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	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:CUL5-ATM

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: CUL5-ATM
	FusionPDB ID: 20693
	FusionGDB2.0 ID: 20693
		Hgene	Tgene
	Gene symbol	CUL5	ATM
	Gene ID	8065	472
	Gene name	cullin 5	ATM serine/threonine kinase
	Synonyms	CUL-5\|VACM-1\|VACM1	AT1\|ATA\|ATC\|ATD\|ATDC\|ATE\|TEL1\|TELO1
	Cytomap	11q22.3	11q22.3
	Type of gene	protein-coding	protein-coding
	Description	cullin-5Cullin-5 (vasopressin-activated calcium-mobilizing receptor-1)Vasopressin-activated calcium-mobilizing receptor-1vasopressin-activated calcium-mobilizing receptor 1	serine-protein kinase ATMA-T mutatedAT mutatedTEL1, telomere maintenance 1, homologataxia telangiectasia mutated
	Modification date	20200327	20200322
	UniProtAcc	Q93034	O43313
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000393094, ENST00000531843,	ENST00000525178, ENST00000278616, ENST00000452508,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	5 X 3 X 4=60	8 X 9 X 8=576
	# samples	5	12
	** MAII score	log2(5/60*10)=-0.263034405833794 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(12/576*10)=-2.26303440583379 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: CUL5 [Title/Abstract] AND ATM [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	CUL5(107969256)-ATM(108235808), # samples:2
Anticipated loss of major functional domain due to fusion event.	CUL5-ATM 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. CUL5-ATM 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. CUL5-ATM 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. CUL5-ATM 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)

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
Tgene	ATM	GO:0006468	protein phosphorylation	15916964
Tgene	ATM	GO:0006974	cellular response to DNA damage stimulus	9733515\|16213212
Tgene	ATM	GO:0010212	response to ionizing radiation	9733515\|11375976
Tgene	ATM	GO:0018105	peptidyl-serine phosphorylation	9733515\|26323318
Tgene	ATM	GO:0046777	protein autophosphorylation	9733515\|15790808
Tgene	ATM	GO:0071044	histone mRNA catabolic process	16086026
Tgene	ATM	GO:0071480	cellular response to gamma radiation	9925639\|16213212
Tgene	ATM	GO:0071481	cellular response to X-ray	26323318
Tgene	ATM	GO:0071500	cellular response to nitrosative stress	23878245

Fusion gene breakpoints across CUL5 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Fusion gene breakpoints across ATM (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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Fusion Gene Sample Information

Fusion gene information from FusionGDB2.0.

Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* 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	Disease	Sample	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
ChimerDB4	HNSC	TCGA-CV-6952	CUL5	chr11	107969256	+	ATM	chr11	108235808	+
ChimerDB4	HNSC	TCGA-CV-6952	CUL5	chr11	107969256	+	ATM	chr11	108235809	+

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Fusion ORF Analysis

Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.

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)

ENST00000393094

CUL5

chr11

107969256

ENST00000278616

ATM

chr11

108235808

6676

2764

445

3084

879

ENST00000393094

CUL5

chr11

107969256

ENST00000452508

ATM

chr11

108235808

6679

2764

445

3084

879

ENST00000393094

CUL5

chr11

107969256

ENST00000278616

ATM

chr11

108235809

6676

2764

445

3084

879

ENST00000393094

CUL5

chr11

107969256

ENST00000452508

ATM

chr11

108235809

6679

2764

445

3084

879

DeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	No-coding score	Coding score
ENST00000393094	ENST00000278616	CUL5	chr11	107969256	+	ATM	chr11	108235808	+	0.000102696	0.99989724
ENST00000393094	ENST00000452508	CUL5	chr11	107969256	+	ATM	chr11	108235808	+	0.000103295	0.99989665
ENST00000393094	ENST00000278616	CUL5	chr11	107969256	+	ATM	chr11	108235809	+	0.000102696	0.99989724
ENST00000393094	ENST00000452508	CUL5	chr11	107969256	+	ATM	chr11	108235809	+	0.000103295	0.99989665

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Fusion Amino Acid Sequences

For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.

