Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT06O7XL)

DOT Name	Embryonal Fyn-associated substrate (EFS)
Synonyms	hEFS; Cas scaffolding protein family member 3
Gene Name	EFS
Related Disease	Childhood acute lymphoblastic leukemia ( ) Neuroblastoma ( ) Uveal Melanoma ( ) Acute monocytic leukemia ( ) Acute myelogenous leukaemia ( ) Advanced cancer ( ) Angiosarcoma ( ) B-cell lymphoma ( ) Chronic granulomatous disease ( ) Disorder of orbital region ( ) Endophthalmitis ( ) Eye neoplasm ( ) Gastric cancer ( ) Graves disease ( ) Immunodeficiency ( ) Malignant glioma ( ) Medulloblastoma ( ) Metastatic malignant neoplasm ( ) Osteosarcoma ( ) Paroxysmal nocturnal haemoglobinuria ( ) Renal fibrosis ( ) Stomach cancer ( ) Vulvar squamous intraepithelial lesion ( ) Cardiovascular disease ( ) Rhabdomyosarcoma ( ) Acute lymphocytic leukaemia ( ) Chromosomal disorder ( ) Cutaneous squamous cell carcinoma ( ) Dental caries ( ) Prostate cancer ( ) Prostate carcinoma ( )
UniProt ID	EFS_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF12026 ; PF14604
Sequence	MAIATSTQLARALYDNTAESPQELSFRRGDVLRVLQREGAGGLDGWCLCSLHGQQGIVPA NRVKLLPAGPAPKPSLSPASPAQPGSPYPAPDHSNEDQEVYVVPPPARPCPTSGPPAGPC PPSPDLIYKIPRASGTQLAAPRDALEVYDVPPTALRVPSSGPYDCPASFSHPLTRVAPQP PGEDDAPYDVPLTPKPPAELEPDLEWEGGREPGPPIYAAPSNLKRASALLNLYEAPEELL ADGEGGGTDEGIYDVPLLGPEAPPSPEPPGALASHDQDTLAQLLARSPPPPHRPRLPSAE SLSRRPLPALPVPEAPSPSPVPSPAPGRKGSIQDRPLPPPPPRLPGYGGPKVEGDPEGRE MEDDPAGHHNEYEGIPMAEEYDYVHLKGMDKAQGSRPPDQACTGDPELPERGMPAPQEAL SPGEPLVVSTGDLQLLYFYAGQCQSHYSALQAAVAALMSSTQANQPPRLFVPHSKRVVVA AHRLVFVGDTLGRLAASAPLRAQVRAAGTALGQALRATVLAVKGAALGYPSSPAIQEMVQ CVTELAGQALQFTTLLTSLAP
Function	Docking protein which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion. May serve as an activator of SRC and a downstream effector. Interacts with the SH3 domain of FYN and with CRK, SRC, and YES.
Tissue Specificity	The protein has been detected in lung and placenta.

