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	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein Structure
	pLDDT scores
	Ramachandran Plot of Fusion Protein Structure
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:SMEK2-ALK

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: SMEK2-ALK
	FusionPDB ID: 84049
	FusionGDB2.0 ID: 84049
		Hgene	Tgene
	Gene symbol	SMEK2	ALK
	Gene ID	57223	238
	Gene name	protein phosphatase 4 regulatory subunit 3B	ALK receptor tyrosine kinase
	Synonyms	FLFL2\|PP4R3B\|PSY2\|SMEK2\|smk1	CD246\|NBLST3
	Cytomap	2p16.1	2p23.2-p23.1
	Type of gene	protein-coding	protein-coding
	Description	serine/threonine-protein phosphatase 4 regulatory subunit 3BSMEK homolog 2, suppressor of mek1	ALK tyrosine kinase receptorCD246 antigenanaplastic lymphoma receptor tyrosine kinasemutant anaplastic lymphoma kinase
	Modification date	20200313	20200329
	UniProtAcc	.	Q96BT7
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000272313, ENST00000345102, ENST00000407823, ENST00000477749,	ENST00000498037, ENST00000389048, ENST00000431873,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	8 X 6 X 8=384	56 X 74 X 20=82880
	# samples	8	57
	** MAII score	log2(8/384*10)=-2.26303440583379 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(57/82880*10)=-7.18391827352181 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: SMEK2 [Title/Abstract] AND ALK [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	SMEK2(55804451)-ALK(29940563), # samples:2
Anticipated loss of major functional domain due to fusion event.	SMEK2-ALK 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. SMEK2-ALK 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. SMEK2-ALK 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. SMEK2-ALK 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	ALK	GO:0016310	phosphorylation	9174053
Tgene	ALK	GO:0046777	protein autophosphorylation	9174053

Fusion gene breakpoints across SMEK2 (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 ALK (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	READ	TCGA-F5-6864-01A	SMEK2	chr2	55804451	-	ALK	chr2	29940563	-
ChimerDB4	READ	TCGA-F5-6864	SMEK2	chr2	55804451	-	ALK	chr2	29940563	-

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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)
ENST00000272313	SMEK2	chr2	55804451	-	ENST00000389048	ALK	chr2	29940563	-	6484	1838	178	6033	1951
ENST00000272313	SMEK2	chr2	55804451	-	ENST00000431873	ALK	chr2	29940563	-	2524	1838	178	2523	782
ENST00000407823	SMEK2	chr2	55804451	-	ENST00000389048	ALK	chr2	29940563	-	6493	1847	187	6042	1951
ENST00000407823	SMEK2	chr2	55804451	-	ENST00000431873	ALK	chr2	29940563	-	2533	1847	187	2532	782
ENST00000345102	SMEK2	chr2	55804451	-	ENST00000389048	ALK	chr2	29940563	-	6554	1908	152	6103	1983
ENST00000345102	SMEK2	chr2	55804451	-	ENST00000431873	ALK	chr2	29940563	-	2594	1908	152	2593	814

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
ENST00000272313	ENST00000389048	SMEK2	chr2	55804451	-	ALK	chr2	29940563	-	0.000927823	0.9990722
ENST00000272313	ENST00000431873	SMEK2	chr2	55804451	-	ALK	chr2	29940563	-	0.001055962	0.9989441
ENST00000407823	ENST00000389048	SMEK2	chr2	55804451	-	ALK	chr2	29940563	-	0.000933559	0.9990664
ENST00000407823	ENST00000431873	SMEK2	chr2	55804451	-	ALK	chr2	29940563	-	0.001044574	0.99895537
ENST00000345102	ENST00000389048	SMEK2	chr2	55804451	-	ALK	chr2	29940563	-	0.00083281	0.9991672
ENST00000345102	ENST00000431873	SMEK2	chr2	55804451	-	ALK	chr2	29940563	-	0.000684193	0.99931586

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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

