Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQU8081)

• DOT Name: SOSS complex subunit B1 (NABP2)
• Synonyms: Nucleic acid-binding protein 2; Oligonucleotide/oligosaccharide-binding fold-containing protein 2B; Sensor of single-strand DNA complex subunit B1; Sensor of ssDNA subunit B1; SOSS-B1; Single-stranded DNA-binding protein 1; hSSB1
• Gene Name: NABP2
• Related Disease:
  Advanced cancer
  Ataxia-telangiectasia
  Cytomegalovirus infection
  Hepatocellular carcinoma
  Pancytopenia
  Schnyder corneal dystrophy
  Obesity
  Respiratory failure
  Lung cancer
  Lung carcinoma
  Neoplasm
• UniProt ID: SOSB1_HUMAN
• PDB ID: 4OWT; 4OWW; 4OWX; 5D8E; 5D8F
• Pfam ID: PF21473
• Sequence:
  MTTETFVKDIKPGLKNLNLIFIVLETGRVTKTKDGHEVRTCKVADKTGSINISVWDDVGN
  LIQPGDIIRLTKGYASVFKGCLTLYTGRGGDLQKIGEFCMVYSEVPNFSEPNPEYSTQQA
  PNKAVQNDSNPSASQPTTGPSAASPASENQNGNGLSAPPGPGGGPHPPHTPSHPPSTRIT
  RSQPNHTPAGPPGPSSNPVSNGKETRRSSKR
• Function: Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. In the SOSS complex, acts as a sensor of single-stranded DNA that binds to single-stranded DNA, in particular to polypyrimidines. The SOSS complex associates with DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. Required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways.
• Reactome Pathway: RNA polymerase II transcribes snRNA genes (R-HSA-6807505)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Ataxia-telangiectasia	DISP3EVR	Strong	Biomarker	[2]
Cytomegalovirus infection	DISCEMGC	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Pancytopenia	DISVKEHV	Strong	Biomarker	[5]
Schnyder corneal dystrophy	DISAYSN1	Strong	Biomarker	[6]
Obesity	DIS47Y1K	moderate	Genetic Variation	[7]
Respiratory failure	DISVMYJO	moderate	Biomarker	[8]
Lung cancer	DISCM4YA	Disputed	Biomarker	[9]
Lung carcinoma	DISTR26C	Limited	Biomarker	[9]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of SOSS complex subunit B1 (NABP2).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SOSS complex subunit B1 (NABP2).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SOSS complex subunit B1 (NABP2).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of SOSS complex subunit B1 (NABP2).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Etoposide increases the acetylation of SOSS complex subunit B1 (NABP2).	[12]
Nicotinamide	DMUPE07	Approved	Nicotinamide decreases the ubiquitination of SOSS complex subunit B1 (NABP2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the ubiquitination of SOSS complex subunit B1 (NABP2).	[12]

References

• [1] hSSB1 associates with and promotes stability of the BLM helicase.BMC Mol Biol. 2017 May 15;18(1):13. doi: 10.1186/s12867-017-0090-3.
• [2] INTS3 controls the hSSB1-mediated DNA damage response.J Cell Biol. 2009 Oct 5;187(1):25-32. doi: 10.1083/jcb.200907026. Epub 2009 Sep 28.
• [3] Down-regulation of single-stranded DNA-binding protein 1 expression induced by HCMV infection promotes lipid accumulation in cells.Braz J Med Biol Res. 2017 Sep 12;50(11):e6389. doi: 10.1590/1414-431X20176389.
• [4] hSSB1 binds and protects p21 from ubiquitin-mediated degradation and positively correlates with p21 in human hepatocellular carcinomas.Oncogene. 2011 May 12;30(19):2219-29. doi: 10.1038/onc.2010.596. Epub 2011 Jan 17.
• [5] Ssb1 and Ssb2 cooperate to regulate mouse hematopoietic stem and progenitor cells by resolving replicative stress.Blood. 2017 May 4;129(18):2479-2492. doi: 10.1182/blood-2016-06-725093. Epub 2017 Mar 7.
• [6] Analysis of fifteen positional candidate genes for Schnyder crystalline corneal dystrophy.Mol Vis. 2005 Sep 2;11:713-6.
• [7] Association of breastfeeding and early exposure to sugar-sweetened beverages with obesity prevalence in offspring born to mothers with and without gestational diabetes mellitus.Pediatr Obes. 2019 Dec;14(12):e12569. doi: 10.1111/ijpo.12569. Epub 2019 Aug 6.
• [8] Essential developmental, genomic stability, and tumour suppressor functions of the mouse orthologue of hSSB1/NABP2.PLoS Genet. 2013;9(2):e1003298. doi: 10.1371/journal.pgen.1003298. Epub 2013 Feb 7.
• [9] UPregulated single-stranded DNA-binding protein 1 induces cell chemoresistance to cisplatin in lung cancer cell lines.Mol Cell Biochem. 2017 Jul;431(1-2):21-27. doi: 10.1007/s11010-017-2970-8. Epub 2017 Feb 16.
• [10] 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.
• [11] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [12] Acetylation-dependent function of human single-stranded DNA binding protein 1. Nucleic Acids Res. 2015 Sep 18;43(16):7878-87. doi: 10.1093/nar/gkv707. Epub 2015 Jul 13.
• [13] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [14] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.