Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQO3Z0R)

• DOT Name: Endoplasmic reticulum lectin 1 (ERLEC1)
• Synonyms: ER lectin; Erlectin; XTP3-transactivated gene B protein
• Gene Name: ERLEC1
• Related Disease:
  Anorexia nervosa cachexia
  Cholestasis
  Lung cancer
  Lung carcinoma
  Neoplasm
• UniProt ID: ERLEC_HUMAN
• Pfam ID: PF07915
• Sequence:
  MEEGGGGVRSLVPGGPVLLVLCGLLEASGGGRALPQLSDDIPFRVNWPGTEFSLPTTGVL
  YKEDNYVIMTTAHKEKYKCILPLVTSGDEEEEKDYKGPNPRELLEPLFKQSSCSYRIESY
  WTYEVCHGKHIRQYHEEKETGQKINIHEYYLGNMLAKNLLFEKEREAEEKEKSNEIPTKN
  IEGQMTPYYPVGMGNGTPCSLKQNRPRSSTVMYICHPESKHEILSVAEVTTCEYEVVILT
  PLLCSHPKYRFRASPVNDIFCQSLPGSPFKPLTLRQLEQQEEILRVPFRRNKEEDLQSTK
  EERFPAIHKSIAIGSQPVLTVGTTHISKLTDDQLIKEFLSGSYCFRGGVGWWKYEFCYGK
  HVHQYHEDKDSGKTSVVVGTWNQEEHIEWAKKNTARAYHLQDDGTQTVRMVSHFYGNGDI
  CDITDKPRQVTVKLKCKESDSPHAVTVYMLEPHSCQYILGVESPVICKILDTADENGLLS
  LPN
• Function: Probable lectin that binds selectively to improperly folded lumenal proteins. May function in endoplasmic reticulum quality control and endoplasmic reticulum-associated degradation (ERAD) of both non-glycosylated proteins and glycoproteins.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway:
  Hedgehog ligand biogenesis (R-HSA-5358346)
  Hh mutants are degraded by ERAD (R-HSA-5362768)
  Defective CFTR causes cystic fibrosis (R-HSA-5678895)
  ABC-family proteins mediated transport (R-HSA-382556)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anorexia nervosa cachexia	DISFO5RQ	Strong	Genetic Variation	[1]
Cholestasis	DISDJJWE	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Strong	Altered Expression	[3]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Endoplasmic reticulum lectin 1 (ERLEC1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Endoplasmic reticulum lectin 1 (ERLEC1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Endoplasmic reticulum lectin 1 (ERLEC1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Endoplasmic reticulum lectin 1 (ERLEC1).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Endoplasmic reticulum lectin 1 (ERLEC1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Endoplasmic reticulum lectin 1 (ERLEC1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Endoplasmic reticulum lectin 1 (ERLEC1).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Endoplasmic reticulum lectin 1 (ERLEC1).	[12]

References

• [1] Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa.Nat Genet. 2019 Aug;51(8):1207-1214. doi: 10.1038/s41588-019-0439-2. Epub 2019 Jul 15.
• [2] Classification of Cholestatic and Necrotic Hepatotoxicants Using Transcriptomics on Human Precision-Cut Liver Slices.Chem Res Toxicol. 2016 Mar 21;29(3):342-51. doi: 10.1021/acs.chemrestox.5b00491. Epub 2016 Mar 9.
• [3] Novel metastasis-related gene CIM functions in the regulation of multiple cellular stress-response pathways.Cancer Res. 2010 Dec 1;70(23):9949-58. doi: 10.1158/0008-5472.CAN-10-1055. Epub 2010 Nov 30.
• [4] Cellular phenotypes of differentiated-type adenocarcinomas and precancerous lesions of the stomach are dependent on the genetic pathways.J Pathol. 2000 Jul;191(3):257-63. doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH631>3.0.CO;2-2.
• [5] 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.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [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] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [11] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.