Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT34P56Z)

• DOT Name: Sister chromatid cohesion protein PDS5 homolog A (PDS5A)
• Synonyms: Cell proliferation-inducing gene 54 protein; Sister chromatid cohesion protein 112; SCC-112
• Gene Name: PDS5A
• Related Disease:
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cardiac failure
  Congestive heart failure
  Cornelia de Lange syndrome
  Esophageal squamous cell carcinoma
  Neoplasm
  Prostate cancer
  Prostate neoplasm
  Rheumatoid arthritis
• UniProt ID: PDS5A_HUMAN
• Pfam ID: PF20168
• Sequence:
  MDFTAQPKPATALCGVVSADGKIAYPPGVKEITDKITTDEMIKRLKMVVKTFMDMDQDSE
  DEKQQYLPLALHLASEFFLRNPNKDVRLLVACCLADIFRIYAPEAPYTSHDKLKDIFLFI
  TRQLKGLEDTKSPQFNRYFYLLENLAWVKSYNICFELEDCNEIFIQLFRTLFSVINNSHN
  KKVQMHMLDLMSSIIMEGDGVTQELLDSILINLIPAHKNLNKQSFDLAKVLLKRTVQTIE
  ACIANFFNQVLVLGRSSVSDLSEHVFDLIQELFAIDPHLLLSVMPQLEFKLKSNDGEERL
  AVVRLLAKLFGSKDSDLATQNRPLWQCFLGRFNDIHVPVRLESVKFASHCLMNHPDLAKD
  LTEYLKVRSHDPEEAIRHDVIVTIITAAKRDLALVNDQLLGFVRERTLDKRWRVRKEAMM
  GLAQLYKKYCLHGEAGKEAAEKVSWIKDKLLHIYYQNSIDDKLLVEKIFAQYLVPHNLET
  EERMKCLYYLYASLDPNAVKALNEMWKCQNMLRSHVRELLDLHKQPTSEANCSAMFGKLM
  TIAKNLPDPGKAQDFVKKFNQVLGDDEKLRSQLELLISPTCSCKQADICVREIARKLANP
  KQPTNPFLEMVKFLLERIAPVHIDSEAISALVKLMNKSIEGTADDEEEGVSPDTAIRSGL
  ELLKVLSFTHPTSFHSAETYESLLQCLRMEDDKVAEAAIQIFRNTGHKIETDLPQIRSTL
  IPILHQKAKRGTPHQAKQAVHCIHAIFTNKEVQLAQIFEPLSRSLNADVPEQLITPLVSL
  GHISMLAPDQFASPMKSVVANFIVKDLLMNDRSTGEKNGKLWSPDEEVSPEVLAKVQAIK
  LLVRWLLGMKNNQSKSANSTLRLLSAMLVSEGDLTEQKRISKSDMSRLRLAAGSAIMKLA
  QEPCYHEIITPEQFQLCALVINDECYQVRQIFAQKLHKALVKLLLPLEYMAIFALCAKDP
  VKERRAHARQCLLKNISIRREYIKQNPMATEKLLSLLPEYVVPYMIHLLAHDPDFTRSQD
  VDQLRDIKECLWFMLEVLMTKNENNSHAFMKKMAENIKLTRDAQSPDESKTNEKLYTVCD
  VALCVINSKSALCNADSPKDPVLPMKFFTQPEKDFCNDKSYISEETRVLLLTGKPKPAGV
  LGAVNKPLSATGRKPYVRSTGTETGSNINVNSELNPSTGNRSREQSSEAAETGVSENEEN
  PVRIISVTPVKNIDPVKNKEINSDQATQGNISSDRGKKRTVTAAGAENIQQKTDEKVDES
  GPPAPSKPRRGRRPKSESQGNATKNDDLNKPINKGRKRAAVGQESPGGLEAGNAKAPKLQ
  DLAKKAAPAERQIDLQR
• Function: Probable regulator of sister chromatid cohesion in mitosis which may stabilize cohesin complex association with chromatin. May couple sister chromatid cohesion during mitosis to DNA replication. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair.
• Tissue Specificity: Highest level in colon. Low levels in lung, ovary, breast and kidney. Reduced level in renal tumor tissue. Isoform 2 is expressed in kidney.
• KEGG Pathway: Cell cycle (hsa04110)
• Reactome Pathway:
  Establishment of Sister Chromatid Cohesion (R-HSA-2468052)
  Cohesin Loading onto Chromatin (R-HSA-2470946)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  Separation of Sister Chromatids (R-HSA-2467813)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Carcinoma	DISH9F1N	Strong	Biomarker	[1]
Cardiac failure	DISDC067	Strong	Biomarker	[2]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[2]
Cornelia de Lange syndrome	DISEQSXO	Strong	Biomarker	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[4]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[4]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[5]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	Sister chromatid cohesion protein PDS5 homolog A (PDS5A) affects the response to substance of Mitomycin.	[17]

10 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 Sister chromatid cohesion protein PDS5 homolog A (PDS5A).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Sister chromatid cohesion protein PDS5 homolog A (PDS5A).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sister chromatid cohesion protein PDS5 homolog A (PDS5A).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sister chromatid cohesion protein PDS5 homolog A (PDS5A).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sister chromatid cohesion protein PDS5 homolog A (PDS5A).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Sister chromatid cohesion protein PDS5 homolog A (PDS5A).	[11]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Sister chromatid cohesion protein PDS5 homolog A (PDS5A).	[12]
APR-246	DMNFADH	Phase 2	APR-246 increases the expression of Sister chromatid cohesion protein PDS5 homolog A (PDS5A).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sister chromatid cohesion protein PDS5 homolog A (PDS5A).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Sister chromatid cohesion protein PDS5 homolog A (PDS5A).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Sister chromatid cohesion protein PDS5 homolog A (PDS5A).	[16]

References

• [1] SCC-112, a novel cell cycle-regulated molecule, exhibits reduced expression in human renal carcinomas.Gene. 2004 Mar 17;328:187-96. doi: 10.1016/j.gene.2003.12.013.
• [2] Dosage effects of cohesin regulatory factor PDS5 on mammalian development: implications for cohesinopathies.PLoS One. 2009;4(5):e5232. doi: 10.1371/journal.pone.0005232. Epub 2009 May 1.
• [3] Enhanced Expression of Fibroblast Growth Factor Receptor 3 IIIc Promotes Human Esophageal Carcinoma Cell Proliferation.J Histochem Cytochem. 2016 Jan;64(1):7-17. doi: 10.1369/0022155415616161. Epub 2015 Oct 20.
• [4] The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
• [5] REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.Nat Genet. 2009 Jul;41(7):820-3. doi: 10.1038/ng.395. Epub 2009 Jun 7.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [10] 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.
• [11] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [12] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [13] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [14] 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.
• [15] 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.
• [16] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [17] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.