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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:PRKAA2_USP24

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: PRKAA2_USP24
KinaseFusionDB ID: KFG4864
FusionGDB2.0 ID: KFG4864
HgeneTgene
Gene symbol

PRKAA2

USP24

Gene ID

5563

23358

Gene nameprotein kinase AMP-activated catalytic subunit alpha 2ubiquitin specific peptidase 24
SynonymsAMPK|AMPK2|AMPKa2|PRKAA-
Cytomap

1p32.2

1p32.3

Type of geneprotein-codingprotein-coding
Description5'-AMP-activated protein kinase catalytic subunit alpha-25'-AMP-activated protein kinase, catalytic alpha-2 chainACACA kinaseAMPK alpha 2AMPK subunit alpha-2AMPK-alpha-2 chainHMGCR kinaseacetyl-CoA carboxylase kinasehydroxymethylglutaryl-CoA reducubiquitin carboxyl-terminal hydrolase 24deubiquitinating enzyme 24ubiquitin specific protease 24ubiquitin thioesterase 24ubiquitin thiolesterase 24ubiquitin-specific processing protease 24
Modification date2024041620240403
UniProtAcc

P54646

Q9UPU5

Ensembl transtripts involved in fusion geneENST idsENST00000371244, ENST00000484447, 
ENST00000294383, ENST00000407756, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: PRKAA2 [Title/Abstract] AND USP24 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PRKAA2(57111154)-USP24(55541196), # samples:3
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgenePRKAA2

GO:0031669

cellular response to nutrient levels

25412657

HgenePRKAA2

GO:0042149

cellular response to glucose starvation

14651849|18439900|34077757|36732624

HgenePRKAA2

GO:1903944

negative regulation of hepatocyte apoptotic process

32029622

HgenePRKAA2

GO:1904262

negative regulation of TORC1 signaling

14651849|18439900|36732624|37079666

HgenePRKAA2

GO:1905691

lipid droplet disassembly

34077757

HgenePRKAA2

GO:1990044

protein localization to lipid droplet

34077757


check buttonKinase Fusion gene breakpoints across PRKAA2 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonKinase Fusion gene breakpoints across USP24 (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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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-EE-A2MD-06APRKAA2chr1

57111154

USP24chr1

55541196



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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)

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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

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/:57111154/:55541196)
- 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
PRKAA2

P54646

USP24

Q9UPU5

FUNCTION: Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (PubMed:7959015). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). Involved in insulin receptor/INSR internalization (PubMed:25687571). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11554766, PubMed:11518699, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Plays an important role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose starvation (By similarity). Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity). Upon glucose starvation, promotes ARF6 activation in a kinase-independent manner leading to cell migration (PubMed:36017701). Upon glucose deprivation mediates the phosphorylation of ACSS2 at 'Ser-659', which exposes the nuclear localization signal of ACSS2, required for its interaction with KPNA1 and nuclear translocation (PubMed:28552616). {ECO:0000250|UniProtKB:Q09137, ECO:0000250|UniProtKB:Q8BRK8, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:25687571, ECO:0000269|PubMed:28552616, ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:32029622, ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:36017701, ECO:0000269|PubMed:36732624, ECO:0000269|PubMed:37079666, ECO:0000269|PubMed:7959015, ECO:0000303|PubMed:17307971, ECO:0000303|PubMed:17712357}.FUNCTION: Ubiquitin-specific protease that regulates cell survival in various contexts through modulating the protein stability of some of its substrates including DDB2, MCL1 or TP53. Plays a positive role on ferritinophagy where ferritin is degraded in lysosomes and releases free iron. {ECO:0000269|PubMed:23159851, ECO:0000269|PubMed:29695420}.

