Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT65Q9M6)

DOT Name	Cell surface glycoprotein CD200 receptor 1 (CD200R1)
Synonyms	CD200 cell surface glycoprotein receptor; Cell surface glycoprotein OX2 receptor 1
Gene Name	CD200R1
Related Disease	Acute myelogenous leukaemia ( ) Cone-rod dystrophy 2 ( ) Acute leukaemia ( ) Advanced cancer ( ) Alzheimer disease ( ) Bacterial infection ( ) Bone disease ( ) Colon carcinoma ( ) Cytomegalovirus infection ( ) Depression ( ) Endometriosis ( ) Fungal lung infectious disease ( ) Hepatitis C virus infection ( ) Hepatocellular carcinoma ( ) Huntington disease ( ) Insomnia ( ) Multiple sclerosis ( ) Narcolepsy ( ) Nervous system inflammation ( ) Nicotine dependence ( ) Parkinson disease ( ) Sarcoidosis ( ) Sleep disorder ( ) Stroke ( ) Tarsal-carpal coalition syndrome ( ) Breast cancer ( ) Breast carcinoma ( ) leukaemia ( ) Leukemia ( ) Metastatic malignant neoplasm ( ) Autoimmune disease ( ) Cutaneous squamous cell carcinoma ( ) Gastric cancer ( ) Periodontitis ( ) Prostate cancer ( ) Prostate carcinoma ( ) Retinopathy ( ) Stomach cancer ( )
UniProt ID	MO2R1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF08205
Sequence	MLCPWRTANLGLLLILTIFLVAEAEGAAQPNNSLMLQTSKENHALASSSLCMDEKQITQN YSKVLAEVNTSWPVKMATNAVLCCPPIALRNLIIITWEIILRGQPSCTKAYKKETNETKE TNCTDERITWVSRPDQNSDLQIRTVAITHDGYYRCIMVTPDGNFHRGYHLQVLVTPEVTL FQNRNRTAVCKAVAGKPAAHISWIPEGDCATKQEYWSNGTVTVKSTCHWEVHNVSTVTCH VSHLTGNKSLYIELLPVPGAKKSAKLYIPYIILTIIILTIVGFIWLLKVNGCRKYKLNKT ESTPVVEEDEMQPYASYTEKNNPLYDTTNKVKASEALQSEVDTDLHTL
Function	Inhibitory receptor for the CD200/OX2 cell surface glycoprotein. Limits inflammation by inhibiting the expression of pro-inflammatory molecules including TNF-alpha, interferons, and inducible nitric oxide synthase (iNOS) in response to selected stimuli. Also binds to HHV-8 K14 viral CD200 homolog with identical affinity and kinetics as the host CD200.
Tissue Specificity	Expressed in granulocytes, monocytes, most T-cells, neutrophils, basophils and a subset of NK, NKT and B-cells (at protein level). Expressed in bone marrow, lymph nodes, spleen, lung, liver, spinal cord, kidney. Expressed in monocyte-derived dendritic and mast cells.
