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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:STIP1-PAK1

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: STIP1-PAK1
	FusionPDB ID: 87428
	FusionGDB2.0 ID: 87428
		Hgene	Tgene
	Gene symbol	STIP1	PAK1
	Gene ID	10963	5585
	Gene name	stress induced phosphoprotein 1	protein kinase N1
	Synonyms	HEL-S-94n\|HOP\|IEF-SSP-3521\|P60\|STI1\|STI1L	DBK\|PAK-1\|PAK1\|PKN\|PKN-ALPHA\|PRK1\|PRKCL1
	Cytomap	11q13.1	19p13.12
	Type of gene	protein-coding	protein-coding
	Description	stress-induced-phosphoprotein 1Hsp70/Hsp90-organizing proteinNY-REN-11 antigenepididymis secretory sperm binding protein Li 94nhsc70/Hsp90-organizing proteinrenal carcinoma antigen NY-REN-11transformation-sensitive protein IEF SSP 3521	serine/threonine-protein kinase N1protease-activated kinase 1protein kinase C-like 1protein kinase C-like PKNprotein kinase C-related kinase 1protein kinase PKN-alphaserine-threonine kinase Nserine/threonine protein kinase N
	Modification date	20200329	20200329
	UniProtAcc	.	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000305218, ENST00000538945, ENST00000543847, ENST00000358794, ENST00000540501,	ENST00000525542, ENST00000278568, ENST00000356341, ENST00000528203, ENST00000530617,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	14 X 8 X 10=1120	22 X 17 X 10=3740
	# samples	15	26
	** MAII score	log2(15/1120*10)=-2.90046432644909 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(26/3740*10)=-3.84645474174655 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: STIP1 [Title/Abstract] AND PAK1 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	STIP1(63953742)-PAK1(77043912), # samples:3
Anticipated loss of major functional domain due to fusion event.	STIP1-PAK1 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. STIP1-PAK1 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	PAK1	GO:0006357	regulation of transcription by RNA polymerase II	12514133
Tgene	PAK1	GO:0006468	protein phosphorylation	17332740
Tgene	PAK1	GO:0035407	histone H3-T11 phosphorylation	18066052

Fusion gene breakpoints across STIP1 (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 PAK1 (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	LUSC	TCGA-94-7557-01A	STIP1	chr11	63953742	+	PAK1	chr11	77043912	-
ChimerDB4	LUSC	TCGA-94-7557	STIP1	chr11	63953742	+	PAK1	chr11	77043912	-

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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)
ENST00000305218	STIP1	chr11	63953742	+	ENST00000356341	PAK1	chr11	77043912	-	1948	156	1230	892	112
ENST00000305218	STIP1	chr11	63953742	+	ENST00000530617	PAK1	chr11	77043912	-	1432	156	1024	686	112
ENST00000305218	STIP1	chr11	63953742	+	ENST00000278568	PAK1	chr11	77043912	-	756	156	147	404	85
ENST00000305218	STIP1	chr11	63953742	+	ENST00000528203	PAK1	chr11	77043912	-	680	156	606	319	95
ENST00000538945	STIP1	chr11	63953742	+	ENST00000356341	PAK1	chr11	77043912	-	1859	67	1141	803	112
ENST00000538945	STIP1	chr11	63953742	+	ENST00000530617	PAK1	chr11	77043912	-	1343	67	935	597	112
ENST00000538945	STIP1	chr11	63953742	+	ENST00000278568	PAK1	chr11	77043912	-	667	67	58	315	85
ENST00000538945	STIP1	chr11	63953742	+	ENST00000528203	PAK1	chr11	77043912	-	591	67	517	230	95
ENST00000543847	STIP1	chr11	63953742	+	ENST00000356341	PAK1	chr11	77043912	-	1838	46	1120	782	112
ENST00000543847	STIP1	chr11	63953742	+	ENST00000530617	PAK1	chr11	77043912	-	1322	46	914	576	112
ENST00000543847	STIP1	chr11	63953742	+	ENST00000278568	PAK1	chr11	77043912	-	646	46	37	294	85
ENST00000543847	STIP1	chr11	63953742	+	ENST00000528203	PAK1	chr11	77043912	-	570	46	496	209	95

