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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:AAK1-KCMF1

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: AAK1-KCMF1
	FusionPDB ID: 61
	FusionGDB2.0 ID: 61
		Hgene	Tgene
	Gene symbol	AAK1	KCMF1
	Gene ID	112268437	56888
	Gene name	uncharacterized protein FLJ45252	potassium channel modulatory factor 1
	Synonyms	AAK1	DEBT91\|FIGC\|PCMF\|ZZZ1
	Cytomap	-	2p11.2
	Type of gene	protein-coding	protein-coding
	Description	uncharacterized protein FLJ45252alternative protein AAK1	E3 ubiquitin-protein ligase KCMF1FGF-induced in gastric cancerFGF-induced ubiquitin-protein ligase in gastric cancersRING-type E3 ubiquitin transferase KCMF1ZZ-type zinc finger-containing protein 1differentially expressed in branching tubulogenesis 9
	Modification date	20200303	20200313
	UniProtAcc	Q2M2I8	Q9P0J7
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000406297, ENST00000409068, ENST00000409085, ENST00000470281,	ENST00000409785,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	19 X 13 X 11=2717	5 X 6 X 3=90
	# samples	22	8
	** MAII score	log2(22/2717*10)=-3.62643913669732 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(8/90*10)=-0.169925001442312 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: AAK1 [Title/Abstract] AND KCMF1 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	AAK1(69870010)-KCMF1(85255012), # samples:3
Anticipated loss of major functional domain due to fusion event.	AAK1-KCMF1 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. AAK1-KCMF1 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. AAK1-KCMF1 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. AAK1-KCMF1 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

Fusion gene breakpoints across AAK1 (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 KCMF1 (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	PRAD	TCGA-HC-7744-01A	AAK1	chr2	69870010	-	KCMF1	chr2	85255012	+
ChimerDB4	PRAD	TCGA-HC-7744	AAK1	chr2	69870010	-	KCMF1	chr2	85255012	+

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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)
ENST00000409068	AAK1	chr2	69870010	-	ENST00000409785	KCMF1	chr2	85255012	+	7670	477	215	1606	463
ENST00000409085	AAK1	chr2	69870010	-	ENST00000409785	KCMF1	chr2	85255012	+	7733	540	278	1669	463
ENST00000406297	AAK1	chr2	69870010	-	ENST00000409785	KCMF1	chr2	85255012	+	7733	540	278	1669	463

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
ENST00000409068	ENST00000409785	AAK1	chr2	69870010	-	KCMF1	chr2	85255012	+	0.001231286	0.9987686
ENST00000409085	ENST00000409785	AAK1	chr2	69870010	-	KCMF1	chr2	85255012	+	0.001267527	0.9987325
ENST00000406297	ENST00000409785	AAK1	chr2	69870010	-	KCMF1	chr2	85255012	+	0.001267527	0.9987325

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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

>61_61_1_AAK1-KCMF1_AAK1_chr2_69870010_ENST00000406297_KCMF1_chr2_85255012_ENST00000409785_length(amino acids)=463AA_BP=87
MRRNPWISFLKKKKKKKKSRNHRYFALLLPIRKMKKFFDSRREQGGSGLGSGSSGGGGSTSGLGSGYIGRVFGIGRQQVTVDEVLAEGVS
CDACLKGNFRGRRYKCLICYDYDLCASCYESGATTTRHTTDHPMQCILTRVDFDLYYGGEAFSVEQPQSFTCPYCGKMGYTETSLQEHVT
SEHAETSTEVICPICAALPGGDPNHVTDDFAAHLTLEHRAPRDLDESSGVRHVRRMFHPGRGLGGPRARRSNMHFTSSSTGGLSSSQSSY
SPSNREAMDPIAELLSQLSGVRRSAGGQLNSSGPSASQLQQLQMQLQLERQHAQAARQQLETARNATRRTNTSSVTTTITQSTATTNIAN
TESSQQTLQNSQFLLTRLNDPKMSETERQSMESERADRSLFVQELLLSTLVREESSSSDEDDRGEMADFGAMGCVDIMPLDVALENLNLK