KEGG Pathway	Kaposi sarcoma-associated herpesvirus infection (hsa05167 )
Reactome Pathway	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933 )

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute myelogenous leukaemia	DISCSPTN	Definitive	Altered Expression	[1]
Cone-rod dystrophy 2	DISX2RWY	Definitive	Biomarker	[2]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[5]
Bacterial infection	DIS5QJ9S	Strong	Biomarker	[6]
Bone disease	DISE1F82	Strong	Biomarker	[7]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[4]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[8]
Depression	DIS3XJ69	Strong	Biomarker	[9]
Endometriosis	DISX1AG8	Strong	Biomarker	[10]
Fungal lung infectious disease	DISH0JV6	Strong	Biomarker	[11]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
Huntington disease	DISQPLA4	Strong	Altered Expression	[14]
Insomnia	DIS0AFR7	Strong	Biomarker	[15]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[16]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[17]
Nervous system inflammation	DISB3X5A	Strong	Altered Expression	[16]
Nicotine dependence	DISZD9W7	Strong	Biomarker	[18]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[19]
Sarcoidosis	DISE5B8Z	Strong	Altered Expression	[20]
Sleep disorder	DIS3JP1U	Strong	Genetic Variation	[17]
Stroke	DISX6UHX	Strong	Altered Expression	[6]
Tarsal-carpal coalition syndrome	DISY90L2	Strong	Biomarker	[21]
Breast cancer	DIS7DPX1	moderate	Biomarker	[22]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[22]
leukaemia	DISS7D1V	moderate	Biomarker	[23]
Leukemia	DISNAKFL	moderate	Biomarker	[23]
Metastatic malignant neoplasm	DIS86UK6	Disputed	Altered Expression	[24]
Autoimmune disease	DISORMTM	Limited	Biomarker	[11]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Altered Expression	[25]
Gastric cancer	DISXGOUK	Limited	Biomarker	[26]
Periodontitis	DISI9JOI	Limited	Biomarker	[27]
Prostate cancer	DISF190Y	Limited	Biomarker	[28]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[28]
Retinopathy	DISB4B0F	Limited	Biomarker	[29]
Stomach cancer	DISKIJSX	Limited	Biomarker	[26]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cell surface glycoprotein CD200 receptor 1 (CD200R1).	[30]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Cell surface glycoprotein CD200 receptor 1 (CD200R1).	[31]
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References

1	Upregulation of CD200 is associated with Foxp3+ regulatory T cell expansion and disease progression in acute myeloid leukemia.Tumour Biol. 2013 Feb;34(1):531-42. doi: 10.1007/s13277-012-0578-x. Epub 2012 Nov 18.
2	CD200 modulates spinal cord injury neuroinflammation and outcome through CD200R1.Brain Behav Immun. 2018 Oct;73:416-426. doi: 10.1016/j.bbi.2018.06.002. Epub 2018 Jun 2.
3	Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia.Curr Drug Targets. 2017;18(3):315-331. doi: 10.2174/1389450116666150518095346.
4	Antitumor Activity of TLR7 Is Potentiated by CD200R Antibody Leading to Changes in the Tumor Microenvironment.Cancer Immunol Res. 2018 Aug;6(8):930-940. doi: 10.1158/2326-6066.CIR-17-0454. Epub 2018 Jul 18.
5	Lack of Association between Genetic Polymorphism of Circadian Genes (PER2, PER3, CLOCK and OX2R) with Late Onset Depression and Alzheimer's Disease in a Sample of a Brazilian Population (Circadian Genes, Late-Onset Depression and Alzheimer's Disease).Curr Alzheimer Res. 2016;13(12):1397-1406. doi: 10.2174/1567205013666160603005630.
6	CD200-CD200R1 inhibitory signaling prevents spontaneous bacterial infection and promotes resolution of neuroinflammation and recovery after stroke.J Neuroinflammation. 2019 Feb 18;16(1):40. doi: 10.1186/s12974-019-1426-3.
7	CD200R/CD200 inhibits osteoclastogenesis: new mechanism of osteoclast control by mesenchymal stem cells in human.PLoS One. 2013 Aug 5;8(8):e72831. doi: 10.1371/journal.pone.0072831. Print 2013.
8	Pre-transplant CD200 and CD200R1 concentrations are associated with post-transplant events in kidney transplant recipients.Medicine (Baltimore). 2019 Sep;98(37):e17006. doi: 10.1097/MD.0000000000017006.
9	C-terminus of OX2R significantly affects downstream signaling pathways.Mol Med Rep. 2017 Jul;16(1):159-166. doi: 10.3892/mmr.2017.6557. Epub 2017 May 9.
10	Soluble CD200 in secretory phase endometriosis endometrial venules may explain endometriosis pathophysiology and provide a novel treatment target.J Reprod Immunol. 2018 Sep;129:59-67. doi: 10.1016/j.jri.2018.05.006. Epub 2018 May 21.
11	CD200R1 regulates eosinophilia during pulmonary fungal infection in mice.Eur J Immunol. 2019 Sep;49(9):1380-1390. doi: 10.1002/eji.201847861. Epub 2019 Aug 7.
12	Inhibitory molecules that regulate expansion and restoration of HCV-specific CD4+ T cells in patients with chronic infection.Gastroenterology. 2011 Oct;141(4):1422-31, 1431.e1-6. doi: 10.1053/j.gastro.2011.07.004. Epub 2011 Jul 18.
