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Center for Computational Systems Medicine
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Kinase Fusion Gene Summary

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Kinase Fusion Gene Sample Information

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Kinase Fusion ORF Analysis

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Kinase Fusion Amino Acid Sequences

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Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase Fusion Protein Functional Features

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Kinase Fusion Protein Structures

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Comparison of Fusion Protein Isoforms

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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

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pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.

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Ramachandran Plot of Kinase Fusion Protein Structure

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Potential Active Site Information

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Virtual Screening Results

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Kinase-Substrate Information

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Related Drugs with This Kinase Fusion Protein

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Related Disease with This Kinase Fusion Protein

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Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:ANXA4_PKN1

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: ANXA4_PKN1
KinaseFusionDB ID: KFG374
FusionGDB2.0 ID: KFG374
HgeneTgene
Gene symbol

ANXA4

PKN1

Gene ID

307

5585

Gene nameannexin A4protein kinase N1
SynonymsANX4|HEL-S-274|P32.5|PAP-II|PIG28|PP4-X|ZAP36DBK|PAK-1|PAK1|PKN|PKN-ALPHA|PRK1|PRKCL1
Cytomap

2p13.3

19p13.12

Type of geneprotein-codingprotein-coding
Descriptionannexin A435-beta calcimedinannexin IV (placental anticoagulant protein II)annexin-4carbohydrate-binding protein p33/p41chromobindin-4endonexin Iepididymis secretory protein Li 274lipocortin IVplacental anticoagulant protein IIproliferation-induserine/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 date2024041120240305
UniProtAcc

P09525

Q16512

Ensembl transtripts involved in fusion geneENST idsENST00000394295, ENST00000409920, 
ENST00000536030, ENST00000418066, 
ENST00000342216, ENST00000587429, 
ENST00000242783, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: ANXA4 [Title/Abstract] AND PKN1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ANXA4(70008706)-PKN1(14578377), # samples:3
PKN1(14574965)-ANXA4(70015186), # samples:2
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneANXA4

GO:0006357

regulation of transcription by RNA polymerase II

20237821

HgeneANXA4

GO:0032088

negative regulation of NF-kappaB transcription factor activity

20237821

TgenePKN1

GO:0006357

regulation of transcription by RNA polymerase II

12514133

TgenePKN1

GO:0006468

protein phosphorylation

17332740

TgenePKN1

GO:0043687

post-translational protein modification

18066052


check buttonKinase Fusion gene breakpoints across ANXA4 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonKinase Fusion gene breakpoints across PKN1 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Kinase Fusion Gene Sample Information

check buttonKinase Fusion gene information.
check button Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE)
* 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.
SourceSampleHgeneHchrHbpTgeneTchrTbp
ChimerDB4TCGA-BC-4072-01BANXA4chr2

70008706

PKN1chr19

14578377

ChimerDB4TCGA-BC-4072ANXA4chr2

70008706

PKN1chr19

14578376



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Kinase Fusion ORF Analysis


check buttonKinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(amino acids)
ENST00000409920ENST00000242783ANXA4chr270008706PKN1chr19145783771430368
ENST00000409920ENST00000242783ANXA4chr270008706PKN1chr19145783761430368

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Kinase Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq

>ENST00000409920_ENST00000242783_ANXA4_chr2_70008706_PKN1_chr19_14578377_length(amino acids)=368
MAMSSPIQESTAPELPSETQETPGPALCSPLRKSPLTLEDFKFLAVLGRGHFGKVLLSEFRPSGELFAIKALKKGDIVARDEVESLMCEK
RILAAVTSAGHPFLVNLFGCFQTPEHVCFVMEYSAGGDLMLHIHSDVFSEPRAIFYSACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYV
KIADFGLCKEGMGYGDRTSTFCGTPEFLAPEVLTDTSYTRAVDWWGLGVLLYEMLVGESPFPGDDEEEVFDSIVNDEVRYPRFLSAEAIG
IMRRLLRRNPERRLGSSERDAEDVKKQPFFRTLGWEALLARRLPPPFVPTLSGRTDVSNFDEEFTGEAPTLSPPRDARPLTAAEQAAFLD

