Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYEL9HZ)

• DOT Name: Testicular acid phosphatase (ACP4)
• Synonyms: EC 3.1.3.2; Acid phosphatase 4
• Gene Name: ACP4
• Related Disease: Amelogenesis imperfecta type 1
• UniProt ID: PPAT_HUMAN
• EC Number: 3.1.3.2
• Pfam ID: PF00328
• Sequence:
  MAGLGFWGHPAGPLLLLLLLVLPPRALPEGPLVFVALVFRHGDRAPLASYPMDPHKEVAS
  TLWPRGLGQLTTEGVRQQLELGRFLRSRYEAFLSPEYRREEVYIRSTDFDRTLESAQANL
  AGLFPEAAPGSPEARWRPIPVHTVPVAEDKLLRFPMRSCPRYHELLREATEAAEYQEALE
  GWTGFLSRLENFTGLSLVGEPLRRAWKVLDTLMCQQAHGLPLPAWASPDVLRTLAQISAL
  DIGAHVGPPRAAEKAQLTGGILLNAILANFSRVQRLGLPLKMVMYSAHDSTLLALQGALG
  LYDGHTPPYAACLGFEFRKHLGNPAKDGGNVTVSLFYRNDSAHLPLPLSLPGCPAPCPLG
  RFYQLTAPARPPAHGVSCHGPYEAAIPPAPVVPLLAGAVAVLVALSLGLGLLAWRPGCLR
  ALGGPV
• Function: May dephosphorylate receptor tyrosine-protein kinase ERBB4 and inhibits its ligand-induced proteolytic cleavage. May play a role in odontogenesis.
• Tissue Specificity: Expressed mainly in the testis. Also expressed in the brain where they are enriched at the postsynaptic sites. Expressed at lower levels in the trachea, prostate, bone marrow, spinal cord, colon, fetal brain, heart, thymus, fetal liver, spleen, leukocytes, ovary, small intestine, pancreas and skeletal muscle. Expression is significantly lower in testicular cancer tissues than in normal testicular tissues. Isoform 3 is expressed in the testis, trachea, prostate and bone marrow.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amelogenesis imperfecta type 1	DISVEG5A	Supportive	Autosomal dominant	[1]

3 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 Testicular acid phosphatase (ACP4).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Testicular acid phosphatase (ACP4).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Testicular acid phosphatase (ACP4).	[4]

References

• [1] Recessive Mutations in ACPT, Encoding Testicular Acid Phosphatase, Cause Hypoplastic Amelogenesis Imperfecta. Am J Hum Genet. 2016 Nov 3;99(5):1199-1205. doi: 10.1016/j.ajhg.2016.09.018. Epub 2016 Oct 27.
• [2] 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.
• [3] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [4] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.