Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXU44F3)

DOT Name Synaptonemal complex central element protein 1-like (SYCE1L)
Synonyms Meiosis-related protein
Gene Name SYCE1L
Related Disease
Carcinoma of esophagus ( )
Esophageal cancer ( )
Neoplasm of esophagus ( )
Non-small-cell lung cancer ( )
Acute monocytic leukemia ( )
Acute myelogenous leukaemia ( )
Adenocarcinoma ( )
Bladder cancer ( )
Carcinoma ( )
Cholangiocarcinoma ( )
Clear cell renal carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Epithelial ovarian cancer ( )
Esophageal squamous cell carcinoma ( )
Hepatitis ( )
Hepatitis A virus infection ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Liver cirrhosis ( )
Lung cancer ( )
Lung carcinoma ( )
Matthew-Wood syndrome ( )
Neoplasm ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Pancreatic cancer ( )
Primary biliary cholangitis ( )
Renal carcinoma ( )
Renal cell carcinoma ( )
Small-cell lung cancer ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Advanced cancer ( )
B-cell lymphoma ( )
Cholestasis ( )
Congenital contractural arachnodactyly ( )
Melanoma ( )
Acute lymphocytic leukaemia ( )
Breast cancer ( )
Breast carcinoma ( )
Childhood acute lymphoblastic leukemia ( )
Dubin-Johnson syndrome ( )
Epilepsy ( )
Gallbladder carcinoma ( )
Mesothelioma ( )
Plasma cell myeloma ( )
Progressive familial intrahepatic cholestasis ( )
UniProt ID
SYC1L_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF15233
Sequence
MAGKLKPLNVEAPEATEEAEGQAKSLKTEDLLAMVIKLQKEGSLEPQIEDLISRINDLQQ
AKKKSSEELRETHSLWEALHRELDSLNGEKVHLEEVLGKKQEALRILQMHCQEKESEAQR
LDVRGQLEDLMGQHKDLWEFHMLEQRLAREIRALERSKEQLLSERRLVRAKLREVERRLH
SPPEVEGAMAVNDGLKAELEIFGEQVRSAPEVGAGEGEAGPELPRARDEEDPEPPVAAPD
AL
Function May be involved in meiosis.

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Carcinoma of esophagus DISS6G4D Definitive Altered Expression [1]
Esophageal cancer DISGB2VN Definitive Altered Expression [1]
Neoplasm of esophagus DISOLKAQ Definitive Altered Expression [1]
Non-small-cell lung cancer DIS5Y6R9 Definitive Biomarker [2]
Acute monocytic leukemia DIS28NEL Strong Altered Expression [3]
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [3]
Adenocarcinoma DIS3IHTY Strong Altered Expression [4]
Bladder cancer DISUHNM0 Strong Biomarker [5]
Carcinoma DISH9F1N Strong Altered Expression [6]
Cholangiocarcinoma DIS71F6X Strong Biomarker [7]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [8]
Colon cancer DISVC52G Strong Altered Expression [9]
Colon carcinoma DISJYKUO Strong Altered Expression [9]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [10]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [11]
Hepatitis DISXXX35 Strong Biomarker [12]
Hepatitis A virus infection DISUMFQV Strong Genetic Variation [13]
Hepatitis C virus infection DISQ0M8R Strong Altered Expression [14]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [7]
Liver cirrhosis DIS4G1GX Strong Altered Expression [15]
Lung cancer DISCM4YA Strong Altered Expression [16]
Lung carcinoma DISTR26C Strong Altered Expression [16]
Matthew-Wood syndrome DISA7HR7 Strong Biomarker [17]
Neoplasm DISZKGEW Strong Altered Expression [18]
Ovarian cancer DISZJHAP Strong Altered Expression [10]
Ovarian neoplasm DISEAFTY Strong Altered Expression [10]
Pancreatic cancer DISJC981 Strong Altered Expression [19]
Primary biliary cholangitis DIS43E0O Strong Biomarker [20]
Renal carcinoma DISER9XT Strong Altered Expression [8]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [8]
Small-cell lung cancer DISK3LZD Strong Altered Expression [21]
Urinary bladder cancer DISDV4T7 Strong Biomarker [5]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [5]
Advanced cancer DISAT1Z9 moderate Biomarker [22]
B-cell lymphoma DISIH1YQ moderate Biomarker [23]
Cholestasis DISDJJWE moderate Biomarker [24]
Congenital contractural arachnodactyly DISOM1K7 moderate Altered Expression [25]
Melanoma DIS1RRCY moderate Altered Expression [26]
Acute lymphocytic leukaemia DISPX75S Limited Altered Expression [27]