13	Role of CD200/CD200R Signaling Pathway in Regulation of CD4+T Cell Subsets During Thermal Ablation of Hepatocellular Carcinoma.Med Sci Monit. 2019 Mar 6;25:1718-1728. doi: 10.12659/MSM.913094.
14	CD200 is up-regulated in R6/1 transgenic mouse model of Huntington's disease.PLoS One. 2019 Dec 2;14(12):e0224901. doi: 10.1371/journal.pone.0224901. eCollection 2019.
15	Promotion of sleep by suvorexant-a novel dual orexin receptor antagonist.J Neurogenet. 2011 Mar;25(1-2):52-61. doi: 10.3109/01677063.2011.566953. Epub 2011 Apr 8.
16	Alterations in CD200-CD200R1 System during EAE Already Manifest at Presymptomatic Stages.Front Cell Neurosci. 2017 May 4;11:129. doi: 10.3389/fncel.2017.00129. eCollection 2017.
17	Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity.Am J Med Genet B Neuropsychiatr Genet. 2004 Aug 15;129B(1):69-75. doi: 10.1002/ajmg.b.30047.
18	Functional crosstalk of nucleus accumbens CB1 and OX2 receptors in response to nicotine-induced place preference.Neurosci Lett. 2019 Apr 17;698:160-164. doi: 10.1016/j.neulet.2019.01.027. Epub 2019 Jan 16.
19	Analysis of the Impact of CD200 on Phagocytosis.Mol Neurobiol. 2017 Sep;54(7):5730-5739. doi: 10.1007/s12035-016-0223-6. Epub 2016 Nov 9.
20	Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis.Sci Rep. 2016 Dec 8;6:38689. doi: 10.1038/srep38689.
21	Posterior hypothalamus glutamate infusion decreases pentylenetetrazol-induced seizures of male rats through hippocampal histamine increase.Pharmacol Biochem Behav. 2017 Jul;158:7-13. doi: 10.1016/j.pbb.2017.05.004. Epub 2017 May 8.
22	Cure of metastatic growth of EMT6 tumor cells in mice following manipulation of CD200:CD200R signaling.Breast Cancer Res Treat. 2013 Nov;142(2):271-82. doi: 10.1007/s10549-013-2735-3. Epub 2013 Oct 29.
23	A CD200R-CD28 fusion protein appropriates an inhibitory signal to enhance T-cell function and therapy of murine leukemia.Blood. 2017 Nov 30;130(22):2410-2419. doi: 10.1182/blood-2017-04-777052. Epub 2017 Oct 17.
24	Interaction of CD200 Overexpression on Tumor Cells with CD200R1 Overexpression on Stromal Cells: An Escape from the Host Immune Response in Rectal Cancer Patients.J Oncol. 2019 Jan 21;2019:5689464. doi: 10.1155/2019/5689464. eCollection 2019.
25	CD200 upregulation in vascular endothelium surrounding cutaneous squamous cell carcinoma.JAMA Dermatol. 2013 Feb;149(2):178-86. doi: 10.1001/jamadermatol.2013.1609.
26	Surface CD200 and CD200R antigens on lymphocytes in advanced gastric cancer: a new potential target for immunotherapy.Arch Med Sci. 2018 Oct;14(6):1271-1280. doi: 10.5114/aoms.2018.73398. Epub 2018 May 21.
27	Gingival Tissue Inflammation Promotes Increased Matrix Metalloproteinase-12 Production by CD200R(low) Monocyte-Derived Cells in Periodontitis.J Immunol. 2017 Dec 15;199(12):4023-4035. doi: 10.4049/jimmunol.1700672. Epub 2017 Nov 3.
28	The orexin type 1 receptor is overexpressed in advanced prostate cancer with a neuroendocrine differentiation, and mediates apoptosis.Eur J Cancer. 2014 Aug;50(12):2126-33. doi: 10.1016/j.ejca.2014.05.008. Epub 2014 Jun 5.
29	Anti-angiogenic and anti-inflammatory effects of CD200-CD200R1 axis in oxygen-induced retinopathy mice model.Inflamm Res. 2019 Nov;68(11):945-955. doi: 10.1007/s00011-019-01276-2. Epub 2019 Aug 23.
30	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.
31	Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.