Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHZT1GR)

• DOT Name: Protocadherin alpha-5 (PCDHA5)
• Synonyms: PCDH-alpha-5
• Gene Name: PCDHA5
• Related Disease:
  Major depressive disorder
  Prostate cancer
• UniProt ID: PCDA5_HUMAN
• Pfam ID: PF00028 ; PF08266 ; PF15974
• Sequence:
  MVYSRRGSLGSRLLLLWLLLAYWKAGSGQLHYSIPEEAKHGTFVGRIAQDLGLELAELVP
  RLFRVASKGRGDLLEVNLQNGILFVNSRIDREELCRRRAECSIHLEVIVDRPLQVFHVEV
  AVKDINDNPPRFSRQEQRLFILESRMPDSRFPLEGASDLDIGANAQLRYRLNPNEYFDLD
  VKTNEEETNFLELVLRKSLDREETQEHRLLVIATDGGKPELTGTVQLLINVLDANDNAPE
  FDKSIYNVRLLENAPSGTLVIKLNASDADEGINKEIVYFFSNLVLDDVKSKFIINSNTGE
  IKVNGELDYEDYNSYEINIDAMDKSTFPLSGHCKVVVKLLDVNDNTPEMAITTLFLPVKE
  DAPLSTVIALISVSDRDSGANGQVTCSLMPHVPFKLVSTFKNYYSLVLDSALDRESVSVY
  ELVVTARDGGSPSLWATASVSVEVADVNDNAPAFAQPQYTVFVKENNPPGCHIFTVSARD
  ADAQENALVSYSLVERRVGERPLSSYVSVHAESGKVYALQPLDHEEVELLQFQVSARDAG
  VPPLGSNVTLQVFVLDENDNAPALLVPRVGGTGGAVSELVPRSVGAGHVVAKVRAVDPDS
  GYNAWLSYELQPAPGSARIPFRVGLYTGEISTTRSLDETEAPRHRLLVLVKDHGEPPLTA
  TATVLVSLVESGQAPKASSRASAGAVGPEAALVDVNVYLIIAICAVSSLLVLTLLLYTAL
  RCSAQPTEAVCTRGKPTLLCSSAVGSWSYSQQRRQRVCSGEAPPKTDLMAFSPSLPQGPT
  STDNPRQPNPDWRYSASLRAGMHSSVHLEEAGILRAGPGGPDQQWPTVSSATPEPEAGEV
  SPPVGAGVNSNSWTFKYGPGNPKQSGPGELPDKFIIPGSPAIISIRQEPTNSQIDKSDFI
  TFGKKEETKKKKKKKKGNKTQEKKEKGNSTTDNSDQ
• Function: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[1]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[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 Protocadherin alpha-5 (PCDHA5).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Protocadherin alpha-5 (PCDHA5).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protocadherin alpha-5 (PCDHA5).	[5]

References

• [1] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [2] A genome-wide association study of prostate cancer in West African men.Hum Genet. 2014 May;133(5):509-21. doi: 10.1007/s00439-013-1387-z. Epub 2013 Nov 2.
• [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] Proteomic analysis of antiproliferative effects by treatment of 5-fluorouracil in cervical cancer cells. DNA Cell Biol. 2004 Nov;23(11):769-76.
• [5] Gene expression profiling of A549 cells exposed to Milan PM2.5. Toxicol Lett. 2012 Mar 7;209(2):136-45.