Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBN3XHN)

• DOT Name: Protein furry homolog-like (FRYL)
• Synonyms: ALL1-fused gene from chromosome 4p12 protein
• Gene Name: FRYL
• Related Disease:
  Acute leukaemia
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Breast carcinoma
  Childhood myelodysplastic syndrome
  Leukemia
  Myelodysplastic syndrome
  Neuroblastoma
• UniProt ID: FRYL_HUMAN
• Pfam ID: PF19421 ; PF14225 ; PF14228 ; PF14222
• Sequence:
  MSNITIDPDVKPGEYVIKSLFAEFAVQAEKKIEVVMAEPLEKLLSRSLQRGEDLQFDQLI
  SSMSSVAEHCLPSLLRTLFDWYRRQNGTEDESYEYRPRSSTKSKGDEQQRERDYLLERRD
  LAVDFIFCLVLVEVLKQIPVHPVPDPLVHEVLNLAFKHFKHKEGYSGTNTGNVHIIADLY
  AEVIGVLAQSKFQAVRKKFVTELKELRQKEQSPHVVQSVISLIMGMKFFRVKMYPVEDFE
  ASFQFMQECAQYFLEVKDKDIKHALAGLFVEILIPVAAAVKNEVNVPCLKNFVEMLYQTT
  FELSSRKKHSLALYPLITCLLCVSQKQFFLNNWHIFLQNCLSHLKNKDPKMSRVALESLY
  RLLWVYVIRIKCESNTVTQSRLMSIVSALFPKGSRSVVPRDTPLNIFVKIIQFIAQERLD
  FAMKEIIFDLLSVGKSTKTFTINPERMNIGLRVFLVIADSLQQKDGEPPMPTTGVILPSG
  NTLRVKKIFLNKTLTDEEAKVIGMSVYYPQVRKALDSILRHLDKEVGRPMCMTSVQMSNK
  EPEDMITGERKPKIDLFRTCIAAIPRLIPDGMSRTDLIELLARLTIHMDEELRALAFNTL
  QALMLDFPDWREDVLSGFVYFIVREVTDVHPTLLDNAVKMLVQLINQWKQAAQMHNKNQD
  TQHGVANGASHPPPLERSPYSNVFHVVEGFALVILCSSRPATRRLAVSVLREIRALFALL
  EIPKGDDELAIDVMDRLSPSILESFIHLTGADQTTLLYCPSSIDLQTLAEWNSSPISHQF
  DVISPSHIWIFAHVTQGQDPWIISLSSFLKQENLPKHCSTAVSYAWMFAYTRLQLLSPQV
  DINSPINAKKVNTTTSSDSYIGLWRNYLILCCSAATSSSSTSAGSVRCSPPETLASTPDS
  GYSIDSKIIGIPSPSSLFKHIVPMMRSESMEITESLVLGLGRTNPGAFRELIEELHPIIK
  EALERRPENMKRRRRRDILRVQLVRIFELLADAGVISHSASGGLDNETHFLNNTLLEYVD
  LTRQLLEAENEKDSDTLKDIRCHFSALVANIIQNVPVHQRRSIFPQQSLRHSLFMLFSHW
  AGPFSIMFTPLDRYSDRNMQINRHQYCALKAMSAVLCCGPVADNVGLSSDGYLYKWLDNI
  LDSLDKKVHQLGCEAVTLLLELNPDQSNLMYWAVDRCYTGSGRVAAGCFKAIANVFQNRD
  YQCDTVMLLNLILFKAADSSRSIYEVAMQLLQILEPKMFRYAHKLEVQRTDGVLSQLSPL
  PHLYSVSYYQLSEELARAYPELTLAIFSEISQRIQTAHPAGRQVMLHYLLPWMNNIELVD
  LKPLPTARRHDEDEDDSLKDRELMVTSRRWLRGEGWGSPQATAMVLNNLMYMTAKYGDEL
  AWSEVENVWTTLADGWPKNLKIILHFLISICGVNSEPSLLPYVKKVIVYLGRDKTMQLLE
  ELVSELQLTDPVSSGVTHMDNPPYYRITSSYKIPSVTSGTTSSSNTMVAPTDGNPDNKPI
  KENIEESYVHLDIYSGLNSHLNRQHHRLESRYSSSSGGSYEEEKSDSMPLYSNWRLKVME
  HNQGEPLPFPPAGGCWSPLVDYVPETSSPGLPLHRCNIAVILLTDLIIDHSVKVEWGSYL
  HLLLHAIFIGFDHCHPEVYEHCKRLLLHLLIVMGPNSNIRTVASVLLRNKEFNEPRVLTV
  KQVAHLDYNFTAGINDFIPDYQPSPMTDSGLSSSSTSSSISLGNNSAAISHLHTTILNEV
  DISVEQDGKVKTLMEFITSRKRGPLWNHEDVSAKNPSIKSAEQLTTFLKHVVSVFKQSSS
  EGIHLEHHLSEVALQTALSCSSRHYAGRSFQIFRALKQPLTATTLSDVLSRLVETVGDPG
  EDAQGFVIELLLTLESAIDTLAETMKHYDLLSALSQTSYHDPIMGNKYAANRKSTGQLNL
  STSPINSSSYLGYNSNARSNSLRLSLIGDRRGDRRRSNTLDIMDGRINHSSSLARTRSLS
  SLREKGMYDVQSTTEPTNLMATIFWIAASLLESDYEYEYLLALRLLNKLLIHLPLDKSES
  REKIENVQSKLKWTNFPGLQQLFLKGFTSASTQEMTVHLLSKLISVSKHTLVDPSQLSGF
  PLNILCLLPHLIQHFDSPTQFCKETASRIAKVCAEEKCPTLVNLAHMMSLYSTHTYSRDC
  SNWINVVCRYLHDSFSDTTFNLVTYLAELLEKGLSSMQQSLLQIIYSLLSHIDLSAAPAK
  QFNLEIIKIIGKYVQSPYWKEALNILKLVVSRSASLVVPSDIPKTYGGDTGSPEISFTKI
  FNNVSKELPGKTLDFHFDISETPIIGNKYGDQHSAAGRNGKPKVIAVTRSTSSTSSGSNS