>84049_84049_1_SMEK2-ALK_SMEK2_chr2_55804451_ENST00000272313_ALK_chr2_29940563_ENST00000389048_length(amino acids)=1951AA_BP=551
MNLWSHGEFGPLRSRRRRHRHYCLYRLLRVRSADEVSEEAAARAVETAATMSDTRRRVKVYTLNEDRQWDDRGTGHVSSTYVEELKGMSL
LVRAESDGSLLLESKINPNTAYQKQQDTLIVWSEAENYDLALSFQEKAGCDEIWEKICQVQGKDPSVEVTQDLIDESEEERFEEMPETSH
LIDLPTCELNKLEEIADLVTSVLSSPIRREKLALALENEGYIKKLLQLFQACENLENTEGLHHLYEIIRGILFLNKATLFEVMFSDECIM
DVVGCLEYDPALAQPKRHREFLTKTAKFKEVIPITDSELRQKIHQTYRVQYIQDIILPTPSVFEENFLSTLTSFIFFNKVEIVSMLQEDE
KFLSEVFAQLTDEATDDDKRRELVNFFKEFCAFSQTLQPQNRDAFFKTLAKLGILPALEIVMGMDDLQVRSAATDIFSYLVEFSPSMVRE
FVMQEAQQSDDDILLINVVIEQMICDTDPELGGAVQLMGLLRTLIDPENMLATTNKTEKSEFLNFFYNHCMHVLTAPLLTNTSEDKCEKD
NIVGSNKNNTICPGHSSLESPTNMPSPSPDYFTWNLTWIMKDSFPFLSHRSRYGLECSFDFPCELEYSPPLHDLRNQSWSWRRIPSEEAS
QMDLLDGPGAERSKEMPRGSFLLLNTSADSKHTILSPWMRSSSEHCTLAVSVHRHLQPSGRYIAQLLPHNEAAREILLMPTPGKHGWTVL
QGRIGRPDNPFRVALEYISSGNRSLSAVDFFALKNCSEGTSPGSKMALQSSFTCWNGTVLQLGQACDFHQDCAQGEDESQMCRKLPVGFY
CNFEDGFCGWTQGTLSPHTPQWQVRTLKDARFQDHQDHALLLSTTDVPASESATVTSATFPAPIKSSPCELRMSWLIRGVLRGNVSLVLV
ENKTGKEQGRMVWHVAAYEGLSLWQWMVLPLLDVSDRFWLQMVAWWGQGSRAIVAFDNISISLDCYLTISGEDKILQNTAPKSRNLFERN
PNKELKPGENSPRQTPIFDPTVHWLFTTCGASGPHGPTQAQCNNAYQNSNLSVEVGSEGPLKGIQIWKVPATDTYSISGYGAAGGKGGKN
TMMRSHGVSVLGIFNLEKDDMLYILVGQQGEDACPSTNQLIQKVCIGENNVIEEEIRVNRSVHEWAGGGGGGGGATYVFKMKDGVPVPLI
IAAGGGGRAYGAKTDTFHPERLENNSSVLGLNGNSGAAGGGGGWNDNTSLLWAGKSLQEGATGGHSCPQAMKKWGWETRGGFGGGGGGCS
SGGGGGGYIGGNAASNNDPEMDGEDGVSFISPLGILYTPALKVMEGHGEVNIKHYLNCSHCEVDECHMDPESHKVICFCDHGTVLAEDGV
SCIVSPTPEPHLPLSLILSVVTSALVAALVLAFSGIMIVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNPNYCFAGKTSSISDLK
EVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILLELM
AGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKIGDFGMARDIYRASYYRKGGCA
MLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMTQCWQHQPEDRPNFAII
LERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTSSGKAAKKPTAAEISVRVPRGP
AVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGSCTVPPNVATGRLPGASLLLEP

