Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6ZJFEC)

• DOT Name: Phosphatidylinositol 4-phosphate 5-kinase-like protein 1 (PIP5KL1)
• Synonyms: PI(4)P 5-kinase-like protein 1; PtdIns(4)P-5-kinase-like protein 1; EC 2.7.1.68
• Gene Name: PIP5KL1
• Related Disease:
  Neoplasm
  Advanced cancer
• UniProt ID: PI5L1_HUMAN
• EC Number: 2.7.1.68
• Pfam ID: PF01504
• Sequence:
  MAAPSPGPREVLAPSPEAGCRAVTSSRRGLLWRLRDKQSRLGLFEISPGHELHGMTCMMQ
  AGLWAATQVSMDHPPTGPPSRDDFSEVLTQVHEGFELGTLAGPAFAWLRRSLGLAEEDYQ
  AALGPGGPYLQFLSTSKSKASFFLSHDQRFFLKTQGRREVQALLAHLPRYVQHLQRHPHS
  LLARLLGVHSLRVDRGKKTYFIVMQSVFYPAGRISERYDIKGCEVSRWVDPAPEGSPLVL
  VLKDLNFQGKTINLGPQRSWFLRQMELDTTFLRELNVLDYSLLIAFQRLHEDERGPGSSL
  IFRTARSVQGAQSPEESRAQNRRLLPDAPNALHILDGPEQRYFLGVVDLATVYGLRKRLE
  HLWKTLRYPGRTFSTVSPARYARRLCQWVEAHTE
• Function: May act as a scaffold to localize and regulate type I PI(4)P 5-kinases to specific compartments within the cell, where they generate PI(4,5)P2 for actin nucleation, signaling and scaffold protein recruitment and conversion to PI(3,4,5)P3.
• KEGG Pathway:
  Inositol phosphate metabolism (hsa00562)
  Metabolic pathways (hsa01100)
  Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Phosphatidylinositol 4-phosphate 5-kinase-like protein 1 (PIP5KL1).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Phosphatidylinositol 4-phosphate 5-kinase-like protein 1 (PIP5KL1).	[4]

References

• [1] Overexpression of PIP5KL1 suppresses the growth of human cervical cancer cells in vitro and in vivo.Cell Biol Int. 2010 Feb 22;34(3):309-15. doi: 10.1042/CBI20090040.
• [2] Overexpression of PIP5KL1 suppresses cell proliferation and migration in human gastric cancer cells.Mol Biol Rep. 2010 Jun;37(5):2189-98. doi: 10.1007/s11033-009-9701-5. Epub 2009 Aug 13.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.