Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0X0ZLC)

• DOT Name: Scavenger receptor class F member 2 (SCARF2)
• Synonyms: SRECRP-1; Scavenger receptor expressed by endothelial cells 2 protein; SREC-II
• Gene Name: SCARF2
• Related Disease:
  Van den Ende-Gupta syndrome
  Chronic recurrent multifocal osteomyelitis
  Sclerocornea
  Intellectual disability
• UniProt ID: SREC2_HUMAN
• Sequence:
  MEGAGPRGAGPARRRGAGGPPSPLLPSLLLLLLLWMLPDTVAPQELNPRGRNVCRAPGSQ
  VPTCCAGWRQQGDECGIAVCEGNSTCSENEVCVRPGECRCRHGYFGANCDTKCPRQFWGP
  DCKELCSCHPHGQCEDVTGQCTCHARRWGARCEHACQCQHGTCHPRSGACRCEPGWWGAQ
  CASACYCSATSRCDPQTGACLCHAGWWGRSCNNQCACNSSPCEQQSGRCQCRERTFGARC
  DRYCQCFRGRCHPVDGTCACEPGYRGKYCREPCPAGFYGLGCRRRCGQCKGQQPCTVAEG
  RCLTCEPGWNGTKCDQPCATGFYGEGCSHRCPPCRDGHACNHVTGKCTRCNAGWIGDRCE
  TKCSNGTYGEDCAFVCADCGSGHCDFQSGRCLCSPGVHGPHCNVTCPPGLHGADCAQACS
  CHEDTCDPVTGACHLETNQRKGVMGAGALLVLLVCLLLSLLGCCCACRGKDPTRRPRPRR
  ELSLGRKKAPHRLCGRFSRISMKLPRIPLRRQKLPKVVVAHHDLDNTLNCSFLEPPSGLE
  QPSPSWSSRASFSSFDTTDEGPVYCVPHEEAPAESRDPEVPTVPAEAPAPSPVPLTTPAS
  AEEAIPLPASSDSERSASSVEGPGGALYARVARREARPARARGEIGGLSLSPSPERRKPP
  PPDPATKPKVSWIHGKHSAAAAGRAPSPPPPGSEAAPSPSKRKRTPSDKSAHTVEHGSPR
  TRDPTPRPPGLPEEATALAAPSPPRARARGRGPGLLEPTDAGGPPRSAPEAASMLAAELR
  GKTRSLGRAEVALGAQGPREKPAPPQKAKRSVPPASPARAPPATETPGPEKAATDLPAPE
  TPRKKTPIQKPPRKKSREAAGELGRAGAPTL
• Function: Probable adhesion protein, which mediates homophilic and heterophilic interactions. In contrast to SCARF1, it poorly mediates the binding and degradation of acetylated low density lipoprotein (Ac-LDL).
• Tissue Specificity: Predominantly expressed in endothelial cells. Expressed in heart, placenta, lung, kidney, spleen, small intestine and ovary.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Van den Ende-Gupta syndrome	DISS3UH3	Definitive	Autosomal recessive	[1]
Chronic recurrent multifocal osteomyelitis	DIST1OU2	Strong	Genetic Variation	[2]
Sclerocornea	DIS7HV8A	moderate	Genetic Variation	[3]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[4]

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 Scavenger receptor class F member 2 (SCARF2).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Scavenger receptor class F member 2 (SCARF2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Scavenger receptor class F member 2 (SCARF2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Scavenger receptor class F member 2 (SCARF2).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Scavenger receptor class F member 2 (SCARF2).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Scavenger receptor class F member 2 (SCARF2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Scavenger receptor class F member 2 (SCARF2).	[11]

References

• [1] Further delineation of the Van den Ende-Gupta syndrome. Am J Med Genet A. 2010 Dec;152A(12):3095-100. doi: 10.1002/ajmg.a.33725.
• [2] Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.PLoS Genet. 2016 May 17;12(5):e1006037. doi: 10.1371/journal.pgen.1006037. eCollection 2016 May.
• [3] Sclerocornea in a patient with van den Ende-Gupta syndrome homozygous for a SCARF2 microdeletion.Am J Med Genet A. 2014 May;164A(5):1170-4. doi: 10.1002/ajmg.a.36425. Epub 2014 Jan 29.
• [4] Diagnosis of Van den Ende-Gupta syndrome: Approach to the Marden-Walker-like spectrum of disorders.Am J Med Genet A. 2016 Sep;170(9):2310-21. doi: 10.1002/ajmg.a.37831. Epub 2016 Jul 4.
• [5] 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.
• [6] 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.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.