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

>ENST00000409920_ENST00000242783_ANXA4_chr2_70008706_PKN1_chr19_14578376_length(amino acids)=368
MAMSSPIQESTAPELPSETQETPGPALCSPLRKSPLTLEDFKFLAVLGRGHFGKVLLSEFRPSGELFAIKALKKGDIVARDEVESLMCEK
RILAAVTSAGHPFLVNLFGCFQTPEHVCFVMEYSAGGDLMLHIHSDVFSEPRAIFYSACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYV
KIADFGLCKEGMGYGDRTSTFCGTPEFLAPEVLTDTSYTRAVDWWGLGVLLYEMLVGESPFPGDDEEEVFDSIVNDEVRYPRFLSAEAIG
IMRRLLRRNPERRLGSSERDAEDVKKQPFFRTLGWEALLARRLPPPFVPTLSGRTDVSNFDEEFTGEAPTLSPPRDARPLTAAEQAAFLD

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Multiple Sequence Alignment of All Fusion Protein Isoforms



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Kinase Fusion Protein Functional Features


check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr2:70008706/chr19:14578377)
- 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.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
ANXA4

P09525

PKN1

Q16512

FUNCTION: Calcium/phospholipid-binding protein which promotes membrane fusion and is involved in exocytosis. {ECO:0000250}.FUNCTION: PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594, ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664, ECO:0000269|PubMed:9175763}.

check buttonRetention 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.

check button - Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


check button - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote
TgeneANXA470008706PKN114578376ENST000004099201122875_942577943DomainNote=AGC-kinase C-terminal;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00618
TgeneANXA470008706PKN114578376ENST000004099201122875_942583949DomainNote=AGC-kinase C-terminal;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00618
TgeneANXA470008706PKN114578377ENST000004099201122875_942577943DomainNote=AGC-kinase C-terminal;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00618
TgeneANXA470008706PKN114578377ENST000004099201122875_942583949DomainNote=AGC-kinase C-terminal;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00618
TgeneANXA470008706PKN114578376ENST000004099201122615_874577943DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgeneANXA470008706PKN114578376ENST000004099201122615_874583949DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgeneANXA470008706PKN114578377ENST000004099201122615_874577943DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgeneANXA470008706PKN114578377ENST000004099201122615_874583949DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159


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Kinase Fusion Protein Structures

check button CIF files of the predicted kinase 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.
Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB)HenstTenstHgeneHchrHbpTgeneTchrTbpAA seqLen(AA seq)
PDB file >>>27_ANXA4_PKN1ENST00000409920ENST00000242783ANXA4chr270008706PKN1chr1914578376
MAMSSPIQESTAPELPSETQETPGPALCSPLRKSPLTLEDFKFLAVLGRGHFGKVLLSEFRPSGELFAIKALKKGDIVARDEVESLMCEK
RILAAVTSAGHPFLVNLFGCFQTPEHVCFVMEYSAGGDLMLHIHSDVFSEPRAIFYSACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYV
KIADFGLCKEGMGYGDRTSTFCGTPEFLAPEVLTDTSYTRAVDWWGLGVLLYEMLVGESPFPGDDEEEVFDSIVNDEVRYPRFLSAEAIG
IMRRLLRRNPERRLGSSERDAEDVKKQPFFRTLGWEALLARRLPPPFVPTLSGRTDVSNFDEEFTGEAPTLSPPRDARPLTAAEQAAFLD
368
3D view using mol* of 27_ANXA4_PKN1
PDB file >>>TKFP_42_ANXA4_PKN1ENST00000409920ENST00000242783ANXA4chr270008706PKN1chr1914578377
MAMSSPIQESTAPELPSETQETPGPALCSPLRKSPLTLEDFKFLAVLGRGHFGKVLLSEFRPSGELFAIKALKKGDIVARDEVESLMCEK
RILAAVTSAGHPFLVNLFGCFQTPEHVCFVMEYSAGGDLMLHIHSDVFSEPRAIFYSACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYV
KIADFGLCKEGMGYGDRTSTFCGTPEFLAPEVLTDTSYTRAVDWWGLGVLLYEMLVGESPFPGDDEEEVFDSIVNDEVRYPRFLSAEAIG
IMRRLLRRNPERRLGSSERDAEDVKKQPFFRTLGWEALLARRLPPPFVPTLSGRTDVSNFDEEFTGEAPTLSPPRDARPLTAAEQAAFLD
368_ANXA4_PKN1
PDB file >>>TKFP_43_ANXA4_PKN1ENST00000409920ENST00000242783ANXA4chr270008706PKN1chr1914578376
MAMSSPIQESTAPELPSETQETPGPALCSPLRKSPLTLEDFKFLAVLGRGHFGKVLLSEFRPSGELFAIKALKKGDIVARDEVESLMCEK
RILAAVTSAGHPFLVNLFGCFQTPEHVCFVMEYSAGGDLMLHIHSDVFSEPRAIFYSACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYV
KIADFGLCKEGMGYGDRTSTFCGTPEFLAPEVLTDTSYTRAVDWWGLGVLLYEMLVGESPFPGDDEEEVFDSIVNDEVRYPRFLSAEAIG
IMRRLLRRNPERRLGSSERDAEDVKKQPFFRTLGWEALLARRLPPPFVPTLSGRTDVSNFDEEFTGEAPTLSPPRDARPLTAAEQAAFLD
368_ANXA4_PKN1


