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	Kinase Fusion Gene Summary
	Kinase Fusion Gene Sample Information
	Kinase Fusion ORF Analysis
	Kinase Fusion Amino Acid Sequences
	Multiple Sequence Alignment of All Fusion Protein Isoforms
	Kinase Fusion Protein Functional Features
	Kinase Fusion Protein Structures
	Comparison of Fusion Protein Isoforms
	Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB
	pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.
	Ramachandran Plot of Kinase Fusion Protein Structure
	Potential Active Site Information
	Virtual Screening Results
	Kinase-Substrate Information
	Related Drugs with This Kinase Fusion Protein
	Related Disease with This Kinase Fusion Protein
	Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:SOS1_MAP4K3

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: SOS1_MAP4K3
	KinaseFusionDB ID: KFG5988
	FusionGDB2.0 ID: KFG5988
		Hgene	Tgene
	Gene symbol	SOS1	MAP4K3
	Gene ID	6654	8491
	Gene name	SOS Ras/Rac guanine nucleotide exchange factor 1	mitogen-activated protein kinase kinase kinase kinase 3
	Synonyms	GF1\|GGF1\|GINGF\|HGF\|NS4\|SOS-1	GLK\|MAPKKKK3\|MEKKK 3\|MEKKK3\|RAB8IPL1
	Cytomap	2p22.1	2p22.1
	Type of gene	protein-coding	protein-coding
	Description	son of sevenless homolog 1gingival fibromatosis, hereditary, 1guanine nucleotide exchange factor	mitogen-activated protein kinase kinase kinase kinase 3MAPK/ERK kinase kinase kinase 3MEK kinase kinase 3germinal center kinase-like kinasegerminal center kinase-related protein kinase
	Modification date	20240411	20240408
	UniProtAcc	Q07889	Q8IVH8
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000395038, ENST00000402219, ENST00000426016, ENST00000428721, ENST00000472480,	ENST00000341681, ENST00000437545, ENST00000484274, ENST00000536018, ENST00000474502, ENST00000263881,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: SOS1 [Title/Abstract] AND MAP4K3 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	SOS1(39278285)-MAP4K3(39605264), # samples:3 SOS1(39283843)-MAP4K3(39605264), # samples:3

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	SOS1	GO:0006357	regulation of transcription by RNA polymerase II	23027131
Hgene	SOS1	GO:0007265	Ras protein signal transduction	23027131
Hgene	SOS1	GO:0042127	regulation of cell population proliferation	9054499
Tgene	MAP4K3	GO:0006468	protein phosphorylation	9275185
Tgene	MAP4K3	GO:0009411	response to UV	9275185
Tgene	MAP4K3	GO:0034612	response to tumor necrosis factor	9275185
Tgene	MAP4K3	GO:0035556	intracellular signal transduction	9275185

Kinase Fusion gene breakpoints across SOS1 (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 MAP4K3 (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-EL-A3H8-01A	SOS1	chr2	39283843	MAP4K3	chr2	39605264
ChimerDB4	TCGA-EL-A3H8	SOS1	chr2	39283842	MAP4K3	chr2	39605264
ChimerDB4	TCGA-XE-AANR-01A	SOS1	chr2	39278285	MAP4K3	chr2	39605264
ChimerDB4	TCGA-HU-8238-01A	SOS1	chr2	39347477	MAP4K3	chr2	39542529

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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)
ENST00000402219	ENST00000263881	SOS1	chr2	39278285	MAP4K3	chr2	39605264	4846	1150
ENST00000402219	ENST00000263881	SOS1	chr2	39283843	MAP4K3	chr2	39605264	4492	1032
ENST00000402219	ENST00000263881	SOS1	chr2	39283842	MAP4K3	chr2	39605264	4492	1032
ENST00000402219	ENST00000263881	SOS1	chr2	39347477	MAP4K3	chr2	39542529	3247	617

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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

