib266738002016-05-1210.1158/1078-0432.ccr-15-2013A Novel Crizotinib-Resistant Solvent-Front Mutation Responsive to Cabozantinib Therapy in a Patient with ROS1-Rearranged Lung Cancer.
CD74-ROS1 AND CrizotinibSLC34A2-ROS1 AND Crizotinib256881572015-05-1410.1158/1078-0432.ccr-14-1350Molecular Changes Associated with Acquired Resistance to Crizotinib in ROS1-Rearranged Non-Small Cell Lung Cancer.
CD74-ROS1 AND Crizotinib 237249142013-09-1910.1056/nejmc1309091Acquired resistance to crizotinib from a mutation in CD74-ROS1.
CD74-ROS1 AND Crizotinib 222157482012-110.1016/j.yonc.2012.06.023ROS1 rearrangements define a unique molecular class of lung cancers.
CD74-ROS1 AND CabozantinibTPM3-ROS1 AND Gilteritinib382930202024-01-2010.1101/2024.01.16.575901TKI Type Switching Overcomes ROS1 L2086F in ROS1 Fusion-Positive Cancers.
CD74-ROS1 AND Cabozantinib 273706052017-01-0110.1158/1078-0432.ccr-15-1601Identification of Existing Drugs That Effectively Target NTRK1 and ROS1 Rearrangements in Lung Cancer.
CD74-ROS1 AND Cabozantinib 253517432015-01-0110.1158/1078-0432.ccr-14-1385Cabozantinib overcomes crizotinib resistance in ROS1 fusion-positive cancer.
CD74-ROS1 AND Lorlatinib 335582792021-210.1136/jitc-2020-001967Short-term response to immune-chemotherapy and immune features of a ceritinib-resistant patient with ROS1-rearranged lung adenocarcinoma.
CD74-ROS1 AND Lorlatinib 329140392019-1210.1200/po.19.00013Dramatic Response to Lorlatinib in a Patient With CD74-ROS1-Positive Lung Adenocarcinoma With Acquired F2004V Mutation.
CD74-ROS1 AND EntrectinibEZR-ROS1 AND Entrectinib349070862022-02-0110.1158/1535-7163.mct-21-0395Resistance Profile and Structural Modeling of Next-Generation ROS1 Tyrosine Kinase Inhibitors.

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Related Diseases to CD74_ROS1


check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID
CD74ROS1Lung AdenocarcinomaPubMed34319660
CD74ROS1Lung AdenocarcinomaMyCancerGenome
CD74ROS1Dedifferentiated LiposarcomaMyCancerGenome
CD74ROS1Non-Small Cell Lung CarcinomaMyCancerGenome
CD74ROS1Breast Invasive Ductal CarcinomaMyCancerGenome
CD74ROS1Anaplastic GangliogliomaMyCancerGenome

check button Related diseases from the literature mentioned this fusion gene and drug.
(PubMed, 04-01-2024)

MeSH IDMeSH term

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
TgeneROS1C0007131Non-Small Cell Lung Carcinoma4CTD_human


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Clinical Trials of the Found Drugs/Small Molecules


check button Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024)


check button Clinical Trials from clinicaltrials.gov (06-17-2024)

Fusion GeneKinase InhibitorNCT IDStudy StatusPhasesDisease# EnrolmentDate
CD74-ROS1CrizotinibNCT03399487Unknown statusPhase 2Non-small Cell Lung Cancer Harboring ROS1 Rearrangement46October 2020
CD74-ROS1CrizotinibNCT01964157Unknown statusPhase 2Non-small Cell Lung Cancer (NSCLC)32December 2019