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

>61_61_2_AAK1-KCMF1_AAK1_chr2_69870010_ENST00000409068_KCMF1_chr2_85255012_ENST00000409785_length(amino acids)=463AA_BP=87
MRRNPWISFLKKKKKKKKSRNHRYFALLLPIRKMKKFFDSRREQGGSGLGSGSSGGGGSTSGLGSGYIGRVFGIGRQQVTVDEVLAEGVS
CDACLKGNFRGRRYKCLICYDYDLCASCYESGATTTRHTTDHPMQCILTRVDFDLYYGGEAFSVEQPQSFTCPYCGKMGYTETSLQEHVT
SEHAETSTEVICPICAALPGGDPNHVTDDFAAHLTLEHRAPRDLDESSGVRHVRRMFHPGRGLGGPRARRSNMHFTSSSTGGLSSSQSSY
SPSNREAMDPIAELLSQLSGVRRSAGGQLNSSGPSASQLQQLQMQLQLERQHAQAARQQLETARNATRRTNTSSVTTTITQSTATTNIAN
TESSQQTLQNSQFLLTRLNDPKMSETERQSMESERADRSLFVQELLLSTLVREESSSSDEDDRGEMADFGAMGCVDIMPLDVALENLNLK

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

>61_61_3_AAK1-KCMF1_AAK1_chr2_69870010_ENST00000409085_KCMF1_chr2_85255012_ENST00000409785_length(amino acids)=463AA_BP=87
MRRNPWISFLKKKKKKKKSRNHRYFALLLPIRKMKKFFDSRREQGGSGLGSGSSGGGGSTSGLGSGYIGRVFGIGRQQVTVDEVLAEGVS
CDACLKGNFRGRRYKCLICYDYDLCASCYESGATTTRHTTDHPMQCILTRVDFDLYYGGEAFSVEQPQSFTCPYCGKMGYTETSLQEHVT
SEHAETSTEVICPICAALPGGDPNHVTDDFAAHLTLEHRAPRDLDESSGVRHVRRMFHPGRGLGGPRARRSNMHFTSSSTGGLSSSQSSY
SPSNREAMDPIAELLSQLSGVRRSAGGQLNSSGPSASQLQQLQMQLQLERQHAQAARQQLETARNATRRTNTSSVTTTITQSTATTNIAN
TESSQQTLQNSQFLLTRLNDPKMSETERQSMESERADRSLFVQELLLSTLVREESSSSDEDDRGEMADFGAMGCVDIMPLDVALENLNLK

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

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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/chr2:69870010/chr2:85255012)
- 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
AAK1 Q2M2I8	KCMF1 Q9P0J7
FUNCTION: Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis (PubMed:17494869, PubMed:11877457, PubMed:11877461, PubMed:12952931, PubMed:14617351, PubMed:25653444). Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1 (PubMed:17494869). Preferentially, may phosphorylate substrates on threonine residues (PubMed:11877457, PubMed:18657069). Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes (PubMed:12952931). Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes (PubMed:18657069). Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity (PubMed:21464124). {ECO:0000269\|PubMed:11877457, ECO:0000269\|PubMed:11877461, ECO:0000269\|PubMed:12952931, ECO:0000269\|PubMed:14617351, ECO:0000269\|PubMed:17494869, ECO:0000269\|PubMed:18657069, ECO:0000269\|PubMed:21464124, ECO:0000269\|PubMed:25653444}.; FUNCTION: (Microbial infection) By regulating clathrin-mediated endocytosis, AAK1 plays a role in the entry of hepatitis C virus as well as for the lifecycle of other viruses such as Ebola and Dengue. {ECO:0000269\|PubMed:25653444, ECO:0000305\|PubMed:31136173}.	FUNCTION: Has intrinsic E3 ubiquitin ligase activity and promotes ubiquitination. {ECO:0000269\|PubMed:15581609}.