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
ENST00000305218	ENST00000356341	STIP1	chr11	63953742	+	PAK1	chr11	77043912	-	0.10166063	0.8983394
ENST00000305218	ENST00000530617	STIP1	chr11	63953742	+	PAK1	chr11	77043912	-	0.30515152	0.6948485
ENST00000305218	ENST00000278568	STIP1	chr11	63953742	+	PAK1	chr11	77043912	-	0.039600857	0.9603991
ENST00000305218	ENST00000528203	STIP1	chr11	63953742	+	PAK1	chr11	77043912	-	0.029192068	0.97080797
ENST00000538945	ENST00000356341	STIP1	chr11	63953742	+	PAK1	chr11	77043912	-	0.16454034	0.83545965
ENST00000538945	ENST00000530617	STIP1	chr11	63953742	+	PAK1	chr11	77043912	-	0.5929421	0.40705788
ENST00000538945	ENST00000278568	STIP1	chr11	63953742	+	PAK1	chr11	77043912	-	0.052714594	0.94728535
ENST00000538945	ENST00000528203	STIP1	chr11	63953742	+	PAK1	chr11	77043912	-	0.024258295	0.97574174
ENST00000543847	ENST00000356341	STIP1	chr11	63953742	+	PAK1	chr11	77043912	-	0.36544713	0.63455284
ENST00000543847	ENST00000530617	STIP1	chr11	63953742	+	PAK1	chr11	77043912	-	0.6595956	0.34040433
ENST00000543847	ENST00000278568	STIP1	chr11	63953742	+	PAK1	chr11	77043912	-	0.050145328	0.9498546
ENST00000543847	ENST00000528203	STIP1	chr11	63953742	+	PAK1	chr11	77043912	-	0.026046855	0.9739532

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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

>87428_87428_1_STIP1-PAK1_STIP1_chr11_63953742_ENST00000305218_PAK1_chr11_77043912_ENST00000278568_length(amino acids)=85AA_BP=2

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

>87428_87428_2_STIP1-PAK1_STIP1_chr11_63953742_ENST00000305218_PAK1_chr11_77043912_ENST00000356341_length(amino acids)=112AA_BP=
MKHHTSRAGQVLMPSLALKVVTIFPDFSTLLSLSMCPRKPLNVINKGQDRGSSLGYAGNQKLLHSREHFTRNSMGTLLGQGPPEQLLEAH

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

>87428_87428_3_STIP1-PAK1_STIP1_chr11_63953742_ENST00000305218_PAK1_chr11_77043912_ENST00000528203_length(amino acids)=95AA_BP=
MQFSSMLDTRFPRIKVLRSARSGNGRSKARRRGHQELEFLKCAFISQKAWHNEAGVSVVLVIVLCCLLSCSNQWSEAGEGLGNLQELMQL

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

>87428_87428_4_STIP1-PAK1_STIP1_chr11_63953742_ENST00000305218_PAK1_chr11_77043912_ENST00000530617_length(amino acids)=112AA_BP=
MKHHTSRAGQVLMPSLALKVVTIFPDFSTLLSLSMCPRKPLNVINKGQDRGSSLGYAGNQKLLHSREHFTRNSMGTLLGQGPPEQLLEAH

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

>87428_87428_5_STIP1-PAK1_STIP1_chr11_63953742_ENST00000538945_PAK1_chr11_77043912_ENST00000278568_length(amino acids)=85AA_BP=2

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

>87428_87428_6_STIP1-PAK1_STIP1_chr11_63953742_ENST00000538945_PAK1_chr11_77043912_ENST00000356341_length(amino acids)=112AA_BP=
MKHHTSRAGQVLMPSLALKVVTIFPDFSTLLSLSMCPRKPLNVINKGQDRGSSLGYAGNQKLLHSREHFTRNSMGTLLGQGPPEQLLEAH

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

>87428_87428_7_STIP1-PAK1_STIP1_chr11_63953742_ENST00000538945_PAK1_chr11_77043912_ENST00000528203_length(amino acids)=95AA_BP=
MQFSSMLDTRFPRIKVLRSARSGNGRSKARRRGHQELEFLKCAFISQKAWHNEAGVSVVLVIVLCCLLSCSNQWSEAGEGLGNLQELMQL

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

>87428_87428_8_STIP1-PAK1_STIP1_chr11_63953742_ENST00000538945_PAK1_chr11_77043912_ENST00000530617_length(amino acids)=112AA_BP=
MKHHTSRAGQVLMPSLALKVVTIFPDFSTLLSLSMCPRKPLNVINKGQDRGSSLGYAGNQKLLHSREHFTRNSMGTLLGQGPPEQLLEAH

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

>87428_87428_9_STIP1-PAK1_STIP1_chr11_63953742_ENST00000543847_PAK1_chr11_77043912_ENST00000278568_length(amino acids)=85AA_BP=2

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

>87428_87428_10_STIP1-PAK1_STIP1_chr11_63953742_ENST00000543847_PAK1_chr11_77043912_ENST00000356341_length(amino acids)=112AA_BP=
MKHHTSRAGQVLMPSLALKVVTIFPDFSTLLSLSMCPRKPLNVINKGQDRGSSLGYAGNQKLLHSREHFTRNSMGTLLGQGPPEQLLEAH

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

>87428_87428_11_STIP1-PAK1_STIP1_chr11_63953742_ENST00000543847_PAK1_chr11_77043912_ENST00000528203_length(amino acids)=95AA_BP=
MQFSSMLDTRFPRIKVLRSARSGNGRSKARRRGHQELEFLKCAFISQKAWHNEAGVSVVLVIVLCCLLSCSNQWSEAGEGLGNLQELMQL

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

>87428_87428_12_STIP1-PAK1_STIP1_chr11_63953742_ENST00000543847_PAK1_chr11_77043912_ENST00000530617_length(amino acids)=112AA_BP=
MKHHTSRAGQVLMPSLALKVVTIFPDFSTLLSLSMCPRKPLNVINKGQDRGSSLGYAGNQKLLHSREHFTRNSMGTLLGQGPPEQLLEAH

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

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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/chr11:63953742/chr11:77043912)
- 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
.	.
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: 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.

