Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI3TUUZ)

DOT Name	Derlin-2 (DERL2)
Synonyms	Degradation in endoplasmic reticulum protein 2; DERtrin-2; Der1-like protein 2; F-LAN-1; F-LANa
Gene Name	DERL2
Related Disease	Gastric cancer ( ) Advanced cancer ( ) Breast cancer ( ) Breast carcinoma ( ) Breast fibrocystic disease ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Diabetic kidney disease ( ) Focal segmental glomerulosclerosis ( ) Hepatocellular carcinoma ( ) Hepatosplenic T-cell lymphoma ( ) Hypercalcaemia ( ) Liver cancer ( ) Liver cirrhosis ( ) Lung cancer ( ) Lung carcinoma ( ) Lymphoma, non-Hodgkin, familial ( ) Medullary thyroid gland carcinoma ( ) Neoplasm ( ) Nephropathy ( ) Non-hodgkin lymphoma ( ) Primary hyperparathyroidism ( ) Promyelocytic leukaemia ( ) Prostate adenocarcinoma ( ) Renal carcinoma ( ) Renal cell carcinoma ( ) Small-cell lung cancer ( ) T-cell lymphoma ( ) Ulcerative colitis ( ) Urinary tract infection ( ) Carcinoma of esophagus ( ) Colorectal carcinoma ( ) Metastatic malignant neoplasm ( ) Stomach cancer ( )
UniProt ID	DERL2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF04511
Sequence	MAYQSLRLEYLQIPPVSRAYTTACVLTTAAVQLELITPFQLYFNPELIFKHFQIWRLITN FLFFGPVGFNFLFNMIFLYRYCRMLEEGSFRGRTADFVFMFLFGGFLMTLFGLFVSLVFL GQAFTIMLVYVWSRRNPYVRMNFFGLLNFQAPFLPWVLMGFSLLLGNSIIVDLLGIAVGH IYFFLEDVFPNQPGGIRILKTPSILKAIFDTPDEDPNYNPLPEERPGGFAWGEGQRLGG
Function	Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal glycoproteins, but not that of misfolded nonglycoproteins. May act by forming a channel that allows the retrotranslocation of misfolded glycoproteins into the cytosol where they are ubiquitinated and degraded by the proteasome. May mediate the interaction between VCP and misfolded glycoproteins. May also be involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation ; (Microbial infection) In contrast to DERL1, it is not involved in the degradation of MHC class I heavy chains following infection by cytomegaloviruses.
Tissue Specificity	Ubiquitous. Overexpressed in various hepatocarcinomas.
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 ) ER Quality Control Compartment (ERQC) (R-HSA-901032 ) ABC-family proteins mediated transport (R-HSA-382556 )

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Gastric cancer	DISXGOUK	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[3]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Breast fibrocystic disease	DISUM7ID	Strong	Biomarker	[4]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[5]
Diabetic kidney disease	DISJMWEY	Strong	Altered Expression	[6]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[5]
Hepatosplenic T-cell lymphoma	DIS7KMY9	Strong	Biomarker	[7]
Hypercalcaemia	DISKQ2K7	Strong	Biomarker	[8]
Liver cancer	DISDE4BI	Strong	Altered Expression	[5]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[9]
Lung cancer	DISCM4YA	Strong	Biomarker	[10]
Lung carcinoma	DISTR26C	Strong	Biomarker	[10]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Biomarker	[11]
Medullary thyroid gland carcinoma	DISHBL3K	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[13]
Nephropathy	DISXWP4P	Strong	Biomarker	[6]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[11]
Primary hyperparathyroidism	DISB4U1Q	Strong	Genetic Variation	[8]
Promyelocytic leukaemia	DISYGG13	Strong	Genetic Variation	[14]
Prostate adenocarcinoma	DISBZYU8	Strong	Genetic Variation	[15]
Renal carcinoma	DISER9XT	Strong	Biomarker	[16]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[16]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[17]
T-cell lymphoma	DISSXRTQ	Strong	Genetic Variation	[11]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[18]
Urinary tract infection	DISMT6UV	Strong	Genetic Variation	[19]
Carcinoma of esophagus	DISS6G4D	moderate	Biomarker	[20]
Colorectal carcinoma	DIS5PYL0	moderate	Genetic Variation	[21]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[22]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[1]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

