Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJL4OB3)

• DOT Name: Calcium homeostasis endoplasmic reticulum protein (CHERP)
• Synonyms: ERPROT 213-21; SR-related CTD-associated factor 6
• Gene Name: CHERP
• Related Disease:
  Advanced cancer
  Chronic obstructive pulmonary disease
  Stroke
  Neuroblastoma
• UniProt ID: CHERP_HUMAN
• Pfam ID: PF04818 ; PF01585 ; PF01805
• Sequence:
  MEMPLPPDDQELRNVIDKLAQFVARNGPEFEKMTMEKQKDNPKFSFLFGGEFYSYYKCKL
  ALEQQQLICKQQTPELEPAATMPPLPQPPLAPAAPIPPAQGAPSMDELIQQSQWNLQQQE
  QHLLALRQEQVTAAVAHAVEQQMQKLLEETQLDMNEFDNLLQPIIDTCTKDAISAGKNWM
  FSNAKSPPHCELMAGHLRNRITADGAHFELRLHLIYLINDVLHHCQRKQARELLAALQKV
  VVPIYCTSFLAVEEDKQQKIARLLQLWEKNGYFDDSIIQQLQSPALGLGQYQATLINEYS
  SVVQPVQLAFQQQIQTLKTQHEEFVTSLAQQQQQQQQQQQQLQMPQMEAEVKATPPPPAP
  PPAPAPAPAIPPTTQPDDSKPPIQMPGSSEYEAPGGVQDPAAAGPRGPGPHDQIPPNKPP
  WFDQPHPVAPWGQQQPPEQPPYPHHQGGPPHCPPWNNSHEGMWGEQRGDPGWNGQRDAPW
  NNQPDAAWNSQFEGPWNSQHEQPPWGGGQREPPFRMQRPPHFRGPFPPHQQHPQFNQPPH
  PHNFNRFPPRFMQDDFPPRHPFERPPYPHRFDYPQGDFPAEMGPPHHHPGHRMPHPGINE
  HPPWAGPQHPDFGPPPHGFNGQPPHMRRQGPPHINHDDPSLVPNVPYFDLPAGLMAPLVK
  LEDHEYKPLDPKDIRLPPPMPPSERLLAAVEAFYSPPSHDRPRNSEGWEQNGLYEFFRAK
  MRARRRKGQEKRNSGPSRSRSRSKSRGRSSSRSNSRSSKSSGSYSRSRSRSCSRSYSRSR
  SRSRSRSRSSRSRSRSQSRSRSKSYSPGRRRRSRSRSPTPPSSAGLGSNSAPPIPDSRLG
  EENKGHQMLVKMGWSGSGGLGAKEQGIQDPIKGGDVRDKWDQYKGVGVALDDPYENYRRN
  KSYSFIARMKARDECK
• Function: Involved in calcium homeostasis, growth and proliferation.
• Tissue Specificity: Expressed in brain, placenta, lung, liver, kidney, pancreas, cardiac and skeletal muscle, and in cultured HEL and Dami cells.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Genetic Variation	[2]
Stroke	DISX6UHX	moderate	Biomarker	[3]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[4]

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 Calcium homeostasis endoplasmic reticulum protein (CHERP).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Calcium homeostasis endoplasmic reticulum protein (CHERP).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Calcium homeostasis endoplasmic reticulum protein (CHERP).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Calcium homeostasis endoplasmic reticulum protein (CHERP).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Calcium homeostasis endoplasmic reticulum protein (CHERP).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Calcium homeostasis endoplasmic reticulum protein (CHERP).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Calcium homeostasis endoplasmic reticulum protein (CHERP).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Calcium homeostasis endoplasmic reticulum protein (CHERP).	[10]

References

• [1] U2-related proteins CHERP and SR140 contribute to colorectal tumorigenesis via alternative splicing regulation.Int J Cancer. 2019 Nov 15;145(10):2728-2739. doi: 10.1002/ijc.32331. Epub 2019 Apr 25.
• [2] Genetic variations in scavenger and ?adrenergic receptors and risk of pulmonary disease.Dan Med J. 2014 Sep;61(9):B4910.
• [3] 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.
• [4] Down-regulation of CHERP inhibits neuroblastoma cell proliferation and induces apoptosis through ER stress induction.Oncotarget. 2017 Sep 15;8(46):80956-80970. doi: 10.18632/oncotarget.20898. eCollection 2017 Oct 6.
• [5] 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.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [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] 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.
• [10] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [11] 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.
• [12] 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.