>ENST00000402219_ENST00000263881_SOS1_chr2_39278285_MAP4K3_chr2_39605264_length(amino acids)=1150
MQAQQLPYEFFSEENAPKWRGLLVPALKKVQGQVHPTLESNDDALQYVEELILQLLNMLCQAQPRSASDVEERVQKSFPHPIDKWAIADA
QSAIEKRKRRNPLSLPVEKIHPLLKEVLGYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKVLMDMFHQDV
EDINILSLTDEEPSTSGEQTYYDLVKAFMAEIRQYIRELNLIIKVFREPFVSNSKLFSANDVENIFSRIVDIHELSVKLLGHIEDTVEMT
DEGSPHPLVGSCFEDLAEARNVNTGELAAIKVIKLEPGEDFAVVQQEIIMMKDCKHPNIVAYFGSYLRRDKLWICMEFCGGGSLQDIYHV
TGPLSELQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAQITATIAKRKSFIGTPYWMAPEVAAVERKGGYNQL
CDLWAVGITAIELAELQPPMFDLHPMRALFLMTKSNFQPPKLKDKMKWSNSFHHFVKMALTKNPKKRPTAEKLLQHPFVTQHLTRSLAIE
LLDKVNNPDHSTYHDFDDDDPEPLVAVPHRIHSTSRNVREEKTRSEITFGQVKFDPPLRKETEPHHELPDSDGFLDSSEEIYYTARSNLD
LQLEYGQGHQGGYFLGANKSLLKSVEEELHQRGHVAHLEDDEGDDDESKHSTLKAKIPPPLPPKPKSIFIPQEMHSTEDENQGTIKRCPM
SGSPAKPSQVPPRPPPPRLPPHKPVALGNGMSSFQLNGERDGSLCQQQNEHRGTNLSRKEKKDVPKPISNGLPPTPKVHMGACFSKVFNG
CPLKIHCASSWINPDTRDQYLIFGAEEGIYTLNLNELHETSMEQLFPRRCTWLYVMNNCLLSISGKASQLYSHNLPGLFDYARQMQKLPV
AIPAHKLPDRILPRKFSVSAKIPETKWCQKCCVVRNPYTGHKYLCGALQTSIVLLEWVEPMQKFMLIKHIDFPIPCPLRMFEMLVVPEQE
YPLVCVGVSRGRDFNQVVRFETVNPNSTSSWFTESDTPQTNVTHVTQLERDTILVCLDCCIKIVNLQGRLKSSRKLSSELTFDFQIESIV

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

>ENST00000402219_ENST00000263881_SOS1_chr2_39283843_MAP4K3_chr2_39605264_length(amino acids)=1032
MQAQQLPYEFFSEENAPKWRGLLVPALKKVQGQVHPTLESNDDALQYVEELILQLLNMLCQAQPRSASDVEERVQKSFPHPIDKWAIADA
QSAIEKRKRRNPLSLPVEKIHPLLKEVLGYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKARNVNTGELA
AIKVIKLEPGEDFAVVQQEIIMMKDCKHPNIVAYFGSYLRRDKLWICMEFCGGGSLQDIYHVTGPLSELQIAYVSRETLQGLYYLHSKGK
MHRDIKGANILLTDNGHVKLADFGVSAQITATIAKRKSFIGTPYWMAPEVAAVERKGGYNQLCDLWAVGITAIELAELQPPMFDLHPMRA
LFLMTKSNFQPPKLKDKMKWSNSFHHFVKMALTKNPKKRPTAEKLLQHPFVTQHLTRSLAIELLDKVNNPDHSTYHDFDDDDPEPLVAVP
HRIHSTSRNVREEKTRSEITFGQVKFDPPLRKETEPHHELPDSDGFLDSSEEIYYTARSNLDLQLEYGQGHQGGYFLGANKSLLKSVEEE
LHQRGHVAHLEDDEGDDDESKHSTLKAKIPPPLPPKPKSIFIPQEMHSTEDENQGTIKRCPMSGSPAKPSQVPPRPPPPRLPPHKPVALG
NGMSSFQLNGERDGSLCQQQNEHRGTNLSRKEKKDVPKPISNGLPPTPKVHMGACFSKVFNGCPLKIHCASSWINPDTRDQYLIFGAEEG
IYTLNLNELHETSMEQLFPRRCTWLYVMNNCLLSISGKASQLYSHNLPGLFDYARQMQKLPVAIPAHKLPDRILPRKFSVSAKIPETKWC
QKCCVVRNPYTGHKYLCGALQTSIVLLEWVEPMQKFMLIKHIDFPIPCPLRMFEMLVVPEQEYPLVCVGVSRGRDFNQVVRFETVNPNST
SSWFTESDTPQTNVTHVTQLERDTILVCLDCCIKIVNLQGRLKSSRKLSSELTFDFQIESIVCLQDSVLAFWKHGMQGRSFRSNEVTQEI