7 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 Derlin-2 (DERL2).	[23]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Derlin-2 (DERL2).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Derlin-2 (DERL2).	[25]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Derlin-2 (DERL2).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Derlin-2 (DERL2).	[27]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Derlin-2 (DERL2).	[28]
L-Serine	DM6WPIS	Investigative	L-Serine increases the expression of Derlin-2 (DERL2).	[30]
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⏷ Show the Full List of 7 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Derlin-2 (DERL2).	[29]
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References

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6	Podocytes exhibit a specialized protein quality control employing derlin-2 in kidney disease.Am J Physiol Renal Physiol. 2018 Mar 1;314(3):F471-F482. doi: 10.1152/ajprenal.00691.2016. Epub 2017 Nov 22.
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9	Disparate Trends in Mortality of Etiology-Specific Chronic Liver Diseases Among Hispanic Subpopulations.Clin Gastroenterol Hepatol. 2019 Jul;17(8):1607-1615.e2. doi: 10.1016/j.cgh.2018.10.045. Epub 2018 Nov 1.
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11	Characterization of two novel cell lines, DERL-2 (CD56+/CD3+/Tcry5+) and DERL-7 (CD56+/CD3-/TCRgammadelta-), derived from a single patient with CD56+ non-Hodgkin's lymphoma.Leukemia. 2001 Oct;15(10):1641-9. doi: 10.1038/sj.leu.2402239.
12	Coexistent familial nonmultiple endocrine neoplasia medullary thyroid carcinoma and papillary thyroid carcinoma associated with RET polymorphism.Am J Med Sci. 2010 Jul;340(1):60-3. doi: 10.1097/MAJ.0b013e3181dfb245.
13	A novel stromal lncRNA signature reprograms fibroblasts to promote the growth of oral squamous cell carcinoma via LncRNA-CAF/interleukin-33.Carcinogenesis. 2018 Mar 8;39(3):397-406. doi: 10.1093/carcin/bgy006.
14	OBFC2A/RARA: a novel fusion gene in variant acute promyelocytic leukemia.Blood. 2013 Feb 21;121(8):1432-5. doi: 10.1182/blood-2012-04-423129. Epub 2013 Jan 3.
15	Multiple structural chromosome rearrangements, including del(7q) and del(10q), in an adenocarcinoma of the prostate.Cancer Genet Cytogenet. 1988 Oct 1;35(1):103-8. doi: 10.1016/0165-4608(88)90128-8.
16	Involvement of erbB4 and tumor marker genes in renal carcinoma regulatory network.Saudi J Biol Sci. 2017 Dec;24(8):1787-1791. doi: 10.1016/j.sjbs.2017.11.013. Epub 2017 Nov 10.
17	Evolution of chromosomal alterations and biologic features in two small cell lung carcinoma cell lines established from one patient during the course of the disease.Cancer Genet Cytogenet. 1995 Mar;80(1):47-54. doi: 10.1016/0165-4608(94)00154-4.
18	I219V polymorphism in hMLH1 gene in patients affected with ulcerative colitis.Genet Test Mol Biomarkers. 2009 Apr;13(2):193-7. doi: 10.1089/gtmb.2008.0088.
19	Impact of enterococcal urinary tract infections in immunocompromised - neoplastic patients.J BUON. 2019 Sep-Oct;24(5):1768-1775.
20	TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/-catenin pathway.J Transl Med. 2018 Jan 17;16(1):7. doi: 10.1186/s12967-018-1383-0.
21	MicroRNA-498 reduces the proliferation and invasion of colorectal cancer cells via targeting Bcl-2.FEBS Open Bio. 2020 Jan;10(1):168-175. doi: 10.1002/2211-5463.12767. Epub 2019 Dec 17.
22	Exosomes in Nasopharyngeal Carcinoma.J Cancer. 2018 Feb 11;9(5):767-777. doi: 10.7150/jca.22505. eCollection 2018.
23	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
24	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.
25	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.
26	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
27	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.
28	Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
29	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.
30	Mechanisms of L-Serine Neuroprotection in vitro Include ER Proteostasis Regulation. Neurotox Res. 2018 Jan;33(1):123-132. doi: 10.1007/s12640-017-9829-3. Epub 2017 Nov 2.