Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT661S7D)

• DOT Name: Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2)
• Synonyms: Protein CEGP1; Scube/You
• Gene Name: SCUBE2
• UniProt ID: SCUB2_HUMAN
• Pfam ID: PF12662 ; PF00431 ; PF12947 ; PF07645 ; PF07699 ; PF14670
• Sequence:
  MGVAGRNRPGAAWAVLLLLLLLPPLLLLAGAVPPGRGRAAGPQEDVDECAQGLDDCHADA
  LCQNTPTSYKCSCKPGYQGEGRQCEDIDECGNELNGGCVHDCLNIPGNYRCTCFDGFMLA
  HDGHNCLDVDECLENNGGCQHTCVNVMGSYECCCKEGFFLSDNQHTCIHRSEEGLSCMNK
  DHGCSHICKEAPRGSVACECRPGFELAKNQRDCILTCNHGNGGCQHSCDDTADGPECSCH
  PQYKMHTDGRSCLEREDTVLEVTESNTTSVVDGDKRVKRRLLMETCAVNNGGCDRTCKDT
  STGVHCSCPVGFTLQLDGKTCKDIDECQTRNGGCDHFCKNIVGSFDCGCKKGFKLLTDEK
  SCQDVDECSLDRTCDHSCINHPGTFACACNRGYTLYGFTHCGDTNECSINNGGCQQVCVN
  TVGSYECQCHPGYKLHWNKKDCVEVKGLLPTSVSPRVSLHCGKSGGGDGCFLRCHSGIHL
  SSDVTTIRTSVTFKLNEGKCSLKNAELFPEGLRPALPEKHSSVKESFRYVNLTCSSGKQV
  PGAPGRPSTPKEMFITVEFELETNQKEVTASCDLSCIVKRTEKRLRKAIRTLRKAVHREQ
  FHLQLSGMNLDVAKKPPRTSERQAESCGVGQGHAENQCVSCRAGTYYDGARERCILCPNG
  TFQNEEGQMTCEPCPRPGNSGALKTPEAWNMSECGGLCQPGEYSADGFAPCQLCALGTFQ
  PEAGRTSCFPCGGGLATKHQGATSFQDCETRVQCSPGHFYNTTTHRCIRCPVGTYQPEFG
  KNNCVSCPGNTTTDFDGSTNITQCKNRRCGGELGDFTGYIESPNYPGNYPANTECTWTIN
  PPPKRRILIVVPEIFLPIEDDCGDYLVMRKTSSSNSVTTYETCQTYERPIAFTSRSKKLW
  IQFKSNEGNSARGFQVPYVTYDEDYQELIEDIVRDGRLYASENHQEILKDKKLIKALFDV
  LAHPQNYFKYTAQESREMFPRSFIRLLRSKVSRFLRPYK
• Function: Lipid-binding protein required for SHH long-range signaling by binding to the dually lipid-modified SHH (ShhNp) and by promoting ShhNp mobilization, solubilization and release from the cell membrane. Acts by enhancing the proteolytic processing (shedding) of the lipid-modified N- and C- terminal of ShhNp at the cell surface. Synergizes with DISP1 to increase SHH secretion. Probable cell surface coreceptor for VEGFR2 involved in VEGFR2-mediated angiogenesis.
• Tissue Specificity: Expressed in a broad spectrum of adult tissues .
• KEGG Pathway: Hedgehog sig.ling pathway (hsa04340)
• Reactome Pathway: Release of Hh-Np from the secreting cell (R-HSA-5362798)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2).	[8]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2).	[12]

2 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 Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Signal peptide, CUB and EGF-like domain-containing protein 2 (SCUBE2).	[10]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [4] 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.
• [5] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [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] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.