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

>ENST00000402219_ENST00000263881_SOS1_chr2_39283842_MAP4K3_chr2_39605264_length(amino acids)=1032
MQAQQLPYEFFSEENAPKWRGLLVPALKKVQGQVHPTLESNDDALQYVEELILQLLNMLCQAQPRSASDVEERVQKSFPHPIDKWAIADA
QSAIEKRKRRNPLSLPVEKIHPLLKEVLGYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKARNVNTGELA
AIKVIKLEPGEDFAVVQQEIIMMKDCKHPNIVAYFGSYLRRDKLWICMEFCGGGSLQDIYHVTGPLSELQIAYVSRETLQGLYYLHSKGK
MHRDIKGANILLTDNGHVKLADFGVSAQITATIAKRKSFIGTPYWMAPEVAAVERKGGYNQLCDLWAVGITAIELAELQPPMFDLHPMRA
LFLMTKSNFQPPKLKDKMKWSNSFHHFVKMALTKNPKKRPTAEKLLQHPFVTQHLTRSLAIELLDKVNNPDHSTYHDFDDDDPEPLVAVP
HRIHSTSRNVREEKTRSEITFGQVKFDPPLRKETEPHHELPDSDGFLDSSEEIYYTARSNLDLQLEYGQGHQGGYFLGANKSLLKSVEEE
LHQRGHVAHLEDDEGDDDESKHSTLKAKIPPPLPPKPKSIFIPQEMHSTEDENQGTIKRCPMSGSPAKPSQVPPRPPPPRLPPHKPVALG
NGMSSFQLNGERDGSLCQQQNEHRGTNLSRKEKKDVPKPISNGLPPTPKVHMGACFSKVFNGCPLKIHCASSWINPDTRDQYLIFGAEEG
IYTLNLNELHETSMEQLFPRRCTWLYVMNNCLLSISGKASQLYSHNLPGLFDYARQMQKLPVAIPAHKLPDRILPRKFSVSAKIPETKWC
QKCCVVRNPYTGHKYLCGALQTSIVLLEWVEPMQKFMLIKHIDFPIPCPLRMFEMLVVPEQEYPLVCVGVSRGRDFNQVVRFETVNPNST
SSWFTESDTPQTNVTHVTQLERDTILVCLDCCIKIVNLQGRLKSSRKLSSELTFDFQIESIVCLQDSVLAFWKHGMQGRSFRSNEVTQEI

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

>ENST00000402219_ENST00000263881_SOS1_chr2_39347477_MAP4K3_chr2_39542529_length(amino acids)=617
MQAQQLPYEFFSEENAPKWRGLLVPALKKPLVAVPHRIHSTSRNVREEKTRSEITFGQVKFDPPLRKETEPHHELPDSDGFLDSSEEIYY
TARSNLDLQLEYGQGHQGGYFLGANKSLLKSVEEELHQRGHVAHLEDDEGDDDESKHSTLKAKIPPPLPPKPKSIFIPQEMHSTEDENQG
TIKRCPMSGSPAKPSQVPPRPPPPRLPPHKPVALGNGMSSFQLNGERDGSLCQQQNEHRGTNLSRKEKKDVPKPISNGLPPTPKVHMGAC
FSKVFNGCPLKIHCASSWINPDTRDQYLIFGAEEGIYTLNLNELHETSMEQLFPRRCTWLYVMNNCLLSISGKASQLYSHNLPGLFDYAR
QMQKLPVAIPAHKLPDRILPRKFSVSAKIPETKWCQKCCVVRNPYTGHKYLCGALQTSIVLLEWVEPMQKFMLIKHIDFPIPCPLRMFEM
LVVPEQEYPLVCVGVSRGRDFNQVVRFETVNPNSTSSWFTESDTPQTNVTHVTQLERDTILVCLDCCIKIVNLQGRLKSSRKLSSELTFD

