Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ2H8DN)

• DOT Name: AP-1 complex subunit sigma-1A (AP1S1)
• Synonyms: Adaptor protein complex AP-1 subunit sigma-1A; Adaptor-related protein complex 1 subunit sigma-1A; Clathrin assembly protein complex 1 sigma-1A small chain; Clathrin coat assembly protein AP19; Golgi adaptor HA1/AP1 adaptin sigma-1A subunit; HA1 19 kDa subunit; Sigma 1a subunit of AP-1 clathrin; Sigma-adaptin 1A; Sigma1A-adaptin
• Gene Name: AP1S1
• Related Disease:
  MEDNIK syndrome
  Copper metabolism disorder
  Neurocutaneous syndrome
  Intellectual disability
  Non-syndromic ichthyosis
  Intrahepatic cholestasis
  Lysosomal lipid storage disorder
• UniProt ID: AP1S1_HUMAN
• PDB ID: 4P6Z
• Pfam ID: PF01217
• Sequence:
  MMRFMLLFSRQGKLRLQKWYLATSDKERKKMVRELMQVVLARKPKMCSFLEWRDLKVVYK
  RYASLYFCCAIEGQDNELITLELIHRYVELLDKYFGSVCELDIIFNFEKAYFILDEFLMG
  GDVQDTSKKSVLKAIEQADLLQEEDESPRSVLEEMGLA
• Function: Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.
• Tissue Specificity: Widely expressed.
• KEGG Pathway:
  Lysosome (hsa04142)
  Human immunodeficiency virus 1 infection (hsa05170)
• Reactome Pathway:
  MHC class II antigen presentation (R-HSA-2132295)
  Lysosome Vesicle Biogenesis (R-HSA-432720)
  Golgi Associated Vesicle Biogenesis (R-HSA-432722)
  Nef mediated downregulation of MHC class I complex cell surface expression (R-HSA-164940)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
MEDNIK syndrome	DISRF06E	Definitive	Autosomal recessive	[1]
Copper metabolism disorder	DISXHPKM	Strong	Biomarker	[2]
Neurocutaneous syndrome	DISNC82H	Strong	Genetic Variation	[3]
Intellectual disability	DISMBNXP	moderate	Biomarker	[2]
Non-syndromic ichthyosis	DISZ9QBQ	moderate	Biomarker	[4]
Intrahepatic cholestasis	DISHITDZ	Limited	Biomarker	[5]
Lysosomal lipid storage disorder	DISXQRTX	Limited	Biomarker	[6]

29 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 subunit sigma-1A (AP1S1).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[12]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[15]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of AP-1 complex subunit sigma-1A (AP1S1).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[17]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[18]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[6]
Fluoxetine	DM3PD2C	Approved	Fluoxetine decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[20]
Tetracycline	DMZA017	Approved	Tetracycline decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[6]
Thioridazine	DM35M8J	Approved	Thioridazine decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[20]
Clomipramine	DMINRKW	Approved	Clomipramine decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[20]
Loratadine	DMF3AN7	Approved	Loratadine decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[21]
Flecainide	DMSQDLE	Approved	Flecainide decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[6]
Perhexiline	DMINO7Z	Approved	Perhexiline decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[6]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[6]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[24]
ZIMELIDINE	DMNI3U2	Withdrawn from market	ZIMELIDINE decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of AP-1 complex subunit sigma-1A (AP1S1).	[25]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[26]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[27]
PP-242	DM2348V	Investigative	PP-242 increases the expression of AP-1 complex subunit sigma-1A (AP1S1).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of AP-1 complex subunit sigma-1A (AP1S1).	[22]

References

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• [20] A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
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