Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT9TMXN)

• DOT Name: Cytokine receptor-like factor 3 (CRLF3)
• Synonyms: Cytokine receptor-like molecule 9; CREME-9; Cytokine receptor-related protein 4; Type I cytokine receptor-like factor p48
• Gene Name: CRLF3
• Related Disease:
  Adult glioblastoma
  Breast carcinoma
  Glioma
  Advanced cancer
  Hepatitis C virus infection
  Influenza
  Matthew-Wood syndrome
  Neoplasm
  Promyelocytic leukaemia
  Transitional cell carcinoma
  Glioblastoma multiforme
  Xeroderma pigmentosum
• UniProt ID: CRLF3_HUMAN
• Sequence:
  MRGAMELEPELLLQEARENVEAAQSYRRELGHRLEGLREARRQIKESASQTRDVLKQHFN
  DLKGTLGKLLDERLVTLLQEVDTIEQETIKPLDDCQKLIEHGVNTAEDLVREGEIAMLGG
  VGEENEKLWSFTKKASHIQLDSLPEVPLLVDVPCLSAQLDDSILNIVKDHIFKHGTVASR
  PPVQIEELIEKPGGIIVRWCKVDDDFTAQDYRLQFRKCTSNHFEDVYVGSETEFIVLHID
  PNVDYQFRVCARGDGRQEWSPWSVPQIGHSTLVPHEWTAGFEGYSLSSRRNIALRNDSES
  SGVLYSRAPTYFCGQTLTFRVETVGQPDRRDSIGVCAEKQDGYDSLQRDQAVCISTNGAV
  FVNGKEMTNQLPAVTSGSTVTFDIEAVTLGTTSNNEGGHFKLRVTISSNNREVVFDWLLD
  QSCGSLYFGCSFFYPGWKVLVF
• Function: May play a role in the negative regulation of cell cycle progression.
• Tissue Specificity: Expressed in several embryonic and adult tissues, including adult and fetal brain, liver, spleen and pancreas. Expressed in adult, but not fetal kidney. Expressed in skin and squamous cell carcinoma (SCC) and in several other cancer types. Also detected in lesion actinic keratosis (AK).

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Glioma	DIS5RPEH	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[4]
Influenza	DIS3PNU3	Strong	Biomarker	[5]
Matthew-Wood syndrome	DISA7HR7	Strong	Genetic Variation	[6]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[7]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[8]
Transitional cell carcinoma	DISWVVDR	Strong	Altered Expression	[9]
Glioblastoma multiforme	DISK8246	moderate	Altered Expression	[1]
Xeroderma pigmentosum	DISQ9H19	Limited	Genetic Variation	[10]

9 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 Cytokine receptor-like factor 3 (CRLF3).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cytokine receptor-like factor 3 (CRLF3).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cytokine receptor-like factor 3 (CRLF3).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cytokine receptor-like factor 3 (CRLF3).	[14]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cytokine receptor-like factor 3 (CRLF3).	[15]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Cytokine receptor-like factor 3 (CRLF3).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cytokine receptor-like factor 3 (CRLF3).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cytokine receptor-like factor 3 (CRLF3).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cytokine receptor-like factor 3 (CRLF3).	[19]

References

• [1] EBP1 protein modulates the expression of human MHC class II molecules in non-hematopoietic cancer cells.Int J Oncol. 2015 Aug;47(2):481-9. doi: 10.3892/ijo.2015.3051. Epub 2015 Jun 16.
• [2] Negative regulation of p53 by the long isoform of ErbB3 binding protein Ebp1 in brain tumors.Cancer Res. 2010 Dec 1;70(23):9730-41. doi: 10.1158/0008-5472.CAN-10-1882. Epub 2010 Nov 23.
• [3] The discovery of potent and stable short peptide FGFR1 antagonist for cancer therapy.Eur J Pharm Sci. 2020 Feb 15;143:105179. doi: 10.1016/j.ejps.2019.105179. Epub 2019 Dec 10.
• [4] Modulation of HCV replication and translation by ErbB3 binding protein1 isoforms.Virology. 2017 Jan;500:35-49. doi: 10.1016/j.virol.2016.10.006. Epub 2016 Oct 19.
• [5] Investigation of the potential of a 48 kDa protein as a vaccine candidate for infection against nontypable Haemophilus influenzae.Vaccine. 2007 May 16;25(20):4012-9. doi: 10.1016/j.vaccine.2007.02.048. Epub 2007 Mar 8.
• [6] A pipeline for rapidly generating genetically engineered mouse models of pancreatic cancer using in vivo CRISPR-Cas9-mediated somatic recombination.Lab Invest. 2019 Jul;99(8):1233-1244. doi: 10.1038/s41374-018-0171-z. Epub 2019 Feb 6.
• [7] Phosphorylation of the N-terminal domain of p48 Ebp1 by CDK2 is required for tumorigenic function of p48.Mol Carcinog. 2015 Nov;54(11):1283-91. doi: 10.1002/mc.22203. Epub 2014 Aug 23.
• [8] Induction of leukemia cell differentiation and apoptosis by recombinant P48, a modulin derived from Mycoplasma fermentans.Biochem Biophys Res Commun. 2000 Mar 5;269(1):284-9. doi: 10.1006/bbrc.2000.2282.
• [9] Impaired alpha-interferon signaling in transitional cell carcinoma: lack of p48 expression in 5637 cells.Cancer Res. 2001 Mar 1;61(5):2261-6.
• [10] Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis.Mol Cell. 2000 Apr;5(4):737-44. doi: 10.1016/s1097-2765(00)80252-x.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [13] 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.
• [14] 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.
• [15] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [16] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.