Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0NW2Q0)

• DOT Name: Macrophage receptor MARCO (MARCO)
• Synonyms: Macrophage receptor with collagenous structure; Scavenger receptor class A member 2
• Gene Name: MARCO
• Related Disease:
  Arthritis
  Mycoses
  Respiratory syncytial virus infection
  Rheumatoid arthritis
  Spondyloarthropathy
  Atopic dermatitis
  Chronic obstructive pulmonary disease
  Crohn disease
  Herpes simplex infection
  IgG4 related disease
  Neoplasm
  Non-small-cell lung cancer
  Pulmonary tuberculosis
  Synovitis
  Ulcerative colitis
  Adenovirus infection
  Latent tuberculosis infection
  Pulmonary fibrosis
  Tuberculosis
  Bacterial infection
  Bacterial meningitis
  Meningitis
  Prostate cancer
  Prostate carcinoma
• UniProt ID: MARCO_HUMAN
• Pfam ID: PF01391 ; PF00530
• Sequence:
  MRNKKILKEDELLSETQQAAFHQIAMEPFEINVPKPKRRNGVNFSLAVVVIYLILLTAGA
  GLLVVQVLNLQARLRVLEMYFLNDTLAAEDSPSFSLLQSAHPGEHLAQGASRLQVLQAQL
  TWVRVSHEHLLQRVDNFTQNPGMFRIKGEQGAPGLQGHKGAMGMPGAPGPPGPPAEKGAK
  GAMGRDGATGPSGPQGPPGVKGEAGLQGPQGAPGKQGATGTPGPQGEKGSKGDGGLIGPK
  GETGTKGEKGDLGLPGSKGDRGMKGDAGVMGPPGAQGSKGDFGRPGPPGLAGFPGAKGDQ
  GQPGLQGVPGPPGAVGHPGAKGEPGSAGSPGRAGLPGSPGSPGATGLKGSKGDTGLQGQQ
  GRKGESGVPGPAGVKGEQGSPGLAGPKGAPGQAGQKGDQGVKGSSGEQGVKGEKGERGEN
  SVSVRIVGSSNRGRAEVYYSGTWGTICDDEWQNSDAIVFCRMLGYSKGRALYKVGAGTGQ
  IWLDNVQCRGTESTLWSCTKNSWGHHDCSHEEDAGVECSV
• Function: Pattern recognition receptor (PRR) which binds Gram-positive and Gram-negative bacteria. Also plays a role in binding of unopsonized particles by alveolar macrophages. Binds to the secretoglobin SCGB3A2.
• Tissue Specificity: Expressed in alveolar macrophages (at protein level). Detected in macrophages from various tissues including thymus, kidney, Kupffer cells of liver, and spleen .
• KEGG Pathway: Phagosome (hsa04145)
• Reactome Pathway: Scavenging by Class A Receptors (R-HSA-3000480)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Definitive	Biomarker	[1]
Mycoses	DIS9K7PB	Definitive	Biomarker	[2]
Respiratory syncytial virus infection	DIS7FWHY	Definitive	Altered Expression	[3]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[1]
Spondyloarthropathy	DISBPYCZ	Definitive	Altered Expression	[1]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[4]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[5]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[6]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[7]
IgG4 related disease	DIS1U0UF	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[10]
Pulmonary tuberculosis	DIS6FLUM	Strong	Genetic Variation	[11]
Synovitis	DISW2GPY	Strong	Altered Expression	[12]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[6]
Adenovirus infection	DISUYSBZ	moderate	Biomarker	[13]
Latent tuberculosis infection	DIS6R1EH	moderate	Biomarker	[14]
Pulmonary fibrosis	DISQKVLA	moderate	Biomarker	[15]
Tuberculosis	DIS2YIMD	moderate	Genetic Variation	[11]
Bacterial infection	DIS5QJ9S	Limited	Biomarker	[16]
Bacterial meningitis	DISRP9SL	Limited	Biomarker	[17]
Meningitis	DISQABAA	Limited	Altered Expression	[17]
Prostate cancer	DISF190Y	Limited	Altered Expression	[18]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Macrophage receptor MARCO (MARCO).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Macrophage receptor MARCO (MARCO).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Macrophage receptor MARCO (MARCO).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Macrophage receptor MARCO (MARCO).	[22]