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


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Kinase-Substrate Information of PRKAA2_USP24


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
PRKAA2P54646humanREEP1Q9H902S152SERLRsFsMQDLTTI
PRKAA2P54646humanPLD1Q13393S505GsVkRVTsGPsLGSL
PRKAA2P54646humanHDAC5Q9UQL6S498RPLSRtQsSPLPQsP
PRKAA2P54646humanHIPK2Q9H2X6S121LMRRStVsLLDTYQK
PRKAA2P54646humanACACAQ13085S80LHIRssMsGLHLVkQ
PRKAA2P54646humanTP53BP1Q12888S1317SSLHRtssGtsLSAM
PRKAA2P54646humanHIPK2Q9H2X6T119HNLMRRStVsLLDTY
PRKAA2P54646humanPARP1P09874S177LGFRPEYsAsQLkGFzf-PARP
PRKAA2P54646humanPDHA1P08559S314IQEVRSksDPIMLLkE1_dh
PRKAA2P54646humanEEF2KO00418S398DsLPssPssAtPHSQ
PRKAA2P54646humanDUSP1P28562S334AVLDRGTsTTTVFNF
PRKAA2P54646humanCDC27P30260S379NALPRRssRLFtsDs
PRKAA2P54646humanFOXO3O43524S626SLECDMEsIIRSELMFOXO-TAD
PRKAA2P54646humanGLI1P08151S408GPLPRAPsISTVEPk
PRKAA2P54646humanPPP1R12CQ9BZL4S452AGLQRsAsssWLEGt
PRKAA2P54646humanPINK1Q9BXM7S228MWNISAGsSSEAILN
PRKAA2P54646humanPDHA1P08559S295RyHGHsMsDPGVsyRE1_dh
PRKAA2P54646humanRPTORQ8N122S792DKMRRAssYSsLNSL
PRKAA2P54646humanSIRT1Q96EB6T344GkLLRNYtQNIDTLESIR2
PRKAA2P54646humanPINK1Q9BXM7S495ALLQREAsKRPSARVPkinase
PRKAA2P54646humanGSDMEO60443T6__MFAkAtRNFLREVGasdermin
PRKAA2P54646humanPHF2O75151S655kALRPPtsPGVFGAL
PRKAA2P54646humanHAS2Q92819T110LQSVKRLtYPGIKVV
PRKAA2P54646humanFOXO3O43524S555RALsNsVsNMGLSES
PRKAA2P54646humanHIPK2Q9H2X6T1114APAALGStGTVAHLV
PRKAA2P54646humanCHKAP35790S279kKLHKLLsYNLPLELCholine_kinase
PRKAA2P54646humanFOXO3O43524T179SSPDKRLtLSQIyEWForkhead
PRKAA2P54646humanFOXO3O43524S588QTLSDSLsGSSLYST
PRKAA2P54646humanPROX1Q92786S79KLLKRANsyEDAMMP
PRKAA2P54646humanPINK1Q9BXM7S284VLRAFTSsVPLLPGAPkinase
PRKAA2P54646humanBAIAP2Q9UQB8S366ktLPRsssMAAGLER
PRKAA2P54646humanFOXO3O43524S413GLMQRSSsFPYTTKG
PRKAA2P54646humanPRKAA2P54646T172sDGEFLRtsCGsPNyPkinase
PRKAA2P54646humanKLC4Q9NSK0S590SNMKRAAsLNyLNQP
PRKAA2P54646humanPAK2Q13177S20APPVRMsstIFstGG
PRKAA2P54646humanIKBKBO14920S177AkELDQGsLCtsFVGPkinase
PRKAA2P54646humanREEP2Q9BRK0S150SEkLRsFsMQDLTLI
PRKAA2P54646humanTBC1D1Q86TI0T596AFRRRANtLsHFPIE
PRKAA2P54646humanFOXO3O43524S399DNItLPPsQPsPTGG
PRKAA2P54646humanHDAC5Q9UQL6S259FPLRkTAsEPNLKVR
PRKAA2P54646humanGLI1P08151S102LQTVIRTsPSSLVAF
PRKAA2P54646humanIKBKBO14920S181DQGsLCtsFVGTLQyPkinase
PRKAA2P54646humanTFAP2AP05549S219CSVPGRLsLLSsTskTF_AP-2
PRKAA2P54646humanTBC1D1Q86TI0S237RPMRKsFsQPGLRSL
PRKAA2P54646humanMFFQ9GZY8S172GQLVRNDsLWHRsDsMiff
PRKAA2P54646humanMYCP01106S82PLsPsRRsGLCsPSyMyc_N
PRKAA2P54646humanGLI1P08151T1074QRGSsGHtPPPsGPP
PRKAA2P54646humanARMC10Q8N2F6S45LGIRSsKsAGALEEG


