Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6HZT6H)

• DOT Name: Complement component C1q receptor (CD93)
• Synonyms: C1q/MBL/SPA receptor; C1qR; C1qR(p); C1qRp; CDw93; Complement component 1 q subcomponent receptor 1; Matrix-remodeling-associated protein 4; CD antigen CD93
• Gene Name: CD93
• Related Disease:
  Acute myelogenous leukaemia
  Acute undifferentiated leukemia
  Adult glioblastoma
  Advanced cancer
  Astrocytoma
  Colorectal carcinoma
  Glioblastoma multiforme
  Glioma
  Malignant glioma
  Myelitis
  Neoplasm
  Nervous system inflammation
  Non-small-cell lung cancer
  Psoriasis
  Age-related macular degeneration
  Asthma
  Coronary atherosclerosis
  Coronary heart disease
  Myocardial infarction
  Nasopharyngeal carcinoma
  Rheumatoid arthritis
• UniProt ID: C1QR1_HUMAN
• PDB ID: 8A59
• Pfam ID: PF12662 ; PF07645 ; PF00059
• Sequence:
  MATSMGLLLLLLLLLTQPGAGTGADTEAVVCVGTACYTAHSGKLSAAEAQNHCNQNGGNL
  ATVKSKEEAQHVQRVLAQLLRREAALTARMSKFWIGLQREKGKCLDPSLPLKGFSWVGGG
  EDTPYSNWHKELRNSCISKRCVSLLLDLSQPLLPSRLPKWSEGPCGSPGSPGSNIEGFVC
  KFSFKGMCRPLALGGPGQVTYTTPFQTTSSSLEAVPFASAANVACGEGDKDETQSHYFLC
  KEKAPDVFDWGSSGPLCVSPKYGCNFNNGGCHQDCFEGGDGSFLCGCRPGFRLLDDLVTC
  ASRNPCSSSPCRGGATCVLGPHGKNYTCRCPQGYQLDSSQLDCVDVDECQDSPCAQECVN
  TPGGFRCECWVGYEPGGPGEGACQDVDECALGRSPCAQGCTNTDGSFHCSCEEGYVLAGE
  DGTQCQDVDECVGPGGPLCDSLCFNTQGSFHCGCLPGWVLAPNGVSCTMGPVSLGPPSGP
  PDEEDKGEKEGSTVPRAATASPTRGPEGTPKATPTTSRPSLSSDAPITSAPLKMLAPSGS
  PGVWREPSIHHATAASGPQEPAGGDSSVATQNNDGTDGQKLLLFYILGTVVAILLLLALA
  LGLLVYRKRRAKREEKKEKKPQNAADSYSWVPERAESRAMENQYSPTPGTDC
• Function: Receptor (or element of a larger receptor complex) for C1q, mannose-binding lectin (MBL2) and pulmonary surfactant protein A (SPA). May mediate the enhancement of phagocytosis in monocytes and macrophages upon interaction with soluble defense collagens. May play a role in intercellular adhesion.
• Tissue Specificity: Highly expressed in endothelial cells, platelets, cells of myeloid origin, such as monocytes and neutrophils. Not expressed in cells of lymphoid origin.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[1]
Acute undifferentiated leukemia	DISJ4SSG	Strong	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Astrocytoma	DISL3V18	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[4]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[5]
Myelitis	DIS1KV65	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[7]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[8]
Age-related macular degeneration	DIS0XS2C	moderate	Altered Expression	[9]
Asthma	DISW9QNS	Disputed	Biomarker	[10]
Coronary atherosclerosis	DISKNDYU	Limited	Biomarker	[11]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[11]
Myocardial infarction	DIS655KI	Limited	Genetic Variation	[11]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[3]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[12]