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

>84049_84049_2_SMEK2-ALK_SMEK2_chr2_55804451_ENST00000272313_ALK_chr2_29940563_ENST00000431873_length(amino acids)=782AA_BP=551
MNLWSHGEFGPLRSRRRRHRHYCLYRLLRVRSADEVSEEAAARAVETAATMSDTRRRVKVYTLNEDRQWDDRGTGHVSSTYVEELKGMSL
LVRAESDGSLLLESKINPNTAYQKQQDTLIVWSEAENYDLALSFQEKAGCDEIWEKICQVQGKDPSVEVTQDLIDESEEERFEEMPETSH
LIDLPTCELNKLEEIADLVTSVLSSPIRREKLALALENEGYIKKLLQLFQACENLENTEGLHHLYEIIRGILFLNKATLFEVMFSDECIM
DVVGCLEYDPALAQPKRHREFLTKTAKFKEVIPITDSELRQKIHQTYRVQYIQDIILPTPSVFEENFLSTLTSFIFFNKVEIVSMLQEDE
KFLSEVFAQLTDEATDDDKRRELVNFFKEFCAFSQTLQPQNRDAFFKTLAKLGILPALEIVMGMDDLQVRSAATDIFSYLVEFSPSMVRE
FVMQEAQQSDDDILLINVVIEQMICDTDPELGGAVQLMGLLRTLIDPENMLATTNKTEKSEFLNFFYNHCMHVLTAPLLTNTSEDKCEKD
NIVGSNKNNTICPGHSSLESPTNMPSPSPDYFTWNLTWIMKDSFPFLSHRSRYGKERSPAAPPPLPTTSSGKAAKKPTAAEISVRVPRGP
AVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGSCTVPPNVATGRLPGASLLLEP

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

>84049_84049_3_SMEK2-ALK_SMEK2_chr2_55804451_ENST00000345102_ALK_chr2_29940563_ENST00000389048_length(amino acids)=1983AA_BP=564
MNLWSHGEFGPLRSRRRRHRHYCLYRLLRVRSADEVSEEAAARAVETAATMSDTRRRVKVYTLNEDRQWDDRGTGHVSSTYVEELKGMSL
LVRAESDGSLLLESKINPNTAYQKQQDTLIVWSEAENYDLALSFQEKAGCDEIWEKICQVQGKDPSVEVTQDLIDESEEERFEEMPETSH
LIDLPTCELNKLEEIADLVTSVLSSPIRREKLALALENEGYIKKLLQLFQACENLENTEGLHHLYEIIRGILFLNKATLFEVMFSDECIM
DVVGCLEYDPALAQPKRHREFLTKTAKFKEVIPITDSELRQKIHQTYRVQYIQDIILPTPSVFEENFLSTLTSFIFFNKVEIVSMLQEDE
KFLSEVFAQLTDEATDDDKRRELVNFFKEFCAFSQTLQPQNRDAFFKTLAKLGILPALEIVMGMDDLQVRSAATDIFSYLVEFSPSMVRE
FVMQEAQQSDDDILLINVVIEQMICDTDPELGGAVQLMGLLRTLIDPENMLATTNKTEKSEFLNFFYNHCMHVLTAPLLTNTSEDKCEKD
FFLKHYRYSWSFICTPSHSHSHSTPSSSISQDNIVGSNKNNTICPGHSSLESPTNMPSPSPDYFTWNLTWIMKDSFPFLSHRSRYGLECS
FDFPCELEYSPPLHDLRNQSWSWRRIPSEEASQMDLLDGPGAERSKEMPRGSFLLLNTSADSKHTILSPWMRSSSEHCTLAVSVHRHLQP
SGRYIAQLLPHNEAAREILLMPTPGKHGWTVLQGRIGRPDNPFRVALEYISSGNRSLSAVDFFALKNCSEGTSPGSKMALQSSFTCWNGT
VLQLGQACDFHQDCAQGEDESQMCRKLPVGFYCNFEDGFCGWTQGTLSPHTPQWQVRTLKDARFQDHQDHALLLSTTDVPASESATVTSA
TFPAPIKSSPCELRMSWLIRGVLRGNVSLVLVENKTGKEQGRMVWHVAAYEGLSLWQWMVLPLLDVSDRFWLQMVAWWGQGSRAIVAFDN
ISISLDCYLTISGEDKILQNTAPKSRNLFERNPNKELKPGENSPRQTPIFDPTVHWLFTTCGASGPHGPTQAQCNNAYQNSNLSVEVGSE
GPLKGIQIWKVPATDTYSISGYGAAGGKGGKNTMMRSHGVSVLGIFNLEKDDMLYILVGQQGEDACPSTNQLIQKVCIGENNVIEEEIRV
NRSVHEWAGGGGGGGGATYVFKMKDGVPVPLIIAAGGGGRAYGAKTDTFHPERLENNSSVLGLNGNSGAAGGGGGWNDNTSLLWAGKSLQ
EGATGGHSCPQAMKKWGWETRGGFGGGGGGCSSGGGGGGYIGGNAASNNDPEMDGEDGVSFISPLGILYTPALKVMEGHGEVNIKHYLNC
SHCEVDECHMDPESHKVICFCDHGTVLAEDGVSCIVSPTPEPHLPLSLILSVVTSALVAALVLAFSGIMIVYRRKHQELQAMQMELQSPE
YKLSKLRTSTIMTDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLME
ALIISKFNHQNIVRCIGVSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLL
TCPGPGRVAKIGDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGR
MDPPKNCPGPVYRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERS
PAAPPPLPTTSSGKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEP
HDRGNLGLEGSCTVPPNVATGRLPGASLLLEPSSLTANMKEVPLFRLRHFPCGNVNYGYQQQGLPLEAATAPGAGHYEDTILKSKNSMNQ

