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Fusion Protein:KLK2-PVRL2

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: KLK2-PVRL2
	FusionPDB ID: 43067
	FusionGDB2.0 ID: 43067
		Hgene	Tgene
	Gene symbol	KLK2	PVRL2
	Gene ID	3817	5819
	Gene name	kallikrein related peptidase 2	nectin cell adhesion molecule 2
	Synonyms	KLK2A2\|hGK-1\|hK2	CD112\|HVEB\|PRR2\|PVRL2\|PVRR2
	Cytomap	19q13.33	19q13.32
	Type of gene	protein-coding	protein-coding
	Description	kallikrein-2glandular kallikrein 2glandular kallikrein-1kallikrein 2, prostatictissue kallikrein-2	nectin-2herpesvirus entry protein Bpoliovirus receptor-like 2poliovirus receptor-related 2 (herpesvirus entry mediator B)
	Modification date	20200313	20200313
	UniProtAcc	P20151 Main function of 5'-partner protein: FUNCTION: Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000391810, ENST00000325321, ENST00000358049, ENST00000597509,	ENST00000252483, ENST00000252485,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	21 X 19 X 4=1596	8 X 6 X 7=336
	# samples	30	12
	** MAII score	log2(30/1596*10)=-2.41142624572647 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(12/336*10)=-1.48542682717024 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: KLK2 [Title/Abstract] AND PVRL2 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: KLK2 [Title/Abstract] AND PVRL2 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	KLK2(51376775)-PVRL2(45368527), # samples:2
Anticipated loss of major functional domain due to fusion event.	KLK2-PVRL2 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. KLK2-PVRL2 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. KLK2-PVRL2 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. KLK2-PVRL2 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	PVRL2	GO:0007156	homophilic cell adhesion via plasma membrane adhesion molecules	9845526
Tgene	PVRL2	GO:0019064	fusion of virus membrane with host plasma membrane	12915581
Tgene	PVRL2	GO:0044406	adhesion of symbiont to host	12915581
Tgene	PVRL2	GO:0046596	regulation of viral entry into host cell	11602758
Tgene	PVRL2	GO:0046814	coreceptor-mediated virion attachment to host cell	12915581
Tgene	PVRL2	GO:0050862	positive regulation of T cell receptor signaling pathway	26755705
Tgene	PVRL2	GO:0060370	susceptibility to T cell mediated cytotoxicity	15039383

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr19:51376775/chr19:45368527)
- 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.

Retention analysis results 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, are available here.

Fusion gene breakpoints across KLK2 (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 PVRL2 (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 Amino Acid Sequences

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)
ENST00000325321	KLK2	chr19	51376775	+	ENST00000252485	PVRL2	chr19	45368527	+	1944	271	27	1622	531
ENST00000325321	KLK2	chr19	51376775	+	ENST00000252483	PVRL2	chr19	45368527	+	2649	271	27	1799	590
ENST00000358049	KLK2	chr19	51376775	+	ENST00000252485	PVRL2	chr19	45368527	+	1735	62	16	1413	465
ENST00000358049	KLK2	chr19	51376775	+	ENST00000252483	PVRL2	chr19	45368527	+	2440	62	16	1590	524
ENST00000325321	KLK2	chr19	51376775	+	ENST00000252485	PVRL2	chr19	45368528	+	1944	271	27	1622	531
ENST00000325321	KLK2	chr19	51376775	+	ENST00000252483	PVRL2	chr19	45368528	+	2649	271	27	1799	590
ENST00000358049	KLK2	chr19	51376775	+	ENST00000252485	PVRL2	chr19	45368528	+	1735	62	16	1413	465
ENST00000358049	KLK2	chr19	51376775	+	ENST00000252483	PVRL2	chr19	45368528	+	2440	62	16	1590	524
ENST00000325321	KLK2	chr19	51376774	+	ENST00000252485	PVRL2	chr19	45368527	+	1944	271	27	1622	531
ENST00000325321	KLK2	chr19	51376774	+	ENST00000252483	PVRL2	chr19	45368527	+	2649	271	27	1799	590
ENST00000358049	KLK2	chr19	51376774	+	ENST00000252485	PVRL2	chr19	45368527	+	1735	62	16	1413	465
ENST00000358049	KLK2	chr19	51376774	+	ENST00000252483	PVRL2	chr19	45368527	+	2440	62	16	1590	524

