Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOBEH24)

DOT Name	Cytoplasmic FMR1-interacting protein 1 (CYFIP1)
Synonyms	Specifically Rac1-associated protein 1; Sra-1; p140sra-1
Gene Name	CYFIP1
Related Disease	Angelman syndrome ( ) Epilepsy ( ) Acute lymphocytic leukaemia ( ) Autism spectrum disorder ( ) Brain disease ( ) Breast cancer ( ) Breast carcinoma ( ) Childhood acute lymphoblastic leukemia ( ) Cutaneous squamous cell carcinoma ( ) Epithelial neoplasm ( ) Fragile X syndrome ( ) Schizophrenia ( ) Temporal lobe epilepsy ( ) Autism ( ) Chronic obstructive pulmonary disease ( ) Fetal growth restriction ( ) Neoplasm ( ) Prader-Willi syndrome ( ) Stroke ( ) Advanced cancer ( ) Intellectual disability ( ) Metastatic malignant neoplasm ( ) Nasopharyngeal carcinoma ( ) Nervous system disease ( )
UniProt ID	CYFP1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3P8C; 4N78; 7USC; 7USD; 7USE
Pfam ID	PF07159 ; PF05994
Sequence	MAAQVTLEDALSNVDLLEELPLPDQQPCIEPPPSSLLYQPNFNTNFEDRNAFVTGIARYI EQATVHSSMNEMLEEGQEYAVMLYTWRSCSRAIPQVKCNEQPNRVEIYEKTVEVLEPEVT KLMNFMYFQRNAIERFCGEVRRLCHAERRKDFVSEAYLITLGKFINMFAVLDELKNMKCS VKNDHSAYKRAAQFLRKMADPQSIQESQNLSMFLANHNKITQSLQQQLEVISGYEELLAD IVNLCVDYYENRMYLTPSEKHMLLKVMGFGLYLMDGSVSNIYKLDAKKRINLSKIDKYFK QLQVVPLFGDMQIELARYIKTSAHYEENKSRWTCTSSGSSPQYNICEQMIQIREDHMRFI SELARYSNSEVVTGSGRQEAQKTDAEYRKLFDLALQGLQLLSQWSAHVMEVYSWKLVHPT DKYSNKDCPDSAEEYERATRYNYTSEEKFALVEVIAMIKGLQVLMGRMESVFNHAIRHTV YAALQDFSQVTLREPLRQAIKKKKNVIQSVLQAIRKTVCDWETGHEPFNDPALRGEKDPK SGFDIKVPRRAVGPSSTQLYMVRTMLESLIADKSGSKKTLRSSLEGPTILDIEKFHRESF FYTHLINFSETLQQCCDLSQLWFREFFLELTMGRRIQFPIEMSMPWILTDHILETKEASM MEYVLYSLDLYNDSAHYALTRFNKQFLYDEIEAEVNLCFDQFVYKLADQIFAYYKVMAGS LLLDKRLRSECKNQGATIHLPPSNRYETLLKQRHVQLLGRSIDLNRLITQRVSAAMYKSL ELAIGRFESEDLTSIVELDGLLEINRMTHKLLSRYLTLDGFDAMFREANHNVSAPYGRIT LHVFWELNYDFLPNYCYNGSTNRFVRTVLPFSQEFQRDKQPNAQPQYLHGSKALNLAYSS IYGSYRNFVGPPHFQVICRLLGYQGIAVVMEELLKVVKSLLQGTILQYVKTLMEVMPKIC RLPRHEYGSPGILEFFHHQLKDIVEYAELKTVCFQNLREVGNAILFCLLIEQSLSLEEVC DLLHAAPFQNILPRVHVKEGERLDAKMKRLESKYAPLHLVPLIERLGTPQQIAIAREGDL LTKERLCCGLSMFEVILTRIRSFLDDPIWRGPLPSNGVMHVDECVEFHRLWSAMQFVYCI PVGTHEFTVEQCFGDGLHWAGCMIIVLLGQQRRFAVLDFCYHLLKVQKHDGKDEIIKNVP LKKMVERIRKFQILNDEIITILDKYLKSGDGEGTPVEHVRCFQPPIHQSLASS
Function	Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit is an adapter between EIF4E and FMR1. Promotes the translation repression activity of FMR1 in brain probably by mediating its association with EIF4E and mRNA. Regulates formation of membrane ruffles and lamellipodia. Plays a role in axon outgrowth. Binds to F-actin but not to RNA. Part of the WAVE complex that regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1. Regulator of epithelial morphogenesis. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes. May act as an invasion suppressor in cancers.