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

>84049_84049_4_SMEK2-ALK_SMEK2_chr2_55804451_ENST00000345102_ALK_chr2_29940563_ENST00000431873_length(amino acids)=814AA_BP=564
MNLWSHGEFGPLRSRRRRHRHYCLYRLLRVRSADEVSEEAAARAVETAATMSDTRRRVKVYTLNEDRQWDDRGTGHVSSTYVEELKGMSL
LVRAESDGSLLLESKINPNTAYQKQQDTLIVWSEAENYDLALSFQEKAGCDEIWEKICQVQGKDPSVEVTQDLIDESEEERFEEMPETSH
LIDLPTCELNKLEEIADLVTSVLSSPIRREKLALALENEGYIKKLLQLFQACENLENTEGLHHLYEIIRGILFLNKATLFEVMFSDECIM
DVVGCLEYDPALAQPKRHREFLTKTAKFKEVIPITDSELRQKIHQTYRVQYIQDIILPTPSVFEENFLSTLTSFIFFNKVEIVSMLQEDE
KFLSEVFAQLTDEATDDDKRRELVNFFKEFCAFSQTLQPQNRDAFFKTLAKLGILPALEIVMGMDDLQVRSAATDIFSYLVEFSPSMVRE
FVMQEAQQSDDDILLINVVIEQMICDTDPELGGAVQLMGLLRTLIDPENMLATTNKTEKSEFLNFFYNHCMHVLTAPLLTNTSEDKCEKD
FFLKHYRYSWSFICTPSHSHSHSTPSSSISQDNIVGSNKNNTICPGHSSLESPTNMPSPSPDYFTWNLTWIMKDSFPFLSHRSRYGKERS
PAAPPPLPTTSSGKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEP
HDRGNLGLEGSCTVPPNVATGRLPGASLLLEPSSLTANMKEVPLFRLRHFPCGNVNYGYQQQGLPLEAATAPGAGHYEDTILKSKNSMNQ

