Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4JY1UY)

• DOT Name: Signal peptide, CUB and EGF-like domain-containing protein 1 (SCUBE1)
• Gene Name: SCUBE1
• Related Disease:
  Diabetic retinopathy
  Hyperglycemia
  Osteoarthritis
  Psoriasis
  Type-1/2 diabetes
  Kidney cancer
  Kidney neoplasm
  Renal cell carcinoma
  Systemic lupus erythematosus
  Thrombosis
  Venous thromboembolism
• UniProt ID: SCUB1_HUMAN
• Pfam ID: PF12662 ; PF00431 ; PF12947 ; PF07645 ; PF07699 ; PF14670
• Sequence:
  MGAAAVRWHLCVLLALGTRGRLAGGSGLPGSVDVDECSEGTDDCHIDAICQNTPKSYKCL
  CKPGYKGEGKQCEDIDECENDYYNGGCVHECINIPGNYRCTCFDGFMLAHDGHNCLDVDE
  CQDNNGGCQQICVNAMGSYECQCHSGFFLSDNQHTCIHRSNEGMNCMNKDHGCAHICRET
  PKGGVACDCRPGFDLAQNQKDCTLTCNYGNGGCQHSCEDTDTGPTCGCHQKYALHSDGRT
  CIETCAVNNGGCDRTCKDTATGVRCSCPVGFTLQPDGKTCKDINECLVNNGGCDHFCRNT
  VGSFECGCRKGYKLLTDERTCQDIDECSFERTCDHICINSPGSFQCLCHRGYILYGTTHC
  GDVDECSMSNGSCDQGCVNTKGSYECVCPPGRRLHWNGKDCVETGKCLSRAKTSPRAQLS
  CSKAGGVESCFLSCPAHTLFVPDSENSYVLSCGVPGPQGKALQKRNGTSSGLGPSCSDAP
  TTPIKQKARFKIRDAKCHLRPHSQARAKETARQPLLDHCHVTFVTLKCDSSKKRRRGRKS
  PSKEVSHITAEFEIETKMEEASDTCEADCLRKRAEQSLQAAIKTLRKSIGRQQFYVQVSG
  TEYEVAQRPAKALEGQGACGAGQVLQDSKCVACGPGTHFGGELGQCVSCMPGTYQDMEGQ
  LSCTPCPSSDGLGLPGARNVSECGGQCSPGFFSADGFKPCQACPVGTYQPEPGRTGCFPC
  GGGLLTKHEGTTSFQDCEAKVHCSPGHHYNTTTHRCIRCPVGTYQPEFGQNHCITCPGNT
  STDFDGSTNVTHCKNQHCGGELGDYTGYIESPNYPGDYPANAECVWHIAPPPKRRILIVV
  PEIFLPIEDECGDVLVMRKSASPTSITTYETCQTYERPIAFTSRSRKLWIQFKSNEGNSG
  KGFQVPYVTYDEDYQQLIEDIVRDGRLYASENHQEILKDKKLIKALFDVLAHPQNYFKYT
  AQESKEMFPRSFIKLLRSKVSRFLRPYK
• Function: Could function as an adhesive molecule and its matrix bound and soluble fragments may play a critical role in vascular biology.
• Tissue Specificity: Detected in endothelial cells. Highly expressed in platelets. Stored in platelet alpha granules, and transferred to the cell surface upon activation and aggregation. A smaller form, probably produced by limited proteolysis, after being released from the storage granules, is associated with thrombus and localized with the subendothelial matrices in atherosclerotic plaques.
• Reactome Pathway: Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diabetic retinopathy	DISHGUJM	Strong	Altered Expression	[1]
Hyperglycemia	DIS0BZB5	Strong	Altered Expression	[2]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[3]
Psoriasis	DIS59VMN	Strong	Altered Expression	[4]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[1]
Kidney cancer	DISBIPKM	moderate	Biomarker	[5]
Kidney neoplasm	DISBNZTN	moderate	Biomarker	[5]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[5]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[6]
Thrombosis	DIS2TXP8	Limited	Altered Expression	[7]
Venous thromboembolism	DISUR7CR	Limited	Genetic Variation	[8]

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 Signal peptide, CUB and EGF-like domain-containing protein 1 (SCUBE1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Signal peptide, CUB and EGF-like domain-containing protein 1 (SCUBE1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Signal peptide, CUB and EGF-like domain-containing protein 1 (SCUBE1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Signal peptide, CUB and EGF-like domain-containing protein 1 (SCUBE1).	[10]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Signal peptide, CUB and EGF-like domain-containing protein 1 (SCUBE1).	[11]

References

• [1] Serum SCUBE-1 levels in patients with diabetic retinopathy.Int Ophthalmol. 2020 Apr;40(4):859-865. doi: 10.1007/s10792-019-01249-8. Epub 2019 Dec 2.
• [2] Evaluation of SCUBE-1 levels as a placental dysfunction marker at gestational diabetes mellitus.Gynecol Endocrinol. 2020 May;36(5):417-420. doi: 10.1080/09513590.2019.1683537. Epub 2019 Oct 31.
• [3] Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet. 2019 Feb;51(2):230-236.
• [4] Can signal peptide-CUB-EGF domain-containing protein (SCUBE) levels be a marker of angiogenesis in patients with psoriasis?.Arch Dermatol Res. 2017 Apr;309(3):203-207. doi: 10.1007/s00403-017-1722-7. Epub 2017 Feb 25.
• [5] SCUBE1: a promising biomarker in renal cell cancer.Int Braz J Urol. 2017 Jul-Aug;43(4):638-643. doi: 10.1590/S1677-5538.IBJU.2016.0316.
• [6] Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci.Nat Genet. 2008 Feb;40(2):204-10. doi: 10.1038/ng.81. Epub 2008 Jan 20.
• [7] Identification of a novel family of cell-surface proteins expressed in human vascular endothelium.J Biol Chem. 2002 Nov 29;277(48):46364-73. doi: 10.1074/jbc.M207410200. Epub 2002 Sep 21.
• [8] Genetic variation within the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways as risk factors for venous thromboembolism.J Thromb Haemost. 2011 Jun;9(6):1133-42. doi: 10.1111/j.1538-7836.2011.04272.x.
• [9] 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.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [12] 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.
• [13] 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.