>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>20693_20693_1_CUL5-ATM_CUL5_chr11_107969256_ENST00000393094_ATM_chr11_108235808_ENST00000278616_length(amino acids)=879AA_BP=1
MVLGTRSALSARCSSAHHTLVRADGPWALVGAPASGQGLAGSATNSRVVSRESKLKNMATSNLLKNKGSLQFEDKWDFMRPIVLKLLRQE
SVTKQQWFDLFSDVHAVCLWDDKGPAKIHQALKEDILEFIKQAQARVLSHQDDTALLKAYIVEWRKFFTQCDILPKPFCQLEITLMGKQG
SNKKSNVEDSIVRKLMLDTWNESIFSNIKNRLQDSAMKLVHAERLGEAFDSQLVIGVRESYVNLCSNPEDKLQIYRDNFEKAYLDSTERF
YRTQAPSYLQQNGVQNYMKYADAKLKEEEKRALRYLETRRECNSVEALMECCVNALVTSFKETILAECQGMIKRNETEKLHLMFSLMDKV
PNGIEPMLKDLEEHIISAGLADMVAAAETITTDSEKYVEQLLTLFNRFSKLVKEAFQDDPRFLTARDKAYKAVVNDATIFKLELPLKQKG
VGLKTQPESKCPELLANYCDMLLRKTPLSKKLTSEEIEAKLKEVLLVLKYVQNKDVFMRYHKAHLTRRLILDISADSEIEENMVEWLREV
GMPADYVNKLARMFQDIKVSEDLNQAFKEMHKNNKLALPADSVNIKILNAGAWSRSSEKVFVSLPTELEDLIPEVEEFYKKNHSGRKLHW
HHLMSNGIITFKNEVGQYDLEVTTFQLAVLFAWNQRPREKISFENLKLATELPDAELRRTLWSLVAFPKLKRQVLLYEPQVNSPKDFTEG
TLFSVNQEFSLIKNAKVQKRGKINLIGRLQLTTERMREEENEGIVQLRILRTQVLLYDPLFDWTMNPLKALYLQQRPEDETELHPTLNAD

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

>20693_20693_2_CUL5-ATM_CUL5_chr11_107969256_ENST00000393094_ATM_chr11_108235808_ENST00000452508_length(amino acids)=879AA_BP=1
MVLGTRSALSARCSSAHHTLVRADGPWALVGAPASGQGLAGSATNSRVVSRESKLKNMATSNLLKNKGSLQFEDKWDFMRPIVLKLLRQE
SVTKQQWFDLFSDVHAVCLWDDKGPAKIHQALKEDILEFIKQAQARVLSHQDDTALLKAYIVEWRKFFTQCDILPKPFCQLEITLMGKQG
SNKKSNVEDSIVRKLMLDTWNESIFSNIKNRLQDSAMKLVHAERLGEAFDSQLVIGVRESYVNLCSNPEDKLQIYRDNFEKAYLDSTERF
YRTQAPSYLQQNGVQNYMKYADAKLKEEEKRALRYLETRRECNSVEALMECCVNALVTSFKETILAECQGMIKRNETEKLHLMFSLMDKV
PNGIEPMLKDLEEHIISAGLADMVAAAETITTDSEKYVEQLLTLFNRFSKLVKEAFQDDPRFLTARDKAYKAVVNDATIFKLELPLKQKG
VGLKTQPESKCPELLANYCDMLLRKTPLSKKLTSEEIEAKLKEVLLVLKYVQNKDVFMRYHKAHLTRRLILDISADSEIEENMVEWLREV
GMPADYVNKLARMFQDIKVSEDLNQAFKEMHKNNKLALPADSVNIKILNAGAWSRSSEKVFVSLPTELEDLIPEVEEFYKKNHSGRKLHW
HHLMSNGIITFKNEVGQYDLEVTTFQLAVLFAWNQRPREKISFENLKLATELPDAELRRTLWSLVAFPKLKRQVLLYEPQVNSPKDFTEG
TLFSVNQEFSLIKNAKVQKRGKINLIGRLQLTTERMREEENEGIVQLRILRTQVLLYDPLFDWTMNPLKALYLQQRPEDETELHPTLNAD

