Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY24CUW)

DOT Name	Peflin (PEF1)
Synonyms	PEF protein with a long N-terminal hydrophobic domain; Penta-EF hand domain-containing protein 1
Gene Name	PEF1
UniProt ID	PEF1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF13405 ; PF13499
Sequence	MASYPYRQGCPGAAGQAPGAPPGSYYPGPPNSGGQYGSGLPPGGGYGGPAPGGPYGPPAG GGPYGHPNPGMFPSGTPGGPYGGAAPGGPYGQPPPSSYGAQQPGLYGQGGAPPNVDPEAY SWFQSVDSDHSGYISMKELKQALVNCNWSSFNDETCLMMINMFDKTKSGRIDVYGFSALW KFIQQWKNLFQQYDRDRSGSISYTELQQALSQMGYNLSPQFTQLLVSRYCPRSANPAMQL DRFIQVCTQLQVLTEAFREKDTAVQGNIRLSFEDFVTMTASRML
Function	Calcium-binding protein that acts as an adapter that bridges unrelated proteins or stabilizes weak protein-protein complexes in response to calcium. Together with PDCD6, acts as a calcium-dependent adapter for the BCR(KLHL12) complex, a complex involved in endoplasmic reticulum (ER)-Golgi transport by regulating the size of COPII coats. In response to cytosolic calcium increase, the heterodimer formed with PDCD6 interacts with, and bridges together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export, which is required for neural crest specification. Its role in the heterodimer formed with PDCD6 is however unclear: some evidence shows that PEF1 and PDCD6 work together and promote association between PDCD6 and SEC31 in presence of calcium. Other reports show that PEF1 dissociates from PDCD6 in presence of calcium, and may act as a negative regulator of PDCD6. Also acts as a negative regulator of ER-Golgi transport; possibly by inhibiting interaction between PDCD6 and SEC31.

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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 Peflin (PEF1).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Peflin (PEF1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Peflin (PEF1).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Peflin (PEF1).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Peflin (PEF1).	[3]
Selenium	DM25CGV	Approved	Selenium increases the expression of Peflin (PEF1).	[5]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Peflin (PEF1).	[6]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Peflin (PEF1).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Peflin (PEF1).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Peflin (PEF1).	[1]
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References

1	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.
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	Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
4	A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
5	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.
6	Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
7	Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.