Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFWNK8G)

• DOT Name: Protein POF1B (POF1B)
• Synonyms: Premature ovarian failure protein 1B
• Gene Name: POF1B
• Related Disease:
  Hypoparathyroidism
  Type-1 diabetes
  Skin disease
  Graves disease
• UniProt ID: POF1B_HUMAN
• PDB ID: 3BH9
• Sequence:
  MSSSYWSETSSSSCGTQQLPEVLQCQPQHYHCYHQSSQAQQPPEKNVVYERVRTYSGPMN
  KVVQALDPFNSREVLSPLKTTSSYQNLVWSDHSQELHSPTLKISTCAPSTLHITQNTEQE
  LHSPTVKLTTYPQTTIRKYVVQNPEQEPLSQFLRGSHFFPGNNVIYEKTIRKVEKLNTDQ
  GCHPQAQCHHHIIQQPQVIHSAHWQQPDSSQQIQAITGNNPISTHIGNELCHSGSSQICE
  QVIIQDDGPEKLDPRYFGELLADLSRKNTDLYHCLLEHLQRIGGSKQDFESTDESEDIES
  LIPKGLSEFTKQQIRYILQMRGMSDKSLRLVLSTFSNIREELGHLQNDMTSLENDKMRLE
  KDLSFKDTQLKEYEELLASVRANNHQQQQGLQDSSSKCQALEENNLSLRHTLSDMEYRLK
  ELEYCKRNLEQENQNLRMQVSETCTGPMLQAKMDEIGNHYTEMVKNLRMEKDREICRLRS
  QLNQYHKDVSKREGSCSDFQFKLHELTSLLEEKDSLIKRQSEELSKLRQEIYSSHNQPST
  GGRTTITTKKYRTQYPILGLLYDDYEYIPPGSETQTIVIEKTEDKYTCP
• Function: Plays a key role in the organization of epithelial monolayers by regulating the actin cytoskeleton. May be involved in ovary development.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypoparathyroidism	DISICS0V	Definitive	Biomarker	[1]
Type-1 diabetes	DIS7HLUB	Definitive	Genetic Variation	[1]
Skin disease	DISDW8R6	Strong	Biomarker	[2]
Graves disease	DISU4KOQ	Disputed	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protein POF1B (POF1B).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein POF1B (POF1B).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein POF1B (POF1B).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein POF1B (POF1B).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Protein POF1B (POF1B).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein POF1B (POF1B).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Protein POF1B (POF1B).	[8]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Protein POF1B (POF1B).	[10]

References

• [1] Autoimmune endocrine diseases.Minerva Endocrinol. 2018 Sep;43(3):305-322. doi: 10.23736/S0391-1977.17.02757-2. Epub 2017 Oct 9.
• [2] POF1B localizes to desmosomes and regulates cell adhesion in human intestinal and keratinocyte cell lines.J Invest Dermatol. 2015 Jan;135(1):192-201. doi: 10.1038/jid.2014.327. Epub 2014 Aug 1.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] 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.
• [9] 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.
• [10] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.