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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/chr2:39278285/chr2:39605264)
- 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
SOS1 Q07889	MAP4K3 Q8IVH8
FUNCTION: Promotes the exchange of Ras-bound GDP by GTP (PubMed:8493579). Probably by promoting Ras activation, regulates phosphorylation of MAP kinase MAPK3 in response to EGF (PubMed:17339331). Catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity (By similarity). {ECO:0000250\|UniProtKB:Q62245, ECO:0000269\|PubMed:17339331, ECO:0000269\|PubMed:8493579}.	FUNCTION: May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. {ECO:0000269\|PubMed:9275185}.

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
download page
* 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
Tgene	SOS1	39278285	MAP4K3	39605264	ENST00000402219	0	33	556_867	32	874	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	SOS1	39278285	MAP4K3	39605264	ENST00000402219	0	34	556_867	32	895	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	SOS1	39283842	MAP4K3	39605264	ENST00000402219	0	33	556_867	32	874	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	SOS1	39283842	MAP4K3	39605264	ENST00000402219	0	34	556_867	32	895	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	SOS1	39283843	MAP4K3	39605264	ENST00000402219	0	33	556_867	32	874	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	SOS1	39283843	MAP4K3	39605264	ENST00000402219	0	34	556_867	32	895	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	SOS1	39347477	MAP4K3	39542529	ENST00000402219	11	33	556_867	306	874	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	SOS1	39347477	MAP4K3	39542529	ENST00000402219	11	34	556_867	306	895	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795

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Kinase Fusion Protein Structures

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)	Henst	Tenst	Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	AA seq	Len(AA seq)
PDB file >>>463_SOS1_MAP4K3	ENST00000402219	ENST00000263881	SOS1	chr2	39347477	MAP4K3	chr2	39542529	MQAQQLPYEFFSEENAPKWRGLLVPALKKPLVAVPHRIHSTSRNVREEKTRSEITFGQVKFDPPLRKETEPHHELPDSDGFLDSSEEIYY TARSNLDLQLEYGQGHQGGYFLGANKSLLKSVEEELHQRGHVAHLEDDEGDDDESKHSTLKAKIPPPLPPKPKSIFIPQEMHSTEDENQG TIKRCPMSGSPAKPSQVPPRPPPPRLPPHKPVALGNGMSSFQLNGERDGSLCQQQNEHRGTNLSRKEKKDVPKPISNGLPPTPKVHMGAC FSKVFNGCPLKIHCASSWINPDTRDQYLIFGAEEGIYTLNLNELHETSMEQLFPRRCTWLYVMNNCLLSISGKASQLYSHNLPGLFDYAR QMQKLPVAIPAHKLPDRILPRKFSVSAKIPETKWCQKCCVVRNPYTGHKYLCGALQTSIVLLEWVEPMQKFMLIKHIDFPIPCPLRMFEM LVVPEQEYPLVCVGVSRGRDFNQVVRFETVNPNSTSSWFTESDTPQTNVTHVTQLERDTILVCLDCCIKIVNLQGRLKSSRKLSSELTFD	617
3D view using mol* of 463_SOS1_MAP4K3