KEGG Pathway	Regulation of actin cytoskeleton (hsa04810 ) Pathogenic Escherichia coli infection (hsa05130 ) Salmonella infection (hsa05132 )
Reactome Pathway	VEGFA-VEGFR2 Pathway (R-HSA-4420097 ) RHO GTPases Activate WASPs and WAVEs (R-HSA-5663213 ) Neutrophil degranulation (R-HSA-6798695 ) RAC1 GTPase cycle (R-HSA-9013149 ) RAC2 GTPase cycle (R-HSA-9013404 ) RHOG GTPase cycle (R-HSA-9013408 ) RAC3 GTPase cycle (R-HSA-9013423 ) FCGR3A-mediated phagocytosis (R-HSA-9664422 ) Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482 )

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Angelman syndrome	DIS4QVXO	Definitive	Biomarker	[1]
Epilepsy	DISBB28L	Definitive	Altered Expression	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[3]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[4]
Brain disease	DIS6ZC3X	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[3]
Cutaneous squamous cell carcinoma	DIS3LXUG	Strong	Altered Expression	[7]
Epithelial neoplasm	DIS0T594	Strong	Biomarker	[7]
Fragile X syndrome	DISE8W3A	Strong	Biomarker	[5]
Schizophrenia	DISSRV2N	Strong	Biomarker	[8]
Temporal lobe epilepsy	DISNOPXX	Strong	Biomarker	[9]
Autism	DISV4V1Z	moderate	Genetic Variation	[8]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Genetic Variation	[10]
Fetal growth restriction	DIS5WEJ5	moderate	Biomarker	[11]
Neoplasm	DISZKGEW	moderate	Biomarker	[12]
Prader-Willi syndrome	DISYWMLU	moderate	Altered Expression	[13]
Stroke	DISX6UHX	moderate	Biomarker	[14]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[15]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[8]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[12]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[12]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[8]
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⏷ Show the Full List of 24 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Cytoplasmic FMR1-interacting protein 1 (CYFIP1).	[16]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cytoplasmic FMR1-interacting protein 1 (CYFIP1).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Cytoplasmic FMR1-interacting protein 1 (CYFIP1).	[26]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cytoplasmic FMR1-interacting protein 1 (CYFIP1).	[27]
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10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cytoplasmic FMR1-interacting protein 1 (CYFIP1).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cytoplasmic FMR1-interacting protein 1 (CYFIP1).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cytoplasmic FMR1-interacting protein 1 (CYFIP1).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cytoplasmic FMR1-interacting protein 1 (CYFIP1).	[20]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cytoplasmic FMR1-interacting protein 1 (CYFIP1).	[22]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cytoplasmic FMR1-interacting protein 1 (CYFIP1).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Cytoplasmic FMR1-interacting protein 1 (CYFIP1).	[24]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Cytoplasmic FMR1-interacting protein 1 (CYFIP1).	[25]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Cytoplasmic FMR1-interacting protein 1 (CYFIP1).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cytoplasmic FMR1-interacting protein 1 (CYFIP1).	[28]
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⏷ Show the Full List of 10 Drug(s)

References

1	Nine patients with a microdeletion 15q11.2 between breakpoints 1 and 2 of the Prader-Willi critical region, possibly associated with behavioural disturbances.Eur J Med Genet. 2009 Mar-Jun;52(2-3):108-15. doi: 10.1016/j.ejmg.2009.03.010. Epub 2009 Mar 27.