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

- 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

STIP1

chr11:63953742

chr11:77043912

ENST00000305218

130_169

3.0

544.0

Domain

Note=STI1 1

Hgene

STIP1

chr11:63953742

chr11:77043912

ENST00000305218

492_531

3.0

544.0

Domain

Note=STI1 2

Hgene

STIP1

chr11:63953742

chr11:77043912

ENST00000305218

222_239

3.0

544.0

Motif

Bipartite nuclear localization signal

Hgene

STIP1

chr11:63953742

chr11:77043912

ENST00000305218

225_258

3.0

544.0

Repeat

Note=TPR 4

Hgene

STIP1

chr11:63953742

chr11:77043912

ENST00000305218

259_292

3.0

544.0

Repeat

Note=TPR 5

Hgene

STIP1

chr11:63953742

chr11:77043912

ENST00000305218

300_333

3.0

544.0

Repeat

Note=TPR 6

Hgene

STIP1

chr11:63953742

chr11:77043912

ENST00000305218

360_393

3.0

544.0

Repeat

Note=TPR 7

Hgene

STIP1

chr11:63953742

chr11:77043912

ENST00000305218

38_71

3.0

544.0

Repeat

Note=TPR 2

Hgene

STIP1

chr11:63953742

chr11:77043912

ENST00000305218

394_427

3.0

544.0

Repeat

Note=TPR 8

Hgene

STIP1

chr11:63953742

chr11:77043912

ENST00000305218

428_461

3.0

544.0

Repeat

Note=TPR 9

Hgene

STIP1

chr11:63953742

chr11:77043912

ENST00000305218

4_37

3.0

544.0

Repeat

Note=TPR 1

Hgene

STIP1

chr11:63953742

chr11:77043912

ENST00000305218

72_105

3.0

544.0

Repeat

Note=TPR 3

Tgene

PAK1

chr11:63953742

chr11:77043912

ENST00000278568

270_521

471.0

554.0

Domain

Protein kinase

Tgene

PAK1

chr11:63953742

chr11:77043912

ENST00000278568

75_88

471.0

554.0

Domain

CRIB

Tgene

PAK1

chr11:63953742

chr11:77043912

ENST00000356341

270_521

471.0

546.0

Domain

Protein kinase

Tgene

PAK1

chr11:63953742

chr11:77043912

ENST00000356341

75_88

471.0

546.0

Domain

CRIB

Tgene

PAK1

chr11:63953742

chr11:77043912

ENST00000278568

276_284

471.0

554.0

Nucleotide binding

Note=ATP

Tgene

PAK1

chr11:63953742

chr11:77043912

ENST00000278568

345_347

471.0

554.0

Nucleotide binding

Note=ATP

Tgene

PAK1

chr11:63953742

chr11:77043912

ENST00000356341

276_284

471.0

546.0

Nucleotide binding

Note=ATP

Tgene

PAK1

chr11:63953742

chr11:77043912

ENST00000356341

345_347

471.0

546.0

Nucleotide binding

Note=ATP

Tgene

PAK1

chr11:63953742

chr11:77043912

ENST00000278568

70_140

471.0

554.0

Region

Note=Autoregulatory region

Tgene

PAK1

chr11:63953742

chr11:77043912

ENST00000278568

75_105

471.0

554.0

Region

Note=GTPase-binding

Tgene

PAK1

chr11:63953742

chr11:77043912

ENST00000356341

70_140

471.0

546.0

Region

Note=Autoregulatory region

Tgene

PAK1

chr11:63953742

chr11:77043912

ENST00000356341

75_105

471.0

546.0

Region

Note=GTPase-binding

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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)
PDB file >>>39_STIP1_63953742_PAK1_77043912_ranked_0.pdb	STIP1	63953742	63953742	ENST00000528203	PAK1	chr11	77043912	-	MKHHTSRAGQVLMPSLALKVVTIFPDFSTLLSLSMCPRKPLNVINKGQDRGSSLGYAGNQKLLHSREHFTRNSMGTLLGQGPPEQLLEAH	112

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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.

STIP1_pLDDT.png

PAK1_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.

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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

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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
STIP1
PAK1

- 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	PAK1	chr11:63953742	chr11:77043912	ENST00000278568		12	16	132_270	471.0	554.0	CRIPAK
Tgene	PAK1	chr11:63953742	chr11:77043912	ENST00000356341		12	15	132_270	471.0	546.0	CRIPAK

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Related Drugs to STIP1-PAK1

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 STIP1-PAK1

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