PDB file >>>TKFP_787_SOS1_MAP4K3	ENST00000402219	ENST00000263881	SOS1	chr2	39278285	MAP4K3	chr2	39605264	MQAQQLPYEFFSEENAPKWRGLLVPALKKVQGQVHPTLESNDDALQYVEELILQLLNMLCQAQPRSASDVEERVQKSFPHPIDKWAIADA QSAIEKRKRRNPLSLPVEKIHPLLKEVLGYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKVLMDMFHQDV EDINILSLTDEEPSTSGEQTYYDLVKAFMAEIRQYIRELNLIIKVFREPFVSNSKLFSANDVENIFSRIVDIHELSVKLLGHIEDTVEMT DEGSPHPLVGSCFEDLAEARNVNTGELAAIKVIKLEPGEDFAVVQQEIIMMKDCKHPNIVAYFGSYLRRDKLWICMEFCGGGSLQDIYHV TGPLSELQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAQITATIAKRKSFIGTPYWMAPEVAAVERKGGYNQL CDLWAVGITAIELAELQPPMFDLHPMRALFLMTKSNFQPPKLKDKMKWSNSFHHFVKMALTKNPKKRPTAEKLLQHPFVTQHLTRSLAIE LLDKVNNPDHSTYHDFDDDDPEPLVAVPHRIHSTSRNVREEKTRSEITFGQVKFDPPLRKETEPHHELPDSDGFLDSSEEIYYTARSNLD LQLEYGQGHQGGYFLGANKSLLKSVEEELHQRGHVAHLEDDEGDDDESKHSTLKAKIPPPLPPKPKSIFIPQEMHSTEDENQGTIKRCPM SGSPAKPSQVPPRPPPPRLPPHKPVALGNGMSSFQLNGERDGSLCQQQNEHRGTNLSRKEKKDVPKPISNGLPPTPKVHMGACFSKVFNG CPLKIHCASSWINPDTRDQYLIFGAEEGIYTLNLNELHETSMEQLFPRRCTWLYVMNNCLLSISGKASQLYSHNLPGLFDYARQMQKLPV AIPAHKLPDRILPRKFSVSAKIPETKWCQKCCVVRNPYTGHKYLCGALQTSIVLLEWVEPMQKFMLIKHIDFPIPCPLRMFEMLVVPEQE YPLVCVGVSRGRDFNQVVRFETVNPNSTSSWFTESDTPQTNVTHVTQLERDTILVCLDCCIKIVNLQGRLKSSRKLSSELTFDFQIESIV	1150_SOS1_MAP4K3
PDB file >>>TKFP_788_SOS1_MAP4K3	ENST00000402219	ENST00000263881	SOS1	chr2	39283843	MAP4K3	chr2	39605264	MQAQQLPYEFFSEENAPKWRGLLVPALKKVQGQVHPTLESNDDALQYVEELILQLLNMLCQAQPRSASDVEERVQKSFPHPIDKWAIADA QSAIEKRKRRNPLSLPVEKIHPLLKEVLGYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKARNVNTGELA AIKVIKLEPGEDFAVVQQEIIMMKDCKHPNIVAYFGSYLRRDKLWICMEFCGGGSLQDIYHVTGPLSELQIAYVSRETLQGLYYLHSKGK MHRDIKGANILLTDNGHVKLADFGVSAQITATIAKRKSFIGTPYWMAPEVAAVERKGGYNQLCDLWAVGITAIELAELQPPMFDLHPMRA LFLMTKSNFQPPKLKDKMKWSNSFHHFVKMALTKNPKKRPTAEKLLQHPFVTQHLTRSLAIELLDKVNNPDHSTYHDFDDDDPEPLVAVP HRIHSTSRNVREEKTRSEITFGQVKFDPPLRKETEPHHELPDSDGFLDSSEEIYYTARSNLDLQLEYGQGHQGGYFLGANKSLLKSVEEE LHQRGHVAHLEDDEGDDDESKHSTLKAKIPPPLPPKPKSIFIPQEMHSTEDENQGTIKRCPMSGSPAKPSQVPPRPPPPRLPPHKPVALG NGMSSFQLNGERDGSLCQQQNEHRGTNLSRKEKKDVPKPISNGLPPTPKVHMGACFSKVFNGCPLKIHCASSWINPDTRDQYLIFGAEEG IYTLNLNELHETSMEQLFPRRCTWLYVMNNCLLSISGKASQLYSHNLPGLFDYARQMQKLPVAIPAHKLPDRILPRKFSVSAKIPETKWC QKCCVVRNPYTGHKYLCGALQTSIVLLEWVEPMQKFMLIKHIDFPIPCPLRMFEMLVVPEQEYPLVCVGVSRGRDFNQVVRFETVNPNST SSWFTESDTPQTNVTHVTQLERDTILVCLDCCIKIVNLQGRLKSSRKLSSELTFDFQIESIVCLQDSVLAFWKHGMQGRSFRSNEVTQEI	1032_SOS1_MAP4K3
3D view using mol* of TKFP_788_SOS1_MAP4K3

