Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5TYJK9)

• DOT Name: FACT complex subunit SSRP1 (SSRP1)
• Synonyms: Chromatin-specific transcription elongation factor 80 kDa subunit; Facilitates chromatin transcription complex 80 kDa subunit; FACT 80 kDa subunit; FACTp80; Facilitates chromatin transcription complex subunit SSRP1; Recombination signal sequence recognition protein 1; Structure-specific recognition protein 1; hSSRP1; T160
• Gene Name: SSRP1
• UniProt ID: SSRP1_HUMAN
• PDB ID: 4IFS; 5UMR; 5UMS; 5VWE; 6L1E; 6L1R; 6L34; 6UPK; 6UPL
• Pfam ID: PF00505 ; PF21103 ; PF17292 ; PF08512 ; PF03531 ; PF21092
• Sequence:
  MAETLEFNDVYQEVKGSMNDGRLRLSRQGIIFKNSKTGKVDNIQAGELTEGIWRRVALGH
  GLKLLTKNGHVYKYDGFRESEFEKLSDFFKTHYRLELMEKDLCVKGWNWGTVKFGGQLLS
  FDIGDQPVFEIPLSNVSQCTTGKNEVTLEFHQNDDAEVSLMEVRFYVPPTQEDGVDPVEA
  FAQNVLSKADVIQATGDAICIFRELQCLTPRGRYDIRIYPTFLHLHGKTFDYKIPYTTVL
  RLFLLPHKDQRQMFFVISLDPPIKQGQTRYHFLILLFSKDEDISLTLNMNEEEVEKRFEG
  RLTKNMSGSLYEMVSRVMKALVNRKITVPGNFQGHSGAQCITCSYKASSGLLYPLERGFI
  YVHKPPVHIRFDEISFVNFARGTTTTRSFDFEIETKQGTQYTFSSIEREEYGKLFDFVNA
  KKLNIKNRGLKEGMNPSYDEYADSDEDQHDAYLERMKEEGKIREENANDSSDDSGEETDE
  SFNPGEEEEDVAEEFDSNASASSSSNEGDSDRDEKKRKQLKKAKMAKDRKSRKKPVEVKK
  GKDPNAPKRPMSAYMLWLNASREKIKSDHPGISITDLSKKAGEIWKGMSKEKKEEWDRKA
  EDARRDYEKAMKEYEGGRGESSKRDKSKKKKKVKVKMEKKSTPSRGSSSKSSSRQLSESF
  KSKEFVSSDESSSGENKSKKKRRRSEDSEEEELASTPPSSEDSASGSDE
• Function: Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of 'Ser-392' of p53/TP53 via its association with CK2 (casein kinase II). Binds specifically to double-stranded DNA and at low levels to DNA modified by the antitumor agent cisplatin. May potentiate cisplatin-induced cell death by blocking replication and repair of modified DNA. Also acts as a transcriptional coactivator for p63/TP63.
• Reactome Pathway:
  Formation of HIV elongation complex in the absence of HIV Tat (R-HSA-167152)
  Formation of HIV-1 elongation complex containing HIV-1 Tat (R-HSA-167200)
  Pausing and recovery of Tat-mediated HIV elongation (R-HSA-167238)
  Tat-mediated HIV elongation arrest and recovery (R-HSA-167243)
  Tat-mediated elongation of the HIV-1 transcript (R-HSA-167246)
  HIV elongation arrest and recovery (R-HSA-167287)
  Pausing and recovery of HIV elongation (R-HSA-167290)
  RNA Polymerase II Pre-transcription Events (R-HSA-674695)
  TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648)
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)
  RNA Polymerase II Transcription Elongation (R-HSA-75955)
  Formation of RNA Pol II elongation complex (R-HSA-112382)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of FACT complex subunit SSRP1 (SSRP1).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of FACT complex subunit SSRP1 (SSRP1).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of FACT complex subunit SSRP1 (SSRP1).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of FACT complex subunit SSRP1 (SSRP1).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of FACT complex subunit SSRP1 (SSRP1).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of FACT complex subunit SSRP1 (SSRP1).	[6]
Selenium	DM25CGV	Approved	Selenium increases the expression of FACT complex subunit SSRP1 (SSRP1).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of FACT complex subunit SSRP1 (SSRP1).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of FACT complex subunit SSRP1 (SSRP1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of FACT complex subunit SSRP1 (SSRP1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of FACT complex subunit SSRP1 (SSRP1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of FACT complex subunit SSRP1 (SSRP1).	[9]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] 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.
• [10] BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.
• [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.
• [12] 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.