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Comparison of Fusion Protein Isoforms

check button Superimpose the 3D Structures Among All Fusion Protein Isoforms
* Download the pdb file and open it from the molstar online viewer.

check button Comparison of the Secondary Structures of Fusion Protein Isoforms

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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

ANXA4_PKN1 does not have any known PDB structures.

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pLDDT score distribution

check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
* The blue color at the bottom marks the best active site residues.


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Potential Active Site Information


check button The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.
Kinase Fusion AA seq ID in KinaseFusionDBSite scoreSizeDscoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues

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Ramachandran Plot of Kinase Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.


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Virtual Screening Results


check button Distribution of the average docking score across all approved kinase inhibitors.
Distribution of the number of occurrence across all approved kinase inhibitors.
5'-kinase fusion protein case
3'-kinase fusion protein case

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check button Drug information from DrugBank of the top 20 interacting small molecules.
* The detailed information of individual kinase inhibitors are available in the download page.
Fusion gene name infoDrugDocking scoreGlide g scoreGlide energy

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Kinase-Substrate Information of ANXA4_PKN1


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
PKN1Q16512humanMAPTP10636-8S352DFKDrVQskIGsLDNTubulin-binding
PKN1Q16512humanMAPTP10636-8S320VDLskVTskCGsLGNTubulin-binding
PKN1Q16512humanEGFRP00533T678RHIVRKRtLRRLLQE
PKN1Q16512humanHDAC5Q9UQL6T292KDGtVIstFKKRAVE
PKN1Q16512humanH3C1P68431T11kQtArkstGGkAPrkHistone
PKN1Q16512humanMAPTP10636-8S258PDLkNVKskIGstENTubulin-binding
PKN1Q16512humanMAPTP10636-8S214GsRsRtPsLPtPPtR
PKN1Q16512humanHDAC9Q9UKV0S253KDGNVVTsFKKRMFE
PKN1Q16512humanMEFVO15553S208VRLRRNAssAGRLQG
PKN1Q16512humanCLIP1P30622S312AsLKRsPsAssLsSM
PKN1Q16512humanPKN1Q16512T774GyGDRtstFCGtPEFPkinase
PKN1Q16512humanMEFVO15553S242SGKMRPRsLEVTIST


check button Biological Network Integration of This Kinase and Substrates
(GeneMANIA website)