PDB file >>>TKFP_789_SOS1_MAP4K3	ENST00000402219	ENST00000263881	SOS1	chr2	39283842	MAP4K3	chr2	39605264	MQAQQLPYEFFSEENAPKWRGLLVPALKKVQGQVHPTLESNDDALQYVEELILQLLNMLCQAQPRSASDVEERVQKSFPHPIDKWAIADA QSAIEKRKRRNPLSLPVEKIHPLLKEVLGYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKARNVNTGELA AIKVIKLEPGEDFAVVQQEIIMMKDCKHPNIVAYFGSYLRRDKLWICMEFCGGGSLQDIYHVTGPLSELQIAYVSRETLQGLYYLHSKGK MHRDIKGANILLTDNGHVKLADFGVSAQITATIAKRKSFIGTPYWMAPEVAAVERKGGYNQLCDLWAVGITAIELAELQPPMFDLHPMRA LFLMTKSNFQPPKLKDKMKWSNSFHHFVKMALTKNPKKRPTAEKLLQHPFVTQHLTRSLAIELLDKVNNPDHSTYHDFDDDDPEPLVAVP HRIHSTSRNVREEKTRSEITFGQVKFDPPLRKETEPHHELPDSDGFLDSSEEIYYTARSNLDLQLEYGQGHQGGYFLGANKSLLKSVEEE LHQRGHVAHLEDDEGDDDESKHSTLKAKIPPPLPPKPKSIFIPQEMHSTEDENQGTIKRCPMSGSPAKPSQVPPRPPPPRLPPHKPVALG NGMSSFQLNGERDGSLCQQQNEHRGTNLSRKEKKDVPKPISNGLPPTPKVHMGACFSKVFNGCPLKIHCASSWINPDTRDQYLIFGAEEG IYTLNLNELHETSMEQLFPRRCTWLYVMNNCLLSISGKASQLYSHNLPGLFDYARQMQKLPVAIPAHKLPDRILPRKFSVSAKIPETKWC QKCCVVRNPYTGHKYLCGALQTSIVLLEWVEPMQKFMLIKHIDFPIPCPLRMFEMLVVPEQEYPLVCVGVSRGRDFNQVVRFETVNPNST SSWFTESDTPQTNVTHVTQLERDTILVCLDCCIKIVNLQGRLKSSRKLSSELTFDFQIESIVCLQDSVLAFWKHGMQGRSFRSNEVTQEI	1032_SOS1_MAP4K3
PDB file >>>TKFP_790_SOS1_MAP4K3	ENST00000402219	ENST00000263881	SOS1	chr2	39347477	MAP4K3	chr2	39542529	MQAQQLPYEFFSEENAPKWRGLLVPALKKPLVAVPHRIHSTSRNVREEKTRSEITFGQVKFDPPLRKETEPHHELPDSDGFLDSSEEIYY TARSNLDLQLEYGQGHQGGYFLGANKSLLKSVEEELHQRGHVAHLEDDEGDDDESKHSTLKAKIPPPLPPKPKSIFIPQEMHSTEDENQG TIKRCPMSGSPAKPSQVPPRPPPPRLPPHKPVALGNGMSSFQLNGERDGSLCQQQNEHRGTNLSRKEKKDVPKPISNGLPPTPKVHMGAC FSKVFNGCPLKIHCASSWINPDTRDQYLIFGAEEGIYTLNLNELHETSMEQLFPRRCTWLYVMNNCLLSISGKASQLYSHNLPGLFDYAR QMQKLPVAIPAHKLPDRILPRKFSVSAKIPETKWCQKCCVVRNPYTGHKYLCGALQTSIVLLEWVEPMQKFMLIKHIDFPIPCPLRMFEM LVVPEQEYPLVCVGVSRGRDFNQVVRFETVNPNSTSSWFTESDTPQTNVTHVTQLERDTILVCLDCCIKIVNLQGRLKSSRKLSSELTFD	617_SOS1_MAP4K3
3D view using mol* of TKFP_790_SOS1_MAP4K3

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Comparison of Fusion Protein Isoforms