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Childhood acute lymphoblastic leukemia	DISJ5D6U	Definitive	Biomarker	[1]
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[2]
Uveal Melanoma	DISA7ZGL	Definitive	Biomarker	[3]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[4]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[6]
Angiosarcoma	DISIYS9W	Strong	Biomarker	[7]
B-cell lymphoma	DISIH1YQ	Strong	Genetic Variation	[8]
Chronic granulomatous disease	DIS9ZR24	Strong	Biomarker	[9]
Disorder of orbital region	DISH0ECJ	Strong	Genetic Variation	[10]
Endophthalmitis	DISCQV4J	Strong	Genetic Variation	[11]
Eye neoplasm	DISMX03T	Strong	Biomarker	[12]
Gastric cancer	DISXGOUK	Strong	Biomarker	[13]
Graves disease	DISU4KOQ	Strong	Genetic Variation	[10]
Immunodeficiency	DIS093I0	Strong	Biomarker	[14]
Malignant glioma	DISFXKOV	Strong	Biomarker	[15]
Medulloblastoma	DISZD2ZL	Strong	Genetic Variation	[16]
Metastatic malignant neoplasm	DIS86UK6	Strong	Posttranslational Modification	[17]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[6]
Paroxysmal nocturnal haemoglobinuria	DISBHMYH	Strong	Biomarker	[18]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[19]
Stomach cancer	DISKIJSX	Strong	Biomarker	[13]
Vulvar squamous intraepithelial lesion	DISULIZR	Strong	Biomarker	[14]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[20]
Rhabdomyosarcoma	DISNR7MS	moderate	Genetic Variation	[21]
Acute lymphocytic leukaemia	DISPX75S	Limited	Biomarker	[1]
Chromosomal disorder	DISM5BB5	Limited	Biomarker	[22]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Genetic Variation	[23]
Dental caries	DISRBCMD	Limited	Biomarker	[24]
Prostate cancer	DISF190Y	Limited	Biomarker	[25]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[25]
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⏷ Show the Full List of 31 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

2 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 Embryonal Fyn-associated substrate (EFS).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Embryonal Fyn-associated substrate (EFS).	[29]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Embryonal Fyn-associated substrate (EFS).	[27]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Embryonal Fyn-associated substrate (EFS).	[28]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Embryonal Fyn-associated substrate (EFS).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Embryonal Fyn-associated substrate (EFS).	[31]
Propanoic Acid	DM9TN2W	Investigative	Propanoic Acid decreases the expression of Embryonal Fyn-associated substrate (EFS).	[32]
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References

1	Preserved global histone H4 acetylation linked to ETV6-RUNX1 fusion and PAX5 deletions is associated with favorable outcome in pediatric B-cell progenitor acute lymphoblastic leukemia.Leuk Res. 2015 Dec;39(12):1455-61. doi: 10.1016/j.leukres.2015.10.006. Epub 2015 Oct 20.
2	MicroRNA-497 increases apoptosis in MYCN amplified neuroblastoma cells by targeting the key cell cycle regulator WEE1.Mol Cancer. 2013 Mar 26;12:23. doi: 10.1186/1476-4598-12-23.
3	DNA Methylation and Uveal Melanoma.Chin Med J (Engl). 2018 Apr 5;131(7):845-851. doi: 10.4103/0366-6999.228229.
4	The stem cell-associated gene expression signature allows risk stratification in pediatric acute myeloid leukemia.Leukemia. 2019 Feb;33(2):348-357. doi: 10.1038/s41375-018-0227-5. Epub 2018 Aug 8.
5	The prognostic impact of tet oncogene family member 2 mutations in patients with acute myeloid leukemia: a systematic-review and meta-analysis.BMC Cancer. 2019 Apr 25;19(1):389. doi: 10.1186/s12885-019-5602-8.
6	The cyclooxygenase-2 inhibitor NS-398 inhibits proliferation and induces apoptosis in human osteosarcoma cells via downregulation of the survivin pathway.Oncol Rep. 2012 Nov;28(5):1693-700. doi: 10.3892/or.2012.1992. Epub 2012 Aug 24.
7	Endothelial cell malignancies in infants, children and adolescents: Treatment results of three Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry.Pediatr Blood Cancer. 2020 Mar;67(3):e28095. doi: 10.1002/pbc.28095. Epub 2019 Dec 8.
8	The prognostic role of end of treatment FDG-PET-CT in patients with diffuse large B cell lymphoma can be improved by considering it with absolute monocyte count at diagnosis.Leuk Lymphoma. 2019 Aug;60(8):1958-1964. doi: 10.1080/10428194.2018.1564049. Epub 2019 Jan 28.
9	Impaired X-CGD T cell compartment is gp91phox-NADPH oxidase independent.Clin Immunol. 2018 Aug;193:52-59. doi: 10.1016/j.clim.2018.01.010. Epub 2018 Feb 3.
10	(99)Tc(m)-octreotide scintigraphy and serum eye muscle antibodies in evaluation of active thyroid-associated ophthalmopathy.Eye (Lond). 2017 May;31(5):668-676. doi: 10.1038/eye.2017.42. Epub 2017 Apr 7.