check button Enriched GO biological processes of the phosphorylation target genes of the kinase
KinaseGOIDGO termP.adjust
PKN1IDDescription0.00e+00
PKN1GO:0031116positive regulation of microtubule polymerization1.66e-02
PKN1GO:0040029epigenetic regulation of gene expression1.66e-02
PKN1GO:0031112positive regulation of microtubule polymerization or depolymerization1.66e-02
PKN1GO:0042113B cell activation1.66e-02
PKN1GO:0010830regulation of myotube differentiation1.66e-02
PKN1GO:0006476protein deacetylation1.66e-02
PKN1GO:0031122cytoplasmic microtubule organization1.66e-02
PKN1GO:0031113regulation of microtubule polymerization1.66e-02
PKN1GO:0035601protein deacylation1.66e-02
PKN1GO:0098732macromolecule deacylation1.66e-02
PKN1GO:0010631epithelial cell migration1.66e-02
PKN1GO:0090132epithelium migration1.66e-02
PKN1GO:0090130tissue migration1.66e-02
PKN1GO:0060191regulation of lipase activity1.68e-02
PKN1GO:0090049regulation of cell migration involved in sprouting angiogenesis1.68e-02
PKN1GO:0043254regulation of protein-containing complex assembly1.76e-02
PKN1GO:0032273positive regulation of protein polymerization1.76e-02
PKN1GO:0046785microtubule polymerization1.76e-02
PKN1GO:0031110regulation of microtubule polymerization or depolymerization1.76e-02
PKN1GO:0002042cell migration involved in sprouting angiogenesis1.76e-02
PKN1GO:0051153regulation of striated muscle cell differentiation1.76e-02
PKN1GO:0001667ameboidal-type cell migration2.15e-02
PKN1GO:0045814negative regulation of gene expressio1.10e-03
PKN1GO:0014902myotube differentiation2.64e-02
PKN1GO:0031109microtubule polymerization or depolymerization2.69e-02
PKN1GO:0030183B cell differentiation3.13e-02
PKN1GO:0043535regulation of blood vessel endothelial cell migration3.13e-02
PKN1GO:0034614cellular response to reactive oxygen species3.13e-02
PKN1GO:0010950positive regulation of endopeptidase activity3.13e-02
PKN1GO:0070507regulation of microtubule cytoskeleton organization3.13e-02
PKN1GO:0051147regulation of muscle cell differentiation3.13e-02
PKN1GO:0030307positive regulation of cell growth3.13e-02
PKN1GO:0010952positive regulation of peptidase activity3.30e-02
PKN1GO:1902905positive regulation of supramolecular fiber organization3.39e-02
PKN1GO:0043534blood vessel endothelial cell migration3.52e-02
PKN1GO:0051495positive regulation of cytoskeleton organization3.54e-02
PKN1GO:0002040sprouting angiogenesis3.67e-02
PKN1GO:2000116regulation of cysteine-type endopeptidase activity3.76e-02
PKN1GO:0031334positive regulation of protein-containing complex assembly3.78e-02
PKN1GO:0032271regulation of protein polymerization3.80e-02
PKN1GO:0000302response to reactive oxygen species3.80e-02
PKN1GO:0032869cellular response to insulin stimulus3.80e-02
PKN1GO:0010594regulation of endothelial cell migration4.65e-02
PKN1GO:0048742regulation of skeletal muscle fiber development4.65e-02
PKN1GO:0034599cellular response to oxidative stress4.65e-02
PKN1GO:0045927positive regulation of growth4.65e-02
PKN1GO:0032886regulation of microtubule-based process4.65e-02
PKN1GO:0010749regulation of nitric oxide mediated signal transduction4.65e-02
PKN1GO:0010917negative regulation of mitochondrial membrane potential4.65e-02

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Related Drugs to ANXA4_PKN1


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

check button Distribution of the number of studies mentioning ANXA4-PKN1 and kinase inhibitors the PubMed Abstract (04-01-2024)

Fusion gene - drug pair 1Fusion gene - drug pair 2PMIDPublication dateDOIStudy title

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Related Diseases to ANXA4_PKN1


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

check button Related diseases from the literature mentioned this fusion gene and drug.
(PubMed, 04-01-2024)
MeSH IDMeSH term

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource


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Clinical Trials of the Found Drugs/Small Molecules


check button Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024)

check button Clinical Trials from clinicaltrials.gov (06-17-2024)

Fusion GeneKinase InhibitorNCT IDStudy StatusPhasesDisease# EnrolmentDate