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

>20693_20693_3_CUL5-ATM_CUL5_chr11_107969256_ENST00000393094_ATM_chr11_108235809_ENST00000278616_length(amino acids)=879AA_BP=1
MVLGTRSALSARCSSAHHTLVRADGPWALVGAPASGQGLAGSATNSRVVSRESKLKNMATSNLLKNKGSLQFEDKWDFMRPIVLKLLRQE
SVTKQQWFDLFSDVHAVCLWDDKGPAKIHQALKEDILEFIKQAQARVLSHQDDTALLKAYIVEWRKFFTQCDILPKPFCQLEITLMGKQG
SNKKSNVEDSIVRKLMLDTWNESIFSNIKNRLQDSAMKLVHAERLGEAFDSQLVIGVRESYVNLCSNPEDKLQIYRDNFEKAYLDSTERF
YRTQAPSYLQQNGVQNYMKYADAKLKEEEKRALRYLETRRECNSVEALMECCVNALVTSFKETILAECQGMIKRNETEKLHLMFSLMDKV
PNGIEPMLKDLEEHIISAGLADMVAAAETITTDSEKYVEQLLTLFNRFSKLVKEAFQDDPRFLTARDKAYKAVVNDATIFKLELPLKQKG
VGLKTQPESKCPELLANYCDMLLRKTPLSKKLTSEEIEAKLKEVLLVLKYVQNKDVFMRYHKAHLTRRLILDISADSEIEENMVEWLREV
GMPADYVNKLARMFQDIKVSEDLNQAFKEMHKNNKLALPADSVNIKILNAGAWSRSSEKVFVSLPTELEDLIPEVEEFYKKNHSGRKLHW
HHLMSNGIITFKNEVGQYDLEVTTFQLAVLFAWNQRPREKISFENLKLATELPDAELRRTLWSLVAFPKLKRQVLLYEPQVNSPKDFTEG
TLFSVNQEFSLIKNAKVQKRGKINLIGRLQLTTERMREEENEGIVQLRILRTQVLLYDPLFDWTMNPLKALYLQQRPEDETELHPTLNAD

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

>20693_20693_4_CUL5-ATM_CUL5_chr11_107969256_ENST00000393094_ATM_chr11_108235809_ENST00000452508_length(amino acids)=879AA_BP=1
MVLGTRSALSARCSSAHHTLVRADGPWALVGAPASGQGLAGSATNSRVVSRESKLKNMATSNLLKNKGSLQFEDKWDFMRPIVLKLLRQE
SVTKQQWFDLFSDVHAVCLWDDKGPAKIHQALKEDILEFIKQAQARVLSHQDDTALLKAYIVEWRKFFTQCDILPKPFCQLEITLMGKQG
SNKKSNVEDSIVRKLMLDTWNESIFSNIKNRLQDSAMKLVHAERLGEAFDSQLVIGVRESYVNLCSNPEDKLQIYRDNFEKAYLDSTERF
YRTQAPSYLQQNGVQNYMKYADAKLKEEEKRALRYLETRRECNSVEALMECCVNALVTSFKETILAECQGMIKRNETEKLHLMFSLMDKV
PNGIEPMLKDLEEHIISAGLADMVAAAETITTDSEKYVEQLLTLFNRFSKLVKEAFQDDPRFLTARDKAYKAVVNDATIFKLELPLKQKG
VGLKTQPESKCPELLANYCDMLLRKTPLSKKLTSEEIEAKLKEVLLVLKYVQNKDVFMRYHKAHLTRRLILDISADSEIEENMVEWLREV
GMPADYVNKLARMFQDIKVSEDLNQAFKEMHKNNKLALPADSVNIKILNAGAWSRSSEKVFVSLPTELEDLIPEVEEFYKKNHSGRKLHW
HHLMSNGIITFKNEVGQYDLEVTTFQLAVLFAWNQRPREKISFENLKLATELPDAELRRTLWSLVAFPKLKRQVLLYEPQVNSPKDFTEG
TLFSVNQEFSLIKNAKVQKRGKINLIGRLQLTTERMREEENEGIVQLRILRTQVLLYDPLFDWTMNPLKALYLQQRPEDETELHPTLNAD