11	Corneal transplantation: study of the data of a regional eye bank for the year 2013 and analysis of the evolution of the adverse events reported in France since 2010.Cell Tissue Bank. 2017 Mar;18(1):83-89. doi: 10.1007/s10561-016-9593-2. Epub 2017 Jan 23.
12	Peripheral neuroblastic tumors with genotype-phenotype discordance: a report from the Children's Oncology Group and the International Neuroblastoma Pathology Committee.Pediatr Blood Cancer. 2013 Mar;60(3):363-70. doi: 10.1002/pbc.24238. Epub 2012 Jun 28.
13	Knockdown of Livin inhibits growth and invasion of gastric cancer cells through blockade of the MAPK pathway in vitro and in vivo.Int J Oncol. 2014 Jan;44(1):276-84. doi: 10.3892/ijo.2013.2171. Epub 2013 Nov 12.
14	New - and SIN -retrovectors for safe transduction and specific transgene expression in pancreatic cell lines.BMC Biotechnol. 2019 Jun 17;19(1):35. doi: 10.1186/s12896-019-0531-9.
15	MGMT as a potential stratification marker in relapsed high-grade glioma of children: the HIT-GBM experience.Pediatr Blood Cancer. 2010 Feb;54(2):228-37. doi: 10.1002/pbc.22323.
16	Childhood medulloblastoma-a single institution's historical perspective on survival and functional morbidity.Childs Nerv Syst. 2019 Dec;35(12):2327-2338. doi: 10.1007/s00381-019-04402-x. Epub 2019 Nov 4.
17	EFS shows biallelic methylation in uveal melanoma with poor prognosis as well as tissue-specific methylation.BMC Cancer. 2011 Aug 26;11:380. doi: 10.1186/1471-2407-11-380.
18	A SIN lentiviral vector containing PIGA cDNA allows long-term phenotypic correction of CD34+-derived cells from patients with paroxysmal nocturnal hemoglobinuria.Mol Ther. 2003 Mar;7(3):304-16. doi: 10.1016/s1525-0016(03)00011-x.
19	Sinomenine Hydrochloride Attenuates Renal Fibrosis by Inhibiting Excessive Autophagy Induced by Adriamycin: An Experimental Study.Evid Based Complement Alternat Med. 2017;2017:6878795. doi: 10.1155/2017/6878795. Epub 2017 Jul 17.
20	Hodgkin lymphoma of the elderly patients: a retrospective multicenter analysis from the Polish Lymphoma Research Group().Leuk Lymphoma. 2019 Feb;60(2):341-348. doi: 10.1080/10428194.2018.1482539. Epub 2018 Jul 6.
21	CYP2B6rs2279343 Is Associated with Improved Survival of Pediatric Rhabdomyosarcoma Treated with Cyclophosphamide.PLoS One. 2016 Jul 7;11(7):e0158890. doi: 10.1371/journal.pone.0158890. eCollection 2016.
22	Gain of 1q is a marker of poor prognosis in Wilms' tumors.Genes Chromosomes Cancer. 2013 Nov;52(11):1065-74. doi: 10.1002/gcc.22101. Epub 2013 Sep 4.
23	Expression and function of NET-1 in human skin squamous cell carcinoma.Arch Dermatol Res. 2014 May;306(4):385-97. doi: 10.1007/s00403-013-1423-9. Epub 2013 Nov 7.
24	Deletion of cas3 gene in Streptococcus mutans affects biofilm formation and increases fluoride sensitivity.Arch Oral Biol. 2019 Mar;99:190-197. doi: 10.1016/j.archoralbio.2019.01.016. Epub 2019 Jan 29.
25	Decreased expression of EFS is correlated with the advanced prostate cancer.Tumour Biol. 2015 Feb;36(2):799-805. doi: 10.1007/s13277-014-2703-5. Epub 2014 Oct 9.
26	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.
27	Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
28	Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
29	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.
30	Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
31	Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
32	Propionic acid induces mitochondrial dysfunction and affects gene expression for mitochondria biogenesis and neuronal differentiation in SH-SY5Y cell line. Neurotoxicology. 2019 Dec;75:116-122. doi: 10.1016/j.neuro.2019.09.009. Epub 2019 Sep 14.