Breast cancer DIS7DPX1 Limited Biomarker [28]
Breast carcinoma DIS2UE88 Limited Biomarker [28]
Childhood acute lymphoblastic leukemia DISJ5D6U Limited Altered Expression [27]
Dubin-Johnson syndrome DISM8TG9 Limited Biomarker [29]
Epilepsy DISBB28L Limited Biomarker [30]
Gallbladder carcinoma DISD6ACL Limited Altered Expression [31]
Mesothelioma DISKWK9M Limited Biomarker [32]
Plasma cell myeloma DIS0DFZ0 Limited Biomarker [23]
Progressive familial intrahepatic cholestasis DIS3J8HT Limited Biomarker [33]
------------------------------------------------------------------------------------
⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Synaptonemal complex central element protein 1-like (SYCE1L). [34]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Synaptonemal complex central element protein 1-like (SYCE1L). [36]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Synaptonemal complex central element protein 1-like (SYCE1L). [37]
------------------------------------------------------------------------------------
1 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 Synaptonemal complex central element protein 1-like (SYCE1L). [35]
------------------------------------------------------------------------------------

References

1 Expression of genes related to activity of oxaliplatin and 5-fluorouracil in endoscopic biopsies of primary esophageal cancer in patients receiving oxaliplatin, 5-flourouracil and radiation: characterization and exploratory analysis with survival.J Chemother. 2006 Oct;18(5):514-24. doi: 10.1179/joc.2006.18.5.514.
2 MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer.Cancer Chemother Pharmacol. 2010 Feb;65(3):437-46. doi: 10.1007/s00280-009-1046-1. Epub 2009 Jul 1.
3 Lung resistance-related protein (LRP) predicts favorable therapeutic outcome in Acute Myeloid Leukemia.Sci Rep. 2019 Jan 23;9(1):378. doi: 10.1038/s41598-018-36780-8.
4 Chemosensitivity assessed by collagen gel droplet embedded culture drug sensitivity test, and MDR1, MRP1, and MRP2 mRNA expression in human colorectal adenocarcinomas.Pharm Res. 2004 Mar;21(3):406-12. doi: 10.1023/B:PHAM.0000019292.03875.3e.
5 Increased expression of multidrug resistance-associated proteins in bladder cancer during clinical course and drug resistance to doxorubicin.Int J Cancer. 2002 Apr 1;98(4):630-5. doi: 10.1002/ijc.10246.
6 Expression of the multidrug resistance proteins MRP2 and MRP3 in human cholangiocellular carcinomas.Eur J Clin Invest. 2008 Feb;38(2):134-42. doi: 10.1111/j.1365-2362.2007.01916.x.
7 Immunohistochemical Assessment of the Expression of Biliary Transportation Proteins MRP2 and MRP3 in Hepatocellular Carcinoma and in Cholangiocarcinoma.Pathol Oncol Res. 2019 Oct;25(4):1363-1371. doi: 10.1007/s12253-018-0386-8. Epub 2018 Feb 20.
8 Involvement of ABC transporters in chemosensitivity of human renal cell carcinoma, and regulation of MRP2 expression by conjugated bilirubin.Anticancer Res. 2005 Jul-Aug;25(4):2729-35.
9 The Circadian Clock Gene Bmal1 Controls Intestinal Exporter MRP2 and Drug Disposition.Theranostics. 2019 Apr 13;9(10):2754-2767. doi: 10.7150/thno.33395. eCollection 2019.
10 ARID1A ablation leads to multiple drug resistance in ovarian cancer via transcriptional activation of MRP2.Cancer Lett. 2018 Jul 28;427:9-17. doi: 10.1016/j.canlet.2018.04.013. Epub 2018 Apr 13.
11 Role of multidrug resistance protein 2 (MRP2) in chemoresistance and clinical outcome in oesophageal squamous cell carcinoma.Br J Cancer. 2011 Feb 15;104(4):707-13. doi: 10.1038/sj.bjc.6606071. Epub 2011 Jan 4.
12 Changes in Radixin Expression and Interaction with Efflux Transporters in the Liver of Adjuvant-Induced Arthritic Rats.Inflammation. 2020 Feb;43(1):85-94. doi: 10.1007/s10753-019-01097-9.
13 MRP2 haplotypes confer differential susceptibility to toxic liver injury.Pharmacogenet Genomics. 2007 Jun;17(6):403-15. doi: 10.1097/01.fpc.0000236337.41799.b3.
14 Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection.J Hepatol. 2001 Dec;35(6):765-73. doi: 10.1016/s0168-8278(01)00216-1.