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_787_SOS1_MAP4K3_vs_TKFP_788_SOS1_MAP4K3_superimposed.pdb.html
3D view using mol* of viewer/superimpose_isoforms/TKFP_787_SOS1_MAP4K3_vs_TKFP_790_SOS1_MAP4K3_superimposed.pdb.html
3D view using mol* of viewer/superimpose_isoforms/TKFP_788_SOS1_MAP4K3_vs_TKFP_790_SOS1_MAP4K3_superimposed.pdb.html

Comparison of the Secondary Structures of Fusion Protein Isoforms

./secondary_str/TKFP_787_SOS1_MAP4K3_vs_TKFP_788_SOS1_MAP4K3.png

./secondary_str/TKFP_787_SOS1_MAP4K3_vs_TKFP_790_SOS1_MAP4K3.png

./secondary_str/TKFP_788_SOS1_MAP4K3_vs_TKFP_790_SOS1_MAP4K3.png

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

SOS1_MAP4K3 does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/463_SOS1_MAP4K3.pngall_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/TKFP_788_SOS1_MAP4K3_updated_violin_plot.pngall_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/TKFP_790_SOS1_MAP4K3_updated_violin_plot.png

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.

463_SOS1_MAP4K3.png

TKFP_788_SOS1_MAP4K3.png

TKFP_790_SOS1_MAP4K3.png

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Potential Active Site Information

The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.

Kinase Fusion AA seq ID in KinaseFusionDB	Site score	Size	Dscore	Volume	Exposure	Enclosure	Contact	Phobic	Philic	Balance	Don/Acc	Residues
TKFP_788_SOS1_MAP4K3	1.064	181	1.055	352.604	0.434	0.794	1.127	0.77	1.11	0.694	0.604	Chain A: 202,269,270,271,273,274,275,296,299,300,3 02,303,305,306,307,308,309,310,311,312,315,316,317 ,320,321,322,323,324,325,327,328,329,333,334,336,3 37,365
TKFP_790_SOS1_MAP4K3	1.038	379	1.056	1370.285	0.571	0.75	0.889	0.463	1.023	0.453	0.948	Chain A: 87,88,89,90,91,92,93,284,285,286,287,289, 296,297,298,311,329,330,331,332,340,396,397,398,39 9,400,401,405,446,447,448,449,450,451,500,501,502, 503,504,505,506,507,509,520,528,530,532,533,545,54 6,547,548,549,550,551,566,567,585,586,587,588,589, 590,591,592,609,610,611,612,613,615,616,617

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Ramachandran Plot of Kinase Fusion Protein Structure

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

463_SOS1_MAP4K3_ramachandran.png

TKFP_788_SOS1_MAP4K3_ramachandran.png

TKFP_790_SOS1_MAP4K3_ramachandran.png

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Virtual Screening Results

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

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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 info

Drug

Docking score

Glide g score

Glide energy

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Kinase-Substrate Information of SOS1_MAP4K3

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
MAP4K3	Q8IVH8	human	ACE2	Q9BYF1	S783	sGENPyAsIDIsKGE
MAP4K3	Q8IVH8	human	TFEB	P19484	S3	_____MAsRIGLrMQ
MAP4K3	Q8IVH8	human	MAP4K3	Q8IVH8	S170	AtIAkRKsFIGTPYW	Pkinase
MAP4K3	Q8IVH8	human	IQGAP1	P46940	S480	NTVWKQLsSSVTGLT
MAP4K3	Q8IVH8	human	PRKCQ	Q04759	T538	LGDAktNtFCGtPDy	Pkinase
MAP4K3	Q8IVH8	human	ACE2	Q9BYF1	S776	KkkNkARsGENPyAs
MAP4K3	Q8IVH8	human	IKBKB	O14920	S733	TVREQDQsFtALDWs	IKKbetaNEMObind