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
PRKAA2IDDescription0.00e+00
PRKAA2GO:0036294cellular response to decreased oxygen levels4.29e-04
PRKAA2GO:0071453cellular response to oxygen levels4.29e-04
PRKAA2GO:2001242regulation of intrinsic apoptotic signaling pathway4.57e-04
PRKAA2GO:0097193intrinsic apoptotic signaling pathway4.57e-04
PRKAA2GO:0043523regulation of neuron apoptotic process9.17e-04
PRKAA2GO:2001233regulation of apoptotic signaling pathway1.29e-03
PRKAA2GO:0071456cellular response to hypoxia1.29e-03
PRKAA2GO:0051402neuron apoptotic process1.62e-03
PRKAA2GO:0045913positive regulation of carbohydrate metabolic process2.08e-03
PRKAA2GO:0048596embryonic camera-type eye morphogenesis2.08e-03
PRKAA2GO:0072332intrinsic apoptotic signaling pathway by p53 class mediator2.08e-03
PRKAA2GO:0036293response to decreased oxygen levels2.10e-03
PRKAA2GO:0062197cellular response to chemical stress2.10e-03
PRKAA2GO:0062012regulation of small molecule metabolic process2.76e-03
PRKAA2GO:0070482response to oxygen levels2.84e-03
PRKAA2GO:0032869cellular response to insulin stimulus2.88e-03
PRKAA2GO:0048048embryonic eye morphogenesis2.88e-03
PRKAA2GO:1902253regulation of intrinsic apoptotic signaling pathway by p53 class mediator2.88e-03
PRKAA2GO:1901796regulation of signal transduction by p53 class mediator2.92e-03
PRKAA2GO:0050679positive regulation of epithelial cell proliferation2.92e-03
PRKAA2GO:0031076embryonic camera-type eye development2.92e-03
PRKAA2GO:0040029epigenetic regulation of gene expression3.40e-03
PRKAA2GO:0051403stress-activated MAPK cascade3.40e-03
PRKAA2GO:0031098stress-activated protein kinase signaling cascade3.58e-03
PRKAA2GO:0071356cellular response to tumor necrosis factor3.58e-03
PRKAA2GO:0045814negative regulation of gene expressio5.52e-05
PRKAA2GO:0050678regulation of epithelial cell proliferation3.83e-03
PRKAA2GO:0031669cellular response to nutrient levels3.83e-03
PRKAA2GO:0140718facultative heterochromatin formation3.83e-03
PRKAA2GO:1902175regulation of oxidative stress-induced intrinsic apoptotic signaling pathway3.83e-03
PRKAA2GO:0034599cellular response to oxidative stress3.88e-03
PRKAA2GO:1900542regulation of purine nucleotide metabolic process3.88e-03
PRKAA2GO:0034612response to tumor necrosis factor3.88e-03
PRKAA2GO:0006140regulation of nucleotide metabolic process3.88e-03
PRKAA2GO:0032873negative regulation of stress-activated MAPK cascade3.88e-03
PRKAA2GO:0070303negative regulation of stress-activated protein kinase signaling cascade3.88e-03
PRKAA2GO:0030099myeloid cell differentiation3.91e-03
PRKAA2GO:0042149cellular response to glucose starvation3.91e-03
PRKAA2GO:0010212response to ionizing radiation4.00e-03
PRKAA2GO:0032868response to insulin4.00e-03
PRKAA2GO:2001235positive regulation of apoptotic signaling pathway4.63e-03
PRKAA2GO:0031668cellular response to extracellular stimulus4.66e-03
PRKAA2GO:0062013positive regulation of small molecule metabolic process4.66e-03
PRKAA2GO:0010508positive regulation of autophagy4.85e-03
PRKAA2GO:1990700nucleolar chromatin organization4.85e-03
PRKAA2GO:0018105peptidyl-serine phosphorylation5.27e-03
PRKAA2GO:0048511rhythmic process5.27e-03
PRKAA2GO:0001666response to hypoxia5.27e-03
PRKAA2GO:0051054positive regulation of DNA metabolic process5.27e-03

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Related Drugs to PRKAA2_USP24


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 PRKAA2-USP24 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 PRKAA2_USP24


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