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 Complement component C1q receptor (CD93).	[13]
Triclosan	DMZUR4N	Approved	Triclosan increases the methylation of Complement component C1q receptor (CD93).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Complement component C1q receptor (CD93).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Complement component C1q receptor (CD93).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Complement component C1q receptor (CD93).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Complement component C1q receptor (CD93).	[16]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Complement component C1q receptor (CD93).	[17]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Complement component C1q receptor (CD93).	[18]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Complement component C1q receptor (CD93).	[20]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Complement component C1q receptor (CD93).	[22]

References

• [1] CD93 Marks a Non-Quiescent Human Leukemia Stem Cell Population and Is Required for Development of MLL-Rearranged Acute Myeloid Leukemia.Cell Stem Cell. 2015 Oct 1;17(4):412-21. doi: 10.1016/j.stem.2015.08.008. Epub 2015 Sep 18.
• [2] Elevated expression of the C-type lectin CD93 in the glioblastoma vasculature regulates cytoskeletal rearrangements that enhance vessel function and reduce host survival.Cancer Res. 2015 Nov 1;75(21):4504-16. doi: 10.1158/0008-5472.CAN-14-3636. Epub 2015 Sep 11.
• [3] Elevated expression of CD93 promotes angiogenesis and tumor growth in nasopharyngeal carcinoma.Biochem Biophys Res Commun. 2016 Aug 5;476(4):467-474. doi: 10.1016/j.bbrc.2016.05.146. Epub 2016 May 30.
• [4] CD93 gene polymorphism is associated with disseminated colorectal cancer.Int J Colorectal Dis. 2015 Jul;30(7):883-90. doi: 10.1007/s00384-015-2247-1. Epub 2015 May 26.
• [5] CD93 promotes 1 integrin activation and fibronectin fibrillogenesis during tumor angiogenesis.J Clin Invest. 2018 Aug 1;128(8):3280-3297. doi: 10.1172/JCI97459. Epub 2018 Jun 25.
• [6] CD93 regulates central nervous system inflammation in two mouse models of autoimmune encephalomyelitis.Immunology. 2018 Nov;155(3):346-355. doi: 10.1111/imm.12974. Epub 2018 Jul 11.
• [7] Radioimmunoimaging of (125)I-labeled anti-CD93 monoclonal antibodies in a xenograft model of non-small cell lung cancer.Oncol Lett. 2019 Dec;18(6):6413-6422. doi: 10.3892/ol.2019.11036. Epub 2019 Nov 1.
• [8] Psoriasis and Pro-angiogenetic Factor CD93: Gene Expression and Association with Gene Polymorphism Suggests a Role in Disease Pathogenesis.Acta Derm Venereol. 2017 Aug 31;97(8):916-921. doi: 10.2340/00015555-2682.
• [9] CD93 as a Potential Target in Neovascular Age-Related Macular Degeneration.J Cell Physiol. 2017 Jul;232(7):1767-1773. doi: 10.1002/jcp.25689. Epub 2016 Nov 30.
• [10] Potential of serum soluble CD93 as a biomarker for asthma in an ovalbumin-induced asthma murine model.Biomarkers. 2018 Jul;23(5):446-452. doi: 10.1080/1354750X.2018.1443510. Epub 2018 Apr 12.
• [11] Plasma CD93 concentration is a potential novel biomarker for coronary artery disease.J Intern Med. 2011 Sep;270(3):229-36. doi: 10.1111/j.1365-2796.2011.02364.x. Epub 2011 Mar 21.
• [12] Increased expression of C1q receptors on neutrophils from inflammatory joint fluids.Immunol Lett. 1993 May;36(2):195-201. doi: 10.1016/0165-2478(93)90052-4.
• [13] 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.
• [14] 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.
• [15] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [16] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [17] 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.
• [18] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [19] Pregnancy exposure to synthetic phenols and placental DNA methylation - An epigenome-wide association study in male infants from the EDEN cohort. Environ Pollut. 2021 Dec 1;290:118024. doi: 10.1016/j.envpol.2021.118024. Epub 2021 Aug 21.
• [20] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [21] 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.
• [22] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.