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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:SIK1_HUNK

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: SIK1_HUNK
KinaseFusionDB ID: KFG5799
FusionGDB2.0 ID: KFG5799
HgeneTgene
Gene symbol

SIK1

HUNK

Gene ID

102724428

30811

Gene namehormonally up-regulated Neu-associated kinase
Synonyms-
Cytomap

21q22.11

Type of geneprotein-coding
Descriptionhormonally up-regulated neu tumor-associated kinaseB19hormonally upregulated Neu-associated kinasehormonally upregulated neu tumor-associated kinaseserine/threonine protein kinase MAK-V
Modification date20240305
UniProtAcc

P57059

P57058

Ensembl transtripts involved in fusion geneENST idsENST00000270162, ENST00000465574, 
ENST00000270112, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: SIK1 [Title/Abstract] AND HUNK [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SIK1(44845287)-HUNK(33312477), # 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

check buttonKinase Fusion gene breakpoints across SIK1 (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 HUNK (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-CR-7372SIK1chr21

44845287

HUNKchr21

33312477



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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/chr21:44845287/chr21:33312477)
- 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
SIK1

P57059

HUNK

P57058

FUNCTION: Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. Phosphorylates HDAC4, HDAC5, PPME1, SREBF1, CRTC1/TORC1. Inhibits CREB activity by phosphorylating and inhibiting activity of TORCs, the CREB-specific coactivators, like CRTC2/TORC2 and CRTC3/TORC3 in response to cAMP signaling (PubMed:29211348). Acts as a tumor suppressor and plays a key role in p53/TP53-dependent anoikis, a type of apoptosis triggered by cell detachment: required for phosphorylation of p53/TP53 in response to loss of adhesion and is able to suppress metastasis. Part of a sodium-sensing signaling network, probably by mediating phosphorylation of PPME1: following increases in intracellular sodium, SIK1 is activated by CaMK1 and phosphorylates PPME1 subunit of protein phosphatase 2A (PP2A), leading to dephosphorylation of sodium/potassium-transporting ATPase ATP1A1 and subsequent increase activity of ATP1A1. Acts as a regulator of muscle cells by phosphorylating and inhibiting class II histone deacetylases HDAC4 and HDAC5, leading to promote expression of MEF2 target genes in myocytes. Also required during cardiomyogenesis by regulating the exit of cardiomyoblasts from the cell cycle via down-regulation of CDKN1C/p57Kip2. Acts as a regulator of hepatic gluconeogenesis by phosphorylating and repressing the CREB-specific coactivators CRTC1/TORC1 and CRTC2/TORC2, leading to inhibit CREB activity. Also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1. In concert with CRTC1/TORC1, regulates the light-induced entrainment of the circadian clock by attenuating PER1 induction; represses CREB-mediated transcription of PER1 by phosphorylating and deactivating CRTC1/TORC1 (By similarity). {ECO:0000250|UniProtKB:Q60670, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:16306228, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:19622832, ECO:0000269|PubMed:29211348}.

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 SIK1_HUNK


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
HUNKP57058humanITM2AO43736T35TVRTQILtGkELRVA
SIK1P57059humanHDAC5Q9UQL6S661QALGRTQsSPAAPGG
SIK1P57059humanNCOR2Q9Y618T1383KLLKREGtPPPPPPs


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
HUNKIDDescription0.00e+00
HUNKGO:0042985negative regulation of amyloid precursor protein biosynthetic process5.65e-03
HUNKGO:0010561negative regulation of glycoprotein biosynthetic process5.65e-03
HUNKGO:0042983amyloid precursor protein biosynthetic process5.65e-03
HUNKGO:0042984regulation of amyloid precursor protein biosynthetic process5.65e-03
HUNKGO:1903019negative regulation of glycoprotein metabolic process5.65e-03
HUNKGO:0002313mature B cell differentiation involved in immune response5.65e-03
HUNKGO:0002335mature B cell differentiation5.75e-03
HUNKGO:0010559regulation of glycoprotein biosynthetic process7.18e-03
HUNKGO:1903018regulation of glycoprotein metabolic process7.18e-03
HUNKGO:0002312B cell activation involved in immune response9.25e-03
HUNKGO:0042982amyloid precursor protein metabolic process9.25e-03
HUNKGO:0030183B cell differentiation1.35e-02
HUNKGO:0002285lymphocyte activation involved in immune response1.74e-02
HUNKGO:0042113B cell activation1.90e-02
HUNKGO:0009101glycoprotein biosynthetic process1.90e-02
HUNKGO:0002366leukocyte activation involved in immune response1.90e-02
HUNKGO:0002263cell activation involved in immune response1.90e-02
HUNKGO:0009100glycoprotein metabolic process2.18e-02
HUNKGO:0030098lymphocyte differentiation2.39e-02
HUNKGO:1903131mononuclear cell differentiation2.55e-02
SIK1IDDescription0.00e+00
SIK1GO:0044849estrous cycle3.20e-02
SIK1GO:0060766negative regulation of androgen receptor signaling pathway3.20e-02
SIK1GO:0010832negative regulation of myotube differentiation3.20e-02
SIK1GO:1902894negative regulation of miRNA transcription3.20e-02
SIK1GO:2000629negative regulation of miRNA metabolic process3.20e-02
SIK1GO:0060765regulation of androgen receptor signaling pathway3.20e-02
SIK1GO:0033144negative regulation of intracellular steroid hormone receptor signaling pathway3.20e-02
SIK1GO:0051154negative regulation of striated muscle cell differentiation3.20e-02
SIK1GO:0007595lactation3.20e-02
SIK1GO:0090051negative regulation of cell migration involved in sprouting angiogenesis3.20e-02
SIK1GO:0010830regulation of myotube differentiation3.20e-02
SIK1GO:0042220response to cocaine3.20e-02
SIK1GO:0030521androgen receptor signaling pathway3.20e-02
SIK1GO:0051148negative regulation of muscle cell differentiation3.20e-02
SIK1GO:1902893regulation of miRNA transcription3.20e-02
SIK1GO:0042698ovulation cycle3.20e-02
SIK1GO:0061614miRNA transcription3.20e-02
SIK1GO:0014823response to activity3.20e-02
SIK1GO:0033143regulation of intracellular steroid hormone receptor signaling pathway3.20e-02
SIK1GO:0043537negative regulation of blood vessel endothelial cell migration3.20e-02
SIK1GO:0090049regulation of cell migration involved in sprouting angiogenesis3.20e-02
SIK1GO:2000628regulation of miRNA metabolic process3.20e-02
SIK1GO:0007589body fluid secretion3.20e-02
SIK1GO:0140747regulation of ncRNA transcription3.20e-02
SIK1GO:0043279response to alkaloid3.20e-02
SIK1GO:0002042cell migration involved in sprouting angiogenesis3.20e-02
SIK1GO:0051153regulation of striated muscle cell differentiation3.20e-02
SIK1GO:0010596negative regulation of endothelial cell migration3.20e-02

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Related Drugs to SIK1_HUNK


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 SIK1-HUNK 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 SIK1_HUNK


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