15 Pre-Hepatectomy Assessment of Bile Transporter Expression by Gadoxetic Acid-Enhanced MRI in a Rat Model of Liver Cirrhosis.J Invest Surg. 2017 Aug;30(4):265-271. doi: 10.1080/08941939.2016.1238983. Epub 2016 Oct 26.
16 New insights into Vinca alkaloids resistance mechanism and circumvention in lung cancer.Biomed Pharmacother. 2017 Dec;96:659-666. doi: 10.1016/j.biopha.2017.10.041. Epub 2017 Nov 6.
17 The oncogenic receptor ErbB2 modulates gemcitabine and irinotecan/SN-38 chemoresistance of human pancreatic cancer cells via hCNT1 transporter and multidrug-resistance associated protein MRP-2.Oncotarget. 2015 May 10;6(13):10853-67. doi: 10.18632/oncotarget.3414.
18 Identification of MRP2 as a targetable factor limiting oxaliplatin accumulation and response in gastrointestinal cancer.Sci Rep. 2019 Feb 19;9(1):2245. doi: 10.1038/s41598-019-38667-8.
19 Expression of multidrug resistance-associated protein 2 is involved in chemotherapy resistance in human pancreatic cancer.Int J Oncol. 2008 Dec;33(6):1187-94.
20 Adaptive changes in hepatobiliary transporter expression in primary biliary cirrhosis.J Hepatol. 2003 Jun;38(6):717-27. doi: 10.1016/s0168-8278(03)00096-5.
21 Expression of multidrug resistance protein-related genes in lung cancer: correlation with drug response.Clin Cancer Res. 1999 Mar;5(3):673-80.
22 The effects of crocetin, extracted from saffron, in chemotherapy against the incidence of multiple drug resistance phenotype.Iran J Basic Med Sci. 2018 Nov;21(11):1192-1197. doi: 10.22038/IJBMS.2018.29474.7118.
23 A p110-specific inhibitor combined with bortezomib blocks drug resistance properties of EBV-related B cell origin cancer cells via regulation of NF-B.Int J Oncol. 2017 May;50(5):1711-1720. doi: 10.3892/ijo.2017.3923. Epub 2017 Mar 21.
24 Hepatoprotection of auraptene from the peels of citrus fruits against 17-ethinylestradiol-induced cholestasis in mice by activating farnesoid X receptor.Food Funct. 2019 Jul 17;10(7):3839-3850. doi: 10.1039/c9fo00318e.
25 Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines. World J Gastroenterol. 2005 May 14;11(18):2748-53. doi: 10.3748/wjg.v11.i18.2748.
26 Protection of platinum-DNA adduct formation and reversal of cisplatin resistance by anti-MRP2 hammerhead ribozymes in human cancer cells.Int J Cancer. 2005 Jun 20;115(3):393-402. doi: 10.1002/ijc.20899.
27 The multidrug resistance-associated protein 3 (MRP3) is associated with a poor outcome in childhood ALL and may account for the worse prognosis in male patients and T-cell immunophenotype.Blood. 2003 Dec 15;102(13):4493-8. doi: 10.1182/blood-2002-11-3461. Epub 2003 Jun 19.
28 The phytoestrogens daidzein and equol inhibit the drug transporter BCRP/ABCG2 in breast cancer cells: potential chemosensitizing effect.Eur J Nutr. 2019 Feb;58(1):139-150. doi: 10.1007/s00394-017-1578-9. Epub 2017 Nov 3.
29 A Time-Dependent Model Describes Methotrexate Elimination and Supports Dynamic Modification of MRP2/ABCC2 Activity.Ther Drug Monit. 2017 Apr;39(2):145-156. doi: 10.1097/FTD.0000000000000381.
30 A comprehensive functional and clinical analysis of ABCC2 and its impact on treatment response to carbamazepine. Pharmacogenomics J. 2014 Oct;14(5):481-7.
31 Expression of multidrug resistance-associated protein 2 in human gallbladder carcinoma.Biomed Res Int. 2013;2013:527534. doi: 10.1155/2013/527534. Epub 2013 Jun 16.
32 The expression of P-glycoprotein and multidrug resistance proteins 1 and 2 (MRP1 and MRP2) in human malignant mesothelioma.Ann Oncol. 2001 Sep;12(9):1239-45. doi: 10.1023/a:1012292230480.
33 Bile acid transport correlative protein mRNA expression profile in human placenta with intrahepatic cholestasis of pregnancy.Saudi Med J. 2009 Nov;30(11):1406-10.
34 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.
35 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
36 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.
37 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.