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

>84049_84049_5_SMEK2-ALK_SMEK2_chr2_55804451_ENST00000407823_ALK_chr2_29940563_ENST00000389048_length(amino acids)=1951AA_BP=551
MNLWSHGEFGPLRSRRRRHRHYCLYRLLRVRSADEVSEEAAARAVETAATMSDTRRRVKVYTLNEDRQWDDRGTGHVSSTYVEELKGMSL
LVRAESDGSLLLESKINPNTAYQKQQDTLIVWSEAENYDLALSFQEKAGCDEIWEKICQVQGKDPSVEVTQDLIDESEEERFEEMPETSH
LIDLPTCELNKLEEIADLVTSVLSSPIRREKLALALENEGYIKKLLQLFQACENLENTEGLHHLYEIIRGILFLNKATLFEVMFSDECIM
DVVGCLEYDPALAQPKRHREFLTKTAKFKEVIPITDSELRQKIHQTYRVQYIQDIILPTPSVFEENFLSTLTSFIFFNKVEIVSMLQEDE
KFLSEVFAQLTDEATDDDKRRELVNFFKEFCAFSQTLQPQNRDAFFKTLAKLGILPALEIVMGMDDLQVRSAATDIFSYLVEFSPSMVRE
FVMQEAQQSDDDILLINVVIEQMICDTDPELGGAVQLMGLLRTLIDPENMLATTNKTEKSEFLNFFYNHCMHVLTAPLLTNTSEDKCEKD
NIVGSNKNNTICPGHSSLESPTNMPSPSPDYFTWNLTWIMKDSFPFLSHRSRYGLECSFDFPCELEYSPPLHDLRNQSWSWRRIPSEEAS
QMDLLDGPGAERSKEMPRGSFLLLNTSADSKHTILSPWMRSSSEHCTLAVSVHRHLQPSGRYIAQLLPHNEAAREILLMPTPGKHGWTVL
QGRIGRPDNPFRVALEYISSGNRSLSAVDFFALKNCSEGTSPGSKMALQSSFTCWNGTVLQLGQACDFHQDCAQGEDESQMCRKLPVGFY
CNFEDGFCGWTQGTLSPHTPQWQVRTLKDARFQDHQDHALLLSTTDVPASESATVTSATFPAPIKSSPCELRMSWLIRGVLRGNVSLVLV
ENKTGKEQGRMVWHVAAYEGLSLWQWMVLPLLDVSDRFWLQMVAWWGQGSRAIVAFDNISISLDCYLTISGEDKILQNTAPKSRNLFERN
PNKELKPGENSPRQTPIFDPTVHWLFTTCGASGPHGPTQAQCNNAYQNSNLSVEVGSEGPLKGIQIWKVPATDTYSISGYGAAGGKGGKN
TMMRSHGVSVLGIFNLEKDDMLYILVGQQGEDACPSTNQLIQKVCIGENNVIEEEIRVNRSVHEWAGGGGGGGGATYVFKMKDGVPVPLI
IAAGGGGRAYGAKTDTFHPERLENNSSVLGLNGNSGAAGGGGGWNDNTSLLWAGKSLQEGATGGHSCPQAMKKWGWETRGGFGGGGGGCS
SGGGGGGYIGGNAASNNDPEMDGEDGVSFISPLGILYTPALKVMEGHGEVNIKHYLNCSHCEVDECHMDPESHKVICFCDHGTVLAEDGV
SCIVSPTPEPHLPLSLILSVVTSALVAALVLAFSGIMIVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNPNYCFAGKTSSISDLK
EVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILLELM
AGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKIGDFGMARDIYRASYYRKGGCA
MLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMTQCWQHQPEDRPNFAII
LERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTSSGKAAKKPTAAEISVRVPRGP
AVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGSCTVPPNVATGRLPGASLLLEP

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

>84049_84049_6_SMEK2-ALK_SMEK2_chr2_55804451_ENST00000407823_ALK_chr2_29940563_ENST00000431873_length(amino acids)=782AA_BP=551
MNLWSHGEFGPLRSRRRRHRHYCLYRLLRVRSADEVSEEAAARAVETAATMSDTRRRVKVYTLNEDRQWDDRGTGHVSSTYVEELKGMSL
LVRAESDGSLLLESKINPNTAYQKQQDTLIVWSEAENYDLALSFQEKAGCDEIWEKICQVQGKDPSVEVTQDLIDESEEERFEEMPETSH
LIDLPTCELNKLEEIADLVTSVLSSPIRREKLALALENEGYIKKLLQLFQACENLENTEGLHHLYEIIRGILFLNKATLFEVMFSDECIM
DVVGCLEYDPALAQPKRHREFLTKTAKFKEVIPITDSELRQKIHQTYRVQYIQDIILPTPSVFEENFLSTLTSFIFFNKVEIVSMLQEDE
KFLSEVFAQLTDEATDDDKRRELVNFFKEFCAFSQTLQPQNRDAFFKTLAKLGILPALEIVMGMDDLQVRSAATDIFSYLVEFSPSMVRE
FVMQEAQQSDDDILLINVVIEQMICDTDPELGGAVQLMGLLRTLIDPENMLATTNKTEKSEFLNFFYNHCMHVLTAPLLTNTSEDKCEKD
NIVGSNKNNTICPGHSSLESPTNMPSPSPDYFTWNLTWIMKDSFPFLSHRSRYGKERSPAAPPPLPTTSSGKAAKKPTAAEISVRVPRGP
AVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGSCTVPPNVATGRLPGASLLLEP

