Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9EEBUJ)

• DOT Name: Prolargin (PRELP)
• Synonyms: Proline-arginine-rich end leucine-rich repeat protein
• Gene Name: PRELP
• Related Disease:
  Matthew-Wood syndrome
  Adult glioblastoma
  Endometriosis
  Glioblastoma multiforme
  Hutchinson-Gilford progeria syndrome
  Meningioma
  Osteoarthritis
  Pancreatic cancer
  Psoriasis
  Mantle cell lymphoma
  Neoplasm
  Small lymphocytic lymphoma
  Inflammation
  Rheumatoid arthritis
• UniProt ID: PRELP_HUMAN
• Pfam ID: PF13855
• Sequence:
  MRSPLCWLLPLLILASVAQGQPTRRPRPGTGPGRRPRPRPRPTPSFPQPDEPAEPTDLPP
  PLPPGPPSIFPDCPRECYCPPDFPSALYCDSRNLRKVPVIPPRIHYLYLQNNFITELPVE
  SFQNATGLRWINLDNNRIRKIDQRVLEKLPGLVFLYMEKNQLEEVPSALPRNLEQLRLSQ
  NHISRIPPGVFSKLENLLLLDLQHNRLSDGVFKPDTFHGLKNLMQLNLAHNILRKMPPRV
  PTAIHQLYLDSNKIETIPNGYFKSFPNLAFIRLNYNKLTDRGLPKNSFNISNLLVLHLSH
  NRISSVPAINNRLEHLYLNNNSIEKINGTQICPNDLVAFHDFSSDLENVPHLRYLRLDGN
  YLKPPIPLDLMMCFRLLQSVVI
• Function: May anchor basement membranes to the underlying connective tissue.
• Tissue Specificity: Connective tissue.
• Reactome Pathway:
  Keratan sulfate degradation (R-HSA-2022857)
  Defective CHST6 causes MCDC1 (R-HSA-3656225)
  Defective ST3GAL3 causes MCT12 and EIEE15 (R-HSA-3656243)
  Defective B4GALT1 causes B4GALT1-CDG (CDG-2d) (R-HSA-3656244)
  Keratan sulfate biosynthesis (R-HSA-2022854)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Matthew-Wood syndrome	DISA7HR7	Definitive	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Endometriosis	DISX1AG8	Strong	Altered Expression	[3]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Hutchinson-Gilford progeria syndrome	DISY55BU	Strong	Biomarker	[4]
Meningioma	DISPT4TG	Strong	Biomarker	[2]
Osteoarthritis	DIS05URM	Strong	Biomarker	[5]
Pancreatic cancer	DISJC981	Strong	Biomarker	[1]
Psoriasis	DIS59VMN	Strong	Altered Expression	[6]
Mantle cell lymphoma	DISFREOV	moderate	Altered Expression	[7]
Neoplasm	DISZKGEW	moderate	Altered Expression	[7]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[7]
Inflammation	DISJUQ5T	Limited	Biomarker	[8]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[9]

1 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 Prolargin (PRELP).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Prolargin (PRELP).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Prolargin (PRELP).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Prolargin (PRELP).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Prolargin (PRELP).	[14]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of Prolargin (PRELP).	[14]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone increases the expression of Prolargin (PRELP).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Prolargin (PRELP).	[15]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Prolargin (PRELP).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the expression of Prolargin (PRELP).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Prolargin (PRELP).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Prolargin (PRELP).	[19]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Prolargin (PRELP).	[20]

References

• [1] Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma.Lab Invest. 2015 Jan;95(1):43-55. doi: 10.1038/labinvest.2014.128. Epub 2014 Oct 27.
• [2] Development of a predictor for human brain tumors based on gene expression values obtained from two types of microarray technologies.OMICS. 2010 Apr;14(2):157-64. doi: 10.1089/omi.2009.0093.
• [3] Increased expression of ID2, PRELP and SMOC2 genes in patients with endometriosis.Braz J Med Biol Res. 2017 Jul 3;50(7):e5782. doi: 10.1590/1414-431X20175782.
• [4] PRELP, collagen, and a theory of Hutchinson-Gilford progeria.Ageing Res Rev. 2003 Jan;2(1):95-105. doi: 10.1016/s1568-1637(02)00044-2.
• [5] Analysis of Endogenous Peptides Released from Osteoarthritic Cartilage Unravels Novel Pathogenic Markers.Mol Cell Proteomics. 2019 Oct;18(10):2018-2028. doi: 10.1074/mcp.RA119.001554. Epub 2019 Jul 27.
• [6] Levels of miR-31 and its target genes in dermal mesenchymal cells of patients with psoriasis.Int J Dermatol. 2019 Feb;58(2):198-204. doi: 10.1111/ijd.14197. Epub 2018 Sep 9.
• [7] A proline/arginine-rich end leucine-rich repeat protein (PRELP) variant is uniquely expressed in chronic lymphocytic leukemia cells.PLoS One. 2013 Jun 24;8(6):e67601. doi: 10.1371/journal.pone.0067601. Print 2013.
• [8] PRELP protein inhibits the formation of the complement membrane attack complex.J Biol Chem. 2012 Mar 9;287(11):8092-100. doi: 10.1074/jbc.M111.291476. Epub 2012 Jan 20.
• [9] Identification of prolargin expression in articular cartilage and its significance in rheumatoid arthritis pathology.Int J Biol Macromol. 2018 Apr 15;110:558-566. doi: 10.1016/j.ijbiomac.2018.01.141. Epub 2018 Feb 1.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [14] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [15] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [16] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [17] High-throughput data integration of RNA-miRNA-circRNA reveals novel insights into mechanisms of benzo[a]pyrene-induced carcinogenicity. Nucleic Acids Res. 2015 Mar 11;43(5):2525-34. doi: 10.1093/nar/gkv115. Epub 2015 Feb 17.
• [18] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [19] 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.
• [20] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.