  NALVPVSWKRPQLSQRRTREKLMNVLSLCGPESGLPKNPSVVFSSNEDLEVGDQQTSLIS
  TTEDINQEEEVAVEDNSSEQQFGVFKDFDFLDVELEDAEGESMDNFNWGVRRRSLDSIDK
  GDTPSLQEYQCSSSTPSLNLTNQEDTDESSEEEAALTASQILSRTQMLNSDSATDETIPD
  HPDLLLQSEDSTGSITTEEVLQIRDETPTLEASLDNANSRLPEDTTSVLKEEHVTTFEDE
  GSYIIQEQQESLVCQGILDLEETEMPEPLAPESYPESVCEEDVTLALKELDERCEEEEAD
  FSGLSSQDEEEQDGFPEVQTSPLPSPFLSAIIAAFQPVAYDDEEEAWRCHVNQMLSDTDG
  SSAVFTFHVFSRLFQTIQRKFGEITNEAVSFLGDSLQRIGTKFKSSLEVMMLCSECPTVF
  VDAETLMSCGLLETLKFGVLELQEHLDTYNVKREAAEQWLDDCKRTFGAKEDMYRINTDA
  QQMEILAELELCRRLYKLHFQLLLLFQAYCKLINQVNTIKNEAEVINMSEELAQLESILK
  EAESASENEEIDISKAAQTTIETAIHSLIETLKNKEFISAVAQVKAFRSLWPSDIFGSCE
  DDPVQTLLHIYFHHQTLGQTGSFAVIGSNLDMSEANYKLMELNLEIRESLRMVQSYQLLA
  QAKPMGNMVSTGF
• Function: Plays a key role in maintaining the integrity of polarized cell extensions during morphogenesis, regulates the actin cytoskeleton and plays a key role in patterning sensory neuron dendritic fields by promoting avoidance between homologous dendrites as well as by limiting dendritic branching. May function as a transcriptional activator.
• Tissue Specificity: Widely expressed with higher expression in colon, placenta, brain and cells of lymphoid origin.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[1]
Acute monocytic leukemia	DIS28NEL	Strong	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Altered Expression	[2]
Leukemia	DISNAKFL	Strong	Genetic Variation	[1]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[2]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[2]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein furry homolog-like (FRYL).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein furry homolog-like (FRYL).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein furry homolog-like (FRYL).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein furry homolog-like (FRYL).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein furry homolog-like (FRYL).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Protein furry homolog-like (FRYL).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Protein furry homolog-like (FRYL).	[9]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Protein furry homolog-like (FRYL).	[12]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein furry homolog-like (FRYL).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein furry homolog-like (FRYL).	[11]

References

• [1] Translocation (4;11)(p12;q23) with rearrangement of FRYL and MLL in therapy-related acute myeloid leukemia.Cancer Genet Cytogenet. 2007 Sep;177(2):143-6. doi: 10.1016/j.cancergencyto.2007.05.021.
• [2] Prospective tracing of MLL-FRYL clone with low MEIS1 expression from emergence during neuroblastoma treatment to diagnosis of myelodysplastic syndrome.Blood. 2008 Apr 1;111(7):3802-12. doi: 10.1182/blood-2007-07-096065. Epub 2008 Jan 14.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.