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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/chr2:55804451/chr2:29940563)
- 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
.	ALK Q96BT7
FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.	FUNCTION: Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain (PubMed:20123966, PubMed:20308323, PubMed:31079898). Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA (PubMed:20123966, PubMed:20308323). Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys)(PubMed:20308323). Binds tRNA and catalyzes the iron and alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-methoxycarbonylhydroxymethyluridine; has a preference for tRNA(Gly) (PubMed:21285950). Required for normal survival after DNA damage (PubMed:20308323). May inhibit apoptosis and promote cell survival and angiogenesis (PubMed:19293182). {ECO:0000269\|PubMed:19293182, ECO:0000269\|PubMed:20123966, ECO:0000269\|PubMed:20308323, ECO:0000269\|PubMed:21285950, ECO:0000269\|PubMed:31079898}.

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

Hgene

SMEK2

chr2:55804451

chr2:29940563

ENST00000272313

1_100

503.3333333333333

765.0

Domain

Note=WH1

Hgene

SMEK2

chr2:55804451

chr2:29940563

ENST00000345102

1_100

535.3333333333334

850.0

Domain

Note=WH1

Hgene

SMEK2

chr2:55804451

chr2:29940563

ENST00000407823

1_100

503.3333333333333

818.0

Domain

Note=WH1

Tgene

ALK

chr2:55804451

chr2:29940563

ENST00000389048

816_940

222.33333333333334

1621.0

Compositional bias

Note=Gly-rich

Tgene

ALK

chr2:55804451

chr2:29940563

ENST00000389048

1116_1392

222.33333333333334

1621.0

Domain

Protein kinase

Tgene

ALK

chr2:55804451

chr2:29940563

ENST00000389048

264_427

222.33333333333334

1621.0

Domain

MAM 1

Tgene

ALK

chr2:55804451

chr2:29940563

ENST00000389048

437_473

222.33333333333334

1621.0

Domain

Note=LDL-receptor class A

Tgene

ALK

chr2:55804451

chr2:29940563

ENST00000389048

478_636

222.33333333333334

1621.0

Domain

MAM 2

Tgene

ALK

chr2:55804451

chr2:29940563

ENST00000389048

1197_1199

222.33333333333334

1621.0

Region

Note=Inhibitor binding

Tgene

ALK

chr2:55804451

chr2:29940563

ENST00000389048

1060_1620

222.33333333333334

1621.0

Topological domain

Cytoplasmic

Tgene

ALK

chr2:55804451

chr2:29940563

ENST00000389048

1039_1059

222.33333333333334

1621.0

Transmembrane

Helical

- 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

Hgene

SMEK2

chr2:55804451

chr2:29940563

ENST00000272313

719_724

503.3333333333333

765.0

Compositional bias

Note=Poly-Glu

Hgene

SMEK2

chr2:55804451

chr2:29940563

ENST00000272313

831_838

503.3333333333333

765.0

Compositional bias

Note=Poly-Glu

Hgene

SMEK2

chr2:55804451

chr2:29940563

ENST00000345102

719_724

535.3333333333334

850.0

Compositional bias

Note=Poly-Glu

Hgene

SMEK2

chr2:55804451

chr2:29940563

ENST00000345102

831_838

535.3333333333334

850.0

Compositional bias

Note=Poly-Glu

Hgene

SMEK2

chr2:55804451

chr2:29940563

ENST00000407823

719_724

503.3333333333333

818.0

Compositional bias

Note=Poly-Glu

Hgene

SMEK2

chr2:55804451

chr2:29940563

ENST00000407823

831_838

503.3333333333333

818.0

Compositional bias

Note=Poly-Glu

Tgene

ALK

chr2:55804451

chr2:29940563

ENST00000389048

19_1038

222.33333333333334

1621.0

Topological domain

Extracellular

Top

Fusion Protein Structures

PDB and CIF files of the predicted 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.

Fusion protein PDB link (fusion AA seq ID in FusionPDB)

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

AA seq

Len(AA seq)

Top

pLDDT score distribution

pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

ALK_pLDDT.png

pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

Top

Ramachandran Plot of 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.

