Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6CFK4K)

• DOT Name: AP-1 complex-associated regulatory protein (AP1AR)
• Synonyms: 2c18; Adaptor-related protein complex 1-associated regulatory protein; Gamma-1-adaptin brefeldin A resistance protein; GBAR; Gamma-BAR; Gamma-A1-adaptin and kinesin interactor; Gadkin
• Gene Name: AP1AR
• Related Disease: Immunodeficiency
• UniProt ID: AP1AR_HUMAN
• Pfam ID: PF15745
• Sequence:
  MGNCCWTQCFGLLRKEAGRLQRVGGGGGSKYFRTCSRGEHLTIEFENLVESDEGESPGSS
  HRPLTEEEIVDLRERHYDSIAEKQKDLDKKIQKELALQEEKLRLEEEALYAAQREAARAA
  KQRKLLEQERQRIVQQYHPSNNGEYQSSGPEDDFESCLRNMKSQYEVFRSSRLSSDATVL
  TPNTESSCDLMTKTKSTSGNDDSTSLDLEWEDEEGMNRMLPMRERSKTEEDILRAALKYS
  NKKTGSNPTSASDDSNGLEWENDFVSAEMDDNGNSEYSGFVNPVLELSDSGIRHSDTDQQ
  TR
• Function: Necessary for adaptor protein complex 1 (AP-1)-dependent transport between the trans-Golgi network and endosomes. Regulates the membrane association of AP1G1/gamma1-adaptin, one of the subunits of the AP-1 adaptor complex. The direct interaction with AP1G1/gamma1-adaptin attenuates the release of the AP-1 complex from membranes. Regulates endosomal membrane traffic via association with AP-1 and KIF5B thus linking kinesin-based plus-end-directed microtubular transport to AP-1-dependent membrane traffic. May act as effector of AP-1 in calcium-induced endo-lysosome secretion. Inhibits Arp2/3 complex function; negatively regulates cell spreading, size and motility via intracellular sequestration of the Arp2/3 complex.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immunodeficiency	DIS093I0	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of AP-1 complex-associated regulatory protein (AP1AR).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of AP-1 complex-associated regulatory protein (AP1AR).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of AP-1 complex-associated regulatory protein (AP1AR).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of AP-1 complex-associated regulatory protein (AP1AR).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of AP-1 complex-associated regulatory protein (AP1AR).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of AP-1 complex-associated regulatory protein (AP1AR).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of AP-1 complex-associated regulatory protein (AP1AR).	[7]

References

• [1] Retroviral transfer of human cytochrome P450 genes for oxazaphosphorine-based cancer gene therapy. Cancer Res. 1998 Oct 1;58(19):4391-401.
• [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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [7] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [8] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.