References

• [1] Expression of host defense scavenger receptors in spondylarthropathy.Arthritis Rheum. 2001 Apr;44(4):931-9. doi: 10.1002/1529-0131(200104)44:4<931::AID-ANR150>3.0.CO;2-T.
• [2] Scavenger Receptor MARCO Orchestrates Early Defenses and Contributes to Fungal Containment during Cryptococcal Infection.J Immunol. 2017 May 1;198(9):3548-3557. doi: 10.4049/jimmunol.1700057. Epub 2017 Mar 15.
• [3] Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants.EBioMedicine. 2016 Sep;11:73-84. doi: 10.1016/j.ebiom.2016.08.011. Epub 2016 Aug 6.
• [4] Vaccinia virus binds to the scavenger receptor MARCO on the surface of keratinocytes.J Invest Dermatol. 2015 Jan;135(1):142-150. doi: 10.1038/jid.2014.330. Epub 2014 Aug 4.
• [5] Genetic variations in scavenger and ?adrenergic receptors and risk of pulmonary disease.Dan Med J. 2014 Sep;61(9):B4910.
• [6] Transcriptomic Analysis and High-dimensional Phenotypic Mapping of Mononuclear Phagocytes in Mesenteric Lymph Nodes Reveal Differences Between Ulcerative Colitis and Crohn's Disease.J Crohns Colitis. 2020 Mar 13;14(3):393-405. doi: 10.1093/ecco-jcc/jjz156.
• [7] Entry of Herpes Simplex Virus 1 into Epidermis and Dermal Fibroblasts Is Independent of the Scavenger Receptor MARCO.J Virol. 2018 Jul 17;92(15):e00490-18. doi: 10.1128/JVI.00490-18. Print 2018 Aug 1.
• [8] DNA Microarray Analysis of Submandibular Glands in IgG4-Related Disease Indicates a Role for MARCO and Other Innate Immune-Related Proteins.Medicine (Baltimore). 2016 Feb;95(7):e2853. doi: 10.1097/MD.0000000000002853.
• [9] Down-regulation of MARCO associates with tumor progression in hepatocellular carcinoma.Exp Cell Res. 2019 Oct 15;383(2):111542. doi: 10.1016/j.yexcr.2019.111542. Epub 2019 Aug 2.
• [10] Expression of scavenger receptor MARCO defines a targetable tumor-associated macrophage subset in non-small cell lung cancer.Int J Cancer. 2018 Oct 1;143(7):1741-1752. doi: 10.1002/ijc.31545. Epub 2018 May 13.
• [11] Human-Specific Mutations and Positively Selected Sites in MARCO Confer Functional Changes.Mol Biol Evol. 2018 Feb 1;35(2):440-450. doi: 10.1093/molbev/msx298.
• [12] Ectopic expression of macrophage scavenger receptor MARCO in synovial membrane-like interface tissue in aseptic loosening of total hip replacement implants.J Biomed Mater Res A. 2010 Feb;92(2):641-9. doi: 10.1002/jbm.a.32409.
• [13] Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages.mBio. 2017 Aug 1;8(4):e00670-17. doi: 10.1128/mBio.00670-17.
• [14] Evaluation of the relationship between MARCO and CD36 single-nucleotide polymorphisms and susceptibility to pulmonary tuberculosis in a Chinese Han population.BMC Infect Dis. 2017 Jul 11;17(1):488. doi: 10.1186/s12879-017-2595-2.
• [15] Therapeutic effects of scavenger receptor MARCO ligand on silica-induced pulmonary fibrosis in rats.Toxicol Lett. 2019 Sep 1;311:1-10. doi: 10.1016/j.toxlet.2019.04.026. Epub 2019 Apr 24.
• [16] Targeting Nrf2 signaling improves bacterial clearance by alveolar macrophages in patients with COPD and in a mouse model.Sci Transl Med. 2011 Apr 13;3(78):78ra32. doi: 10.1126/scitranslmed.3002042.
• [17] The formyl peptide receptor like-1 and scavenger receptor MARCO are involved in glial cell activation in bacterial meningitis.J Neuroinflammation. 2011 Feb 7;8(1):11. doi: 10.1186/1742-2094-8-11.
• [18] Heme oxygenase-1 in macrophages controls prostate cancer progression.Oncotarget. 2015 Oct 20;6(32):33675-88. doi: 10.18632/oncotarget.5284.
• [19] 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.
• [20] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.