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

AAK1

chr2:69870010

chr2:85255012

ENST00000406297

12_42

54.333333333333336

864.0

Compositional bias

Note=Gly-rich

Hgene

AAK1

chr2:69870010

chr2:85255012

ENST00000409085

12_42

54.333333333333336

962.0

Compositional bias

Note=Gly-rich

Tgene

KCMF1

chr2:69870010

chr2:85255012

ENST00000409785

225_257

5.333333333333333

382.0

Coiled coil

Ontology_term=ECO:0000255

Tgene

KCMF1

chr2:69870010

chr2:85255012

ENST00000409785

333_336

5.333333333333333

382.0

Compositional bias

Note=Poly-Ser

Tgene

KCMF1

chr2:69870010

chr2:85255012

ENST00000409785

376_380

5.333333333333333

382.0

Compositional bias

Note=Poly-Pro

Tgene

KCMF1

chr2:69870010

chr2:85255012

ENST00000409785

3_50

5.333333333333333

382.0

Zinc finger

ZZ-type

Tgene

KCMF1

chr2:69870010

chr2:85255012

ENST00000409785

78_101

5.333333333333333

382.0

Zinc finger

C2H2-type

- 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

AAK1

chr2:69870010

chr2:85255012

ENST00000406297

397_614

54.333333333333336

864.0

Compositional bias

Note=Gln-rich

Hgene

AAK1

chr2:69870010

chr2:85255012

ENST00000406297

658_663

54.333333333333336

864.0

Compositional bias

Note=Poly-Ala

Hgene

AAK1

chr2:69870010

chr2:85255012

ENST00000409085

397_614

54.333333333333336

962.0

Compositional bias

Note=Gln-rich

Hgene

AAK1

chr2:69870010

chr2:85255012

ENST00000409085

658_663

54.333333333333336

962.0

Compositional bias

Note=Poly-Ala

Hgene

AAK1

chr2:69870010

chr2:85255012

ENST00000406297

46_315

54.333333333333336

864.0

Domain

Protein kinase

Hgene

AAK1

chr2:69870010

chr2:85255012

ENST00000409085

46_315

54.333333333333336

962.0

Domain

Protein kinase

Hgene

AAK1

chr2:69870010

chr2:85255012

ENST00000406297

52_60

54.333333333333336

864.0

Nucleotide binding

ATP

Hgene

AAK1

chr2:69870010

chr2:85255012

ENST00000409085

52_60

54.333333333333336

962.0

Nucleotide binding

ATP

Hgene

AAK1

chr2:69870010

chr2:85255012

ENST00000406297

823_960

54.333333333333336

864.0

Region

Clathrin-binding domain (CBD)

Hgene

AAK1

chr2:69870010

chr2:85255012

ENST00000409085

823_960

54.333333333333336

962.0

Region

Clathrin-binding domain (CBD)

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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 >>>968_AAK1_69870010_KCMF1_85255012_968_AAK1_69870010_KCMF1_85255012_ranked_0.pdb	AAK1	69870010	69870010	ENST00000409785	KCMF1	chr2	85255012	+	MRRNPWISFLKKKKKKKKSRNHRYFALLLPIRKMKKFFDSRREQGGSGLGSGSSGGGGSTSGLGSGYIGRVFGIGRQQVTVDEVLAEGVS CDACLKGNFRGRRYKCLICYDYDLCASCYESGATTTRHTTDHPMQCILTRVDFDLYYGGEAFSVEQPQSFTCPYCGKMGYTETSLQEHVT SEHAETSTEVICPICAALPGGDPNHVTDDFAAHLTLEHRAPRDLDESSGVRHVRRMFHPGRGLGGPRARRSNMHFTSSSTGGLSSSQSSY SPSNREAMDPIAELLSQLSGVRRSAGGQLNSSGPSASQLQQLQMQLQLERQHAQAARQQLETARNATRRTNTSSVTTTITQSTATTNIAN TESSQQTLQNSQFLLTRLNDPKMSETERQSMESERADRSLFVQELLLSTLVREESSSSDEDDRGEMADFGAMGCVDIMPLDVALENLNLK	463

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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.

AAK1_pLDDT.png

KCMF1_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
AAK1
KCMF1

- 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

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Related Drugs to AAK1-KCMF1

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 AAK1-KCMF1

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