2	Expression Analysis of CYFIP1 and CAMKK2 Genes in the Blood of Epileptic and Schizophrenic Patients.J Mol Neurosci. 2018 Jul;65(3):336-342. doi: 10.1007/s12031-018-1106-2. Epub 2018 Jul 11.
3	Cyfip1 is downregulated in acute lymphoblastic leukemia and may be a potential biomarker in acute lymphoblastic leukemia.Tumour Biol. 2016 Jul;37(7):9285-8. doi: 10.1007/s13277-016-4786-7. Epub 2016 Jan 15.
4	Behavioral training rescues motor deficits in Cyfip1 haploinsufficiency mouse model of autism spectrum disorders.Transl Psychiatry. 2019 Jan 21;9(1):29. doi: 10.1038/s41398-018-0338-9.
5	Neuronal function and dysfunction of CYFIP2: from actin dynamics to early infantile epileptic encephalopathy.BMB Rep. 2019 May;52(5):304-311. doi: 10.5483/BMBRep.2019.52.5.097.
6	Wild-type p53 upregulates an early onset breast cancer-associated gene GAS7 to suppress metastasis via GAS7-CYFIP1-mediated signaling pathway.Oncogene. 2018 Jul;37(30):4137-4150. doi: 10.1038/s41388-018-0253-9. Epub 2018 Apr 30.
7	CYFIP1 is directly controlled by NOTCH1 and down-regulated in cutaneous squamous cell carcinoma.PLoS One. 2017 Apr 14;12(4):e0173000. doi: 10.1371/journal.pone.0173000. eCollection 2017.
8	Autism and Schizophrenia-Associated CYFIP1 Regulates the Balance of Synaptic Excitation and Inhibition.Cell Rep. 2019 Feb 19;26(8):2037-2051.e6. doi: 10.1016/j.celrep.2019.01.092.
9	Up-regulated cytoplasmic FMRP-interacting protein 1 in intractable temporal lobe epilepsy patients and a rat model.Int J Neurosci. 2016 Jun;126(6):542-551. doi: 10.3109/00207454.2015.1038711. Epub 2015 Aug 21.
10	Genetic variations in scavenger and ?adrenergic receptors and risk of pulmonary disease.Dan Med J. 2014 Sep;61(9):B4910.
11	Prenatal diagnosis of a familial 15q11.2 (BP1-BP2) microdeletion encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1 in a fetus with ventriculomegaly, microcephaly and intrauterine growth restriction on prenatal ultrasound.Taiwan J Obstet Gynecol. 2018 Oct;57(5):730-733. doi: 10.1016/j.tjog.2018.08.022.
12	Low expression of Cyfip1 may be a potential biomarker in nasopharyngeal carcinoma.Neoplasma. 2018;65(2):292-295. doi: 10.4149/neo_2018_170318N194.
13	Expression of 4 genes between chromosome 15 breakpoints 1 and 2 and behavioral outcomes in Prader-Willi syndrome.Pediatrics. 2006 Oct;118(4):e1276-83. doi: 10.1542/peds.2006-0424. Epub 2006 Sep 18.
14	Further Evidence of the Positive Influence of Repetitive Transcranial Magnetic Stimulation on Speech and Language in Patients with Aphasia after Stroke: Results from a Double-Blind Intervention with Sham Condition.Neuropsychobiology. 2017;75(4):185-192. doi: 10.1159/000486144. Epub 2018 Jan 16.
15	Targeting the WASF3-CYFIP1 Complex Using Stapled Peptides Suppresses Cancer Cell Invasion.Cancer Res. 2016 Feb 15;76(4):965-73. doi: 10.1158/0008-5472.CAN-15-1680. Epub 2015 Dec 16.
16	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
17	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
18	Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
19	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.
20	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.
21	Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
22	Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
23	Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
24	A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
25	Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
26	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.
27	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.
28	Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.