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

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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/chr11:107969256/chr11:108235808)
- 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
CUL5 Q93034	ATM O43313
FUNCTION: Core component of multiple SCF-like ECS (Elongin-Cullin 2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. ECS(SOCS1) seems to direct ubiquitination of JAK2. Seems to be involved in proteosomal degradation of p53/TP53 stimulated by adenovirus E1B-55 kDa protein. May form a cell surface vasopressin receptor.	FUNCTION: Transcription factor. Plays a crucial role in cell survival and RAD51 foci formation in response to methylating DNA damage. Involved in regulating the activity of ATM in the absence of DNA damage. May play a role in stabilizing ATM. Binds to the DYNLL1 promoter and activates its transcription. {ECO:0000269\|PubMed:15933716, ECO:0000269\|PubMed:17525732, ECO:0000269\|PubMed:22167198}.

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 protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Tgene

ATM

chr11:107969256

chr11:108235808

ENST00000278616

3024_3056

2950.0

3057.0

Domain

FATC

Tgene

ATM

chr11:107969256

chr11:108235808

ENST00000452508

3024_3056

2950.0

3057.0

Domain

FATC

Tgene

ATM

chr11:107969256

chr11:108235809

ENST00000278616

3024_3056

2950.0

3057.0

Domain

FATC

Tgene

ATM

chr11:107969256

chr11:108235809

ENST00000452508

3024_3056

2950.0

3057.0

Domain

FATC

- Not-retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Tgene

ATM

chr11:107969256

chr11:108235808

ENST00000278616

1940_2566

2950.0

3057.0

Domain

FAT

Tgene

ATM

chr11:107969256

chr11:108235808

ENST00000278616

2712_2962

2950.0

3057.0

Domain

PI3K/PI4K

Tgene

ATM

chr11:107969256

chr11:108235808

ENST00000452508

1940_2566

2950.0

3057.0

Domain

FAT

Tgene

ATM

chr11:107969256

chr11:108235808

ENST00000452508

2712_2962

2950.0

3057.0

Domain

PI3K/PI4K

Tgene

ATM

chr11:107969256

chr11:108235809

ENST00000278616

1940_2566

2950.0

3057.0

Domain

FAT

Tgene

ATM

chr11:107969256

chr11:108235809

ENST00000278616

2712_2962

2950.0

3057.0

Domain

PI3K/PI4K

Tgene

ATM

chr11:107969256

chr11:108235809

ENST00000452508

1940_2566

2950.0

3057.0

Domain

FAT

Tgene

ATM

chr11:107969256

chr11:108235809

ENST00000452508

2712_2962

2950.0

3057.0

Domain

PI3K/PI4K

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Fusion Protein-Protein Interaction

Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in
ChiPPI page.

Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)

Gene

PPI interactors

Protein-protein interactors based on sequence similarity (STRING)

Gene	STRING network
CUL5
ATM

- Retained interactions in fusion protein (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost interactions due to fusion (protein functional feature from UniProt).

Partner	Gene	Hbp	Tbp	ENST	Strand	BPexon	TotalExon	Protein feature loci	*BPloci	TotalLen	Interaction lost with
Tgene	ATM	chr11:107969256	chr11:108235808	ENST00000278616		60	63	1373_1382	2950.0	3057.0	ABL1
Tgene	ATM	chr11:107969256	chr11:108235808	ENST00000452508		61	64	1373_1382	2950.0	3057.0	ABL1
Tgene	ATM	chr11:107969256	chr11:108235809	ENST00000278616		60	63	1373_1382	2950.0	3057.0	ABL1
Tgene	ATM	chr11:107969256	chr11:108235809	ENST00000452508		61	64	1373_1382	2950.0	3057.0	ABL1

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Related Drugs to CUL5-ATM

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

Hgene

Tgene

Drug

Source

PMID

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Related Diseases to CUL5-ATM

Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Disease

Source

PMID

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source