Fusion AA seq ID in FusionPDB and their Ramachandran plots

Top

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
SMEK2
ALK

- 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

Top

Related Drugs to SMEK2-ALK

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

Hgene

Tgene

Drug

Source

PMID

Top

Related Diseases to SMEK2-ALK

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
Tgene	ALK	C0007131	Non-Small Cell Lung Carcinoma	28	CGI;CTD_human
Tgene	ALK	C0027819	Neuroblastoma	13	CGI;CTD_human;ORPHANET
Tgene	ALK	C0152013	Adenocarcinoma of lung (disorder)	8	CGI;CTD_human
Tgene	ALK	C2751681	NEUROBLASTOMA, SUSCEPTIBILITY TO, 3	8	CLINGEN;UNIPROT
Tgene	ALK	C0206180	Ki-1+ Anaplastic Large Cell Lymphoma	6	CGI;CTD_human
Tgene	ALK	C0334121	Inflammatory Myofibroblastic Tumor	4	CGI;CTD_human;ORPHANET
Tgene	ALK	C0018199	Granuloma, Plasma Cell	3	CTD_human
Tgene	ALK	C0007621	Neoplastic Cell Transformation	2	CTD_human
Tgene	ALK	C0027627	Neoplasm Metastasis	2	CTD_human
Tgene	ALK	C0238463	Papillary thyroid carcinoma	2	ORPHANET
Tgene	ALK	C0001973	Alcoholic Intoxication, Chronic	1	PSYGENET
Tgene	ALK	C0006118	Brain Neoplasms	1	CGI;CTD_human
Tgene	ALK	C0006142	Malignant neoplasm of breast	1	CTD_human
Tgene	ALK	C0007134	Renal Cell Carcinoma	1	CTD_human
Tgene	ALK	C0011570	Mental Depression	1	PSYGENET
Tgene	ALK	C0011581	Depressive disorder	1	PSYGENET
Tgene	ALK	C0027643	Neoplasm Recurrence, Local	1	CTD_human
Tgene	ALK	C0036341	Schizophrenia	1	PSYGENET
Tgene	ALK	C0079744	Diffuse Large B-Cell Lymphoma	1	CTD_human
Tgene	ALK	C0085269	Plasma Cell Granuloma, Pulmonary	1	CTD_human
Tgene	ALK	C0153633	Malignant neoplasm of brain	1	CGI;CTD_human
Tgene	ALK	C0278601	Inflammatory Breast Carcinoma	1	CTD_human
Tgene	ALK	C0279702	Conventional (Clear Cell) Renal Cell Carcinoma	1	CTD_human
Tgene	ALK	C0496899	Benign neoplasm of brain, unspecified	1	CTD_human
Tgene	ALK	C0678222	Breast Carcinoma	1	CTD_human
Tgene	ALK	C0750974	Brain Tumor, Primary	1	CTD_human
Tgene	ALK	C0750977	Recurrent Brain Neoplasm	1	CTD_human
Tgene	ALK	C0750979	Primary malignant neoplasm of brain	1	CTD_human
Tgene	ALK	C1257931	Mammary Neoplasms, Human	1	CTD_human
Tgene	ALK	C1266042	Chromophobe Renal Cell Carcinoma	1	CTD_human
Tgene	ALK	C1266043	Sarcomatoid Renal Cell Carcinoma	1	CTD_human
Tgene	ALK	C1266044	Collecting Duct Carcinoma of the Kidney	1	CTD_human
Tgene	ALK	C1306837	Papillary Renal Cell Carcinoma	1	CTD_human
Tgene	ALK	C1332079	Anaplastic Large Cell Lymphoma, ALK-Positive	1	ORPHANET
Tgene	ALK	C1458155	Mammary Neoplasms	1	CTD_human
Tgene	ALK	C1527390	Neoplasms, Intracranial	1	CTD_human
Tgene	ALK	C2931189	Neural crest tumor	1	ORPHANET
Tgene	ALK	C3899155	hereditary neuroblastoma	1	GENOMICS_ENGLAND
Tgene	ALK	C4704874	Mammary Carcinoma, Human	1	CTD_human