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
ENST00000325321	ENST00000252485	KLK2	chr19	51376775	+	PVRL2	chr19	45368527	+	0.011878492	0.9881215
ENST00000325321	ENST00000252483	KLK2	chr19	51376775	+	PVRL2	chr19	45368527	+	0.005747922	0.9942521
ENST00000358049	ENST00000252485	KLK2	chr19	51376775	+	PVRL2	chr19	45368527	+	0.011811555	0.98818845
ENST00000358049	ENST00000252483	KLK2	chr19	51376775	+	PVRL2	chr19	45368527	+	0.005427793	0.9945722
ENST00000325321	ENST00000252485	KLK2	chr19	51376775	+	PVRL2	chr19	45368528	+	0.011878492	0.9881215
ENST00000325321	ENST00000252483	KLK2	chr19	51376775	+	PVRL2	chr19	45368528	+	0.005747922	0.9942521
ENST00000358049	ENST00000252485	KLK2	chr19	51376775	+	PVRL2	chr19	45368528	+	0.011811555	0.98818845
ENST00000358049	ENST00000252483	KLK2	chr19	51376775	+	PVRL2	chr19	45368528	+	0.005427793	0.9945722
ENST00000325321	ENST00000252485	KLK2	chr19	51376774	+	PVRL2	chr19	45368527	+	0.011878492	0.9881215
ENST00000325321	ENST00000252483	KLK2	chr19	51376774	+	PVRL2	chr19	45368527	+	0.005747922	0.9942521
ENST00000358049	ENST00000252485	KLK2	chr19	51376774	+	PVRL2	chr19	45368527	+	0.011811555	0.98818845
ENST00000358049	ENST00000252483	KLK2	chr19	51376774	+	PVRL2	chr19	45368527	+	0.005427793	0.9945722

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

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for KLK2-PVRL2

+/-13 AA sequence from the breakpoints of the fusion protein sequences.

Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	Length(fusion protein)	BP in fusion protein	Peptide
KLK2	chr19	51376774	PVRL2	chr19	45368527	271	79	MWDLVLSIALSVGCTGAQDVRVQVLP
KLK2	chr19	51376774	PVRL2	chr19	45368527	62	13	MWDLVLSIALSVGCTGAQDVRVQVLP
KLK2	chr19	51376775	PVRL2	chr19	45368527	271	79	MWDLVLSIALSVGCTGAQDVRVQVLP
KLK2	chr19	51376775	PVRL2	chr19	45368527	62	13	MWDLVLSIALSVGCTGAQDVRVQVLP
KLK2	chr19	51376775	PVRL2	chr19	45368528	271	79	MWDLVLSIALSVGCTGAQDVRVQVLP
KLK2	chr19	51376775	PVRL2	chr19	45368528	62	13	MWDLVLSIALSVGCTGAQDVRVQVLP

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Potential FusionNeoAntigen Information of KLK2-PVRL2 in HLA I

Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)

Fusion gene

Hchr

Hbp

Tgene

Tchr

Tbp

HLA I

FusionNeoAntigen peptide

Binding score

Immunogenic score

Neoantigen start (at BP 13)

Neoantigen end (at BP 13)

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Potential FusionNeoAntigen Information of KLK2-PVRL2 in HLA II

Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).

Fusion gene

Hchr

Hbp

Tgene

Tchr

Tbp

HLA II

FusionNeoAntigen peptide

Neoantigen start (at BP 13)

Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of KLK2-PVRL2

3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KLK2-PVRL2

Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.

HLA allele

PDB ID

File name

BPseq

Docking score

Glide score

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Vaccine Design for the FusionNeoAntigens of KLK2-PVRL2

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.

Fusion gene

Hchr

Hbp

Tchr

Tbp

Start in +/-13AA

End in +/-13AA

FusionNeoAntigen peptide sequence

FusionNeoAntigen RNA sequence

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.

Fusion gene

Hchr

Hbp

Tchr

Tbp

Start in +/-13AA

End in +/-13AA

FusionNeoAntigen peptide

FusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of KLK2-PVRL2

These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.

Cancer type

Fusion gene

Hchr

Hbp

Henst

Tchr

Tbp

Tenst

Sample

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Potential target of CAR-T therapy development for KLK2-PVRL2

Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features

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

- In-frame and retained 'Transmembrane'.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Tgene

PVRL2

chr19:51376774

chr19:45368527

ENST00000252483

361_381

539.0

Transmembrane

Helical

Tgene

PVRL2

chr19:51376774

chr19:45368527

ENST00000252485

361_381

480.0

Transmembrane

Helical

Tgene

PVRL2

chr19:51376775

chr19:45368527

ENST00000252483

361_381

539.0

Transmembrane

Helical

Tgene

PVRL2

chr19:51376775

chr19:45368527

ENST00000252485

361_381

480.0

Transmembrane

Helical

Tgene

PVRL2

chr19:51376775

chr19:45368528

ENST00000252483

361_381

539.0

Transmembrane

Helical

Tgene

PVRL2

chr19:51376775

chr19:45368528

ENST00000252485

361_381

480.0

Transmembrane

Helical

Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.

Hgene

Hchr

Hbp

Henst

Tgene

Tchr

Tbp

Tenst

DeepLoc result

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Related Drugs to KLK2-PVRL2

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 KLK2-PVRL2

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
Hgene	KLK2	C0033578	Prostatic Neoplasms	2	CTD_human
Hgene	KLK2	C0376358	Malignant neoplasm of prostate	2	CTD_human

	Fusion Gene and Fusion Protein Summary
	Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)
	Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)
	Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)
	Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)
	Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)
	Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)
	Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)
	Potential target of CAR-T therapy development
	Information on the samples that have these potential fusion neoantigens
	Fusion Protein Targeting Drugs - (Manual Curation)
	Fusion Protein Related diseases - (Manual Curation)