Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOVA96E)

• DOT Name: Scavenger receptor class A member 5 (SCARA5)
• Synonyms: Scavenger receptor hlg
• Gene Name: SCARA5
• Related Disease:
  Colorectal carcinoma
  Subarachnoid hemorrhage
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Depression
  Esophageal squamous cell carcinoma
  Hepatocellular carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Retinopathy
  Vascular disease
  Carcinoma of liver and intrahepatic biliary tract
  Hepatitis B virus infection
  Liver cancer
  Bone osteosarcoma
  Osteosarcoma
  Squamous cell carcinoma
• UniProt ID: SCAR5_HUMAN
• PDB ID: 7C00
• Pfam ID: PF01391 ; PF00530
• Sequence:
  MENKAMYLHTVSDCDTSSICEDSFDGRSLSKLNLCEDGPCHKRRASICCTQLGSLSALKH
  AVLGLYLLVFLILVGIFILAVSRPRSSPDDLKALTRNVNRLNESFRDLQLRLLQAPLQAD
  LTEQVWKVQDALQNQSDSLLALAGAVQRLEGALWGLQAQAVQTEQAVALLRDRTGQQSDT
  AQLELYQLQVESNSSQLLLRRHAGLLDGLARRVGILGEELADVGGVLRGLNHSLSYDVAL
  HRTRLQDLRVLVSNASEDTRRLRLAHVGMELQLKQELAMLNAVTEDLRLKDWEHSIALRN
  ISLAKGPPGPKGDQGDEGKEGRPGIPGLPGLRGLPGERGTPGLPGPKGDDGKLGATGPMG
  MRGFKGDRGPKGEKGEKGDRAGDASGVEAPMMIRLVNGSGPHEGRVEVYHDRRWGTVCDD
  GWDKKDGDVVCRMLGFRGVEEVYRTARFGQGTGRIWMDDVACKGTEETIFRCSFSKWGVT
  NCGHAEDASVTCNRH
• Function: Ferritin receptor that mediates non-transferrin-dependent delivery of iron. Mediates cellular uptake of ferritin-bound iron by stimulating ferritin endocytosis from the cell surface with consequent iron delivery within the cell. Delivery of iron to cells by ferritin is required for the development of specific cell types, suggesting the existence of cell type-specific mechanisms of iron traffic in organogenesis, which alternatively utilize transferrin or non-transferrin iron delivery pathways. Ferritin mediates iron uptake in capsule cells of the developing kidney. Preferentially binds ferritin light chain (FTL) compared to heavy chain (FTH1).
• Reactome Pathway: Scavenging by Class A Receptors (R-HSA-3000480)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Subarachnoid hemorrhage	DISI7I8Y	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Depression	DIS3XJ69	Strong	Genetic Variation	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[9]
Retinopathy	DISB4B0F	Strong	Biomarker	[10]
Vascular disease	DISVS67S	Strong	Biomarker	[4]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Posttranslational Modification	[11]
Hepatitis B virus infection	DISLQ2XY	moderate	Genetic Variation	[11]
Liver cancer	DISDE4BI	moderate	Posttranslational Modification	[11]
Bone osteosarcoma	DIST1004	Limited	Altered Expression	[12]
Osteosarcoma	DISLQ7E2	Limited	Altered Expression	[12]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[9]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Hexane-1,6-diamine	DMSHF0K	Investigative	Scavenger receptor class A member 5 (SCARA5) increases the abundance of Hexane-1,6-diamine.	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Scavenger receptor class A member 5 (SCARA5).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Scavenger receptor class A member 5 (SCARA5).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Scavenger receptor class A member 5 (SCARA5).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Scavenger receptor class A member 5 (SCARA5).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Scavenger receptor class A member 5 (SCARA5).	[16]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Scavenger receptor class A member 5 (SCARA5).	[18]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Scavenger receptor class A member 5 (SCARA5).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Scavenger receptor class A member 5 (SCARA5).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Scavenger receptor class A member 5 (SCARA5).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Scavenger receptor class A member 5 (SCARA5).	[21]

References

• [1] Screening for epigenetically masked genes in colorectal cancer Using 5-Aza-2'-deoxycytidine, microarray and gene expression profile.Cancer Genomics Proteomics. 2012 Mar-Apr;9(2):67-75.
• [2] Novel Drug Targets for Ischemic Stroke Identified Through Mendelian Randomization Analysis of the Blood Proteome.Circulation. 2019 Sep 9;140(10):819-830. doi: 10.1161/CIRCULATIONAHA.119.040180. Epub 2019 Jun 18.
• [3] Downregulation of SCARA5 may contribute to breast cancer via promoter hypermethylation.Gene. 2018 Oct 5;673:102-106. doi: 10.1016/j.gene.2018.06.036. Epub 2018 Jun 13.
• [4] Knockdown of SCARA5 inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration through suppression of the PDGF signaling pathway.Mol Med Rep. 2016 May;13(5):4455-60. doi: 10.3892/mmr.2016.5074. Epub 2016 Mar 30.
• [5] Gene-level genome-wide association analysis of suicide attempt, a preliminary study in a psychiatric Mexican population.Mol Genet Genomic Med. 2019 Dec;7(12):e983. doi: 10.1002/mgg3.983. Epub 2019 Oct 2.
• [6] The analyses of SRCR genes based on protein-protein interaction network in esophageal squamous cell carcinoma.Am J Transl Res. 2019 May 15;11(5):2683-2705. eCollection 2019.
• [7] CSN5 Promotes Hepatocellular Carcinoma Progression by SCARA5 Inhibition Through Suppressing -Catenin Ubiquitination.Dig Dis Sci. 2018 Jan;63(1):155-165. doi: 10.1007/s10620-017-4855-9. Epub 2017 Nov 30.
• [8] Genetic and epigenetic silencing of SCARA5 may contribute to human hepatocellular carcinoma by activating FAK signaling.J Clin Invest. 2010 Jan;120(1):223-41. doi: 10.1172/JCI38012. Epub 2009 Dec 14.
• [9] Identification of SCARA5 as a Potential Biomarker for Oral Squamous Cell Carcinoma using MALDI-TOF-MS Analysis.Proteomics Clin Appl. 2018 Sep;12(5):e1700180. doi: 10.1002/prca.201700180. Epub 2018 May 30.
• [10] Correction: L-Ferritin Binding to Scara5: A New Iron Traffic Pathway Potentially Implicated in Retinopathy.PLoS One. 2017 Jun 22;12(6):e0180288. doi: 10.1371/journal.pone.0180288. eCollection 2017.
• [11] Methylation analysis of p16, SLIT2, SCARA5, and Runx3 genes in hepatocellular carcinoma.Medicine (Baltimore). 2017 Oct;96(41):e8279. doi: 10.1097/MD.0000000000008279.
• [12] Overexpression of SCARA5 inhibits tumor proliferation and invasion in osteosarcoma via suppression of the FAK signaling pathway.Mol Med Rep. 2016 Mar;13(3):2885-91. doi: 10.3892/mmr.2016.4857. Epub 2016 Feb 3.
• [13] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [14] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [15] 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.
• [16] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [17] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [18] 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.
• [19] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [20] 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.
• [21] 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.
• [22] DNA methylation modifies urine biomarker levels in 1,6-hexamethylene diisocyanate exposed workers: a pilot study. Toxicol Lett. 2014 Dec 1;231(2):217-26. doi: 10.1016/j.toxlet.2014.10.024. Epub 2014 Oct 22.