Details of Drug Off-Target (DOT)

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

• DOT Name: Phosducin-like protein (PDCL)
• Synonyms: PHLP
• Gene Name: PDCL
• Related Disease:
  Glioblastoma multiforme
  Neoplasm
• UniProt ID: PHLP_HUMAN
• PDB ID: 8SFF; 8SG8; 8SGC; 8SH9; 8SHA; 8SHF; 8SHG; 8SHL; 8SHO; 8SHP; 8SHQ; 8SHT
• Pfam ID: PF02114
• Sequence:
  MTTLDDKLLGEKLQYYYSSSEDEDSDHEDKDRGRCAPASSSVPAEAELAGEGISVNTGPK
  GVINDWRRFKQLETEQREEQCREMERLIKKLSMTCRSHLDEEEEQQKQKDLQEKISGKMT
  LKEFAIMNEDQDDEEFLQQYRKQRMEEMRQQLHKGPQFKQVFEISSGEGFLDMIDKEQKS
  IVIMVHIYEDGIPGTEAMNGCMICLAAEYPAVKFCKVKSSVIGASSQFTRNALPALLIYK
  GGELIGNFVRVTDQLGDDFFAVDLEAFLQEFGLLPEKEVLVLTSVRNSATCHSEDSDLEI
  D
• Function: Acts as a positive regulator of hedgehog signaling and regulates ciliary function; [Isoform 1]: Functions as a co-chaperone for CCT in the assembly of heterotrimeric G protein complexes, facilitates the assembly of both Gbeta-Ggamma and RGS-Gbeta5 heterodimers.; [Isoform 2]: Acts as a negative regulator of heterotrimeric G proteins assembly by trapping the preloaded G beta subunits inside the CCT chaperonin.
• Reactome Pathway: Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding (R-HSA-6814122)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[1]
Neoplasm	DISZKGEW	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Phosducin-like protein (PDCL).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Phosducin-like protein (PDCL).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phosducin-like protein (PDCL).	[4]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Phosducin-like protein (PDCL).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Phosducin-like protein (PDCL).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Phosducin-like protein (PDCL).	[7]
EMODIN	DMAEDQG	Terminated	EMODIN decreases the expression of Phosducin-like protein (PDCL).	[8]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Phosducin-like protein (PDCL).	[9]

References

• [1] Multi-omics analysis of primary glioblastoma cell lines shows recapitulation of pivotal molecular features of parental tumors.Neuro Oncol. 2017 Feb 1;19(2):219-228. doi: 10.1093/neuonc/now160.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] Gene expression alteration during redox-dependent enhancement of arsenic cytotoxicity by emodin in HeLa cells. Cell Res. 2005 Jul;15(7):511-22.
• [9] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.