Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH2PZWH)

• DOT Name: Single-stranded DNA-binding protein, mitochondrial (SSBP1)
• Synonyms: Mt-SSB; MtSSB; PWP1-interacting protein 17
• Gene Name: SSBP1
• Related Disease:
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Autosomal dominant optic atrophy
  Autosomal dominant optic atrophy, classic form
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Cytomegalovirus infection
  Nephropathy
  Non-small-cell lung cancer
  Optic atrophy 13 with retinal and foveal abnormalities
  Skin disease
  Triple negative breast cancer
  Optic nerve disorder
  Lung cancer
  Leigh syndrome
  Lung carcinoma
  Neuroblastoma
• UniProt ID: SSBP_HUMAN
• PDB ID: 1S3O; 2DUD; 3ULL; 6RUP
• Pfam ID: PF00436
• Sequence:
  MFRRPVLQVLRQFVRHESETTTSLVLERSLNRVHLLGRVGQDPVLRQVEGKNPVTIFSLA
  TNEMWRSGDSEVYQLGDVSQKTTWHRISVFRPGLRDVAYQYVKKGSRIYLEGKIDYGEYM
  DKNNVRRQATTIIADNIIFLSDQTKEKE
• Function: Binds preferentially and cooperatively to pyrimidine rich single-stranded DNA (ss-DNA). In vitro, required to maintain the copy number of mitochondrial DNA (mtDNA) and plays a crucial role during mtDNA replication by stimulating the activity of the replisome components POLG and TWNK at the replication fork. Promotes the activity of the gamma complex polymerase POLG, largely by organizing the template DNA and eliminating secondary structures to favor ss-DNA conformations that facilitate POLG activity. In addition it is able to promote the 5'-3' unwinding activity of the mtDNA helicase TWNK. May also function in mtDNA repair.
• Tissue Specificity: Expressed in retinal ganglion cells, photoreceptors, pigmented epithelium and fibroblasts (at protein level).
• KEGG Pathway:
  D. replication (hsa03030)
  Mismatch repair (hsa03430)
  Homologous recombi.tion (hsa03440)
• Reactome Pathway: Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[2]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[2]
Autosomal dominant optic atrophy	DISOCR1N	Strong	Genetic Variation	[3]
Autosomal dominant optic atrophy, classic form	DISXUAV9	Strong	Genetic Variation	[4]
Colon cancer	DISVC52G	Strong	Biomarker	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[2]
Nephropathy	DISXWP4P	Strong	Biomarker	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[7]
Optic atrophy 13 with retinal and foveal abnormalities	DISMO1Q1	Strong	Autosomal dominant	[8]
Skin disease	DISDW8R6	Strong	Biomarker	[9]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[10]
Optic nerve disorder	DISSOQM8	moderate	Genetic Variation	[11]
Lung cancer	DISCM4YA	Disputed	Biomarker	[12]
Leigh syndrome	DISWQU45	Limited	Autosomal dominant	[8]
Lung carcinoma	DISTR26C	Limited	Biomarker	[12]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[14]

17 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 Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[16]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[19]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[21]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[22]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[23]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[24]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[25]
Dopamine	DMPGUCF	Approved	Dopamine increases the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[27]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[28]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[29]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[30]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide increases the expression of Single-stranded DNA-binding protein, mitochondrial (SSBP1).	[31]

References

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• [5] SSBP1 Upregulation In Colorectal Cancer Regulates Mitochondrial Mass.Cancer Manag Res. 2019 Dec 2;11:10093-10106. doi: 10.2147/CMAR.S211292. eCollection 2019.
• [6] SSBP1 mutations cause mtDNA depletion underlying a complex optic atrophy disorder.J Clin Invest. 2020 Jan 2;130(1):108-125. doi: 10.1172/JCI128514.
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• [10] SSBP1 Suppresses TGF-Driven Epithelial-to-Mesenchymal Transition and Metastasis in Triple-Negative Breast Cancer by Regulating Mitochondrial Retrograde Signaling.Cancer Res. 2016 Feb 15;76(4):952-64. doi: 10.1158/0008-5472.CAN-15-1630. Epub 2015 Dec 16.
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• [18] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
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