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
MAP4K3	ID	Description	0.00e+00
MAP4K3	GO:0038095	Fc-epsilon receptor signaling pathway	9.14e-03
MAP4K3	GO:0035305	negative regulation of dephosphorylation	9.14e-03
MAP4K3	GO:0030866	cortical actin cytoskeleton organization	9.14e-03
MAP4K3	GO:0030865	cortical cytoskeleton organization	9.74e-03
MAP4K3	GO:0038093	Fc receptor signaling pathway	9.79e-03
MAP4K3	GO:0035303	regulation of dephosphorylation	2.93e-02
MAP4K3	GO:0051092	positive regulation of NF-kappaB transcription factor activity	4.22e-02
MAP4K3	GO:0007043	cell-cell junction assembly	4.22e-02
MAP4K3	GO:1901888	regulation of cell junction assembly	4.22e-02
MAP4K3	GO:0002064	epithelial cell development	4.22e-02
MAP4K3	GO:0045216	cell-cell junction organization	4.22e-02
MAP4K3	GO:0051403	stress-activated MAPK cascade	4.22e-02
MAP4K3	GO:0031098	stress-activated protein kinase signaling cascade	4.22e-02
MAP4K3	GO:0051091	positive regulation of DNA-binding transcription factor activity	4.22e-02
MAP4K3	GO:0034612	response to tumor necrosis factor	4.22e-02
MAP4K3	GO:0002002	regulation of angiotensin levels in blood	4.22e-02
MAP4K3	GO:0042756	drinking behavior	4.22e-02
MAP4K3	GO:0044650	adhesion of symbiont to host cell	4.22e-02
MAP4K3	GO:0044837	actomyosin contractile ring organization	4.22e-02
MAP4K3	GO:1903596	regulation of gap junction assembly	4.22e-02
MAP4K3	GO:2000563	positive regulation of CD4-positiv	3.18e-03
MAP4K3	GO:0035666	TRIF-dependent toll-like receptor signaling pathway	4.22e-02
MAP4K3	GO:0072015	podocyte development	4.22e-02
MAP4K3	GO:0018105	peptidyl-serine phosphorylation	4.22e-02
MAP4K3	GO:0016311	dephosphorylation	4.22e-02
MAP4K3	GO:0015801	aromatic amino acid transport	4.22e-02
MAP4K3	GO:0035524	proline transmembrane transport	4.22e-02
MAP4K3	GO:0072310	glomerular epithelial cell development	4.22e-02
MAP4K3	GO:0018209	peptidyl-serine modification	4.22e-02
MAP4K3	GO:0015824	proline transport	4.22e-02
MAP4K3	GO:0044406	adhesion of symbiont to host	4.22e-02
MAP4K3	GO:0075509	endocytosis involved in viral entry into host cell	4.22e-02
MAP4K3	GO:0001976	nervous system process involved in regulation of systemic arterial blood pressure	4.22e-02
MAP4K3	GO:0045989	positive regulation of striated muscle contraction	4.22e-02
MAP4K3	GO:0002768	immune response-regulating cell surface receptor signaling pathway	4.22e-02
MAP4K3	GO:0002756	MyD88-independent toll-like receptor signaling pathway	4.22e-02
MAP4K3	GO:0010958	regulation of amino acid import across plasma membrane	4.22e-02
MAP4K3	GO:1903789	regulation of amino acid transmembrane transport	4.22e-02
MAP4K3	GO:2000318	positive regulation of T-helper 17 type immune response	4.22e-02
MAP4K3	GO:0001991	regulation of systemic arterial blood pressure by circulatory renin-angiotensin	4.22e-02
MAP4K3	GO:1901550	regulation of endothelial cell development	4.22e-02
MAP4K3	GO:1903140	regulation of establishment of endothelial barrier	4.22e-02
MAP4K3	GO:1904355	positive regulation of telomere capping	4.22e-02
MAP4K3	GO:0045936	negative regulation of phosphate metabolic process	4.22e-02
MAP4K3	GO:0010563	negative regulation of phosphorus metabolic process	4.22e-02
MAP4K3	GO:0016264	gap junction assembly	4.22e-02
MAP4K3	GO:0002755	MyD88-dependent toll-like receptor signaling pathway	4.22e-02
MAP4K3	GO:0032515	negative regulation of phosphoprotein phosphatase activity	4.22e-02
MAP4K3	GO:0051090	regulation of DNA-binding transcription factor activity	4.22e-02

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Related Drugs to SOS1_MAP4K3

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 SOS1-MAP4K3 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 SOS1_MAP4K3

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